Patrick Griffin

Patrick Griffin, Ph.D.

Scientific Director And Professor

Department: SR-HA-ADMINISTRATION
Business Phone: (561) 228-2200
Business Email: pgriffin2@ufl.edu

About Patrick Griffin

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.

Additional Positions:
Professor, Molecular Therapeutics
2007 – 2017 · Scripps Research
Chairman, Molecular Therapeutics
2007 – 2015 · Scripps Research
Professor, Biochemistry
2004 – 2007 · Scripps Research
Chief Scientific Officer
2002 – 2004 · ExSAR Corporation
Senior Director, Basic Chemistry and Molecular Profiling Proteomics
2001 – 2002 · Merck & Co., Inc.
Director, Basic Chemistry and Molecular Profiling Proteomics
1999 – 2001 · Merck & Co., Inc.
Senior Research Fellow, Molecular Design and Diversity
1996 – 1999 · Merck & Co., Inc.
Research Fellow, Inflammation Research
1991 – 1996 · Merck & Co., Inc.
Postdoctoral Fellow
1990 – 1991 · California Institute of Technology
Associate Scientist
1989 – 1990 · Genentech

Research Profile

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.

Publications

2022
Cryo-EM structure of human GPR158 receptor coupled to the RGS7-Gβ5 signaling complex.
Science (New York, N.Y.). 375(6576):86-91 [DOI] 10.1126/science.abl4732. [PMID] 34793198.
2022
Differential Modulation of Nuclear Receptor LRH-1 through Targeting Buried and Surface Regions of the Binding Pocket.
Journal of medicinal chemistry. [DOI] 10.1021/acs.jmedchem.2c00235. [PMID] 35503419.
2022
The intrinsically disordered CARDs-Helicase linker in RIG-I is a molecular gate for RNA proofreading.
The EMBO journal. [DOI] 10.15252/embj.2021109782. [PMID] 35437807.
2021
CMT2N-causing aminoacylation domain mutants enable Nrp1 interaction with AlaRS.
Proceedings of the National Academy of Sciences of the United States of America. 118(13) [DOI] 10.1073/pnas.2012898118. [PMID] 33753480.
2021
Conformational Changes of RORγ During Response Element Recognition and Coregulator Engagement.
Journal of molecular biology. 433(22) [DOI] 10.1016/j.jmb.2021.167258. [PMID] 34547329.
2021
Discovery of Selective Inhibitors for In Vitro and In Vivo Interrogation of Skeletal Myosin II.
ACS chemical biology. 16(11):2164-2173 [DOI] 10.1021/acschembio.1c00067. [PMID] 34558887.
2021
Dual-mechanism estrogen receptor inhibitors.
Proceedings of the National Academy of Sciences of the United States of America. 118(35) [DOI] 10.1073/pnas.2101657118. [PMID] 34452998.
2021
Insights into the structure and RNA-binding specificity of Caenorhabditis elegans Dicer-related helicase 3 (DRH-3).
Nucleic acids research. 49(17):9978-9991 [DOI] 10.1093/nar/gkab712. [PMID] 34403472.
2021
One-step construction of circularized nanodiscs using SpyCatcher-SpyTag.
Nature communications. 12(1) [DOI] 10.1038/s41467-021-25737-7. [PMID] 34521837.
2021
Ordered assembly of the cytosolic RNA-sensing MDA5-MAVS signaling complex via binding to unanchored K63-linked poly-ubiquitin chains.
Immunity. 54(10):2218-2230.e5 [DOI] 10.1016/j.immuni.2021.09.008. [PMID] 34644557.
2021
Resolving the Dynamic Motions of SARS-CoV-2 nsp7 and nsp8 Proteins Using Structural Proteomics.
bioRxiv : the preprint server for biology. [DOI] 10.1101/2021.03.06.434214. [PMID] 33688660.
2021
Revealing the Structural Plasticity of SARS-CoV-2 nsp7 and nsp8 Using Structural Proteomics.
Journal of the American Society for Mass Spectrometry. 32(7):1618-1630 [DOI] 10.1021/jasms.1c00086. [PMID] 34121407.
2021
Structural basis for heme-dependent NCoR binding to the transcriptional repressor REV-ERBβ.
Science advances. 7(5) [DOI] 10.1126/sciadv.abc6479. [PMID] 33571111.
2021
Structure of an AMPK complex in an inactive, ATP-bound state.
Science (New York, N.Y.). 373(6553):413-419 [DOI] 10.1126/science.abe7565. [PMID] 34437114.
2021
Structure-Activity Relationship and Biological Investigation of SR18292 (16), a Suppressor of Glucagon-Induced Glucose Production.
Journal of medicinal chemistry. 64(2):980-990 [DOI] 10.1021/acs.jmedchem.0c01450. [PMID] 33434430.
2021
Structures of the human LONP1 protease reveal regulatory steps involved in protease activation.
Nature communications. 12(1) [DOI] 10.1038/s41467-021-23495-0. [PMID] 34050165.
2021
Synthetic fluorescent MYC probe: Inhibitor binding site elucidation and development of a high-throughput screening assay.
Bioorganic & medicinal chemistry. 42 [DOI] 10.1016/j.bmc.2021.116246. [PMID] 34130216.
2020
A molecular switch regulating transcriptional repression and activation of PPARγ.
Nature communications. 11(1) [DOI] 10.1038/s41467-020-14750-x. [PMID] 32075969.
2020
A simple and robust cell-based assay for the discovery of novel cytokinesis inhibitors.
Journal of biological methods. 7(3) [DOI] 10.14440/jbm.2020.335. [PMID] 33204739.
2020
Binding interface and impact on protease cleavage for an RNA aptamer to HIV-1 reverse transcriptase.
Nucleic acids research. 48(5):2709-2722 [DOI] 10.1093/nar/gkz1224. [PMID] 31943114.
2020
Comparative Analysis of Cleavage Specificities of Immobilized Porcine Pepsin and Nepenthesin II under Hydrogen/Deuterium Exchange Conditions.
Analytical chemistry. 92(16):11018-11028 [DOI] 10.1021/acs.analchem.9b05694. [PMID] 32658454.
2020
High-Throughput Screening for Drugs That Inhibit Papain-Like Protease in SARS-CoV-2.
SLAS discovery : advancing life sciences R & D. 25(10):1152-1161 [DOI] 10.1177/2472555220963667. [PMID] 33043784.
2020
Integrative structural biology studies of HIV-1 reverse transcriptase binding to a high-affinity DNA aptamer.
Current research in structural biology. 2:116-129 [DOI] 10.1016/j.crstbi.2020.06.002. [PMID] 33870216.
2020
Multivalent interactions drive nucleosome binding and efficient chromatin deacetylation by SIRT6.
Nature communications. 11(1) [DOI] 10.1038/s41467-020-19018-y. [PMID] 33067423.
2019
A Decoupled Automation Platform for Hydrogen/Deuterium Exchange Mass Spectrometry Experiments.
Journal of the American Society for Mass Spectrometry. 30(12):2580-2583 [DOI] 10.1007/s13361-019-02331-2. [PMID] 31724102.
2019
Correction: HDX-MS reveals structural determinants for RORγ hyperactivation by synthetic agonists.
eLife. 8 [DOI] 10.7554/eLife.52847. [PMID] 31625909.
2019
Defining a Canonical Ligand-Binding Pocket in the Orphan Nuclear Receptor Nurr1.
Structure (London, England : 1993). 27(1):66-77.e5 [DOI] 10.1016/j.str.2018.10.002. [PMID] 30416039.
2019
Definition of functionally and structurally distinct repressive states in the nuclear receptor PPARγ.
Nature communications. 10(1) [DOI] 10.1038/s41467-019-13768-0. [PMID] 31862968.
2019
Discovery and Optimization of a Series of Sulfonamide Inverse Agonists for the Retinoic Acid Receptor-Related Orphan Receptor-α.
Medicinal chemistry (Shariqah (United Arab Emirates)). 15(6):676-684 [DOI] 10.2174/1573406415666190222124745. [PMID] 30799793.
2019
HDX-MS reveals structural determinants for RORγ hyperactivation by synthetic agonists.
eLife. 8 [DOI] 10.7554/eLife.47172. [PMID] 31172947.
2019
Histone H3 binding to the PHD1 domain of histone demethylase KDM5A enables active site remodeling.
Nature communications. 10(1) [DOI] 10.1038/s41467-018-07829-z. [PMID] 30626866.
2019
Identification of Antimalarial Inhibitors Using Late-Stage Gametocytes in a Phenotypic Live/Dead Assay.
SLAS discovery : advancing life sciences R & D. 24(1):38-46 [DOI] 10.1177/2472555218796410. [PMID] 30142014.
2019
Irisin Mediates Effects on Bone and Fat via αV Integrin Receptors.
Cell. 178(2):507-508 [DOI] 10.1016/j.cell.2019.06.028. [PMID] 31299203.
2019
Protein dynamics and conformational changes explored by hydrogen/deuterium exchange mass spectrometry.
Current opinion in structural biology. 58:305-313 [DOI] 10.1016/j.sbi.2019.06.007. [PMID] 31351767.
2019
Quantitative structural assessment of graded receptor agonism.
Proceedings of the National Academy of Sciences of the United States of America. 116(44):22179-22188 [DOI] 10.1073/pnas.1909016116. [PMID] 31611383.
2019
Recommendations for performing, interpreting and reporting hydrogen deuterium exchange mass spectrometry (HDX-MS) experiments.
Nature methods. 16(7):595-602 [DOI] 10.1038/s41592-019-0459-y. [PMID] 31249422.
2019
Structural Basis of Altered Potency and Efficacy Displayed by a Major in Vivo Metabolite of the Antidiabetic PPARγ Drug Pioglitazone.
Journal of medicinal chemistry. 62(4):2008-2023 [DOI] 10.1021/acs.jmedchem.8b01573. [PMID] 30676741.
2019
Structural insights into RNA recognition by the Chikungunya virus nsP2 helicase.
Proceedings of the National Academy of Sciences of the United States of America. 116(19):9558-9567 [DOI] 10.1073/pnas.1900656116. [PMID] 31000599.
2019
Structure-guided design of immunomodulatory RNAs specifically targeting the cytoplasmic viral RNA sensor RIG-I.
FEBS letters. 593(21):3003-3014 [DOI] 10.1002/1873-3468.13564. [PMID] 31369683.
2019
Structures of AMP-activated protein kinase bound to novel pharmacological activators in phosphorylated, non-phosphorylated, and nucleotide-free states.
The Journal of biological chemistry. 294(3):953-967 [DOI] 10.1074/jbc.RA118.004883. [PMID] 30478170.
2019
The Scripps Molecular Screening Center and Translational Research Institute.
SLAS discovery : advancing life sciences R & D. 24(3):386-397 [DOI] 10.1177/2472555218820809. [PMID] 30682260.
2019
Unique Polypharmacology Nuclear Receptor Modulator Blocks Inflammatory Signaling Pathways.
ACS chemical biology. 14(5):1051-1062 [DOI] 10.1021/acschembio.9b00236. [PMID] 30951276.
2018
A Novel Polar Core and Weakly Fixed C-Tail in Squid Arrestin Provide New Insight into Interaction with Rhodopsin.
Journal of molecular biology. 430(21):4102-4118 [DOI] 10.1016/j.jmb.2018.08.009. [PMID] 30120952.
2018
A structural mechanism for directing corepressor-selective inverse agonism of PPARγ.
Nature communications. 9(1) [DOI] 10.1038/s41467-018-07133-w. [PMID] 30409975.
2018
Biophysical Interactions of Direct AMPK Activators.
Methods in molecular biology (Clifton, N.J.). 1732:29-55 [DOI] 10.1007/978-1-4939-7598-3_3. [PMID] 29480467.
2018
Chemical Crosslinking Mass Spectrometry Reveals the Conformational Landscape of the Activation Helix of PPARγ; a Model for Ligand-Dependent Antagonism.
Structure (London, England : 1993). 26(11):1431-1439.e6 [DOI] 10.1016/j.str.2018.07.007. [PMID] 30146169.
2018
CINPA1 binds directly to constitutive androstane receptor and inhibits its activity.
Biochemical pharmacology. 152:211-223 [DOI] 10.1016/j.bcp.2018.03.029. [PMID] 29608908.
2018
Defining a conformational ensemble that directs activation of PPARγ.
Nature communications. 9(1) [DOI] 10.1038/s41467-018-04176-x. [PMID] 29728618.
2018
Design, synthesis, and evaluation of simple phenol amides as ERRγ agonists.
Bioorganic & medicinal chemistry letters. 28(8):1313-1319 [DOI] 10.1016/j.bmcl.2018.03.019. [PMID] 29548571.
2018
Discovery of Hydrolysis-Resistant Isoindoline N-Acyl Amino Acid Analogues that Stimulate Mitochondrial Respiration.
Journal of medicinal chemistry. 61(7):3224-3230 [DOI] 10.1021/acs.jmedchem.8b00029. [PMID] 29533650.
2018
HDX-MS reveals dysregulated checkpoints that compromise discrimination against self RNA during RIG-I mediated autoimmunity.
Nature communications. 9(1) [DOI] 10.1038/s41467-018-07780-z. [PMID] 30560918.
2018
Identification of an aminothiazole series of RORβ modulators.
Bioorganic & medicinal chemistry letters. 28(7):1178-1181 [DOI] 10.1016/j.bmcl.2018.03.001. [PMID] 29534930.
2018
Identification of potent RORβ modulators: Scaffold variation.
Bioorganic & medicinal chemistry letters. 28(19):3210-3215 [DOI] 10.1016/j.bmcl.2018.08.017. [PMID] 30143422.
2018
Irisin Mediates Effects on Bone and Fat via αV Integrin Receptors.
Cell. 175(7):1756-1768.e17 [DOI] 10.1016/j.cell.2018.10.025. [PMID] 30550785.
2018
Lipid binding promotes the open conformation and tumor-suppressive activity of neurofibromin 2.
Nature communications. 9(1) [DOI] 10.1038/s41467-018-03648-4. [PMID] 29626191.
2018
Noncanonical agonist PPARγ ligands modulate the response to DNA damage and sensitize cancer cells to cytotoxic chemotherapy.
Proceedings of the National Academy of Sciences of the United States of America. 115(3):561-566 [DOI] 10.1073/pnas.1717776115. [PMID] 29295932.
2018
Structural and Dynamic Elucidation of a Non-acid PPARγ Partial Agonist: SR1988.
Nuclear receptor research. 5 [DOI] 10.11131/2018/101350. [PMID] 30906767.
2018
Structural Basis for the RNA-Guided Ribonuclease Activity of CRISPR-Cas13d.
Cell. 175(1):212-223.e17 [DOI] 10.1016/j.cell.2018.09.001. [PMID] 30241607.
2018
Structural organization of a major neuronal G protein regulator, the RGS7-Gβ5-R7BP complex.
eLife. 7 [DOI] 10.7554/eLife.42150. [PMID] 30540250.
2017
A Residue-Resolved Bayesian Approach to Quantitative Interpretation of Hydrogen-Deuterium Exchange from Mass Spectrometry: Application to Characterizing Protein-Ligand Interactions.
The journal of physical chemistry. B. 121(15):3493-3501 [DOI] 10.1021/acs.jpcb.6b09358. [PMID] 27807976.
2017
Corrigendum: Full antagonism of the estrogen receptor without a prototypical ligand side chain.
Nature chemical biology. 13(6) [DOI] 10.1038/nchembio0617-691c. [PMID] 28514424.
2017
Crystal structure of a multi-domain human smoothened receptor in complex with a super stabilizing ligand.
Nature communications. 8 [DOI] 10.1038/ncomms15383. [PMID] 28513578.
2017
Deconvoluting AMP-activated protein kinase (AMPK) adenine nucleotide binding and sensing.
The Journal of biological chemistry. 292(30):12653-12666 [DOI] 10.1074/jbc.M117.793018. [PMID] 28615457.
2017
Erratum: Full antagonism of the estrogen receptor without a prototypical ligand side chain.
Nature chemical biology. 13(6) [DOI] 10.1038/nchembio0617-691b. [PMID] 28514419.
2017
Full antagonism of the estrogen receptor without a prototypical ligand side chain.
Nature chemical biology. 13(1):111-118 [DOI] 10.1038/nchembio.2236. [PMID] 27870835.
2017
GABAB receptor allosteric modulators exhibit pathway-dependent and species-selective activity.
Pharmacology research & perspectives. 5(2) [DOI] 10.1002/prp2.288. [PMID] 28357120.
2017
HDX reveals the conformational dynamics of DNA sequence specific VDR co-activator interactions.
Nature communications. 8(1) [DOI] 10.1038/s41467-017-00978-7. [PMID] 29030554.
2017
Nucleotide Binding to ARL2 in the TBCD∙ARL2∙β-Tubulin Complex Drives Conformational Changes in β-Tubulin.
Journal of molecular biology. 429(23):3696-3716 [DOI] 10.1016/j.jmb.2017.09.016. [PMID] 28970104.
2017
Proteolysis by Granzyme B Enhances Presentation of Autoantigenic Peptidylarginine Deiminase 4 Epitopes in Rheumatoid Arthritis.
Journal of proteome research. 16(1):355-365 [DOI] 10.1021/acs.jproteome.6b00617. [PMID] 27700100.
2017
SPA70 is a potent antagonist of human pregnane X receptor.
Nature communications. 8(1) [DOI] 10.1038/s41467-017-00780-5. [PMID] 28963450.
2017
Structure and Dynamics of the Liver Receptor Homolog 1-PGC1α Complex.
Molecular pharmacology. 92(1):1-11 [DOI] 10.1124/mol.117.108514. [PMID] 28363985.
2017
Structure of the full-length glucagon class B G-protein-coupled receptor.
Nature. 546(7657):259-264 [DOI] 10.1038/nature22363. [PMID] 28514451.
2017
Structure-Activity Relationship of 2,4-Dichloro-N-(3,5-dichloro-4-(quinolin-3-yloxy)phenyl)benzenesulfonamide (INT131) Analogs for PPARγ-Targeted Antidiabetics.
Journal of medicinal chemistry. 60(11):4584-4593 [DOI] 10.1021/acs.jmedchem.6b01727. [PMID] 28485590.
2017
Synergistic Regulation of Coregulator/Nuclear Receptor Interaction by Ligand and DNA.
Structure (London, England : 1993). 25(10):1506-1518.e4 [DOI] 10.1016/j.str.2017.07.019. [PMID] 28890360.
2017
Synthesis of novel steroidal agonists, partial agonists, and antagonists for the glucocorticoid receptor.
Bioorganic & medicinal chemistry letters. 27(2):347-353 [DOI] 10.1016/j.bmcl.2016.11.007. [PMID] 27919657.
2017
Unique Interactome Network Signatures for Peroxisome Proliferator-activated Receptor Gamma (PPARγ) Modulation by Functional Selective Ligands.
Molecular & cellular proteomics : MCP. 16(12):2098-2110 [DOI] 10.1074/mcp.RA117.000308. [PMID] 28972081.
2016
Estrogen receptor alpha somatic mutations Y537S and D538G confer breast cancer endocrine resistance by stabilizing the activating function-2 binding conformation.
eLife. 5 [DOI] 10.7554/eLife.12792. [PMID] 26836308.
2016
N-Arylsulfonyl Indolines as Retinoic Acid Receptor-Related Orphan Receptor γ (RORγ) Agonists.
ChemMedChem. 11(23):2607-2620 [DOI] 10.1002/cmdc.201600491. [PMID] 27879053.
2016
SR2067 Reveals a Unique Kinetic and Structural Signature for PPARγ Partial Agonism.
ACS chemical biology. 11(1):273-83 [DOI] 10.1021/acschembio.5b00580. [PMID] 26579553.
2016
Synthetic RORγt Agonists Enhance Protective Immunity.
ACS chemical biology. 11(4):1012-8 [DOI] 10.1021/acschembio.5b00899. [PMID] 26785144.
2016
The Secreted Enzyme PM20D1 Regulates Lipidated Amino Acid Uncouplers of Mitochondria.
Cell. 166(2):424-435 [DOI] 10.1016/j.cell.2016.05.071. [PMID] 27374330.
2016
Two-Site Evaluation of the Repeatability and Precision of an Automated Dual-Column Hydrogen/Deuterium Exchange Mass Spectrometry Platform.
Analytical chemistry. 88(12):6607-14 [DOI] 10.1021/acs.analchem.6b01650. [PMID] 27224086.
2015
A General Method for Insertion of Functional Proteins within Proteins via Combinatorial Selection of Permissive Junctions.
Chemistry & biology. 22(8):1134-43 [DOI] 10.1016/j.chembiol.2015.07.011. [PMID] 26278185.
2015
Antiobesity Effect of a Small Molecule Repressor of RORγ.
Molecular pharmacology. 88(1):48-56 [DOI] 10.1124/mol.114.097485. [PMID] 25904554.
2015
Antiproliferation activity of a small molecule repressor of liver receptor homolog 1.
Molecular pharmacology. 87(2):296-304 [DOI] 10.1124/mol.114.095554. [PMID] 25473120.
2015
Autocrine selection of a GLP-1R G-protein biased agonist with potent antidiabetic effects.
Nature communications. 6 [DOI] 10.1038/ncomms9918. [PMID] 26621478.
2015
CMT2D neuropathy is linked to the neomorphic binding activity of glycyl-tRNA synthetase.
Nature. 526(7575):710-4 [DOI] 10.1038/nature15510. [PMID] 26503042.
2015
Conformational states of the full-length glucagon receptor.
Nature communications. 6 [DOI] 10.1038/ncomms8859. [PMID] 26227798.
2015
Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser.
Nature. 523(7562):561-7 [DOI] 10.1038/nature14656. [PMID] 26200343.
2015
Design, Synthesis, and Biological Evaluation of Indole Biphenylcarboxylic Acids as PPARγ Antagonists.
ACS medicinal chemistry letters. 6(9):998-1003 [DOI] 10.1021/acsmedchemlett.5b00218. [PMID] 26396687.
2015
Differential isotopic enrichment to facilitate characterization of asymmetric multimeric proteins using hydrogen/deuterium exchange mass spectrometry.
Analytical chemistry. 87(7):4015-4022 [DOI] 10.1021/acs.analchem.5b00372. [PMID] 25763479.
2015
Identification of Bexarotene as a PPARγ Antagonist with HDX.
PPAR research. 2015 [DOI] 10.1155/2015/254560. [PMID] 26451138.
2015
Pharmacological repression of PPARγ promotes osteogenesis.
Nature communications. 6 [DOI] 10.1038/ncomms8443. [PMID] 26068133.
2015
SERBP1 Is a Component of the Liver Receptor Homologue-1 Transcriptional Complex.
Journal of proteome research. 14(11):4571-80 [DOI] 10.1021/acs.jproteome.5b00379. [PMID] 26398198.
2015
Software Analysis of Uncorrelated MS1 Peaks for Discovery of Post-Translational Modifications.
Journal of the American Society for Mass Spectrometry. 26(12):2133-40 [DOI] 10.1007/s13361-015-1229-4. [PMID] 26265041.
2015
Structural basis of JAZ repression of MYC transcription factors in jasmonate signalling.
Nature. 525(7568):269-73 [DOI] 10.1038/nature14661. [PMID] 26258305.
2015
Structural mechanism for signal transduction in RXR nuclear receptor heterodimers.
Nature communications. 6 [DOI] 10.1038/ncomms9013. [PMID] 26289479.
2014
An alternate binding site for PPARγ ligands.
Nature communications. 5 [DOI] 10.1038/ncomms4571. [PMID] 24705063.
2014
Defining the communication between agonist and coactivator binding in the retinoid X receptor α ligand binding domain.
The Journal of biological chemistry. 289(2):814-26 [DOI] 10.1074/jbc.M113.476861. [PMID] 24187139.
2014
Glucagon-like peptide-1 receptor ligand interactions: structural cross talk between ligands and the extracellular domain.
PloS one. 9(9) [DOI] 10.1371/journal.pone.0105683. [PMID] 25180755.
2014
HDX reveals unique fragment ligands for the vitamin D receptor.
Bioorganic & medicinal chemistry letters. 24(15):3459-63 [DOI] 10.1016/j.bmcl.2014.05.070. [PMID] 24974344.
2014
HDX-MS guided drug discovery: small molecules and biopharmaceuticals.
Current opinion in structural biology. 28:105-11 [DOI] 10.1016/j.sbi.2014.08.007. [PMID] 25179005.
2014
Influence of domain interactions on conformational mobility of the progesterone receptor detected by hydrogen/deuterium exchange mass spectrometry.
Structure (London, England : 1993). 22(7):961-73 [DOI] 10.1016/j.str.2014.04.013. [PMID] 24909783.
2014
Inhibiting AMPylation: a novel screen to identify the first small molecule inhibitors of protein AMPylation.
ACS chemical biology. 9(2):433-42 [DOI] 10.1021/cb4006886. [PMID] 24274060.
2014
Nitric oxide-induced conformational changes in soluble guanylate cyclase.
Structure (London, England : 1993). 22(4):602-11 [DOI] 10.1016/j.str.2014.01.008. [PMID] 24560804.
2014
Pharmacologic repression of retinoic acid receptor-related orphan nuclear receptor γ is therapeutic in the collagen-induced arthritis experimental model.
Arthritis & rheumatology (Hoboken, N.J.). 66(3):579-88 [DOI] 10.1002/art.38272. [PMID] 24574218.
2014
Resveratrol modulates the inflammatory response via an estrogen receptor-signal integration network.
eLife. 3 [DOI] 10.7554/eLife.02057. [PMID] 24771768.
2014
RORs in autoimmune disease.
Current topics in microbiology and immunology. 378:171-82 [DOI] 10.1007/978-3-319-05879-5_8. [PMID] 24728598.
2014
Structural basis for ligand regulation of the fatty acid-binding protein 5, peroxisome proliferator-activated receptor β/δ (FABP5-PPARβ/δ) signaling pathway.
The Journal of biological chemistry. 289(21):14941-54 [DOI] 10.1074/jbc.M113.514646. [PMID] 24692551.
2014
The therapeutic potential of nuclear receptor modulators for treatment of metabolic disorders: PPARγ, RORs, and Rev-erbs.
Cell metabolism. 19(2):193-208 [DOI] 10.1016/j.cmet.2013.12.009. [PMID] 24440037.
2013
Activation of AMP-activated protein kinase revealed by hydrogen/deuterium exchange mass spectrometry.
Structure (London, England : 1993). 21(11):1942-53 [DOI] 10.1016/j.str.2013.08.023. [PMID] 24076403.
2013
Divergent sequence tunes ligand sensitivity in phospholipid-regulated hormone receptors.
The Journal of biological chemistry. 288(28):20702-12 [DOI] 10.1074/jbc.M113.472837. [PMID] 23737522.
2013
Protein conformation ensembles monitored by HDX reveal a structural rationale for abscisic acid signaling protein affinities and activities.
Structure (London, England : 1993). 21(2):229-35 [DOI] 10.1016/j.str.2012.12.001. [PMID] 23290725.
2013
Small molecule amides as potent ROR-γ selective modulators.
Bioorganic & medicinal chemistry letters. 23(2):532-6 [DOI] 10.1016/j.bmcl.2012.11.025. [PMID] 23232056.
2013
Targeting the Peroxisome Proliferator-Activated Receptor-γ to Counter the Inflammatory Milieu in Obesity.
Diabetes & metabolism journal. 37(6):395-403 [DOI] 10.4093/dmj.2013.37.6.395. [PMID] 24404510.
2013
Time window expansion for HDX analysis of an intrinsically disordered protein.
Journal of the American Society for Mass Spectrometry. 24(10):1584-92 [DOI] 10.1007/s13361-013-0669-y. [PMID] 23884631.
2012
Antidiabetic phospholipid-nuclear receptor complex reveals the mechanism for phospholipid-driven gene regulation.
Nature structural & molecular biology. 19(5):532-S2 [DOI] 10.1038/nsmb.2279. [PMID] 22504882.
2012
Automated hydrogen/deuterium exchange electron transfer dissociation high resolution mass spectrometry measured at single-amide resolution.
Journal of the American Society for Mass Spectrometry. 23(2):301-9 [DOI] 10.1007/s13361-011-0298-2. [PMID] 22131230.
2012
Binding of the N-terminal region of coactivator TIF2 to the intrinsically disordered AF1 domain of the glucocorticoid receptor is accompanied by conformational reorganizations.
The Journal of biological chemistry. 287(53):44546-60 [DOI] 10.1074/jbc.M112.411330. [PMID] 23132854.
2012
Development of novel pharmacotherapeutics for tobacco dependence: progress and future directions.
Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco. 14(11):1300-18 [DOI] 10.1093/ntr/nts201. [PMID] 23024249.
2012
HDX workbench: software for the analysis of H/D exchange MS data.
Journal of the American Society for Mass Spectrometry. 23(9):1512-21 [DOI] 10.1007/s13361-012-0419-6. [PMID] 22692830.
2012
Hydrophobic Interactions Improve Selectivity to ERα for Ben-zothiophene SERMs.
ACS medicinal chemistry letters. 3(3):207-210 [PMID] 22582136.
2012
Identification and mechanism of 10-carbon fatty acid as modulating ligand of peroxisome proliferator-activated receptors.
The Journal of biological chemistry. 287(1):183-195 [DOI] 10.1074/jbc.M111.294785. [PMID] 22039047.
2012
Identification of a selective RORγ ligand that suppresses T(H)17 cells and stimulates T regulatory cells.
ACS chemical biology. 7(9):1515-9 [PMID] 22769242.
2012
Identification of SR2211: a potent synthetic RORγ-selective modulator.
ACS chemical biology. 7(4):672-7 [DOI] 10.1021/cb200496y. [PMID] 22292739.
2012
Ligand and receptor dynamics contribute to the mechanism of graded PPARγ agonism.
Structure (London, England : 1993). 20(1):139-50 [DOI] 10.1016/j.str.2011.10.018. [PMID] 22244763.
2012
Molecular mimicry regulates ABA signaling by SnRK2 kinases and PP2C phosphatases.
Science (New York, N.Y.). 335(6064):85-8 [DOI] 10.1126/science.1215106. [PMID] 22116026.
2012
PubChem promiscuity: a web resource for gathering compound promiscuity data from PubChem.
Bioinformatics (Oxford, England). 28(1):140-1 [DOI] 10.1093/bioinformatics/btr622. [PMID] 22084255.
2012
Targeting orphan nuclear receptors for treatment of metabolic diseases and autoimmunity.
Chemistry & biology. 19(1):51-9 [DOI] 10.1016/j.chembiol.2011.12.011. [PMID] 22284354.
2012
The therapeutic potential of RORγ modulators in the treatment of human disease.
Journal of experimental pharmacology. 4:141-8 [DOI] 10.2147/JEP.S27078. [PMID] 27186126.
2011
A combined ligand- and structure-based virtual screening protocol identifies submicromolar PPARγ partial agonists.
ChemMedChem. 6(1):94-103 [DOI] 10.1002/cmdc.201000428. [PMID] 21162086.
2011
A Java API for working with PubChem datasets.
Bioinformatics (Oxford, England). 27(5):741-2 [DOI] 10.1093/bioinformatics/btq715. [PMID] 21216779.
2011
A nuclear-receptor-dependent phosphatidylcholine pathway with antidiabetic effects.
Nature. 474(7352):506-10 [DOI] 10.1038/nature10111. [PMID] 21614002.
2011
Antidiabetic actions of a non-agonist PPARγ ligand blocking Cdk5-mediated phosphorylation.
Nature. 477(7365):477-81 [DOI] 10.1038/nature10383. [PMID] 21892191.
2011
Development of an HTS-compatible assay for discovery of RORα modulators using AlphaScreen® technology.
Journal of biomolecular screening. 16(2):183-91 [DOI] 10.1177/1087057110389040. [PMID] 21297105.
2011
Differential hydrogen/deuterium exchange mass spectrometry analysis of protein-ligand interactions.
Expert review of proteomics. 8(1):43-59 [DOI] 10.1586/epr.10.109. [PMID] 21329427.
2011
Disorder-to-order transition underlies the structural basis for the assembly of a transcriptionally active PGC-1α/ERRγ complex.
Proceedings of the National Academy of Sciences of the United States of America. 108(46):18678-83 [DOI] 10.1073/pnas.1113813108. [PMID] 22049338.
2011
DNA binding alters coactivator interaction surfaces of the intact VDR-RXR complex.
Nature structural & molecular biology. 18(5):556-63 [DOI] 10.1038/nsmb.2046. [PMID] 21478866.
2011
Helix 11 dynamics is critical for constitutive androstane receptor activity.
Structure (London, England : 1993). 19(1):37-44 [DOI] 10.1016/j.str.2010.11.008. [PMID] 21220114.
2011
Identification of a novel non-retinoid pan inverse agonist of the retinoic acid receptors.
ACS chemical biology. 6(6):618-27 [DOI] 10.1021/cb100396s. [PMID] 21381756.
2011
Identification of SR3335 (ML-176): a synthetic RORα selective inverse agonist.
ACS chemical biology. 6(3):218-22 [DOI] 10.1021/cb1002762. [PMID] 21090593.
2011
Ligand-dependent perturbation of the conformational ensemble for the GPCR β2 adrenergic receptor revealed by HDX.
Structure (London, England : 1993). 19(10):1424-32 [DOI] 10.1016/j.str.2011.08.001. [PMID] 21889352.
2011
Methods for the Analysis of High Precision Differential Hydrogen Deuterium Exchange Data.
International journal of mass spectrometry. 302(1-3):59-68 [PMID] 21528013.
2011
Mutual information identifies sequence positions conserved within the nuclear receptor superfamily: approach reveals functionally important regions for DNA binding specificity.
Nuclear receptor signaling. 9 [DOI] 10.1621/nrs.09001. [PMID] 21383938.
2011
Structural basis for basal activity and autoactivation of abscisic acid (ABA) signaling SnRK2 kinases.
Proceedings of the National Academy of Sciences of the United States of America. 108(52):21259-64 [DOI] 10.1073/pnas.1118651109. [PMID] 22160701.
2011
Suppression of TH17 differentiation and autoimmunity by a synthetic ROR ligand.
Nature. 472(7344):491-4 [DOI] 10.1038/nature10075. [PMID] 21499262.
2011
The structural basis for recognition of base J containing DNA by a novel DNA binding domain in JBP1.
Nucleic acids research. 39(13):5715-28 [DOI] 10.1093/nar/gkr125. [PMID] 21415010.
2010
A second class of nuclear receptors for oxysterols: Regulation of RORalpha and RORgamma activity by 24S-hydroxycholesterol (cerebrosterol).
Biochimica et biophysica acta. 1801(8):917-23 [DOI] 10.1016/j.bbalip.2010.02.012. [PMID] 20211758.
2010
Anti-diabetic drugs inhibit obesity-linked phosphorylation of PPARgamma by Cdk5.
Nature. 466(7305):451-6 [DOI] 10.1038/nature09291. [PMID] 20651683.
2010
Dynamics of the beta2-adrenergic G-protein coupled receptor revealed by hydrogen-deuterium exchange.
Analytical chemistry. 82(3):1100-8 [DOI] 10.1021/ac902484p. [PMID] 20058880.
2010
Hydrogen/deuterium exchange reveals distinct agonist/partial agonist receptor dynamics within vitamin D receptor/retinoid X receptor heterodimer.
Structure (London, England : 1993). 18(10):1332-41 [DOI] 10.1016/j.str.2010.07.007. [PMID] 20947021.
2010
Identification of SR1078, a synthetic agonist for the orphan nuclear receptors RORα and RORγ.
ACS chemical biology. 5(11):1029-34 [DOI] 10.1021/cb100223d. [PMID] 20735016.
2010
Ligand regulation of retinoic acid receptor-related orphan receptors: implications for development of novel therapeutics.
Current opinion in lipidology. 21(3):204-11 [DOI] 10.1097/MOL.0b013e328338ca18. [PMID] 20463469.
2010
Modulation of retinoic acid receptor-related orphan receptor alpha and gamma activity by 7-oxygenated sterol ligands.
The Journal of biological chemistry. 285(7):5013-25 [DOI] 10.1074/jbc.M109.080614. [PMID] 19965867.
2010
Regulation of adipogenesis by natural and synthetic REV-ERB ligands.
Endocrinology. 151(7):3015-25 [DOI] 10.1210/en.2009-0800. [PMID] 20427485.
2010
The benzenesulfoamide T0901317 [N-(2,2,2-trifluoroethyl)-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]-benzenesulfonamide] is a novel retinoic acid receptor-related orphan receptor-alpha/gamma inverse agonist.
Molecular pharmacology. 77(2):228-36 [DOI] 10.1124/mol.109.060905. [PMID] 19887649.
2009
Apo-human carbonic anhydrase II revisited: implications of the loss of a metal in protein structure, stability, and solvent network.
Biochemistry. 48(31):7365-72 [DOI] 10.1021/bi9007512. [PMID] 19583303.
2009
Efficient methodology for the synthesis of 3-amino-1,2,4-triazoles.
The Journal of organic chemistry. 74(19):7595-7 [DOI] 10.1021/jo9016502. [PMID] 19731897.
2009
HD desktop: an integrated platform for the analysis and visualization of H/D exchange data.
Journal of the American Society for Mass Spectrometry. 20(4):601-10 [DOI] 10.1016/j.jasms.2008.11.019. [PMID] 19135386.
2009
Identification of specific hemopexin-like domain residues that facilitate matrix metalloproteinase collagenolytic activity.
The Journal of biological chemistry. 284(36):24017-24 [DOI] 10.1074/jbc.M109.016873. [PMID] 19574232.
2009
Unique ligand binding patterns between estrogen receptor alpha and beta revealed by hydrogen-deuterium exchange.
Biochemistry. 48(40):9668-76 [DOI] 10.1021/bi901149t. [PMID] 19739677.
2008
Potent, selective and cell penetrant inhibitors of SF-1 by functional ultra-high-throughput screening.
Molecular pharmacology. 73(6):1776-84 [DOI] 10.1124/mol.108.045963. [PMID] 18334597.
2008
Prediction of the tissue-specificity of selective estrogen receptor modulators by using a single biochemical method.
Proceedings of the National Academy of Sciences of the United States of America. 105(20):7171-6 [DOI] 10.1073/pnas.0710802105. [PMID] 18474858.
2007
A two-stage differential hydrogen deuterium exchange method for the rapid characterization of protein/ligand interactions.
Journal of biomolecular techniques : JBT. 18(4):194-204 [PMID] 17916792.
2007
Partial agonists activate PPARgamma using a helix 12 independent mechanism.
Structure (London, England : 1993). 15(10):1258-71 [PMID] 17937915.
2007
The Deuterator: software for the determination of backbone amide deuterium levels from H/D exchange MS data.
BMC bioinformatics. 8 [PMID] 17506883.
2006
Hydrogen/deuterium-exchange (H/D-Ex) of PPARgamma LBD in the presence of various modulators.
Protein science : a publication of the Protein Society. 15(8):1883-92 [PMID] 16823031.
2006
Probing protein ligand interactions by automated hydrogen/deuterium exchange mass spectrometry.
Analytical chemistry. 78(4):1005-14 [PMID] 16478090.
2006
Structural mobility in human manganese superoxide dismutase.
Biochemistry. 45(27):8209-15 [PMID] 16819819.
2005
High-throughput analysis of protein structure by hydrogen/deuterium exchange mass spectrometry.
Methods of biochemical analysis. 45:131-57 [PMID] 19235294.
2003
Rapid analysis of protein structure and dynamics by hydrogen/deuterium exchange mass spectrometry.
Journal of biomolecular techniques : JBT. 14(3):171-82 [PMID] 13678147.
1993
Mass spectrometry and characterization of Aedes aegypti trypsin modulating oostatic factor (TMOF) and its analogs.
Insect biochemistry and molecular biology. 23(6):703-12 [PMID] 8353526.
1990
Mosquito oostatic factor: a novel decapeptide modulating trypsin-like enzyme biosynthesis in the midgut.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 4(12):3015-20 [PMID] 2394318.

Grants

Apr 2022 ACTIVE
Molecular basis of activation of the orphan nuclear receptor Nurr1
Role: Co-Investigator
Funding: NATL INST OF HLTH NIA
Apr 2022 ACTIVE
Ultra-potent HIV capsid inhibitors
Role: Principal Investigator
Funding: UNIV OF COLORADO DENVER & ANSCHUTZ MED via NATL INST OF HLTH NIAID
Apr 2022 ACTIVE
Chemistry and Biology of ADP-Ribosylation-Dependent Signaling
Role: Principal Investigator
Funding: UNIV OF SOUTHERN CALIFORNIA via NATL INST OF HLTH NIGMS
Apr 2022 ACTIVE
Structural Biology of Connexin Membrane Channels
Role: Principal Investigator
Funding: UNIV OF VIRGINIA via NATL INST OF HLTH NIGMS
Apr 2022 ACTIVE
Small molecules targeting hepatic glucose production and insulin resistance
Role: Principal Investigator
Funding: DANA FARBER CANCER INST via NATL INST OF HLTH NIDDK
Apr 2022 ACTIVE
Developing nonmuscle myosin II inhibitors for the treatment of glioblastoma
Role: Co-Investigator
Funding: NATL INST OF HLTH NINDS
Apr 2022 ACTIVE
Mechanistic studies of corepressor-mediated PPAR? transcriptional repression
Role: Co-Investigator
Funding: NATL INST OF HLTH NIDDK
Apr 2022 ACTIVE
Mechanistic analysis of therapeutic targets using hydrogen/deuterium exchange mass spectrometry (HDX MS)
Role: Principal Investigator
Funding: ELI LILLY AND CO
Apr 2022 ACTIVE
Developing chemoproteomic approaches to decipher the regulatory network of LRH-1,a nuclear receptor implicated in hepatic metabolism
Role: Principal Investigator
Funding: NATL INST OF HLTH NIDDK
Apr 2022 ACTIVE
HIV Interactions in Viral Evolution
Role: Principal Investigator
Funding: SEATTLE CHILDRENS HOSPITAL via NATL INST OF HLTH NIAID
Apr 2022 ACTIVE
ALDH1a1 Inhibition As A Therapeutic Target In Visceral Adiposity and Type 2 Diabetes
Role: Principal Investigator
Funding: BRIGHAM AND WOMENS HOSPITAL via NATL INST OF HLTH NIDDK

Education

Ph.D. in Chemistry
1989 · University of Virginia
Bachelor's of Science in Chemistry
1985 · Syracuse University

Contact Details

Phones:
Business:
(561) 228-2200
Emails:
Business:
pgriffin2@ufl.edu
Addresses:
Business Mailing:
120 SCRIPPS WAY
JUPITER FL 33458