Chemistry: Faculty Directory

Kate Carroll

Kate Carroll Ph.D.

Professor
Phone: (561) 228-2460
Mailing Address:
130 SCRIPPS WAY # 3A3
JUPITER FL 33458

Kate S Carroll is an Associate Professor with Tenure in the Department of Chemistry at The Scripps Research Institute in Jupiter, Florida. She received her BA degree in Biochemistry from Mills College in 1996 and PhD in Biochemistry from Stanford University in 2003. Her postdoctoral work was completed at the University of California, Berkeley, where she was a Damon Runyon-Walter Winchell Chancer Fund Fellow with Prof. Carolyn Bertozzi. She was an assistant professor at the University of Michigan until 2010, when she joined the Chemistry faculty at Scripps. Her research interests span the disciplines of chemistry and biology with an emphasis on studies of sulfur biochemistry pertinent to disease states. Her lab focuses on the development of novel tools to study redox modifications of cysteine thiols, profiling changes in protein oxidation associated with disease, and exploiting this information for development of diagnostic and therapeutic approaches. In addition, her group investigates sulfur pathways that are essential for infection and long-term survival of human pathogens such as Mycobacterium tuberculosis. Dr. Carroll currently serves on the editorial board of Cell Chemical Biology, Molecular Biosystems, Journal of Biology Chemistry, and is a contributing member of ‘Faculty of 1000’. She is also the recipient of the ACS Pfizer Award in Enzyme Chemistry (2013), Camille Dreyfus Teacher-Scholar Award (2010), Scientist Development Award from American Heart Association (2008), and Special Fellow Award from the Leukemia and Lymphoma Society (2006).

Accomplishments:
  • Recipient
    2013 · ACS Pfizer Award in Enzyme Chemistry
  • Awarded
    2010 · Camille Dreyfus Teacher-Scholar Award
  • Scientist Development Award
    2008 · American Heart Association
  • Special Fellow Award
    2006 · Leukemia and Lymphoma Society
Research Summary:

The Carroll lab has an proven track record of attacking fundamental problems in redox biology through a powerful, interdisciplinary approach that integrates synthetic chemistry with proteomics, biochemistry, and cell biology.

An overarching goal of our research program is to understand the biological chemistry and molecular mechanisms of redox-based cellular regulation and signal transduction, with particular emphasis on the role of cysteine oxidation, a ubiquitous and conserved mechanism for controlling protein function. We are also exploring the therapeutic potential of redox-regulated protein function by developing an entirely new class of inhibitors that targets oxidized cysteine residues of key proteins involved in human disease, such as kinases and phosphatases. We also investigate sulfur metabolic pathways that are essential for infection and long-term survival of human pathogens, such as Mycobacterium tuberculosis and leverage novel discoveries to develop new antimicrobial therapies.

Ultimately, our goal is to accelerate the discovery of key regulatory nodes of redox-signaling networks, profile changes in protein cysteine oxidation associated with disease, and harness this information for the development of new diagnostic and therapeutic approaches.

Students in the lab receive broad-based training in experimental techniques ranging from synthetic chemistry and mass spectrometry to cellular and in vivo animal studies. Representative skill sets and expertise in the group are given below, and students are encouraged to take multiple apporaches to ask and answer new scientific questions.

— Chemical tool development: Synthetic chemistry with analytical characterization — Cell culture: Mammalian cell lines, bacteria, and primary cultures — Proteomics: Solid-phase capture, fractionation, LC-MS/MS, bioinformatics — Molecular imaging: Confocal microscopy and flow cytometry — Gene discovery: Activity-based protein profiling — Animal studies: Mouse physiology — Molecular biology: Cloning, transfections, RNAi, PCR, and CRISPR — In vitro biochemistry: Protein preparation, purification, and protein engineering

Publications:
Grants:
  • Mar 2023 ACTIVE
    Chemical Tools for Probing Cysteine Sulfenation and Sulfination Redox Biology
    NATL INST OF HLTH NIGMS · Principal Investigator
  • Apr 2022 ACTIVE
    Chemistry and Biology of Bacterial Sulfonucleotide Reductases
    NATL INST OF HLTH NIGMS · Principal Investigator
  • Apr 2022 ACTIVE
    Redox Modification and Targeting of Mutant KRas in Cancer
    NATL INST OF HLTH NCI · Principal Investigator
Education:
  • 2003
    Ph.D. in Biochemistry
    Stanford University
  • 1996
    Bachelor's of Art in Biochemistry
    Mills College
Luiz Pedro Sorio de Carvalho

Luiz Pedro Sorio de Carvalho Ph.D.

Professor
Phone: (561) 228-2209
Physical Address:
130 SCRIPPS WAY
JUPITER FL 33458
Accomplishments:
  • Horizon Award (Group effort, included two lab members)
    2021 · Royal Society of Chemistry
  • ACS Infectious Diseases/Biological Chemistry Division Young Investigator Award
    2021 · American Chemical Society
  • New Investigator Award
    2014 · Wellcome Trust
  • Irving S. Sigal Memorial Award
    2014 · American Society for Microbiology
  • MRC Centenary Early Career Award
    2012 · Medical Research Council (MRC)
Research Summary:

Diseases caused by bacteria from the genus Mycobacterium afflict humankind for millennia and currently represent a significant source of mortality and morbidity. Examples are human tuberculosis, leprosy, Buruli ulcer and other soft-tissue and lung infections. Tuberculosis alone is still responsible for 1.5 million deaths annually. The increased prevalence of antibiotic resistance in mycobacteria is a significant problem, causing nearly untreatable infections. The Carvalho group is interested in defining how soil-dwelling and water-born mycobacteria became adapted to the human host, a pre-requisite for a human pathogen. In particular, our group is focused on understanding how mycobacterial metabolism and chemistry evolved in the last 50 million years, to allow for optimal growth and virulence in humans. Once these processes have been mapped and characterized at cellular and molecular levels, we will employ state-of-the-art methods, some of which have been pioneered at UF Scripps, to discover and develop novel small molecules capable of killing these pathogens and transform the therapy of tuberculosis and other mycobacterial diseases.

Key recent advances include:

(i) discovery of the first example of target-mediated antibiotic inactivation

(ii) identification of the metabolic requirements for pyruvate and lactate utilization by M. tuberculosis

(iii) discovery of itaconate catabolism in M. tuberculosis and its intersection with amino acid metabolism

(iv) carried out the first fine mapping of nitrogen metabolism in M. tuberculosis.

(v) demonstration of the crucial role of metabolism in bacterial L-form

(vi) discovery of the first NAD+ phosphorylase and its role in M. tuberculosis cell death

Publications:
Education:
  • 2006
    Ph.D. in Biochemistry
    Albert Einstein College of Medicine
  • 2001
    M.Sc. in Cell and Molecular Biology
    Federal University of Rio Grande do Sul
  • 1999
    Pharmacy Degree
    Federal University of Rio Grande do Sul
Matthew Disney

Matthew Disney Ph.D.

Chair, Department Of Chemistry
Phone: (561) 228-2203
Mailing Address:
Location A331
130 SCRIPPS WAY BLDG 3A2
JUPITER FL 33458
Accomplishments:
  • Recipient
    2021 · The ACS 2022 Nobel Laureate Signature Award for Graduate Education in Chemistry
  • Awarded
    2019 · The Raymond and Beverly Sackler International Prize in Chemistry
  • Awarded
    2018 · BioFlorida's Weaver H. Gaines Entrepreneur of the Year
  • The Barry Cohen Prize
    2018 · Medicinal Chemistry Section of the Israel Chemical Society and Teva Pharmaceutical Industries.
  • Outstanding Mentor Award
    2017 · Scripps Florida
  • Tetrahedron Young Investigator Award in Bioorganic and Medicinal Chemistry
    2016 ·
  • Blavatnik Young Scientists Award Finalist
    2015-2017 ·
  • NIH Director’s Pioneer Award
    2015 · National Institutes of Health
  • David W. Robertson Award in Medicinal Chemistry
    2014 · American Chemical Society’s Division of Medicinal Chemistry
  • Eli Lilly Award in Biological Chemistry
    2013 · American Chemical Society
  • Excellence Award in the field of Research in Science and Technology
    2013 · India-US Chamber of Commerce, Inc.
  • David Gin Award in Carbohydrate Chemistry
    2012 · American Chemical Society
  • Dreyfus Teacher-Scholar Award
    2010-2015 ·
  • Excellent Scholar, Young Investigator Award
    2010 · University at Buffalo
  • Research Corporation Cottrell Scholar Award
    2008-2010 ·
  • NYSTAR JD Watson Young Investigator Award
    2007-2009 ·
  • Camille and Henry Dreyfus New Faculty Award
    2005-2010 ·
  • Second Year Roche Foundation Postdoctoral Fellowship
    2004-2005 · Swiss Federal Institute of Technology
  • Roche Foundation Postdoctoral Fellowship
    2003-2004 · Swiss Federal Institute of Technology
  • Arnold Weissberger Memorial Fellow
    2001-2002 · University of Rochester
  • Elon Huntington Hooker Memorial Fellow
    2000-2001 · University of Rochester
  • Sherman-Clark Memorial Fellow
    1997-1999 · University of Rochester
  • Eric A. Batista Award
    1997 · University of Maryland at College Park
  • Howard Hughes Medical Institute Undergraduate Research Fellow
    1995-1997 · University of Maryland at College Park
Research Summary:

The Disney group develops rational approaches to design selective therapeutics from only genome sequence. One of the major advantages that genome sequencing efforts potentially provides is advancing patient-specific therapies, yet such developments have been only sparsely reported. We have developed general approach to provide lead Targeted Therapeutics and Precise Medicines that target RNAs that cause disease broadly and include rare neuromuscular (muscular dystrophy), neurodegenerative (Alzheimer’s, ALS), infectious diseases as well as difficult-to-treat cancers (breast, pancreatic, prostate, and others), and infectious diseases that can emerge through seasonal exposures. Designed compounds have demonstrated activity in human derived cellular disease models as well as pre-clinical animal models of disease. We train the next-generation of scientists to ensure our work has an exponential impact in studying disease biology and leveraging it into making Precision Medicines.

To achieve these goals, we developed a proprietary platform dubbed Inforna over the past 13 years. It merges chemoinformatics and RNA structure to identify lead compounds that target an RNA of interest; that is, Inforna houses a database of RNA three dimensional motifs that bind small molecule medicines, identified via an experimental library-versus-library screen. The bioinformatics pipeline rapidly and accurately identifies disease-associated RNA sequences that adopt targetable three-dimensional folds by comparison to the database. This pipeline has been validated in various peer-review publications that demonstrated that the platform can be used to target RNAs that cause neuromuscular, neurodegenerative, and infectious diseases as well as difficult-to-treat cancers in pre-clinical animal models. Additionally, lead small molecule medicines can also be rapidly developed into compounds that recruit cellular nucleases to selectively destroy the RNAs that cause these diseases in a catalytic and substoichiometric manner (e.g. one molecule of the small molecule cleaves more than one molecule of the RNA target) coined RIBOTACs. Two of the major perceived concerns in the area of RNA-targeted small molecules are selectivity and potency. We have broadly demonstrated that these issues can be rapidly overcome via rational design and fragment assembly.

Key recent advances include:

(i) Sequence-based drug design across the human transcriptome to provide precision lead medicines

(ii) Small molecule cleavage of RNAs (RIBOTACS) in a catalytic and sub-stoichiometric manner via recruitment of cellular nucleases

(iii) Tools and technologies to study ligand binding capacity of RNAs across the transcriptome (Chem-CLIP and Ribo-SNAP)

(iv) Showing broad classes of known drugs target RNA and that their activity may be traced to targeting non-coding RNA

(v) Chemical biology approaches to understand RNA biology. We uncovered the mechanistic cause of Fragule X-Syndrome and Autism and also can define precisely the effect that non-coding RNAs have on the proteome.

(vi) Study druggability broadly. We have the ability to answer fundamental questions about how druggable the genome really is. Thus, we have launched the Druggable Transcriptome Project.

Publications:
Grants:
  • Sep 2022 ACTIVE
    Design and evaluation of drug-like small molecules targeting repeat expansion (MDA 963835)
    MUSCULAR DYSTROPHY ASSO · Other
  • Sep 2022 ACTIVE
    Expanding Ribonuclease Targeting Chimeras (RIBOTACs) to Advance Targeted Degradation of Disease-Causing RNAs
    AMER CHEMICAL SOC · Other
  • May 2022 ACTIVE
    Center for Antiviral Medicines & Pandemic Preparedness (CAMPP) – PROJECT 4
    SCRIPPS RESEARCH INST · Principal Investigator
  • May 2022 ACTIVE
    Development of outpatient antiviral cocktails against SARS-CoV-2 and other potential pandemic RNA viruses
    STANFORD UNIV · Principal Investigator
  • Apr 2022 ACTIVE
    Design of precision small molecules targeting RNA repeating transcripts to manipulate and study disease biology
    NATL INST OF HLTH NINDS · Principal Investigator
  • Apr 2022 ACTIVE
    RNA-Targeted Drug Discovery and Development for Parkinson's Disease
    RUTGERS STATE UNIV · Principal Investigator
  • Apr 2022 ACTIVE
    Targeted degradation of RNAs by using small molecules
    NATL INST OF HLTH NCI · Principal Investigator
  • Apr 2022 ACTIVE
    Targeting mRNAs that Contribute to Neurological Disease
    EXPANSION THERAPEUTICS · Principal Investigator
  • Apr 2022 ACTIVE
    Pre-clinical evaluation of small molecules that rescue aberrant Tau mRNA splicing
    RAINWATER CHARITABLE FOUNDATION · Principal Investigator
  • Apr 2022 ACTIVE
    Advance Therapeutic Targets & Biomarkers for ALS FTD
    TARGET ALS FOUNDATION · Principal Investigator
  • Apr 2022 ACTIVE
    Design and Study of Small Molecules That Cleave the RNA That Causes Myotonic Dystrophy Type 1 (DM1)
    US ARMY MED RES ACQUISITION · Principal Investigator
  • Apr 2022 ACTIVE
    Small Molecules That Target the RNAs That Cause Pulmonary Fibrosis and Polycystic Kidney Disease
    US ARMY MED RES ACQUISITION · Principal Investigator
  • Apr 2022 ACTIVE
    Small Molecule Targeting of mRNAs Encoding Proteins relevant for Cardiovascular, Renal and Metabolic Diseases
    ASTRAZENECA · Principal Investigator
  • Apr 2022 ACTIVE
    Pathophysiology of genetically defined dementia and neurodegeneration: Defining therapeutic targets and pathways
    NATL INST OF HLTH NINDS · Principal Investigator
  • Apr 2022 – Dec 2022
    Developing Pre-Clinical Candidates Against miRNAs Implicated in Autoimmune Diseases
    EMD SERONO RESEARCH & DEVELOPMENT INST · Principal Investigator
  • Apr 2022 ACTIVE
    Targeting RNAs Associated with Tauopathies with Small Molecules
    RAINWATER CHARITABLE FOUNDATION · Principal Investigator
  • Apr 2022 – Dec 2022
    Small Molecule Targeting of DUX4 mRNA for treatment of Fascioscapulohumeral Dystrophy (FSHD)
    PFIZER INC · Principal Investigator
Education:
  • 2003
    Ph.D. in Biophysical Chemistry
    University of Rochester
  • 1999
    Master's of Science in Chemistry
    University of Rochester
  • 1997
    Bachelor's of Science in Chemistry
    University of Maryland, College Park
Thomas Kodadek

Thomas Kodadek Ph.D.

Professor Of Chemistry
Phone: (561) 228-2461
Mailing Address:
Location A335
130 SCRIPPS WAY BLDG 3A2
JUPITER FL 33458
Physical Address:
130 SCRIPPS WAY # A335
JUPITER FL 33458
Accomplishments:
  • Co-Founder
    2022 · Triana Biosciences
  • Makineni Award
    2017 · American Peptide Society
  • Co-Founder
    2017 · Deluge Biotechnologies
  • Cope Scholar Award
    2016 · American Chemical Society
  • Chemical Biology Faculty Member of the Year
    2007 · Faculty of 1000
  • Pioneer Award
    2006 · NIH
  • Elected Fellow
    1999 · American Association for the Advancement of Science
  • Junior Faculty Research Award
    1991 · American Cancer Society
  • Post-doctoral Fellowship
    1985 · Jane Coffin Childs Foundation
Research Summary:

The Kodadek laboratory works in the general area of chemical biology with an emphasis on translational research. The laboratory employs a broad spectrum of techniques that span organic chemistry to molecular genetics. Recently, significant effort has been focused on the development of novel strategies to tackle the “undraggable” proteome. We have developed DNA-encoded libraries of non-peptidic macrocycles and other novel molecular species that we believe will be better suitable to engage difficult protein targets than traditional drug candidates. We are also developing novel techniques to screen these libraries for molecules with novel functions, for example the ability to recruit to target proteins post-translational modifying enzymes that alter the levels or activity of the target.

Another focus is to use the chemical tools we have developed to monitor and manipulate the immune system. One goal of these efforts is to discover effective and early diagnostic tests for a variety of disease states, including cancers, autoimmune diseases and neurodegenerative conditions. Another is to identify compounds that act as “antigen surrogates” in that they have the ability to recognize the antigen-binding sites of antibodies and T cell receptors. These compounds are being developed as potential therapeutic agents to block autoimmune responses selectively without interfering with normal functions of the immune system.

Publications:
Grants:
  • Sep 2022 ACTIVE
    Molecular Cloaking Devices for Manipulation of Cysteine Post-Translational Modifications
    NATL INST OF HLTH NCI · Principal Investigator
  • Apr 2022 – Aug 2022
    Phenotypic screening using DNA-encoded libraries
    NATL INST OF HLTH NIGMS · Principal Investigator
Education:
  • 1985-1987
    Jane Coffin Childs Post-doctoral Scholar
    UCSF
  • 1985
    Ph.D. in Chemistry
    Stanford University
  • 1981
    Bachelor's of Science in Chemistry
    University of Miami
Roy Periana

Roy Periana Ph.D.

Professor
Phone: (561) 228-2457
Mailing Address:
Location A315
130 SCRIPPS WAY BLDG, 3A1
JUPITER FL 33458

B. S. University of Michigan, 1979; Ph.D. University of California, Berkeley, 1985, Ph.D. advisor: Robert G. Bergman; Previously worked at Dow Chemical company, Monsanto Company in Missouri, Catalytica, Catalytica Advanced Technologies, SRI International and an Associate Professor at the University of Southern California’s Loker Hydrocarbon Research Institute. Currently he is a Professor of chemistry at the Scripps Research Institute and Director of the Scripps Energy Laboratories.

Accomplishments:
  • Co-Founder and Member of Board of Directors
    2015-2022 · Hyconix, Inc.
  • Founder and Member of Board of Directors
    2005-2007 · Qateomix, Inc.
  • Fellowship
    1999 · Society for the Promotion of Science (JSPS)
Research Summary:

Design and Study of Molecular Catalysts for Small Molecule Conversion

CH4 (and other light alkanes in Natural Gas), N2, O2, H2O and CO2 are among the most abundant raw materials on Earth. Chemical reactions of these small molecules generate most of the world’s energy, emissions and materials. However, in spite of a century of research, current technologies still operate at higher costs, generate substantially more emissions and lead to greater dependence on petroleum than required. At the foundation of these inefficiencies is the high strength of the bonds in all of the small molecules. In spite of intensive effort over more than 50 years, failure to develop chemistry to controllably make and break these bonds has led to the unfortunate assignment of these small molecule challenges as “Holy Grails” in chemistry. The focus of our research is to overcome these challenges through the design of next generation catalysts for the direct, selective, conversion of these molecules. One particular emphasis continues to be the design of systems that will enable the direct conversion of alkanes to fuels and chemicals at lower temperatures. This could replace or augment the use of petroleum with cleaner, more abundant Natural Gas as a transition to a cleaner future. Our approach is based on the rational, de novo design of molecular (s-called homogeneous or single-site) catalysts through an iterative process involving conceptual design, computational study, synthesis, characterization and study of reaction chemistry and mechanisms. Our research interests include the design of catalysts for: CH hydroxylation; CH aminations, N2 fixation, O2 activation and CO2 reduction.

Research Interests:
  • Chemical protein synthesis
  • Inorganic Chemistry
  • Organic Chemistry
  • Organometallic Chemistry
  • Reaction Mechanisms
  • Synthesis
  • Synthetic organic chemistry
Publications:
Education:
  • 1985
    Ph.D. in Organic Chemistry
    University of California, Berkeley
  • 1979
    Bachelor's of Science in Chemistry
    University of Michigan
Ciaran Seath

Ciaran Seath

AST PROF
Phone: (561) 228-2241
Physical Address:
110 SCRIPPS WAY
JUPITER FL 33458

Ciaran completed his PhD in chemistry from the University of Strathclyde in 2017 under the supervision of Dr Allan Watson studying chemoselective transition-metal catalysis. During this time he also spent time in the labs of Prof. Tom Snaddon at Indiana University working on total synthesis of complex natural products, and with Prof. Glenn Burley on the development of novel click chemistries for nucleoside bioconjugation.

He then moved to Emory University as a postdoctoral researcher working in the laboratory of Professor Nathan Jui developing novel reductive photoredox methodologies. During this time, Ciaran worked on new synthetic methods to access alkylated heterocycles and complex fluorinated scaffolds.

In 2019, Ciaran moved to Princeton University to work with Professors David MacMillan and Tom Muir where he explored new photocatalytic methods for proximity labelling to investigate critical aspects of cancer biology.

Currently, Ciaran is an Assistant Professor of Chemistry at Scripps-UF in Jupiter, Florida.

Research Summary:

A critical component of the development of new medicines is the identification and validation of new protein targets. Our laboratory is focused on using state-of the-art methods in chemical biology to discover new therapeutically relevant protein-biomolecule interactions that contribute to disease.

Research Interests:
  • Biochemistry and Cell Biology
  • Clinical and translational science
  • Pediatric brain tumors
Ben Shen

Ben Shen Ph.D.

Professor
Phone: (561) 228-2456
Mailing Address:
Location A309
130 SCRIPPS WAY BLDG 3A1
JUPITER FL 33458
Accomplishments:
  • Fellow
    2021 · American Society of Pharmacognosy
  • Guest Co-Editor
    2021 · J. Ind. Microbiol. Biotechnol. March-April special issue on Natural Product Discovery and Development in the Genomic Era: 2021
  • Outstanding Mentor Award
    2020 · Society of Research Fellows, TSRI, Jupiter, FL
  • Charles Thom Award
    2018 · Society of Industrial Microbiology and Biotechnology
  • Editor
    2017-2022 · J. Ind. Microbiol. Biotechnol.
  • Promega Biotechnology Research Award
    2015 · American Society for Microbiology
  • Guest Co-Editor
    2012 · Curr. Opinion Chem. Biol. April issue on Biocatalysis and Biotransformation
  • Fellow
    2011 · American Academy of Microbiology
  • Fellow
    2011 · American Association for the Advancement of Science
  • Guest Co-Editor
    2011 · J. Antibiot. January issue in memory of C. Richard Hutchinson
  • Member, Editorial Board
    2009-2022 · J. Antibiot.
  • Associate Editor
    2006-2022 · Acta Microbiologica Sinica
  • Member, Advisory Board
    2005-2017 · Mol. BioSyst.
  • Member, Editorial Advisory Board
    2003-2017 · J. Nat. Prod.
  • Member
    2002-2016 · Editorial Board of J. Ind. Microbiol. Biotechnol.
  • Jack L. Beal Award
    2002 · American Society of Pharmacognosy
  • Independent Scientist Award
    2001-2006 · National Institutes of Health
  • Matt Suffness Award
    2000 · American Society of Pharmacognosy
  • CAREER Award
    1998-2003 · NSF
  • Searle Scholar
    1997-2000 · Searle Scholars Program
  • FIRST Award
    1996-2001 · National Institutes of Health
Research Summary:

Natural Product Biosynthesis, Engineering, and Drug Discovery. Microorganisms produce a large variety of biologically active substances representing a vast diversity of fascinating molecular architecture not available in any other systems. Our research centers on the chemistry, biochemistry and genetics of the biosynthesis of these secondary metabolites. Blending organic chemistry, biochemistry, and molecular biology, we take a multidisciplinary approach to study the secondary metabolism by asking the following questions: what reactions are available in nature, what are the enzymatic mechanisms of these reactions, how are these reactions linked to produce complex structures, what are the regulatory mechanisms of these pathways, and, ultimately, how can we leverage a large microbial strain collection and develop enabling genome mining and synthetic biology technologies for natural product discovery and production, and manipulate nature’s biosynthetic machinery for the discovery and development of new drugs. Members of our group gain broad training spanning organic chemistry, biochemistry, microbiology and molecular biology, a qualification that is becoming essential for the modern bioorganic chemists who seek career opportunity in both academia and pharmaceutical and biotechnology industry (http://www.scripps.edu/shen/).

Natural Products Discovery Center at Scripps Research. Natural products are significantly underrepresented in current small molecule libraries. The current Natural Products Library (NPL) at Scripps Research’s Natural Product Discovery Center consists of: (i) purified natural products with fully assigned structures, (b) MPLC (on C-18 semipreparative column) fractions, and (c) crude extracts. The NPL is presented in 384-well format with all materials dissolved in DMSO (1 mM for pure compounds and 50 mg/mL for fractions and extracts), compatible with most of the HTS platforms. The NPL currently available for screening includes: (a) ~600 pure natural products, (b) ~53,500 MPLC fractions, (c) ~205,000 crude extracts. The NPL provides an unprecedented molecular diversity to screen emerging targets for drug leads, and selected members of the NPL serves as outstanding small molecule probes to interrogate biology. Central to the Natural Products Discovery Center is the large microbial strain collection, containing a total of 217,352 bacterial and fungal strains, of which 62,328 are actinobacteria, 14,465 other bacteria, 92,225 fungi, and 48,334 unidentified (bacteria or fungi). Promising leads could therefore be produced in sufficient quantities by microbial fermentation for follow up studies and, ultimately, clinical development.

Publications:
Grants:
  • Apr 2022 – May 2022
    Biosynthesis of the Leinamycin Family of Natural Products: Mechanistic Studies and Chemoenzymatic Analog Synthesis
    NATL INST OF HLTH NIGMS · Other
  • Apr 2022 – Jul 2022
    Characterization of the Thioacid Biosynthetic Machinery and Isolation of a Novel Thioacid Enediyne Natural Product
    NATL INST OF HLTH NIGMS · Other
  • Apr 2022 – Sep 2022
    Graduate Research Fellowship Program (GRFP) – Cepeda
    SCRIPPS RESEARCH INST · Principal Investigator
  • Apr 2022 – Nov 2022
    Novel Enediyne-Based Antibody-Drug Conjugates for Cancers
    NATL INST OF HLTH NCI · Principal Investigator
  • Apr 2022 – Nov 2022
    Mining Actinomycetal Genomes for Natural Product Discovery and Biosynthesis
    NATL INST OF HLTH NIGMS · Principal Investigator
  • Apr 2022 ACTIVE
    Monodisperse Microbubbles for Noninvasive Pressure Estimation
    THOMAS JEFFERSON UNIV · Principal Investigator
Education:
  • 1991
    Ph.D. in Organic Chemistry and Biochemistry
    Oregon State University
  • 1984
    Master's of Science in Chemistry
    Chinese Academy of Sciences
  • 1982
    Bachelor's of Science in Chemistry
    Hangzhou University

Chemistry: Scientific Directors, Joint Appointments and Collaborators

Thomas Bannister

Thomas Bannister Ph.D.

Research Professor (Sr. Scientific Director), Department Of Molecular Medicine
Phone: (561) 228-2206
Mailing Address:
Location A229
130 SCRIPPS WAY BLDG 2A2
Jupiter FL 33458
Physical Address:
Location A229
130 SCRIPPS WAY BLDG 2A2
Jupiter FL 33458
Research Summary:

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.

Publications:
Education:
  • 1991
    Ph.D. in Organic Chemistry
    Indiana University
  • 1987
    Master's of Philosophy
    Yale University
  • 1986
    Master of Science
    Yale University
  • 1984
    A.B. in Chemistry
    Wabash College
Theodore Kamenecka

Theodore Kamenecka Ph.D.

Sr. Scientific Director, Department Of Molecular Medicine
Phone: (561) 228-2207
Mailing Address:
Location A207
130 SCRIPPS WAY BLDG 2A2
JUPITER FL 33458
Physical Address:
Room A230
110 Scripps Way
Jupiter FL 33458
Research Summary:

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.

Publications:
Education:
  • 1996-1998
    Post-doctorate
    Memorial Sloan Kettering Cancer Center
  • 1990-1996
    Ph.D. in Chemistry
    University of California, Irvine
  • 1986-1990
    Bachelor of Science in Chemistry
    University of Rochester
Michael Cameron

Michael Cameron Ph.D.

Sr Scientific Director, Associate Professor Of Molecular Medicine, Department Of Molecular Medicine
Phone: (561) 228-2223
Mailing Address:
Location A201
130 SCRIPPS WAY BLDG 2A1
JUPITER FL 33458
Research Summary:

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.

Publications:
Education:
  • 2000
    Ph.D. in Biochemistry
    Utah State University
  • 1994
    Bachelor's of Science in Chemistry
    Gonzaga University