Laura Bohn Ph.D.
- Mailing Address:
-
Location A235
130 SCRIPPS WAY BLDG 2A2
JUPITER FL 33458
Research in the Bohn laboratory is focused on understanding how G protein-coupled receptors function in an endogenous setting to control physiologically relevant processes. We are most interested in receptors that mediate neurological functions, particularly those of the opioid, serotonin and cannabinoid families. Ultimately, our goal is to refine therapeutics- to enhance the benefits and eliminate the side effects. In this manner, we hope to inspire new approaches in treating pain, addiction and mood disorders.
The Bohn laboratory is most widely known for our work in opioid receptors. Early work while in the laboratory of Marc Caron and in collaboration with Robert Lefkowitz at Duke University indicated that barrestin2 plays a critical role in determining the physiological role of the mu opioid receptor (MOR) in vivo. Our laboratory has shown that barrestin2 plays different roles in regulating the MOR depending upon the physiological function assessed. This is very important as activation of the MOR results in multiple physiological processes ranging from the highly desirable suppression of pain perception to the deadly effects of respiratory failure. By determining which barrestin2-mediated signaling pathways are associated with these different physiological outcomes, we aim to elucidate a means to develop potent opioid analgesics that circumvent the adverse side effects. The bulk of our work to date suggests that if we preserve MOR coupling to G proteins, but eliminate the interactions between the receptor and the scaffolding protein, barrestin2, then we may be able to separate analgesic potency from constipation, respiratory suppression, tolerance and physical dependence.
Our lab is now focused on developing tool compounds that will allow us to test these hypotheses. Our agonists are designed, in collaboration with Dr. Tom Bannister of TSRI, to activate MOR in a manner that preserves or improves G protein signaling while eliminating the recruitment of barrestins. In addition to generating potential therapeutic leads, we are very interested in using these tools to elucidate MOR function in vivo. As we refine the pathways underlying different physiological responses, we will then know the signaling mechanisms to preserve and the ones to avoid.
We are also taking a similar approach with the kappa opioid receptors (KOR). The KOR in the midbrain acts to regulate dopamine and serotonin levels and thereby serves as an attractive target for modulating mood and reward thresholds. KOR ligands that display bias towards or against recruiting barrestins are of interest as barrestin2 has been implicated in facilitating aversive KOR-mediated behaviors. In our work with Dr. Jeff Aubé of Kansas University, we have been developing and evaluating KOR biased agonists to determine which physiologies are preserved or disrupted in mouse models. Since the KOR is involved in diverse physiological functions, compounds generated in this project may serve as interesting candidates for the treatment of depressive disorders and addiction. Moreover, KOR agonism produces antinociception and blocks itch and may also represent potential therapeutic avenues.
Recently, we have begun evaluating ligands for biased agonism among cannabinoid receptor (CB1 and CB2) agonists in collaboration with Dr. Alex Makriyannis at Northeastern University. Given the emerging implications for using cannabinoids as therapeutics for a wide-range of disorders, there are many opportunities for new drug development. This collaboration has also involved working with Dr. Ray Stevens (USC) and Dr. James Liu (Shanghai Tech) to solve the first crystal structures of antagonist and agonist bound CB1 receptors. Additional efforts in the laboratory focus on evaluating how antipsychotic drugs and mood altering neurotransmitters such as serotonin act at serotonin receptors.
Since the receptors described above are involved in modulating mood, motivation, and sensory perception, it stands to reason that our laboratory is most interested in developing means to treat pain, whether due to injury, disease or mental state, in a manner that adequately manages the pain, without causing deabilitating side effects.
- 2023 ACS Central Science
- 2023 Biochemical Society Transactions
- 2022 ACS Central Science
- 2022 British Journal of Pharmacology
- 2022 European Journal of Medicinal Chemistry
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2022
Low Intrinsic Efficacy Alone Cannot Explain the Improved Side Effect Profiles of New Opioid AgonistsBiochemistry
- 2022 ACS Chemical Neuroscience
- 2021 Journal of the American Chemical Society
- 2021 Neuropharmacology
- 2021 Cell
- 2021 Proceedings of the National Academy of Sciences
- 2021 Journal of medicinal chemistry
- 2021 Behavioural pharmacology
- 2020 Biological psychiatry
- 2020 Molecular psychiatry
- 2020 Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
- 2020 Cell
- 2019 Cell
- 2019 Molecular pharmacology
- 2019 Methods in molecular biology (Clifton, N.J.)
- 2018 Science Signaling
- 2018 Bioorganic & medicinal chemistry letters
- 2018 Journal of medicinal chemistry
- 2018 ACS omega
- 2018 Drug and alcohol dependence
- 2017 Journal of the American Chemical Society
- 2017 ACS medicinal chemistry letters
- 2017 ACS central science
- 2017 ACS chemical neuroscience
- 2017 Cell
- 2017 Methods in enzymology
- 2017 Nature
-
2016
5-HT1A Autoreceptors in the Dorsal Raphe Nucleus Convey Vulnerability to Compulsive Cocaine Seeking.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
- 2016 Bioorganic & medicinal chemistry letters
- 2016 Science signaling
- 2016 Cell
- 2016 Science signaling
- 2016 Molecular and cellular biology
- 2016 The Journal of organic chemistry
- 2016 G3 (Bethesda, Md.)
- 2015 ACS chemical neuroscience
- 2015 Bioorganic & medicinal chemistry
- 2015 ACS chemical neuroscience
- 2015 Neuropharmacology
- 2015 Methods in molecular biology (Clifton, N.J.)
- 2015 Molecular pharmacology
- 2015 Neuropharmacology
- 2015 Molecular pharmacology
- 2015 Molecular pharmacology
- 2014 Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
- 2014 Current opinion in cell biology
- 2014 Handbook of experimental pharmacology
- 2013 The Journal of biological chemistry
- 2013 The Journal of biological chemistry
- 2012 Drug and alcohol dependence
- 2012 Bioorganic & medicinal chemistry letters
- 2012 ACS chemical neuroscience
- 2012 Proceedings of the National Academy of Sciences of the United States of America
- 2012 Biological psychiatry
- 2011 The Journal of biological chemistry
- 2011 Pharmacological reviews
- 2011 Digestive diseases and sciences
- 2011 Nature chemistry
- 2011 Neuropharmacology
- 2010 Critical reviews in biochemistry and molecular biology
- 2010 The Journal of neuroscience : the official journal of the Society for Neuroscience
- 2010 The Journal of pharmacology and experimental therapeutics
- 2010 Drug discovery today. Technologies
- 2009 Drug and alcohol dependence
- 2009 Biochemical and biophysical research communications
- 2009 Pharmacology & therapeutics
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2009
Stimulation of mucosal secretion by lubiprostone (SPI-0211) in guinea pig small intestine and colon.American journal of physiology. Gastrointestinal and liver physiology
- 2008 Proceedings of the National Academy of Sciences of the United States of America
- 2008 Journal of medicinal chemistry
- 2008 Journal of neurochemistry
- 2008 The Journal of biological chemistry
- 2007 Synapse (New York, N.Y.)
- 2007 Molecular pharmacology
- 2007 Molecular pharmacology
- 2006 Current opinion in pharmacology
- 2006 Molecular interventions
- 2005 The Journal of pharmacology and experimental therapeutics
- 2005 The AAPS journal
- 2005 Molecular pharmacology
- 2005 Psychopharmacology
- 2004 Annual review of neuroscience
- 2004 The Journal of experimental biology
- 2004 Neuromolecular medicine
- 2004 Molecular pharmacology
- 2003 Neuron
- 2003 The Journal of neuroscience : the official journal of the Society for Neuroscience
- 2003 The Journal of biological chemistry
- 2003 Proceedings of the National Academy of Sciences of the United States of America
- 2000 The Journal of neuroscience : the official journal of the Society for Neuroscience
- 2000 Nature
- 2000 Nature neuroscience
- 2000 Journal of neurochemistry
- 2000 Journal of neurochemistry
- 1999 Science (New York, N.Y.)
- 1999 Neuron
- 1999 The Journal of neuroscience : the official journal of the Society for Neuroscience
- 1998 Brain research. Developmental brain research
- 1998 Journal of neurochemistry
- 1998 Cancer
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Jun 2023
ACTIVE
Deconvolution of Galbulimima bark pharmacology through chemical synthesis and target assignmentSCRIPPS RESEARCH INST · Principal Investigator
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Aug 2022
ACTIVE
Molecular pharmacology of cannabinoid receptor probesNORTHEASTERN UNIV · Principal Investigator
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Aug 2022
ACTIVE
Biasing Mu Opioid Receptor Signaling in vivoNATL INST OF HLTH NIDA · Principal Investigator
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Apr 2022
–
Apr 2022
Pharmacological interactions between conventional and biased MOR agonistsNATL INST OF HLTH NIDA · Principal Investigator
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Apr 2022
–
Jun 2023
Opioid Impacts on T Cell Pathways and Epigenetics to Modulate HIV Integration, Latency and ReservoirsUNIV OF CALIFORNIA SAN DIEGO · Principal Investigator
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Apr 2022
–
Aug 2023
Structure and Function of CB2 ReceptorNORTHEASTERN UNIV · Principal Investigator
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Apr 2022
ACTIVE
Biased Kappa Opioid Agonists as Non-addictive AnalgesicsWAKE FOREST UNIV · Principal Investigator
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Apr 2022
ACTIVE
Synthesis and Evaluation of Functionally Biased Opioid AnalgesicsNATL INST OF HLTH NIDA · Principal Investigator
-
1999
Ph.D. in Biochemistry & Molecular BiologySaint Louis University, School of Medicine
-
1993
Bachelor's of Arts in ChemistryVirginia Polytechnic Institute and State University
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1993
Bachelor's of Science in BiochemistryVirginia Polytechnic Institute and State University
James Burke
- Physical Address:
-
Location B211A
130 SCRIPPS WAY BLDG 2B2
JUPITER FL 33458
- 2023 Methods in enzymology
- 2022 Journal of cell science
- 2022 Wiley interdisciplinary reviews. RNA
- 2022 The EMBO journal
- 2022 PLoS pathogens
- 2022 Proceedings of the National Academy of Sciences of the United States of America
- 2021 Journal of cell science
- 2021 Epilepsy & behavior : E&B
- 2021 bioRxiv : the preprint server for biology
- 2021 Science advances
- 2021 RNA (New York, N.Y.)
- 2021 Science advances
- 2020 Genes & development
- 2020 PLoS pathogens
- 2020 The Journal of biological chemistry
- 2019 Molecular cell
- 2018 Journal of virology
- 2017 Nucleic acids research
- 2017 RNA biology
- 2016 Genes & development
- 2016 Neurology
- 2015 Methods (San Diego, Calif.)
- 2014 RNA (New York, N.Y.)
- 2014 Nucleic acids research
- 2014 PloS one
- 2014 Journal of virology
- 2014 Medical care
- 2013 Journal of virology
- 2013 Cell host & microbe
- 2012 Proceedings of the National Academy of Sciences of the United States of America
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Sep 2023
ACTIVE
Understanding the OAS/RNase L pathway during pathogenic viral infectionsNATL INST OF HLTH NIGMS · Principal Investigator
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2017-2022
Postdoctoral FellowUniversity of Colorado Boulder
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2010-2016
Ph.D.University of Texas at Austin
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2006-2009
B.S. BiochemistryUniversity of North Texas
Michael Cameron Ph.D.
- Mailing Address:
-
Location A201
130 SCRIPPS WAY BLDG 2A1
JUPITER FL 33458
The Cameron Laboratory works on a variety of independent and collaborative projects centered on the metabolic fate of new chemical compounds. We explore the role of drug metabolism in chemical induced toxicity and drug-drug interactions. Current projects include evaluation of reactive metabolites and their role in drug induced toxicity, time and mechanism based inhibition of cytochrome P450, and the development of chemical tools to differentiate CYP3A4 and CYP3A5 activity in biological samples. The lab is also involved in several translational projects focused on the development of clinical candidates or molecular probes for the study of biological pathways. The lab offers Drug Metabolism and Pharmacokinetics (DMPK) expertise, collaborating with medicinal chemistry, biology and pharmacology groups. The lab evaluates such factors as chemical and metabolic stability, solubility, oral absorption, rat and mouse pharmacokinetics, tissue distribution, protein binding, P450 inhibition, reactive intermediate formation, and metabolite identification to help refine molecules. Current projects include optimization of neuropeptide Y Y2 receptor antagonists, orexin-1 receptor antagonists, (GABA) B receptor positive allosteric modulators, neurotensin 1 receptor agonists, a5* nicotinic acetylcholine receptors, positive allosteric modulators, kappa opioid receptor antagonists, and functionally biased mu opioid receptor agonists.
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2024
HDAC specificity and kinase off-targeting by purine-benzohydroxamate anti-hematological tumor agentsEuropean Journal of Medicinal Chemistry
- 2023 Journal of Medicinal Chemistry
- 2023 Scientific Reports
- 2023 International Journal for Parasitology: Drugs and Drug Resistance
- 2022 Journal of Medicinal Chemistry
- 2022 Journal of the American Chemical Society
- 2022 Journal of the American Chemical Society
- 2022 Cancer research
- 2022 Nature cancer
- 2022 ACS Chemical Neuroscience
- 2022 Bioorganic & medicinal chemistry letters
- 2021 Journal of medicinal chemistry
- 2021 Human molecular genetics
- 2021 Journal of Medicinal Chemistry
- 2021 Blood
- 2021 Neuropharmacology
- 2021 Nature Chemical Biology
- 2021 Neuropharmacology
- 2021 ACS Chemical Biology
- 2021 Journal of the American Chemical Society
- 2020 Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
- 2020 Nature chemistry
- 2020 Nature Chemical Biology
- 2020 ACS chemical biology
- 2020 Science Advances
- 2020 Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
- 2020 ACS infectious diseases
- 2019 Cancer discovery
- 2019 Cell chemical biology
- 2019 Proceedings of the National Academy of Sciences of the United States of America
- 2019 Journal of medicinal chemistry
- 2019 Medicinal chemistry (Shariqah (United Arab Emirates))
- 2018 Bioorganic & medicinal chemistry
- 2018 PLoS biology
- 2018 Journal of medicinal chemistry
- 2018 Bioorganic & medicinal chemistry letters
- 2018 Journal of medicinal chemistry
- 2018 Cell reports
- 2018 Bioorganic & medicinal chemistry letters
- 2017 Nature chemical biology
- 2017 Bioorganic & medicinal chemistry
- 2017 Chemical biology & drug design
- 2017 Cell
-
2017
Fentanyl-related designer drugs W-18 and W-15 lack appreciable opioid activity in vitro and in vivo.JCI insight
- 2016 Science signaling
- 2016 Proceedings of the National Academy of Sciences of the United States of America
- 2016 ChemMedChem
- 2016 Molecular psychiatry
- 2016 Chemical research in toxicology
- 2016 Journal of medicinal chemistry
- 2016 ACS medicinal chemistry letters
- 2016 Molecular metabolism
- 2016 ACS chemical biology
- 2015 Molecular pharmacology
- 2015 ACS medicinal chemistry letters
- 2015 ACS chemical biology
- 2014 Journal of medicinal chemistry
- 2014 Cancer research
- 2014 Drug metabolism and disposition: the biological fate of chemicals
- 2014 ACS medicinal chemistry letters
- 2014 Bioorganic & medicinal chemistry letters
- 2014 Bioorganic & medicinal chemistry letters
- 2014 Journal of medicinal chemistry
- 2013 Angewandte Chemie (International ed. in English)
- 2013 ACS chemical biology
- 2013 Journal of medicinal chemistry
- 2013 Bioorganic & medicinal chemistry letters
- 2013 Bioorganic & medicinal chemistry letters
- 2013 The Journal of biological chemistry
- 2013 Bioorganic & medicinal chemistry letters
- 2013 Bioorganic & medicinal chemistry letters
- 2013 Journal of medicinal chemistry
- 2012 Molecular pharmacology
- 2012 Bioorganic & medicinal chemistry letters
- 2012 Bioorganic & medicinal chemistry letters
- 2012 Nature
- 2012 ACS medicinal chemistry letters
- 2012 Bioorganic & medicinal chemistry letters
- 2012 Bioorganic & medicinal chemistry letters
- 2012 Drug metabolism and disposition: the biological fate of chemicals
- 2012 Chemical research in toxicology
- 2011 Nature chemistry
- 2011 Bioorganic & medicinal chemistry letters
- 2011 Bioorganic & medicinal chemistry letters
- 2011 Bioorganic & medicinal chemistry letters
- 2011 Bioorganic & medicinal chemistry letters
- 2011 ACS chemical neuroscience
- 2011 Bioorganic & medicinal chemistry letters
- 2011 ACS chemical biology
- 2011 ACS chemical biology
- 2011 Bioorganic & medicinal chemistry letters
- 2011 Nature
- 2011 ACS chemical neuroscience
- 2010 Drug metabolism and disposition: the biological fate of chemicals
- 2010 ACS medicinal chemistry letters
- 2010 Expert opinion on drug metabolism & toxicology
- 2010 Journal of medicinal chemistry
- 2010 Journal of medicinal chemistry
- 2010 Bioorganic & medicinal chemistry letters
- 2009 Drug metabolism and disposition: the biological fate of chemicals
- 2009 Bioorganic & medicinal chemistry letters
- 2009 Chemical research in toxicology
- 2008 Bioorganic & medicinal chemistry letters
- 2008 Bioorganic & medicinal chemistry letters
- 2008 Journal of medicinal chemistry
- 2008 Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
- 2008 Proceedings of the National Academy of Sciences of the United States of America
- 2008 Molecular pharmacology
- 2007 Drug metabolism and disposition: the biological fate of chemicals
- 2007 Bioorganic & medicinal chemistry letters
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Sep 2023
ACTIVE
Development of Clinical Candidates for the Treatment of Myotonic DystrophyUS ARMY MED RES ACQUISITION · Co-Investigator
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Sep 2022
ACTIVE
Mitochondrial therapeutics for healthy brain agingNATL INST OF HLTH NIA · Co-Investigator
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May 2022
ACTIVE
Midwest AViDD Center – CORE CUNIV OF MINNESOTA · Co-Investigator
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Apr 2022
–
Aug 2022
Mitochondrial therapeutics for healthy brain agingNATL INST OF HLTH NIA · Co-Investigator
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Apr 2022
–
Jun 2023
Synthesis of peripherally active CB1 agonists as analgesicsUNIV OF HLTH SCIENCES & PHARM ST LOUIS · Principal Investigator
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Apr 2022
ACTIVE
Identification of small molecules for neurological complications of HIV and substance abuse comorbiditySCRIPPS RESEARCH INST · Co-Project Director/Principal Investigator
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Apr 2022
ACTIVE
Identification of REV-ERB inverse agonists for cancer immunotherapyNATL INST OF HLTH NCI · Project Manager
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Apr 2022
ACTIVE
Synthesis and Evaluation of Functionally Biased Opioid AnalgesicsNATL INST OF HLTH NIDA · Co-Investigator
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Apr 2022
ACTIVE
Covalent Inhibition as a Method to Counteract Botulinum IntoxicationSCRIPPS RESEARCH INST · Principal Investigator
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Apr 2022
ACTIVE
Development of novel therapeutics for opioid dependenceICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · Project Manager
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Apr 2022
ACTIVE
Identification of novel anthelmintics through a target-based screen of a parasite ion channelMEDICAL COLLEGE OF WISCONSIN · Co-Investigator
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2000
Ph.D. in BiochemistryUtah State University
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1994
Bachelor's of Science in ChemistryGonzaga University
Michalina Janiszewska Ph.D.
- Mailing Address:
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Location C251
130 SCRIPPS WAY BLDG 2C1
JUPITER FL 33458
- 2023 Nature Structural & Molecular Biology
- 2023 Cell Reports
- 2021 Neuro-oncology advances
- 2021 JCI Insight
- 2020 Journal of Biological Chemistry
- 2020 Cancer cell
- 2020 Oncogene
- 2020 Cancer Research
- 2019 Nature Cell Biology
- 2018 Nature cell biology
- 2018 Cell reports
- 2017 Nature reviews. Cancer
- 2016 Genes & development
- 2016 Cancer research
- 2016 Cell reports
- 2016 Nature
- 2015 Cell stem cell
- 2015 Nature genetics
- 2014 Oncology (Williston Park, N.Y.)
- 2012 Genes & development
- 2011 PloS one
- 2010 Genes & development
- 2010 The Journal of biological chemistry
- 2009 PloS one
- 2009 Cancer research
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Jan 2022
ACTIVE
American Cancer Society Institutional Research GrantAMERICAN CANCER SOCIETY · Project Manager
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2012
Ph.D. in Life SciencesUniversity of Lausanne
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2007
Master's of Science in Medical BiotechnologyUniversity of Wroclaw
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2005
Bachelor's of Science in BiotechnologyUniversity of Wroclaw
Donald G Phinney Ph.D.
- Mailing Address:
-
Location A215
130 SCRIPPS WAY BLDG 2A2
JUPITER FL 33458
Dr. Phinney received his B.A. in Chemistry and Mathematics from the University of Vermont and a Ph.D. in Biochemistry from Temple University School of Medicine in Philadelphia. He then completed his post-doctoral studies at the Fox Chase Cancer Center where he was awarded an American Cancer Society Fellowship to examine the transcriptional regulation of the JunB oncogene. Dr. Phinney then spent nine years at Tulane University Health Sciences Center where he advanced through the ranks to Professor of Immunology and Microbiology and Associate Director of Research for the Center for Gene Therapy. He joined Scripps Florida in 2009 and is currently a Professor in the Department of Molecular Medicine.
The Phinney lab combines basic and translational research and drug discovery to deliver highly efficacious cell-based and drug-based therapies for the treatment of skeletal-related pathologies and cancer. Currently the lab is pursuing several different areas of investigation to achieve these goals. One area of focus is directed at enhancing the potency and improving the efficacy of mesenchymal stem cell (MSC)-based therapies, which are widely used in regenerative medicine for the treatment of ischemic and immune-related diseases. These efforts have culminated in the development of a Clinical Indications Prediction (CLIP) Scale that may be used to develop MSC-based therapies tailored to specific disease indications. Ongoing work is directed at validating the CLIP scale and expanding its range of applications. Another area of focus is directed at understanding the molecular mechanism that drive skeletal pathology in response to diet-induced obesity, mechanical unloading (disuse), and chronological aging using mouse models. In these studies, emphasis is on evaluating how these conditions impact the frequency and function of nice resident skeletal stem cells in bone marrow and developing therapeutics to preserve bone integrity. Lastly, the laboratory is also pursuing development of small molecule therapeutics to augment the efficacy and reduce the toxicity of existing chemotherapeutics and immuno-therapies for treating breast cancer.
- 2023 SLAS Discovery
- 2023 Science Advances
- 2023 Stem Cells
- 2023 Cytotherapy
- 2023 Stem Cells
- 2022 Cytotherapy
- 2022 Cytotherapy
- 2022 Biology
- 2021 Cytotherapy
- 2021 Aging cell
- 2021 Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
- 2021 npj Microgravity
- 2021 Cytotherapy
- 2021 Nature Chemical Biology
- 2021 npj Microgravity
- 2021 Cytotherapy
- 2020 Cytotherapy
- 2020 Cytotherapy
- 2020 Cytotherapy
- 2020 Cytotherapy
- 2020 Cytotherapy
- 2020 Cytotherapy
- 2020 Cytotherapy
- 2019 npj Regenerative Medicine
- 2019 Cytotherapy
- 2019 Cytotherapy
- 2019 Cytotherapy
- 2019 Cytotherapy
- 2018 Stem Cells
- 2018 Cell Death & Differentiation
- 2018 Journal of extracellular vesicles
- 2017 Neural regeneration research
- 2017 Stem cells (Dayton, Ohio)
- 2017 Stem Cells
- 2017 Stem cells translational medicine
- 2017 Cardiovascular diagnosis and therapy
- 2017 Methods in molecular biology (Clifton, N.J.)
- 2017 Journal of the American Chemical Society
- 2016 Clinical orthopaedics and related research
- 2016 Journal of stem cell research & therapy
- 2016 Methods in molecular biology (Clifton, N.J.)
- 2016 Cytotherapy
- 2016 EBioMedicine
- 2016 Proceedings of the National Academy of Sciences of the United States of America
- 2015 Nature communications
- 2015 Stem cells international
- 2015 Nature communications
- 2015 ACS chemical biology
- 2014 PloS one
- 2014 Stem cells international
- 2014 Brain research
- 2014 Journal of immunology (Baltimore, Md. : 1950)
- 2013 Cytotherapy
- 2013 Nature medicine
- 2013 Cytotherapy
- 2012 Stem cells (Dayton, Ohio)
- 2012 Journal of cellular biochemistry
- 2012 Cell stem cell
- 2012 The Journal of biological chemistry
- 2012 BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy
- 2011 Biotechnology and bioengineering
- 2011 Stem cells (Dayton, Ohio)
- 2011 BMC proceedings
- 2011 Stroke
- 2011 Stem cells (Dayton, Ohio)
- 2010 Biotechnology letters
- 2010 Stem cells (Dayton, Ohio)
- 2010 Experimental hematology
- 2010 In vitro cellular & developmental biology. Animal
- 2010 Cytotherapy
- 2009 International journal of stem cells
- 2009 Tissue engineering. Part A
- 2008 Stem cells (Dayton, Ohio)
- 2008 Methods in molecular biology (Clifton, N.J.)
- 2008 Methods in molecular biology (Clifton, N.J.)
- 2008 Stem cells (Dayton, Ohio)
- 2007 Proceedings of the National Academy of Sciences of the United States of America
- 2007 Brain pathology (Zurich, Switzerland)
- 2007 Experimental hematology
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2007
Biochemical heterogeneity of mesenchymal stem cell populations: clues to their therapeutic efficacy.Cell cycle (Georgetown, Tex.)
- 2007 Stem cells (Dayton, Ohio)
- 2007 Stem cells (Dayton, Ohio)
- 2006 Stem cells (Dayton, Ohio)
- 2006 Experimental neurology
- 2006 Stem cells and development
- 2006 Molecular therapy : the journal of the American Society of Gene Therapy
- 2006 Tissue engineering
- 2005 Biochemical and biophysical research communications
- 2005 Current pharmaceutical design
- 2003 Journal of cellular biochemistry
- 2003 Proceedings of the National Academy of Sciences of the United States of America
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2003
Quantifying levels of transplanted murine and human mesenchymal stem cells in vivo by real-time PCR.Cytotherapy
- 2001 Stem cells (Dayton, Ohio)
- 2000 Biochemical Society transactions
- 2000 Leukemia & lymphoma
- 2000 Progress in brain research
- 1999 Journal of cellular biochemistry
- 1999 The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society
- 1999 Proceedings of the National Academy of Sciences of the United States of America
- 1999 Journal of cellular biochemistry
- 1999 British journal of haematology
- 1998 Matrix biology : journal of the International Society for Matrix Biology
- 1996 Oncogene
- 1995 The Journal of biological chemistry
- 1995 Genomics
- 1994 Oncogene
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Sep 2022
ACTIVE
Tissue Selective GlucocorticoidsNATL INST OF HLTH NIGMS · Co-Investigator
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Aug 2022
ACTIVE
A novel miR-544 targeting small molecule as an adjuvant therapy for preventing breast cancer metastasis and relapseUS ARMY MED RES ACQUISITION · Principal Investigator
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Apr 2022
–
Aug 2023
A Clinical Indications Prediction (CLIP) Scale for Human Mesenchymal Stem CellsNATL INST OF HLTH NHLBI · Principal Investigator
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1990
Ph.D. in BiochemistryTemple University, School of Medicine
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1984
Bachelor's of Arts in Chemistry and MathematicsThe University of Vermont
Thomas Bannister Ph.D.
- Mailing Address:
-
Location A229
130 SCRIPPS WAY BLDG 2A2
Jupiter FL 33458
- Physical Address:
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Location A229
130 SCRIPPS WAY BLDG 2A2
Jupiter FL 33458
Organic/Medicinal Chemistry and Drug Discovery
The discovery of possible drug candidates is a highly collaborative endeavor, with medicinal chemistry as a core, problem-solving component. My major research efforts are joint projects with world experts in cancer biology and neuroscience, wherein my group provides the organic and medicinal chemistry expertise and drug design insights. In general, we strive to find novel ways to target poorly-treated, common, and devastating disorders that increasingly burden world health care systems.
Neuroscience studies include:
— Biased mu opioid agonists, aiming for a holy grail of sorts: to separate the robust pain relief –provided by opiates from their many unwanted side effects. This collaboration with Laura Bohn’s group has led to findings published in 2017 in Cell, with follow-up chemistry disclosure in the Journal of Medicinal Chemistry in late 2018 (featured on the cover). — NOP agonists, for post-traumatic stress disorder (PTSD) and alcohol addiction relapse therapy. — NAD-elevating neuroprotectants, for Alzheimer’s and Parkinson’s Diseases, and for ALS.
Cancer projects include:
— KLF5 inhibitors for colorectal cancer therapy. — TBK1 and IKKi dual kinase inhibitors, for hormone-refractory prostate cancer. — Inhibitors of kinases CK1delta, ASK1, and ULK1, for various cancers. — Modulators of the HIPPO-YAP pathway, for various cancers. — Other exploratory efforts include:
High-throughput screening-based “chemical probe development”, seeking first-in-class small molecules for investigating the therapeutic potential of new target proteins. Probe development efforts encompass multiple therapeutic areas, including treatments for cancers, glaucoma, amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD), addiction, infectious diseases, and mood disorders. One chemical probe effort targets the orphan GPCR GPR151, a target that may be relevant for the development of treatments for addiction, depression, and schizophrenia.The discovery of possible drug candidates is a highly collaborative endeavor, with medicinal chemistry as a core, problem-solving component. Our major efforts are thus joint projects with world experts in cancer biology and neuroscience, wherein our group provides the organic and medicinal chemistry expertise.
Our cancer projects target unique metabolic phenotypes of tumor cells, identifying defining molecular characteristics to be exploited for the development of targeted therapies. Most tumor types have a shared reliance upon active transport of nutrients and building blocks to drive rapid cancer cell growth and to sustain survival. They also largely rely upon glycolysis for ATP production (the Warburg effect). As examples, we have created molecules to keep tumor cells from exporting lactate, the end product of glycolysis. We have also designed compounds to block amino acid transporters that are up-regulated by many tumors. We have a program targeting expression of a transcription factor that drives colon cancer progression. We also have a number of kinase inhibitor programs aimed the discovery of treatments for brain cancers, triple-negative breast cancer, hormone-resistant prostate cancer, and perhaps other forms as well. This are collaborative efforts with top TSRI cancer biologists including Derek Duckett, Joseph Kissil, Jun-li Luo, and also including John Cleveland from the Moffitt Cancer Center.
Many of our anticancer programs have a computational chemistry-directed focus, relying on molecular modeling based upon published coordinates, virtual screening, scoring, and validation of predicted hits through chemical synthesis. We use the Schrodinger suite of modeling software in these studies. For future work we may have a need to hire postdoctoral scientists with both computational and synthesis experience. Please contact me for further information.
In our neuroscience studies we are developing GPCR agonists that have targeted effects in the brain. We are exploring GPCR signaling bias in mu opioid receptor activation, aiming for a holy grail of sorts: to separate the robust pain relief provided by opiates from their many unwanted side effects. This collaboration with Laura Bohn’s group has led to pain relievers that seem to be devoid of many of the side effects of morphine and related opiates, such as respiratory suppression, heart rate effects, and GI effects (constipation). In a separate study we identified tool compound with promise in an animal model of post-traumatic stress disorder (PTSD).
Other exploratory efforts use medicinal chemistry in concert with high-throughput screening or following HTS campaigns, where we seek to discover and optimize “chemical probes”, or first-in-class small molecules that should prove useful for investigating the therapeutic potential of new target proteins. Such probe development efforts encompass multiple therapeutic areas, including treatments for ALS, Parkinson’s Disease, addiction, infectious diseases, cancers, glaucoma, and mood disorders.
One such chemical probe effort, a collaboration with Patsy McDonald, targets the orphan GPCR GPR151, a target that may be relevant for the development of treatments for addiction, depression, and schizophrenia. In a collaboration with Sathya Puthanveettil we are investigating the potential of facilitating the function of kinesin motor proteins as a novel approach to therapies for Alzheimer’s disease (AD) and frontal temporal dementia (FTD), which are poorly-treated, common, and devastating disorders that increasingly burden world health care systems. In a collaboration with Corinne Lasmezas, we are developing compounds that rescue neurons from toxicity of protein aggregates, relevant for developing new therapies for ALS and Parkinson’s Disease.
As you can tell, collaborative drug discovery research is order of the day in my lab!
Members of my group benefit from interactions not only with other chemists but with top biologists and pharmacologists, as they partake in project team meetings as well as in our weekly chemistry group meetings. My research is funded currently by 8 NIH grants on which I am a co-principal investigator and 8 others NIH grants where I am a named investigator or co-investigator.
On occasion I have openings for outstanding postdoctoral fellows in my labs. As mentioned above, an especially good fit would be a postdoc with lab synthesis experience and with prior expertise in using the Schrodinger suite of molecular modeling software, to aid our virtual screening-based efforts. Our postdoctoral scientists collaborate with a team of biological co-investigators, applying knowledge and experience in modern organic, heterocyclic, and/or medicinal chemistry toward an ongoing drug discovery effort. Excellent communication skills, good synthetic organic chemistry laboratory skills, ability to work in the US, and familiarity with modern synthetic techniques and instrumentation are required in this role. Contact me for further details.
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2024
HDAC specificity and kinase off-targeting by purine-benzohydroxamate anti-hematological tumor agentsEuropean Journal of Medicinal Chemistry
- 2023 SLAS Discovery
- 2023 Scientific Reports
- 2022 SLAS discovery : advancing life sciences R & D
- 2021 Circulation
- 2021 Neuropharmacology
- 2021 Pharmaceuticals (Basel, Switzerland)
- 2021 Pharmaceuticals (Basel, Switzerland)
- 2021 Proceedings of the National Academy of Sciences
- 2021 SLAS discovery : advancing life sciences R & D
- 2021 SLAS discovery : advancing life sciences R & D
- 2021 Circulation research
- 2020 Journal of virology
- 2020 Scientific reports
- 2020 Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
- 2019 Molecular cancer therapeutics
- 2019 ACS Catalysis
- 2018 SLAS discovery : advancing life sciences R & D
- 2018 The Biochemical journal
- 2018 Assay and drug development technologies
- 2018 Journal of Medicinal Chemistry
- 2018 Chemistry (Weinheim an der Bergstrasse, Germany)
- 2017 Cell
- 2017 PloS one
- 2016 Scientific reports
- 2016 MedChemComm
- 2016 Journal of biomolecular screening
- 2016 Molecular cancer therapeutics
- 2016 The Journal of organic chemistry
- 2016 Molecular and cellular endocrinology
- 2015 Journal of biomolecular screening
- 2015 PloS one
- 2015 European journal of organic chemistry
- 2015 Tetrahedron letters
- 2015 ACS chemical biology
- 2014 Cancer research
- 2014 The Journal of organic chemistry
- 2014 Organic letters
- 2014 Journal of medicinal chemistry
- 2013 Science translational medicine
- 2013 Bioorganic & medicinal chemistry
- 2013 Bioorganic & medicinal chemistry letters
- 2012 ACS chemical biology
- 2011 Bioorganic & medicinal chemistry letters
- 2011 Bioorganic & medicinal chemistry letters
- 2011 Molecular cancer therapeutics
- 2011 Bioorganic & medicinal chemistry letters
- 2010 Bioorganic & medicinal chemistry letters
- 2008 Bioorganic & medicinal chemistry letters
- 2008 Bioorganic & medicinal chemistry letters
- 2006 Journal of medicinal chemistry
- 1975 Current therapeutic research, clinical and experimental
- 1974 Antimicrobial agents and chemotherapy
- 1969 Applied microbiology
-
Aug 2022
ACTIVE
Biasing Mu Opioid Receptor Signaling in vivoNATL INST OF HLTH NIDA · Co-Investigator
-
May 2022
ACTIVE
Midwest AViDD Center – Project 5UNIV OF MINNESOTA · Principal Investigator
-
May 2022
ACTIVE
Midwest AViDD Center – CORE CUNIV OF MINNESOTA · Principal Investigator
-
Apr 2022
–
Nov 2023
Therapeutic Targeting of Casein Kinase-1-delta in Primary Metastatic Breast CancerH LEE MOFFITT CANCER CTR & RES INST · Principal Investigator
-
Apr 2022
–
Nov 2023
Development of New Casein Kinase 1 Inhibitor for the Treatment of Brain CancersH LEE MOFFITT CANCER CTR & RES INST · Principal Investigator
-
Apr 2022
ACTIVE
Identification of small molecules for neurological complications of HIV and substance abuse comorbiditySCRIPPS RESEARCH INST · Co-Project Director/Principal Investigator
-
Apr 2022
ACTIVE
Synthesis and Evaluation of Functionally Biased Opioid AnalgesicsNATL INST OF HLTH NIDA · Principal Investigator
-
Apr 2022
ACTIVE
Identification of novel anthelmintics through a target-based screen of a parasite ion channelMEDICAL COLLEGE OF WISCONSIN · Co-Investigator
-
1991
Ph.D. in Organic ChemistryIndiana University
-
1987
Master's of PhilosophyYale University
-
1986
Master of ScienceYale University
-
1984
A.B. in ChemistryWabash College
Theodore Kamenecka Ph.D.
- Mailing Address:
-
Location A207
130 SCRIPPS WAY BLDG 2A2
JUPITER FL 33458
- Physical Address:
-
Room A230
110 Scripps Way
Jupiter FL 33458
Medicinal Chemistry and Drug Discovery
The research interest in my group is in the design, synthesis and evaluation of novel compounds of biological and therapeutic interest. Currently, we are involved in the design and synthesis of novel small molecule modulators of nuclear receptors, GPCR’s, ion channels, kinases and mitochondria for the therapeutic treatment of addiction, diabetes and obesity, multiple sclerosis, cognitive health and aging. Working closely with other departments such as molecular biology, pharmacology, and drug metabolism, we optimize lead compounds for potency, ADME (absorption, distribution, metabolism, and excretion), safety pharmacology, and toxicology in order to generate compounds suitable for preclinical development.
- 2023 ACS chemical biology
- 2023 Journal of medicinal chemistry
- 2022 Redox biology
- 2022 Bioorganic chemistry
- 2022 SLAS discovery : advancing life sciences R & D
- 2021 Nature chemical biology
- 2021 Science advances
- 2021 Journal of molecular biology
- 2021 Journal of Medicinal Chemistry
- 2021 ACS Chemical Biology
- 2021 Nature communications
- 2021 Aging cell
- 2021 Journal of Medicinal Chemistry
- 2020 Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
- 2020 Biochemical and Biophysical Research Communications
- 2020 Science advances
- 2020 Journal of biological methods
- 2020 Journal of Medicinal Chemistry
- 2020 The Journal of neuroscience : the official journal of the Society for Neuroscience
- 2019 ACS Catalysis
- 2019 ACS Chemical Biology
- 2019 Proceedings of the National Academy of Sciences of the United States of America
- 2019 Proceedings of the National Academy of Sciences
- 2019 eLife
- 2019 Nature communications
- 2019 The Journal of biological chemistry
- 2019 Medicinal chemistry (Shariqah (United Arab Emirates))
- 2019 eLife
- 2019 Nature
- 2018 Proceedings of the National Academy of Sciences of the United States of America
- 2018 Nuclear receptor research
- 2018 Molecular metabolism
- 2018 Chemistry – A European Journal
- 2018 Biochemical pharmacology
- 2018 Cell reports
- 2018 iScience
- 2018 Bioorganic & medicinal chemistry letters
- 2018 PLoS biology
- 2018 Journal of Medicinal Chemistry
- 2018 Bioorganic & medicinal chemistry letters
- 2018 Nature communications
- 2018 Proceedings of the National Academy of Sciences of the United States of America
- 2018 Bioorganic & medicinal chemistry letters
- 2018 Nature communications
- 2018 Structure (London, England : 1993)
- 2017 Nature neuroscience
- 2017 ACS chemical biology
- 2017 FASEB journal : official publication of the Federation of American Societies for Experimental Biology
- 2017 Cell
- 2017 Journal of medicinal chemistry
- 2017 Bioorganic & medicinal chemistry letters
- 2016 Molecular metabolism
- 2016 Cell
- 2016 The Journal of biological chemistry
- 2016 ACS chemical biology
- 2016 Tetrahedron letters
- 2016 ACS chemical biology
- 2016 ChemMedChem
- 2016 EBioMedicine
- 2016 PloS one
- 2016 Tetrahedron letters
- 2016 The Journal of biological chemistry
- 2016 The Journal of clinical investigation
- 2016 Journal of medicinal chemistry
- 2016 PloS one
- 2015 The Journal of biological chemistry
- 2015 Molecular pharmacology
- 2015 Cancer cell
- 2015 ACS medicinal chemistry letters
- 2015 Proceedings of the National Academy of Sciences of the United States of America
- 2015 Nature communications
- 2015 Endocrinology
- 2015 Nature communications
- 2015 Biochemical and biophysical research communications
- 2015 The Journal of biological chemistry
- 2014 Bioorganic & medicinal chemistry letters
- 2014 Bioorganic & medicinal chemistry letters
- 2014 Bioorganic & medicinal chemistry letters
- 2014 Nature communications
- 2014 Arthritis & rheumatology (Hoboken, N.J.)
- 2014 Proceedings of the National Academy of Sciences of the United States of America
- 2014 Nature communications
- 2013 Bioorganic & medicinal chemistry letters
- 2013 Nature medicine
- 2013 Assay and drug development technologies
- 2013 Bioorganic & medicinal chemistry letters
- 2013 ACS chemical biology
- 2012 Drug metabolism and disposition: the biological fate of chemicals
- 2012 Bioorganic & medicinal chemistry letters
- 2012 ACS chemical biology
- 2012 ACS chemical biology
- 2012 Bioorganic & medicinal chemistry letters
- 2012 Structure (London, England : 1993)
- 2012 PloS one
- 2012 Nature
- 2012 Bioorganic & medicinal chemistry letters
- 2012 Bioorganic & medicinal chemistry letters
- 2012 Cell
- 2011 Bioorganic & medicinal chemistry letters
- 2011 Bioorganic & medicinal chemistry letters
- 2011 Bioorganic & medicinal chemistry letters
- 2011 Nature
- 2011 ACS chemical biology
- 2011 ACS chemical biology
- 2011 Nature
- 2010 Nature
- 2010 Drug metabolism and disposition: the biological fate of chemicals
- 2010 Endocrinology
- 2009 Chemical research in toxicology
- 2009 The Journal of organic chemistry
- 2009 Bioorganic & medicinal chemistry letters
- 2008 Mini reviews in medicinal chemistry
- 2008 Proceedings of the National Academy of Sciences of the United States of America
- 2008 The Journal of pharmacology and experimental therapeutics
- 2007 Bioorganic & medicinal chemistry letters
- 2007 Structure (London, England : 1993)
- 2005 Bioorganic & medicinal chemistry letters
- 2005 Bioorganic & medicinal chemistry letters
- 2005 Bioorganic & medicinal chemistry letters
- 2005 Bioorganic & medicinal chemistry letters
- 2004 Bioorganic & medicinal chemistry letters
- 2004 Bioorganic & medicinal chemistry letters
- 2004 Bioorganic & medicinal chemistry letters
- 2003 Bioorganic & medicinal chemistry letters
- 2002 Organic letters
- 2002 Bioorganic & medicinal chemistry letters
- 2002 Bioorganic & medicinal chemistry letters
- 2002 Bioorganic & medicinal chemistry letters
- 1998 Angewandte Chemie (International ed. in English)
- 1998 Angewandte Chemie (International ed. in English)
-
Jul 2023
ACTIVE
Understanding the role of RORa in T-cell mediated colitisCROHNS & COLITIS FOUNDATION · Other
-
Apr 2023
ACTIVE
Drug Discovery for First-In-Class Myosin 10 Inhibitors as a Novel Target for GlioblastomaNATL INST OF HLTH NINDS · Principal Investigator
-
Mar 2023
ACTIVE
Ligand-dependent regulation of the nuclear receptor REV-ERBa in TH17 cell development and inflammationNATL INST OF HLTH NIDDK · Co-Investigator
-
Mar 2023
ACTIVE
Demo batch scale-up of MT-125MYOSIN THERAPEUTICS · Principal Investigator
-
Sep 2022
ACTIVE
Mitochondrial therapeutics for healthy brain agingNATL INST OF HLTH NIA · Co-Investigator
-
Sep 2022
ACTIVE
Tissue Selective GlucocorticoidsNATL INST OF HLTH NIGMS · Co-Investigator
-
Apr 2022
ACTIVE
Targeting Go and Grow in GlioblastomaMAYO CLINIC · Co-Investigator
-
Apr 2022
ACTIVE
Development of novel therapeutics for opioid dependenceICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · Principal Investigator
-
Apr 2022
ACTIVE
Identification of REV-ERB inverse agonists for cancer immunotherapyNATL INST OF HLTH NCI · Co-Investigator
-
Apr 2022
ACTIVE
Small molecules targeting hepatic glucose production and insulin resistanceDANA FARBER CANCER INST · Co-Investigator
-
Apr 2022
ACTIVE
Targeting Cellular Senescence to Extend HealthspanMAYO CLINIC · Principal Investigator
-
Apr 2022
ACTIVE
Mechanistic studies of corepressor-mediated PPAR? transcriptional repressionNATL INST OF HLTH NIDDK · Co-Investigator
-
Apr 2022
–
Mar 2023
Drug Discovery for First-In-Class Myosin 10 Inhibitors as a Novel Target for GlioblastomaNATL INST OF HLTH NINDS · Principal Investigator
-
Apr 2022
–
Feb 2023
Molecular basis of activation of the orphan nuclear receptor Nurr1NATL INST OF HLTH NIA · Co-Investigator
-
Apr 2022
–
Sep 2022
Parallel Multimodal High-throughput screening to identify activators of the orexin receptorsNATL INST OF HLTH NIMH · Principal Investigator
-
Apr 2022
–
Aug 2022
Mitochondrial therapeutics for healthy brain agingNATL INST OF HLTH NIA · Co-Investigator
-
Apr 2022
–
Jul 2022
Optimization of SR1903 and SR10171SYNKINE THERAPEUTICS · Co-Project Director/Principal Investigator
-
Apr 2022
–
Jun 2022
ALDH1a1 Inhibition As A Therapeutic Target In Visceral Adiposity and Type 2 DiabetesBRIGHAM AND WOMENS HOSPITAL · Co-Project Director/Principal Investigator
-
Apr 2022
ACTIVE
Developing nonmuscle myosin II inhibitors for the treatment of glioblastomaNATL INST OF HLTH NINDS · Co-Investigator
-
Apr 2022
–
May 2022
Identification of Chemical Probes for the Orphan Nuclear Receptor NR2F6NATL INST OF HLTH NCI · Co-Investigator
-
1996-1998
Post-doctorateMemorial Sloan Kettering Cancer Center
-
1990-1996
Ph.D. in ChemistryUniversity of California, Irvine
-
1986-1990
Bachelor of Science in ChemistryUniversity of Rochester
Patrick Griffin Ph.D.
- Mailing Address:
-
Location A223
130 SCRIPPS WAY BLDG 2A2
JUPITER FL 33458
My scientific career has focused on the study of protein structure and approaches to modulating protein function via synthetic small molecules with a focus on nuclear receptors. I have a broad background in drug discovery and development that spans the last 25+ years. I received a Ph.D. in Chemistry from the University of Virginia under the direction of Professor Donald F. Hunt where I was involved in methodology development in the field of Biological Mass Spectrometry. After graduating from UVa, I was a Postdoctoral Fellow for Professor Leroy Hood at Caltech where I was involved in the application of mass spectrometry to systems biology.
Prior to Scripps, I was Chief Science Officer of ExSAR Corporation, NJ, a biotech company focused the use of HDX mass spectrometry (HDX-MS) to aid in the development of chemical chaperones for protein misfolding disorders. Prior to ExSAR, I was Senior Director, Chemistry, at Merck Research Laboratories where he spent over 11 years applying biological mass spectrometry and proteomics to a wide range of therapeutic areas including metabolic disorders, cardiovascular disease, and infectious diseases. At Merck, I headed the discovery DMPK operation within the Chemistry Department and the Molecular Profiling Proteomics group. My team made significant contributions to over 35 safety assessment programs. Most significant were my team’s contributions towards the discovery and development of MK-0431, a DPP4 inhibitor now in clinical use (Januvia), and towards clinical development of DMP-777, an elastase inhibitor for treatment of cystic fibrosis that progressed to phase IIb trials.
In 2004, I joined The Scripps Research Institute (TSRI) Scripps Florida as Professor and in 2007 was named Professor and founding Chair of the Department of Molecular Therapeutics. As PI, Co-PI, and co-investigator on several NIH-funded grants, my research continues to focus on protein structure and function, particularly on mutational- and ligand-mediated alterations in protein structural plasticity, as well as quantitative SAR to facilitate lead optimization of molecules targeting therapeutic proteins. Using mutagenesis, HDX-MS, crystallography, proteomics and genomics my research is focused on structure-function of nuclear receptors, enzymes, and G protein coupled receptors (GPCRs). My research program has a major focus on understanding nuclear receptor (NR) signaling using structural, chemical and biological approaches. We have made significant contributions to understanding the mechanism of ligand activation of NRs such as PPARs, RORs, REV-ERBs, LRH1, VDR, ER, GR, and PR. We have also made significant contributions dissecting domain-domain interactions in control of positive and negative allostery. Our chemical biology program is focused on the RORs, PPARs, VDR and LRH1. In each of these programs we are developing functionally selective and promoter-specific modulators targeting disease such as cancer, autoimmune, obesity, and diabetes. My lab is well known for the development and application of biophysical methods including our HDX and XL-MS platform for the analysis of protein plasticity with a focus on NRs, enzymes, and GPCRs.
For the first half of my career I was in industry where there was less of an emphasis on publications. However, over the last 16 years as an academic I have published >240 peer-reviewed manuscripts. According to Google Scholar I have an h-index of 83 (58 since 2016) and an i10-index of 223. Below is a URL for My Bibliography of Patrick R. Griffin; some papers are under Griffin P.
As a graduate student at the University of Virginia, I worked in Don Hunt’s lab alongside John Yates and together we performed ground-breaking studies in the use of mass spectrometry to determine the primary structure of proteins. I am first author on a paper describing the complete sequence of a protein using tandem mass spectrometry. Prior, only a few small proteins for which their amino sequence was known had been sequenced by tandem mass spectrometry. This work helped validate that it was possible to sequence proteins using tandem mass spectrometry. I am first author on one of the first papers describing the using low nano-LC coupled with ESI. I contributed to many other publications demonstrating the use of mass spectrometry for structural analysis of proteins.
While at Merck Research Laboratories, my lab made significant contributions to a wide range of projects including key contributions to the development of the DPP4 program which led to the approval and marketing of Januiva. The range of contributions to drug discovery and development are exemplified in manuscripts listed below. My efforts in drug discovery have continued in the academic setting.
In 2002 I became interested in the application of hydrogen/deuterium exchange mass spectrometry. My lab focused on the development of a fully automated system, advanced software to facilitate robust high precision analysis, and applications of HDX in protein-ligand interactions with an emphasis on nuclear receptors, enzymes, and GPCRs. The publications listed below include an extensive list of key contributions to the HDX field.
In addition to the advancement of structural proteomics, my research has focused on chemical biology approaches to better understand nuclear receptor signaling. Our group described the first synthetic ligand for the orphan nuclear receptor NR1F subfamily (ROR)s and subsequently showed the utility of advanced compounds as anti-inflammatory and anti-obesity agents as well as RORG agonists for enhancing protective immunity in the context of cancer therapy. Our lab has also contributed to a fundamentally new understanding of the mechanism by which the nuclear receptor PPARG impacts insulin sensitivity.
Highlights on grant funding related to drug development programs
• I was consortium PI of the “The Comprehensive Center for Chemical Probe Discovery and Optimization at Scripps,” I had both a leadership role and a scientific role on this large multi-center 6-year U54 MLPCN Roadmap initiative.
• I was consortium PI of a RC4 program in collaboration with Bruce Spiegelman at the Dana Faber, I was involved in the discovery and development of novel molecules for the treatment of obesity and diabetes. Work from our labs in this area led us to co-found Ember, a private biotech funded by Third Rock Ventures.
• I was Co-PI on a NIDA funded U19 NCDDDG focused on the discovery and development of novel positive allosteric modulators of GABAB receptor for treatment of nicotine addiction.
• I served on the Scripps-Pfizer collaboration Steering Committee for its 5 year term coordinating collaborative drug discovery programs.
• I am PI of a 13-year long collaboration between my lab and Eli Lilly. • I am PI on a collaborative grant with the private Biotech Synkine Therapeutics.
• I am Co-PI on a NIH Blueprint UH3 titled, “Developing nonmuscle myosin II inhibitors for substance use relapse.” Co-founder of Myosin Therapeutics. The Myosin Therapeutics’ clinical candidate emerged from the NIH Blueprint program.
- 2023 Israel Journal of Chemistry
- 2023 Science signaling
- 2023 ACS Chemical Biology
- 2023 Analytical Chemistry
- 2023 Frontiers in endocrinology
- 2022 Science Advances
- 2022 The EMBO journal
- 2022 Nature Communications
- 2022 Journal for immunotherapy of cancer
- 2022 Science
- 2022 PLOS ONE
- 2022 Chemical science
- 2022 Journal of Medicinal Chemistry
- 2022 Science
- 2022 ACS Omega
- 2021 bioRxiv : the preprint server for biology
- 2021 Bioorganic & medicinal chemistry
- 2021 Journal of Medicinal Chemistry
- 2021 Nature Communications
- 2021 Science Advances
- 2021 Journal of the American Society for Mass Spectrometry
- 2021 Bone
- 2021 Science
- 2021 Nature Communications
- 2021 Nucleic acids research
- 2021 Proceedings of the National Academy of Sciences
- 2021 ACS Chemical Biology
- 2021 ACS Chemical Biology
- 2021 Journal of molecular biology
- 2021 Proceedings of the National Academy of Sciences
- 2021 Immunity
- 2020 Science
- 2020 Viruses 2020—Novel Concepts in Virology
- 2020 Nature Communications
- 2020 SLAS discovery : advancing life sciences R & D
- 2020 Current Research in Structural Biology
- 2020 Nucleic Acids Research
- 2020 Cell reports
- 2020 Journal of biological methods
- 2020 Nature Communications
- 2020 Analytical Chemistry
- 2019 ACS Chemical Biology
- 2019 SLAS discovery : advancing life sciences R & D
- 2019 The Journal of biological chemistry
- 2019 FEBS letters
- 2019 Cell
- 2019 Journal of Medicinal Chemistry
- 2019 Proceedings of the National Academy of Sciences
- 2019 Current opinion in structural biology
- 2019 SLAS discovery : advancing life sciences R & D
- 2019 Proceedings of the National Academy of Sciences of the United States of America
- 2019 eLife
- 2019 Nature Communications
- 2019 Journal of the American Society for Mass Spectrometry
- 2019
- 2019 eLife
- 2019 Structure (London, England : 1993)
- 2019 Nature methods
- 2019 Medicinal chemistry (Shariqah (United Arab Emirates))
-
2019
Definition of functionally and structurally distinct repressive states in the nuclear receptor PPARγNature Communications
-
2019
Federating Structural Models and Data: Outcomes from A Workshop on Archiving Integrative Structures.Structure (London, England : 1993)
- 2018 eLife
- 2018 eLife
- 2018 Cell
- 2018 iScience
- 2018 Proceedings of the National Academy of Sciences of the United States of America
- 2018 Nature communications
- 2018 Cell
- 2018 Journal of proteome research
- 2018 Bioorganic & medicinal chemistry letters
- 2018 Bioorganic & medicinal chemistry letters
- 2018 Nuclear receptor research
- 2018 Journal of medicinal chemistry
- 2018 Nature Communications
- 2018 Nature communications
- 2018 Proceedings of the National Academy of Sciences of the United States of America
- 2018
- 2018 Methods in molecular biology (Clifton, N.J.)
- 2018 Journal of molecular biology
- 2018 Biochemical pharmacology
- 2018 Nature communications
- 2018 Bioorganic & medicinal chemistry letters
- 2018 Structure (London, England : 1993)
- 2017 Nature communications
- 2017 Molecular & cellular proteomics : MCP
- 2017 Bioorganic & medicinal chemistry letters
- 2017 Structure (London, England : 1993)
- 2017 Journal of medicinal chemistry
- 2017 Nature
- 2017 Molecular pharmacology
- 2017 Structure (London, England : 1993)
- 2017 Cell
- 2017 Journal of molecular biology
- 2017 Cell
- 2017 Nature communications
- 2017 Pharmacology research & perspectives
- 2017 Nature chemical biology
- 2017 The Journal of biological chemistry
- 2017 Nature communications
- 2017 Journal of proteome research
- 2017 The journal of physical chemistry. B
- 2016 Nature structural & molecular biology
- 2016 Nature
- 2016 The Journal of biological chemistry
- 2016 eLife
- 2016 The EMBO journal
- 2016 ChemMedChem
- 2016 Diabetes
- 2016 ACS chemical biology
- 2016 ACS chemical biology
- 2016 The Journal of biological chemistry
- 2016 Cell
- 2016 Analytical chemistry
- 2016 ACS chemical biology
- 2015 Nature communications
- 2015 Nature
- 2015 Journal of the American Society for Mass Spectrometry
- 2015 Journal of proteome research
- 2015 Nature communications
- 2015 The Journal of biological chemistry
- 2015 Analytical chemistry
- 2015 Cell research
- 2015 PPAR research
- 2015 Nature
- 2015 ACS medicinal chemistry letters
- 2015 Cell
- 2015 Molecular pharmacology
- 2015 Molecular pharmacology
- 2015 Chemistry & biology
- 2015 Nature
- 2015 Nature communications
- 2015 Nature communications
- 2014 Structure (London, England : 1993)
- 2014 Cell metabolism
- 2014 The Journal of biological chemistry
- 2014 Current topics in microbiology and immunology
-
2014
Resveratrol modulates the inflammatory response via an estrogen receptor-signal integration network.eLife
- 2014 Arthritis & rheumatology (Hoboken, N.J.)
- 2014 Structure (London, England : 1993)
- 2014 ACS chemical biology
- 2014 PloS one
- 2014 PloS one
- 2014 Current opinion in structural biology
- 2014 Bioorganic & medicinal chemistry letters
- 2014 Cell
- 2014 The Journal of biological chemistry
- 2014 The Journal of biological chemistry
- 2014 Cancer research
- 2014 Angewandte Chemie (International ed. in English)
- 2014 Nature communications
- 2014 Diabetes
- 2013 Journal of the American Society for Mass Spectrometry
- 2013 Diabetes & metabolism journal
- 2013 Bioorganic & medicinal chemistry letters
- 2013 The Journal of biological chemistry
- 2013 Structure (London, England : 1993)
- 2013 Proceedings of the National Academy of Sciences of the United States of America
- 2013 Structure (London, England : 1993)
- 2013 The Journal of biological chemistry
- 2012 Cell
- 2012 Journal of experimental pharmacology
- 2012 Chemistry & biology
- 2012 Structure (London, England : 1993)
- 2012 Bioinformatics (Oxford, England)
- 2012 Science (New York, N.Y.)
- 2012 ACS chemical biology
- 2012 Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco
- 2012 The Journal of biological chemistry
- 2012 ACS medicinal chemistry letters
- 2012 Journal of the American Society for Mass Spectrometry
- 2012 The Journal of biological chemistry
- 2012 Journal of the American Society for Mass Spectrometry
- 2012 Nature structural & molecular biology
- 2012 ACS chemical biology
-
2011
The structural basis for recognition of base J containing DNA by a novel DNA binding domain in JBP1.Nucleic acids research
- 2011 Nature
- 2011 Proceedings of the National Academy of Sciences of the United States of America
- 2011 Nuclear receptor signaling
- 2011 International journal of mass spectrometry
- 2011 Structure (London, England : 1993)
- 2011 ACS chemical biology
- 2011 ACS chemical biology
- 2011 Nature structural & molecular biology
- 2011 Proceedings of the National Academy of Sciences of the United States of America
- 2011 Expert review of proteomics
- 2011 Journal of biomolecular screening
- 2011 Nature
- 2011 Nature
- 2011 Bioinformatics (Oxford, England)
- 2011 ChemMedChem
- 2011 Structure (London, England : 1993)
- 2010 The Journal of biological chemistry
- 2010 Molecular pharmacology
- 2010 Endocrinology
- 2010 Current opinion in lipidology
- 2010 Biochimica et biophysica acta
- 2010 Structure (London, England : 1993)
-
2010
Dynamics of the beta2-adrenergic G-protein coupled receptor revealed by hydrogen-deuterium exchange.Analytical chemistry
- 2010 Nature
- 2010 ACS chemical biology
- 2009 Biochemistry
- 2009 The Journal of organic chemistry
- 2009 Journal of the American Society for Mass Spectrometry
- 2009 The Journal of biological chemistry
- 2009 Biochemistry
- 2008 Proceedings of the National Academy of Sciences of the United States of America
- 2008 Molecular pharmacology
- 2007 Journal of biomolecular techniques : JBT
- 2007 Structure (London, England : 1993)
- 2006 Protein science : a publication of the Protein Society
- 2006 Analytical chemistry
- 2006 Biochemistry
- 2003 Journal of biomolecular techniques : JBT
- 2003 The Journal of biological chemistry
- 1990 FASEB journal : official publication of the Federation of American Societies for Experimental Biology
-
May 2023
ACTIVE
Architecture of inhibitory G protein signaling in the hippocampusUNIV OF MINNESOTA · Co-Investigator
-
Apr 2023
ACTIVE
Probing SNARE assembly and disassembly in vitro and in live cellsNATL INST OF HLTH NIGMS · Other
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Feb 2023
–
Feb 2023
Molecular mechanism of PIN1-mediated regulation of the nuclear receptor PPAR?NATL INST OF HLTH NIDDK · Other
-
Jan 2023
ACTIVE
Elucidating transsynaptic regulation of metabotropic glutamate receptorsNATL INST OF HLTH NINDS · Other
-
Nov 2022
ACTIVE
Structural Biology of Connexin Membrane ChannelsUNIV OF MIAMI · Principal Investigator
-
Sep 2022
ACTIVE
Quantifying and modeling ligand-dependent control of RORy dynamics via structural proteomicsNATL INST OF HLTH NIDDK · Principal Investigator
-
Jun 2022
–
Mar 2023
Behavior of HIV in Viral Environments (B-HIVE)SEATTLE CHILDRENS HOSPITAL · Principal Investigator
-
May 2022
ACTIVE
Structural dynamics of progesterone receptor-coactivator complexesNATL INST OF HLTH NCI · Principal Investigator
-
Apr 2022
ACTIVE
Roles of HIV-1 capsid-binding FG-motif containing cellular cofactors in infectionUNIV OF COLORADO DENVER & ANSCHUTZ MED · Principal Investigator
-
Apr 2022
ACTIVE
PPARG regulates osteocyte bioenergetics and function during agingUNIV OF TOLEDO · Principal Investigator
-
Apr 2022
ACTIVE
Ultra-potent HIV capsid inhibitorsUNIV OF COLORADO DENVER & ANSCHUTZ MED · Principal Investigator
-
Apr 2022
ACTIVE
Chemistry and Biology of ADP-Ribosylation-Dependent SignalingUNIV OF SOUTHERN CALIFORNIA · Principal Investigator
-
Apr 2022
ACTIVE
Developing nonmuscle myosin II inhibitors for the treatment of glioblastomaNATL INST OF HLTH NINDS · Co-Investigator
-
Apr 2022
ACTIVE
Mechanistic analysis of therapeutic targets using hydrogen/deuterium exchange mass spectrometry (HDX MS)ELI LILLY AND CO · Principal Investigator
-
Apr 2022
ACTIVE
Mechanistic studies of corepressor-mediated PPAR? transcriptional repressionNATL INST OF HLTH NIDDK · Co-Investigator
-
Apr 2022
–
Feb 2023
Molecular basis of activation of the orphan nuclear receptor Nurr1NATL INST OF HLTH NIA · Co-Investigator
-
Apr 2022
–
Oct 2022
Structural Biology of Connexin Membrane ChannelsUNIV OF VIRGINIA · Principal Investigator
-
Apr 2022
–
Aug 2022
Developing chemoproteomic approaches to decipher the regulatory network of LRH-1,a nuclear receptor implicated in hepatic metabolismNATL INST OF HLTH NIDDK · Principal Investigator
-
Apr 2022
–
Aug 2022
HIV Interactions in Viral EvolutionSEATTLE CHILDRENS HOSPITAL · Principal Investigator
-
Apr 2022
–
Jul 2022
Optimization of SR1903 and SR10171SYNKINE THERAPEUTICS · Principal Investigator
-
Apr 2022
ACTIVE
Small molecules targeting hepatic glucose production and insulin resistanceDANA FARBER CANCER INST · Principal Investigator
-
Apr 2022
–
Jun 2022
ALDH1a1 Inhibition As A Therapeutic Target In Visceral Adiposity and Type 2 DiabetesBRIGHAM AND WOMENS HOSPITAL · Principal Investigator
-
1989
Ph.D. in ChemistryUniversity of Virginia
-
1985
Bachelor's of Science in ChemistrySyracuse University
Scott Hansen Ph.D.
- Mailing Address:
-
Location C260
130 SCRIPPS WAY BLDG 2C1
JUPITER FL 33458
Our laboratory studies the role of cholesterol in setting thresholds of anesthesia, mechanosensation, amyloid formation, and viral entry. In each area of research, we study how cholesterol controls the threshold that regulates biological function and the severity of disease. By understanding the thresholds, we aim to treat diseases caused by altered cholesterol levels and signaling lipids.
Anesthesia: For hundred years scientist believed that membrane lipids were involved in the anesthesia (reversible loss of consciousness). At the heart of the question was the following, How can disrupting a lipid membrane activate or inhibit and ion channel? We have shown that anesthetics disrupt compartmentalization of signaling molecules in cholesterol dependent lipid compartments. The anesthetics counteract cholesterol causing the proteins to escape and activate an ion channel. This established at least one clear molecular mechanism for the membrane as a target of inhaled anesthetics. We are studying this mechanism for additional ion channels that mediate anesthesia in people.
Pain threshold (mechanosensation): We have shown mechanical force disrupts cholesterol dependent compartmentalization of proteins, similar to anesthetics. In addition to defining a novel mechanosensation pathway, we are developing potential therapeutic compounds that will activate an analgesic channel downstream of mu opioid receptor. We aim to develop therapeutics that will have similar pain reducing benefits as opioids, but without the addiction.
Viral entry: We have recently proposed a model for cholesterol dependent SARS-COV-2 viral infectivity, based on our understanding of cholesterol mediated membrane protein translocation. As cholesterol increases the ability of the virus to enter the cell increases. Increased viral entry increases inflammation, which in turn increases cholesterol and more viral entry. We are currently studying cholesterol loading in lung tissues in aged animals.
- 2023 Cell chemical biology
- 2023 The Journal of biological chemistry
- 2023 bioRxiv : the preprint server for biology
- 2022 Communications biology
- 2022 Communications biology
- 2021 Proceedings of the National Academy of Sciences of the United States of America
- 2021 bioRxiv : the preprint server for biology
- 2020 Biochimica et biophysica acta. Biomembranes
- 2020 bioRxiv : the preprint server for biology
- 2020 Proceedings of the National Academy of Sciences of the United States of America
- 2020 Proceedings of the National Academy of Sciences of the United States of America
- 2019 Journal of molecular biology
- 2019 Anesthesia and analgesia
- 2017 Cell reports
- 2016 Nature communications
- 2015 Biochimica et biophysica acta
- 2011 Nature
- 2006 Journal of molecular neuroscience : MN
- 2004 Nature
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Sep 2022
ACTIVE
Regulation of amyloid production by focused ultrasoundNATL INST OF HLTH NIA · Principal Investigator
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Apr 2022
ACTIVE
The role of lipid raft disruption in the activation of TREK-1 channels by anestheticsNATL INST OF HLTH NINDS · Principal Investigator
-
2006
Ph.D.University of California, San Diego
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1999
Bachelor's of Science in ChemistryUtah State University
Claudio A Joazeiro Ph.D.
- Mailing Address:
-
Location C238
130 SCRIPPS WAY BLDG 2C1
Jupiter FL 33458
website: www.joazeirolab.com
See lab website: www.joazeirolab.com
Role of the ubiquitin-proteasome system in cellular regulation and disease
E3 ubiquitin ligases are the components that confer specificity to the ubiquitin system. Consistent with their critical role in cellular regulation, mutations affecting E3s can cause human disease—as illustrated by the cases of BRCA1 in breast cancer and of Parkin in Parkinsonism. Our laboratory is engaged in three main areas of research related to E3s:
1] We are interested in elucidating E3s’ function and mechanisms. For this purpose, we utilize cell and molecular biology approaches with mammalian cells, mice and yeast; our expertise is complemented by close collaborations on structural biology, bioinformatics, mass spectrometry, next-generation sequencing, and fly models;
2]We utilize the information we learn from the above studies to develop assays that are amenable to high-throughput screening, which are then used to identify small molecule inhibitors of E3 ligases. Such compounds can then be both turned into tools to interrogate biology, and developed as pharmaceutical drug candidates;
3] We collaborate with clinicians to translate our basic research findings into therapeutically-relevant discoveries.
- Microbiology
- Molecular therapy
- Neurodegenerative diseases
- Protein biochemistry
- RNA binding proteins
- Rare neuromuscular disorders
- Small molecule drug discovery
- 2023 Cell Reports
- 2023 bioRxiv : the preprint server for biology
- 2022 Molecular cell
- 2022 Nature
- 2021 Molecular cell
- 2021 Molecular cell
- 2020 Nature communications
- 2020 Nature communications
- 2019 Cell
- 2019 Nature reviews. Molecular cell biology
- 2017 Annual review of cell and developmental biology
- 2016 eLife
- 2016
- 2016 Proceedings of the National Academy of Sciences of the United States of America
- 2014 FEBS letters
- 2014 Proceedings of the National Academy of Sciences of the United States of America
- 2014 The Journal of cell biology
- 2013 Proceedings of the National Academy of Sciences of the United States of America
- 2011 Human molecular genetics
- 2010 Nature
- 2009 Proceedings of the National Academy of Sciences of the United States of America
- 2009 Annual review of biochemistry
- 2008 PloS one
- 2006 Journal of the American Chemical Society
- 2006 Cancer research
- 2006 Genes & development
- 2005 Methods in enzymology
- 2005 Molecular cell
- 2003 Molecular cell
- 2003 Current biology : CB
- 2003 Proceedings of the National Academy of Sciences of the United States of America
- 2001 Proceedings of the National Academy of Sciences of the United States of America
- 2001 Journal of biomedical science
- 2001 Nature cell biology
- 2000 The Journal of biological chemistry
- 2000 Molecular biology of the cell
- 2000 Cell
- 2000 Plant physiology
- 2000 Science (New York, N.Y.)
- 2000 The Journal of biological chemistry
- 1999 Science (New York, N.Y.)
- 1996 Genes & development
- 1995 Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas
- 1994 Molecular and cellular biology
- 1992 Cell
- 1991 Proceedings of the National Academy of Sciences of the United States of America
- 1990 Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas
- 1988 Archivos de biologia y medicina experimentales
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Jun 2022
ACTIVE
POLYALANINE TAILS: A NOVEL TYPE OF PROTEIN MODIFICATION IMPLICATED IN NEURODEGENERATIONTHE JACKSON LABORATORY · Principal Investigator
-
1996
Ph.D.University of California, San Diego
-
1990
Master's of ScienceUniversity of Sao Paulo
Courtney Miller Ph.D.
- Mailing Address:
-
Location B309A
130 SCRIPPS WAY BLDG 3B3
JUPITER FL 33458
The Miller Lab is working to develop new medications for the treatment of disorders marked by persistent, unwanted memories – specifically substance use disorder (SUD; addiction) and posttraumatic stress disorder (PTSD). Mechanistically, our efforts are large focused on epigenetic and synaptic structural players.
DEVELOPMENT OF THERAPEUTICS TO PREVENT ADDICTION RELAPSE
Dr. Miller has long been interested in ways to selectively disrupt drug-associated memories (Reconsolidation; Miller and Marshall, Neuron, 2005) and the mechanisms that contribute to the persistence of memory (DNA methylation; Miller et al, Nature Neuroscience, 2010). In bringing these two areas together, the Miller Lab made the surprising discovery that memories associated with the commonly abused stimulant, methamphetamine, employ a unique, actin-based storage mechanism in the brain’s emotional memory center, the amygdala, that allows for their selective disruption (Young et al, Biological Psychiatry, 2014). This was followed by identification of nonmuscle myosin II (NMII) as a viable therapeutic target (Young et al, Molecular Psychiatry, 2015) and we are now in the middle of a drug development program supported by the NIH’s Blueprint Neurotherapeutics Network to develop a clinically safe NMII inhibitor. The goal is to enter a Phase 1a safety trial in 2020.
REGULATION OF TRAUMATIC MEMORY RELATED TO PTSD
We recently developed an animal model with PTSD-like features, including differential susceptibility, which has been replicated by other groups. The stress susceptible subgroup displays persistent, stress-enhanced fear memory, hyperarousal, amygdala hyperactivation and differential expression of genes with known polymorphisms in human PTSD genomic studies (Sillivan et al, Biological Psychiatry, 2017). Importantly, the stress susceptible population can be identified by training behavior, removing the need for additional phenotyping that introduces a molecular confound. Because the model was developed in an inbred mouse line (c57’s), it’s an excellent opportunity to investigate epigenetic mechanisms. To date we have largely focused on noncoding RNAs, including miRNAs. Small RNA-sequencing integrated with quantitative proteomics revealed a panel of miRNAs persistently upregulated in the amygdala of stress susceptible mice. We recently completed a study demonstrating a functional role for one of these miRNAs, which is also expressed in the human amygdala. Working with our collaborators, we also discovered the miRNA’s passenger strand is elevated in serum of a Dutch military cohort diagnosed with PTSD six months after a combat deployment to Afghanistan, indicating this miRNA may be a therapeutic target and biomarker for PTSD. Efforts are now shifting to in vivo calcium imaging and manipulation of the activity-dependent neuronal ensembles regulating differential susceptibility to stress.
- 2021 ACS Chemical Biology
- 2019 Addiction Biology
- 2011 Neuron
- 2011 Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
- 2010 Nature neuroscience
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Jul 2023
ACTIVE
The Impact of Individual Vulnerability to Stress on Alcohol and Drug SeekingNATL INST OF HLTH NINDS · Other
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Apr 2023
ACTIVE
Drug Discovery for First-In-Class Myosin 10 Inhibitors as a Novel Target for GlioblastomaNATL INST OF HLTH NINDS · Principal Investigator
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Jan 2023
ACTIVE
Intersection of causal neurodevelopmental disorder risk genes, cortical circuit function, and cognitive processing required for behavioral adaptionsNATL INST OF HLTH NIMH · Co-Investigator
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Sep 2022
ACTIVE
Neurodevelopmental Disorder Risk Gene Regulation of Intrinsic Membrane Excitability: A Rheostat that Tunes Dendritic Morphogenesis to Regulate Circuit Assembly During DevelopmentNATL INST OF HLTH NIMH · Principal Investigator
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Apr 2022
–
Dec 2022
Circuit-level substrates of ASD-related cognitive and behavioral impairmentsNATL INST OF HLTH NIMH · Principal Investigator
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Apr 2022
ACTIVE
Integrated Platform for Discovery and Validation of Probes that Restore Protein Expression in Single-Gene Causes of Autism and Related DisordersNATL INST OF HLTH NIMH · Principal Investigator
-
Apr 2022
–
Mar 2023
Drug Discovery for First-In-Class Myosin 10 Inhibitors as a Novel Target for GlioblastomaNATL INST OF HLTH NINDS · Principal Investigator
-
Apr 2022
–
Jun 2023
Assessing the role of circRNAs in memory consolidationNATL INST OF HLTH NIMH · Co-Investigator
-
Apr 2022
ACTIVE
Developing nonmuscle myosin II inhibitors for the treatment of glioblastomaNATL INST OF HLTH NINDS · Principal Investigator
-
Apr 2022
ACTIVE
Preventing alcohol seeking with a nonmuscle myosin II inhibitor under clinical developmentNATL INST OF HLTH NIAAA · Principal Investigator
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Apr 2022
ACTIVE
Myosin II regulation of actin dynamics and the selective vulnerability of methamphetamine- and opioid-associated memoryNATL INST OF HLTH NIDA · Principal Investigator
-
Apr 2022
ACTIVE
Targeting Go and Grow in GlioblastomaMAYO CLINIC · Principal Investigator
-
Apr 2022
–
Sep 2023
Development of AI-driven model for anti-SUD drug development based on neuronal plasticityVERISIM LIFE · Principal Investigator
-
2005
Ph.D. in NeurobiologyUniversity of California, Irvine
-
1999
Bachelor's of Science in BiopsychologyUniversity of California, Santa Barbara
Louis Scampavia Ph.D.
- Mailing Address:
-
130 SCRIPPS WAY
JUPITER FL 33458
- Physical Address:
-
Location A111
130 SCRIPPS WAY BLDG 1A1
JUPITER FL 33458
Progress in drug discovery is often coupled to parallel advancements in instrument technology. In our department, High Throughput Screening (HTS) robotics is employed to accelerate the drug discovery process thorough full automation of large scale screening experiments. HTS technology can be used to execute and analyze hundreds of thousand of experiments against large compound libraries to identify a few select compounds of therapeutic value. These “therapeutic leads” provide important insight and basis for the medicinal development of novel drugs for clinical application.
Research efforts are currently focused on:
— Working with collaborators to develop biological assays for HTS compatibility.
— Performing exploratory HTS campaigns for drug lead discovery.
— Technology development and instrumentation for the advancement of HTS robotics.
Collaborative efforts are coordinated with a large community of scientists and include TSRI and UF faculty, Florida researchers, and academia often funded through the National Institutes of Health, Department of Defense and private foundations.
- 2023 Cell death & disease
- 2023 SLAS Discovery
- 2023 SLAS Discovery
- 2023 bioRxiv : the preprint server for biology
- 2023 SLAS Discovery
- 2022 mBio
- 2022 SLAS discovery : advancing life sciences R & D
- 2022 SLAS discovery : advancing life sciences R & D
- 2022 SLAS Discovery
- 2022 ACS chemical biology
-
2022
Rapid deployment of inexpensive open-source orbital shakers in support of high-throughput screening.SLAS technology
- 2022 SLAS discovery : advancing life sciences R & D
- 2021 Bioorganic & medicinal chemistry
- 2021 SLAS discovery : advancing life sciences R & D
- 2021 SLAS discovery : advancing life sciences R & D
- 2021 PLOS Neglected Tropical Diseases
- 2021 Pharmaceuticals (Basel, Switzerland)
- 2021 Pharmaceuticals (Basel, Switzerland)
- 2021 Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
- 2021 SLAS discovery : advancing life sciences R & D
- 2020 The Journal of neuroscience : the official journal of the Society for Neuroscience
- 2020 Scientific reports
- 2020 Science Advances
- 2020 SLAS discovery : advancing life sciences R & D
- 2020 Molecular oncology
- 2020 Nature chemical biology
- 2019 Journal of visualized experiments : JoVE
- 2019 SLAS technology
- 2019 SLAS technology
- 2019 ACS infectious diseases
- 2019 SLAS discovery : advancing life sciences R & D
- 2019 SLAS discovery : advancing life sciences R & D
- 2019 Scientific reports
- 2018 Assay and drug development technologies
- 2018 SLAS discovery : advancing life sciences R & D
- 2018 Oncotarget
- 2018 The Biochemical journal
- 2018 SLAS discovery : advancing life sciences R & D
- 2018 BioProcess international
- 2018 Oncogene
- 2018 Molecular neuropsychiatry
- 2018 SLAS discovery : advancing life sciences R & D
- 2018 SLAS discovery : advancing life sciences R & D
- 2018 Assay and drug development technologies
- 2018 SLAS technology
- 2018 Talanta
- 2017 PloS one
- 2017 SLAS discovery : advancing life sciences R & D
- 2017 SLAS discovery : advancing life sciences R & D
- 2017 Assay and drug development technologies
- 2017 SLAS discovery : advancing life sciences R & D
- 2016 eLife
- 2016 Journal of biomolecular screening
- 2016 ACS chemical biology
- 2016 Molecular and cellular endocrinology
- 2016 Scientific reports
- 2016 Journal of biomolecular screening
- 2016 Assay and drug development technologies
- 2016 Antimicrobial agents and chemotherapy
- 2016 Journal of biomolecular screening
- 2015 Journal of biomolecular screening
- 2015 Trends in pharmacological sciences
- 2015 Assay and drug development technologies
- 2015 Journal of biomolecular screening
- 2015 PloS one
- 2015 ACS chemical biology
- 2014 Journal of biomolecular screening
- 2014 Biopolymers
- 2014 Assay and drug development technologies
- 2011 Journal of laboratory automation
- 2010 Assay and drug development technologies
- 2008 Journal of biomolecular screening
- 2006 Analytical sciences : the international journal of the Japan Society for Analytical Chemistry
- 2004 The Analyst
- 2004 Analytical biochemistry
- 2004 Neurosurgery
- 2003 The Analyst
- 2003 The Analyst
- 2002 The Analyst
- 2002 The Analyst
- 2001 The Analyst
- 1999 Trends in biotechnology
- 1999 Analytical chemistry
- 1999 Talanta
- 1999 Analytical chemistry
- 1999 Analytical chemistry
- 1996 Cytometry
- 1995 Analytical chemistry
- 1994 Cytometry
-
Oct 2023
ACTIVE
Altos HTS Discovery for ISR Inhibitors 640K HTS with 1 counterscreenALTOS LABS · Co-Investigator
-
Oct 2023
ACTIVE
TCAL USP11 Biochemcial FRET INH Assay 640K HTS Proprosal with 2 CounterscreensTAKEDA PHARM NORTH AMERICA · Co-Investigator
-
Jul 2023
ACTIVE
Arvinas: Ataxin-2 Degraders HiBit cell based 665K HTS with 2 counterscreensARVINAS OPERATIONS · Co-Investigator
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May 2023
–
Oct 2023
Lilly NPY2R AG TR-FRET cAMP High Throughput Screen Assay 880K HTS Proposal with 1 CounterscreenSCIENCE EXCHANGE · Co-Investigator
-
May 2023
–
Oct 2023
TCAL TREM-2TAKEDA PHARM NORTH AMERICA · Co-Investigator
-
Apr 2023
ACTIVE
Drug Discovery for First-In-Class Myosin 10 Inhibitors as a Novel Target for GlioblastomaNATL INST OF HLTH NINDS · Principal Investigator
-
Jan 2023
ACTIVE
Annexon Bio -Complement C1s Protease Fluorescence INH HTS Campaign with UF Scripps 640K Deck plus 1 CounterscreenANNEXON · Co-Investigator
-
Dec 2022
–
Nov 2023
Kainomyx -PfMyo-A Absorbance INH HTS Campaign with UF Scripps 640K Deck plus 1 CounterscreenKAINOMYX · Co-Investigator
-
Oct 2022
ACTIVE
TCAL OMA-1 FRET Biochemical INH Assay 666K SDDL HTS Proposal with 1 CounterscreenTAKEDA PHARM NORTH AMERICA · Co-Investigator
-
Sep 2022
–
Mar 2023
Lilly AMY3R PAM TR-FRET cAMP High Throughput Screen Assay 665K HTS Proprosal with 1 CounterscreenSCIENCE EXCHANGE · Co-Investigator
-
Jul 2022
–
Dec 2022
TCAL OXR1 AG and PAM Ca++ High Throughput Screen Assay 665K HTS Proprosal with 2 CounterscreensTAKEDA PHARM NORTH AMERICA · Co-Investigator
-
Jun 2022
–
Jan 2023
HEK AAV2 Induction and GFP Reporter Assay 600K HTSTHERMOFISHER SCIENTIFIC · Co-Investigator
-
Jun 2022
ACTIVE
Takeda TCAL GPCR HTSTAKEDA PHARM NORTH AMERICA · Co-Investigator
-
May 2022
ACTIVE
Midwest AViDD Center – CORE BUNIV OF MINNESOTA · Principal Investigator
-
May 2022
ACTIVE
Midwest AViDD Center – Project 3UNIV OF MINNESOTA · Principal Investigator
-
Apr 2022
ACTIVE
Integrated Platform for Discovery and Validation of Probes that Restore Protein Expression in Single-Gene Causes of Autism and Related DisordersNATL INST OF HLTH NIMH · Principal Investigator
-
Apr 2022
ACTIVE
High-Throughput Screen for the Oncoprotein MYCSCRIPPS RESEARCH INST · Co-Investigator
-
Apr 2022
ACTIVE
Identification of novel anthelmintics through a target-based screen of a parasite ion channelMEDICAL COLLEGE OF WISCONSIN · Principal Investigator
-
Apr 2022
ACTIVE
Identification of REV-ERB inverse agonists for cancer immunotherapyNATL INST OF HLTH NCI · Principal Investigator
-
Apr 2022
ACTIVE
Identification of small molecules for neurological complications of HIV and substance abuse comorbiditySCRIPPS RESEARCH INST · Co-Investigator
-
Apr 2022
–
Aug 2023
An Innovative Approach to Identify Correctors of Metabolic Complications in HIVSCRIPPS RESEARCH INST · Co-Investigator
-
Apr 2022
–
Mar 2023
Drug Discovery for First-In-Class Myosin 10 Inhibitors as a Novel Target for GlioblastomaNATL INST OF HLTH NINDS · Principal Investigator
-
Apr 2022
–
Sep 2022
Parallel Multimodal High-throughput screening to identify activators of the orexin receptorsNATL INST OF HLTH NIMH · Principal Investigator
-
Apr 2022
–
Sep 2022
Tandem Multi-modal Plate Readers for a High Throughput Screening platformNATL INST OF HLTH OD · Principal Investigator
-
Apr 2022
–
May 2022
Identification of Chemical Probes for the Orphan Nuclear Receptor NR2F6NATL INST OF HLTH NCI · Principal Investigator
-
Apr 2022
–
Apr 2022
Development of neutral ceramidase inhibitor tool compoundsTHE RES FOU FOR THE SUNY STONY BROOK UNI · Principal Investigator
-
1996
Doctor of Philosophy in ChemistryUniversity of Washington, Seattle
-
1991
Bachelor's of Science in ChemistryUniversity of Washington, Seattle
-
1979
Bachelor's of Science in GeneticsUniversity of California, Berkeley
Timothy P Spicer Ph.D.
- Mailing Address:
-
130 Scripps Way #1A1
The Herbert Wertheim UF Scripps Institute
Jupiter FL 33458
The focus of our research involves enabling technologies for High Throughput Screening (HTS) of any target of unmet therapeutic need. Our facility supports scientist and faculty locally as well as those in the US and throughout the world. We do this by implementing their biological applications into high density plates for HTS. The breadth of biology we deal with is virtually unlimited due to the diversity of skill sets of the scientist and engineers within our group as well as the expanded capability of the readers associated to our system. We operate a fully automated 1536 well compatible platform and perform HTS on large compound libraries such as the Scripps Drug Discovery Library (645K) or small focused collections (FDA approved drugs). We have expertise in microfluidics, low nanoliter volume liquid handling, ultra-sensitive plate reader technologies and informatics set-up to handle large volume data sets. Key components are high-content readers, imaging detectors such as the ViewLux and FLIPR Tetra, as well as pintool and acoustic transfer devices. Through collaborative efforts we have successfully translated multiple small molecules into the clinics. We are open to any pharmacology desired (agonist, PAMs, NAMs, inverse agonist, etc.) vs. kinases, GPCR, NHRs, proteases, phenotypic assays, etc. which can be applied to any therapeutic area; i.e. CNS, infectious diseases, cardiovascular, oncology, metabolic diseases. In addition, we are currently funded (R33CA206949) to develop 3D spheroid based uHTS assays for the purpose of testing molecules in a more phenotypically relevant format to cancer biology.
- 2023 Cell death & disease
- 2023 SLAS Discovery
- 2023 SLAS Discovery
- 2023 bioRxiv : the preprint server for biology
- 2023 Signal transduction and targeted therapy
- 2023 SLAS Discovery
- 2022 mBio
- 2022 SLAS discovery : advancing life sciences R & D
- 2022 SLAS discovery : advancing life sciences R & D
- 2022 SLAS discovery : advancing life sciences R & D
- 2022 ACS Chemical Biology
-
2022
Rapid deployment of inexpensive open-source orbital shakers in support of high-throughput screening.SLAS technology
- 2022 SLAS discovery : advancing life sciences R & D
- 2022 SLAS discovery : advancing life sciences R & D
- 2021 Bioorganic & medicinal chemistry
- 2021 SLAS Discovery
- 2021 SLAS Discovery
- 2021 PLOS Neglected Tropical Diseases
- 2021 Pharmaceuticals (Basel, Switzerland)
- 2021 Pharmaceuticals (Basel, Switzerland)
- 2021 Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
- 2021 SLAS Discovery
- 2020 Scientific reports
- 2020 The Journal of neuroscience : the official journal of the Society for Neuroscience
- 2020 Nature chemical biology
- 2020 Science Advances
- 2020 SLAS discovery : advancing life sciences R & D
- 2020 Molecular oncology
- 2020 SLAS Discovery
- 2019 Scientific reports
- 2019 SLAS Discovery
- 2019 Proceedings of the National Academy of Sciences of the United States of America
- 2019 ACS infectious diseases
- 2019 SLAS discovery : advancing life sciences R & D
- 2019 SLAS technology
- 2019 Journal of visualized experiments : JoVE
- 2019 Bioorganic & medicinal chemistry letters
- 2019 SLAS technology
- 2018 SLAS discovery : advancing life sciences R & D
- 2018 Talanta
- 2018 SLAS technology
- 2018 Molecular neuropsychiatry
- 2018 Assay and drug development technologies
- 2018 Oncotarget
- 2018 BioProcess international
- 2018 SLAS discovery : advancing life sciences R & D
- 2018 SLAS discovery : advancing life sciences R & D
- 2018 Oncogene
- 2018 Assay and drug development technologies
- 2018 SLAS discovery : advancing life sciences R & D
-
2018
Chemical validation and optimization of pharmacoperones targeting vasopressin type 2 receptor mutantBiochemical Journal
- 2017 SLAS discovery : advancing life sciences R & D
- 2017 Assay and drug development technologies
- 2017 SLAS discovery : advancing life sciences R & D
- 2017 PloS one
- 2017 SLAS discovery : advancing life sciences R & D
- 2016 Journal of biomolecular screening
- 2016 Scientific reports
- 2016 Antimicrobial agents and chemotherapy
- 2016 ACS chemical biology
- 2016 Journal of biomolecular screening
- 2016 Journal of biomolecular screening
- 2016 Molecular and cellular endocrinology
- 2016 eLife
- 2016 Assay and drug development technologies
- 2015 ACS chemical biology
- 2015 ACS chemical biology
- 2015 PloS one
- 2015 Journal of biomolecular screening
- 2015 Trends in pharmacological sciences
- 2015 Journal of biomolecular screening
- 2015 Assay and drug development technologies
- 2014 Assay and drug development technologies
- 2014 Journal of medicinal chemistry
- 2014 Assay and drug development technologies
- 2014 Biopolymers
- 2014 Assay and drug development technologies
- 2014 Journal of biomolecular screening
- 2013 Proceedings of the National Academy of Sciences of the United States of America
- 2013 Bioorganic & medicinal chemistry letters
- 2013 Bioorganic & medicinal chemistry letters
- 2013 Bioorganic & medicinal chemistry letters
- 2013 Bioorganic & medicinal chemistry
- 2013 Bioorganic & medicinal chemistry
- 2012 Journal of the American Chemical Society
- 2012 ACS chemical biology
- 2011 Molecular and biochemical parasitology
- 2011 Journal of the American Chemical Society
- 2011 Proceedings of the National Academy of Sciences of the United States of America
- 2011 Journal of biomolecular screening
- 2011 Molecular cancer therapeutics
- 2011 Journal of the American Chemical Society
- 2010 Molecular pharmacology
- 2010 Bioorganic & medicinal chemistry letters
- 2010 Assay and drug development technologies
- 2010 ACS medicinal chemistry letters
- 2009 Bioorganic & medicinal chemistry letters
- 2009 Bioorganic & medicinal chemistry letters
- 2009 Bioorganic & medicinal chemistry letters
- 2009 Bioorganic & medicinal chemistry
- 2008 Journal of biomolecular screening
- 2008 ACS chemical biology
- 2008 Analytical biochemistry
- 2003 Proceedings of the National Academy of Sciences of the United States of America
- 2003 Drug discovery today
- 2003 Journal of medicinal chemistry
- 2000 Antimicrobial agents and chemotherapy
-
2019
Ph.D. in MedicineUniversity of Queensland
-
1996
Master's of MicrobiologyState University of New York Health Science Center
-
1990
Bachelor's of Science in BiologyState University of New York at Albany