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Patrick Griffin, Ph.D.

Chairman
Professor
Department of Molecular Therapeutics
Florida Campus
Laboratory Website
pgriffin@scripps.edu
(561) 228-2200

Scripps Research Joint Appointments

Director, Translational Research Institute
Faculty, Graduate Program

Research Focus

Group Members: Ruben D. Garcia-Ordonez, Devrishi Goswami, Dana Kuruvilla, Scott Novick, Bruce Pascal, Mi Ra Chang, Alex Corzo, Vinh Lam, Venkat Dharmarajan, Tanya Khan (former members of the lab: D. Marciano, Y. Mari, M.J. Chalmers, N. Kumar, J. Lauer, S.A. Busby, R. Landgraf, S. Willis, M. Istrate, D. Policastro, C. Griffin, E. Tracy, J. Zhang, X. Zhang, S. Dai, S. Prasad, G. West, R. Leon).

Structural and Chemical Biology of Enzymes and Receptors Involved in Cancer, Metabolic Disease, and Autoimmune Disorders
Our group combines chemical, cellular, and structural biology to study mechanism and structure-function of enzymes and receptors; particularly kinases (i.e, AMP Kinase), G-protein coupled receptors (GPCRs) and nuclear receptors (NRs). During the past few years we have focused on developing hydrogen/deuterium exchange (HDX) technology for probing the mechanism of activation of intact nuclear receptor complexes. Specifically we have used HDX, chemical libraries and cell-based assays to better understand ligand activation and co-receptor/co-factor interaction within the vitamin D receptor (VDR) and the peroxisome proliferator-activated receptor gamma (PPARG) complex. We have applied HDX and chemical approaches to the study of the orphan nuclear receptors LRH-1 and RORA/RORB/RORG. These receptors have been implicated in cancer, metabolic and immune disorders.

Mechanistic studies of ligand activation of Nuclear Receptors
HDX was applied to the characterization of ligand activation of the vitamin D receptor (VDR) in complex with its co-receptor retinoid X receptor (RXR) and probed the dynamics of the functional domains of both VDR and RXR as a function of ligand and DNA interaction. As shown in our 2011 paper in NSMB, these data demonstrate the role of DNA interaction in the functional state of the VDR/RXR heterodimer complex by directly controlling conformational mobility of surfaces of the receptor complex that interact with NR co-factors. Currently HDX is being used to guide lead optimization and SAR of selective VDR modulators (VDRMs).

Probing ligand interaction with GPCRs
GPCRs are an important family of trans-membrane signaling proteins and are therapeutic targets in many disorders. The characterization of the structure and conformational dynamics of these receptors present a considerable analytical challenge due to the hydrophobic nature of their transmembrane domains. Recently we have used HDX to probe ligand interactions with the beta-2 adrenergic receptor.

Structural and Chemical Biology of the orphan nuclear receptor LRH-1
Our laboratory has taken a multi-pronged approach to understanding the biology of the orphan nuclear receptor LRH-1 (liver receptor homolog-1). Modulation of LRH-1 activity has been implicated in cancer, cholesterol homeostasis, and in intestinal inflammation. We have developed several HTS assays to facilitate screening for small molecules that positively modulate (agonize) or negatively modulate (inverse agonize) the activity of the receptor. More importantly, we have developed several functional assays to better understand the potential utility of small molecule modulators of LRH-1 for treatment of cancer, inflammation and metabolic disorders. We have discovered synthetic modulators of LRH-1 that demonstrate a range of activities in various cancer cell lines as well as models of inflammation. Several manuscripts are in preparation describing these studies.

Novel modulators of RORα
Using a unique human nuclear receptor library we have discovered novel modulators of RORα. HDX is being employed for mechanism of action studies and to guide SAR. Read our recent articles in Molecular Pharmacology, JBC, and ACS Chemical Biology and Nature on synthetic and natural ligands for the RORs. We have a paper under submission on the effects of SR2211 in rheumatoid arthritis.

Education

B.S., Chemistry, Syracuse University, 1985
Ph.D., Chemistry, University of Virginia, 1989

Professional Experience

Professor and Chair, Molecular Therapeutics, 03/07 to present
Director, Translational Research Institute, 06/06 to present
Co-founder, Ember Therapeutics, 08/10
Member of Scripps Florida Steering Committee, 01/07 to 01/11
Member of Pfizer/TSRI Joint Steering Committee, 01/07 to 12/11
Member, Board of Directors, Centre for Drug Research and Development, 08/09 to present
Member, Scientific Advisory Board, ExSAR Corp, NJ, 2004 – present
Professor Biochemistry, Scripps Florida, 05/04 - 3/07
Chief Scientific Officer, ExSAR Corporation, 07/02 - 05/04
Senior Director, Basic Chemistry and Molecular Profiling Proteomics, Merck, 09/01 - 06/02
Director, Basic Chemistry and Molecular Profiling Proteomics, Merck, 05/99 – 09/01
Senior Research Fellow, Molecular Design and Diversity, Merck, 04/96 – 05/99
Research Fellow, Inflammation Research, Merck, 12/91-04/96
Post-Doctoral Fellow, California Institute of Technology 5/90 - 12/91
Associate Scientist, Genentech, Inc. 4/89 - 4/90

Awards & Professional Activities

Dupont Chemistry Fellow, University of Virginia
Dean's Fellow, University of Virginia

Selected References

Marciano DP, Kuruvilla DS, Boregowda SV, Asteian A, Hughes TS, Garcia-Ordonez R, Corzo CA, Khan TM, Novick SJ, Park H, Kojetin DJ, Phinney DG, Bruning JB, Kamenecka TM, Griffin PR. Pharmacological repression of PPARγ promotes osteogenesis, Nat Commun. 2015 Jun 12;6:7443, doi: 10.1038/ncomms8443.

Schreiber SL, Kotz JD, Li M, Aubé J, Austin CP, Reed JC, Rosen H, White EL, Sklar LA, Lindsley CW, Alexander BR, Bittker JA, Clemons PA, de Souza A, Foley MA, Palmer M, Shamji AF, Wawer MJ, McManus O, Wu M, Zou B, Yu H, Golden JE, Schoenen FJ, Simeonov A, Jadhav A, Jackson MR, Pinkerton AB, Chung TD, Griffin PR, Cravatt BF, Hodder PS, Roush WR, Roberts E, Chung DH, Jonsson CB, Noah JW, Severson WE, Ananthan S, Edwards B, Oprea TI, Conn PJ, Hopkins CR, Wood MR, Stauffer SR, Emmitte KA; NIH Molecular Libraries Project Team.  Advancing Biological Understanding and Therapeutics Discovery with Small-Molecule Probes. Cell2015, 161, 1252-1265. doi: 10.1016/j.cell.2015.05.023. Review.

Chang MR, He Y, Khan TM, Kuruvilla DS, Garcia-Ordonez R, Corzo CA, Unger TJ, White DW, Khan S, Lin L, Cameron MD, Kamenecka TM, Griffin PR. Antiobesity Effect of a Small Molecule Repressor of RORγ.  Mol Pharmacol., 2015, 88, 48-56.

Goswami D, Tuske S, Pascal BD, Bauman JD, Patel D, Arnold E, Griffin PR. Differential isotopic enrichment to facilitatecharacterization of asymmetric multimeric proteins using hydrogen/deuterium exchange mass spectrometry. Anal Chem.2015, 87, 4015-22. 

Brown NE, Goswami D, Branch MR, Ramineni S, Ortlund EA, Griffin PR, Hepler JR. Integration of G protein α (Gα) signaling by the regulator of G protein signaling 14 (RGS14). J Biol Chem. 2015, 290, 9037-49.

Corzo C, Mari Y, Chang MR, Kuruvilla D, Nuhant P, Kumar N, West GM, Duckett DR, Roush WR, Griffin PR. Anti-proliferation Activity of a Small Molecule Repressor of LRH-1. Mol Pharmacol. 2015, 87, 296-304 PMID: 25473120

Marciano DP, Dharmarajan V, Griffin PR. HDX-MS guided drug discovery: small molecules and biopharmaceuticals. Curr Opin Struct Biol. 2014, 28, 105-111. Review. PMID: 25179005

Shkriabai N, Dharmarajan V, Slaughter A, Kessl JJ, Larue RC, Feng L, Fuchs JR, Griffin PR, Kvaratskhelia M. A critical role of the C-terminal segment for allosteric inhibitor-induced aberrant multimerization of HIV-1 integrase. J Biol Chem. 2014 Sep 19;289(38):26430-40. Epub 2014 Aug 12. PMID: 25118283

Cameron M, Kamenecka T, Madoux F, Chase P, Roush W, Hodder P, Griffin PR. ML368 Identification of Imidazopyridines as Selective Inhibitors of the Cytochrome P450 Enzyme CYP3A4. Probe Reports from the NIH Molecular Libraries Program [Internet].
Bethesda (MD): National Center for Biotechnology Information (US); 2010-2013 Apr 15 [updated 2014 Sep 18]. PMID: 24479199

West GM, Willard FS, Sloop KW, Showalter AD, Pascal BD, Griffin PR. Glucagon-like peptide-1 receptor ligand interactions: structural cross talk between ligands and the extracellular domain. PLoS One. 2014 Sep 2;9(9):e105683. eCollection 2014. PMID: 25180755

Carson MW, Zhang J, Chalmers MJ, Bocchinfuso WP, Holifield KD, Masquelin T, Stites RE, Stayrook KR, Griffin PR, Dodge JA. HDX reveals unique fragment ligands for the vitamin D receptor. Bioorg Med Chem Lett. 2014 Aug 1;24(15):3459-63. Epub 2014 May 29. PMID: 24974344

Goswami D, Callaway C, Pascal BD, Kumar R, Edwards DP, Griffin PR. Influence of domain interactions on conformational mobility of the progesterone receptor detected by hydrogen/deuterium exchange mass spectrometry. Structure. 2014 Jul 8;22(7):961-73. Epub 2014 Jun 5. PMID: 24909783

Kirschke E, Goswami D, Southworth D, Griffin PR, Agard DA. Glucocorticoid receptor function regulated by coordinated action of the Hsp90 and Hsp70 chaperone cycles. Cell. 2014 Jun 19;157(7):1685-97. PMID: 24949977

Armstrong EH, Goswami D, Griffin PR, Noy N, Ortlund EA. Structural basis for ligand regulation of the fatty acid-binding protein 5, peroxisome proliferator-activated receptor β/δ (FABP5-PPARβ/δ) signaling pathway. J Biol Chem. 2014 May 23;289(21):14941-54. Epub 2014 Apr 1. PMID: 24692551

Nwachukwu JC, Srinivasan S, Bruno NE, Parent AA, Hughes TS, Pollock JA, Gjyshi O, Cavett V, Nowak J, Garcia-Ordonez RD, Houtman R, Griffin PR, Kojetin DJ, Katzenellenbogen JA, Conkright MD, Nettles KW. Resveratrol modulates the inflammatory response via an estrogen receptor-signal integration network. Elife. 2014 Apr 25;3:e02057. PMID: 24771768

Yan F, Yu Y, Chow DC, Palzkill T, Madoux F, Hodder P, Chase P, Griffin PR, O'Malley BW, Lonard DM. Identification of verrucarin a as a potent and selective steroid receptor coactivator-3 small molecule inhibitor. PLoS One. 2014 Apr 17;9(4):e95243. eCollection
2014. PMID: 24743578

Hughes TS, Giri PK, de Vera IM, Marciano DP, Kuruvilla DS, Shin Y, Blayo AL, Kamenecka TM, Burris TP, Griffin PR, Kojetin DJ. An alternate binding site for PPARγ ligands. Nat Commun. 2014 Apr 7;5:3571. PMID: 24705063

Qiang G, Xue S, Yang JJ, Du G, Pang X, Li X, Goswami D, Griffin PR, Ortlund EA, Chan CB, Ye K. Identification of a small molecular insulin receptor agonist with potent antidiabetes activity. Diabetes. 2014 Apr;63(4):1394-409. PMID: 24651808

Underbakke ES, Iavarone AT, Chalmers MJ, Pascal BD, Novick S, Griffin PR, Marletta MA. Nitric oxide-induced conformational changes in soluble guanylate cyclase. Structure. 2014 Apr 8;22(4):602-11. Epub 2014 Feb 20. PMID: 24560804

Chang MR, Lyda B, Kamenecka TM, Griffin PR. Pharmacologic repression of retinoic acid receptor-related orphan nuclear receptor γ is therapeutic in the collagen-induced arthritis experimental model. Arthritis Rheumatol. 2014 Mar;66(3):579-88. PMID: 24574218

Wang Y, Lonard DM, Yu Y, Chow DC, Palzkill TG, Wang J, Qi R, Matzuk AJ, Song X, Madoux F, Hodder P, Chase P, Griffin PR, Zhou S, Liao L, Xu J, O'Malley BW. Bufalin is a potent small-molecule inhibitor of the steroid receptor coactivators SRC-3 and SRC-1. Cancer Res. 2014 Mar 1;74(5):1506-17. Epub 2014 Jan 3. PMID: 24390736

Lewallen DM, Sreelatha A, Dharmarajan V, Madoux F, Chase P, Griffin PR, Orth K, Hodder P, Thompson PR. Inhibiting AMPylation: a novel screen to identify the first small molecule inhibitors of protein AMPylation. ACS Chem Biol. 2014 Feb 21;9(2):433-42. Epub 2013 Nov 25. PMID: 24274060

Marciano DP, Chang MR, Corzo CA, Goswami D, Lam VQ, Pascal BD, Griffin PR. The therapeutic potential of nuclear receptor modulators for treatment of metabolic disorders: PPARγ, RORs, and Rev-erbs. Cell Metab. 2014 Feb 4;19(2):193-208. Epub 2014 Jan 16. Review. PMID: 24440037

Boerma LJ, Xia G, Qui C, Cox BD, Chalmers MJ, Smith CD, Lobo-Ruppert S, Griffin PR, Muccio DD, Renfrow MB. Defining the communication between agonist and coactivator binding in the retinoid Xreceptor α ligand binding domain. J Biol Chem. 2014 Jan 10;289(2):814-26. Epub 2013 Nov 1. PMID: 24187139

Chang MR, Rosen H, Griffin PR. RORs in autoimmune disease. Curr Top Microbiol Immunol. 2014; 378:171-82. Review. PMID: 24728598

Corzo C, Griffin PR. Targeting the Peroxisome Proliferator-Activated Receptor-γ to Counter the Inflammatory Milieu in Obesity. Diabetes Metab J. 2013 Dec;37(6):395-403. PMID: 24404510

Zhang Y, Goswami D, Wang D, Wang TS, Sen S, Magliery TJ, Griffin PR, Wang F, Schultz PG. An antibody with a variable-region coiled-coil "knob" domain. Angew Chem Int Ed Engl. 2014 Jan 3;53(1):132-5. Epub 2013 Nov 19. PMID: 24254636

Landgraf RR, Goswami D, Rajamohan F, Harris MS, Calabrese MF, Hoth LR, Magyar R, Pascal BD, Chalmers MJ, Busby SA, Kurumbail RG, Griffin PR. Activation of AMP-activated protein kinase revealed by hydrogen/deuterium exchange mass spectrometry. Structure. 2013 Nov 5;21(11):1942-53. Epub 2013 Sep 26. PMID: 24076403

Goswami D, Devarakonda S, Chalmers MJ, Pascal BD, Spiegelman BM, Griffin PR. Time window expansion for HDX analysis of an intrinsically disordered protein. J Am Soc Mass Spectrom. 2013 Oct 24(10):1584-92. Epub 2013 Jul 25. PMID: 23884631

Musille PM, Pathak M, Lauer JL, Griffin PR, Ortlund EA. Divergent sequence tunes ligand sensitivity in phospholipid-regulated hormone receptors. J Biol Chem. 2013 Jul 12;288(28):20702-12. Epub 2013 Jun 4. PMID:23737522

Kumar R, Moure CM, Khan SH, Callaway C, GrimmSL, Goswami D, Griffin PR, Edwards DP. Regulation of the structurally dynamic N-terminal domain of progesterone receptor by protein-induced folding. J Biol Chem. 2013 Oct 18;288(42):30285-99. Epub 2013 Aug 30. PMID: 23995840

Harms MJ, Eick GN, Goswami D, Colucci JK, Griffin PR, Ortlund EA, Thornton JW. Biophysical mechanisms for large-effect mutations in the evolution of steroid hormone receptors. Proc Natl Acad Sci U S A. 2013 Jul 9;110(28):11475-80. Epub 2013 Jun 24. PMID: 23798447

Kumar N, Kamenecka T, Lyda B, Khan P, Chang MR, Garcia-Ordonez RD, Cameron M, Ferguson J, Mercer BA, Hodder P, Rosen H, Griffin PR. Identification of a novel selective inverse agonist probe and analogs for the Retinoic acid receptor-related Orphan Receptor Gamma (RORγ). Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-.2012 Apr 16 [updated 2013 Mar 14]. PMID: 23762937

Kumar N, Nuhant P, Solt LA, Conkright JJ, Wang Y, Istrate MA, Busby SA, Ruben DGO, Burris TP, Cameron M, Mercer BA, Hodder P, Roush WR, Rosen H, Griffin PR. Identification of a novel selective inverse agonist probe and analogs for the Retinoic acid receptor-related Orphan Receptor Alpha (RORα). Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-2010 Sep 1 [updated 2013 Mar 14]. PMID: 23762959

Kamenecka TM, Busby SA, Kumar N, Choi JH, Banks AS, Vidovic D, Cameron MD, Schurer C, Mercer BA, Hodder P, Spiegelman BM, Griffin PR. Potent Anti-Diabetic Actions of a Novel Non-Agonist PPARγ Ligand that Blocks Cdk5-Mediated Phosphorylation. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology nformation (US); 2010-2011 Jul 5 [updated 2013 Mar 7]. PMID: 23762958

Kamenecka TM, Lyda B, Chang MR and Griffin PR, Synthetic modulators of the retinoic acid receptor-related orphan receptors, Med. Chem. Commun., 2013, Advance Article, DOI: 10.1039/C3MD00005B

West GM, Pascal BD, Ng LM, Soon FF, Melcher K, Xu HE, Chalmers MJ, Griffin PR. Protein Conformation Ensembles Monitored by HDX Reveal a Structural Rationale for Abscisic Acid Signaling Protein Affinities and Activities, Structure, 2013, Feb 5;21(2):229-35. doi: 10.1016/j.str.2012.12.001. Epub 2013 Jan 3. PMID:23290725

Khan PM, El-Gendy Bel-D, Kumar N, Garcia-Ordonez R, Lin L, Ruiz CH, Cameron MD, Griffin PR, Kamenecka TM. Small molecule amides as potent ROR-y selective modulators. Bioorg Med Chem Lett., 2013, Jan 15; 23(2): 532-6. Epub 2012 Nov 22. PMID: 23232056

Chang MR, Goswami D, Mercer BA, Griffin PR, The therapeutic potential of RORγ modulators in the treatment of human disease, J. Exp. Pharmacol., 2012, 4, 141 – 148, DOI: http://dx.doi.org/10.2147/JEP.S27078

Busby S, Nuhant P, Cameron M, Mercer BA, Hodder P, Roush WR, Griffin PR. Discovery of Inverse Agonists for the Liver Receptor Homologue-1 (LRH1;NR5A2). Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. 2010 Oct 12 [updated 2011 Dec 12]. PMID:23166964

Khan SH, Awasthi S, Guo C, Goswami D, Ling J, Griffin PR, Simons SS Jr, Kumar R. Binding of the N-terminal region of coactivator TIF2 to the intrinsically disordered AF1 domain of the glucocorticoid receptor is accompanied by conformational reorganizations. J Biol Chem., 2012 Dec 28;287(53):44546-60. doi: 10.1074/jbc.M112.411330. Epub 2012 Nov 6. PMID: 23132854

Harmey D, Griffin PR, Kenny PJ. Development of novel pharmacotherapeutics for tobaccco dependence: progress and future directions. Nicotine Tob Res., 2012, Nov;(11):1300-18. Epub 2012 Sep 27. PMID:23024249

Ye L, Kleiner S, Wu J, Sah R, Gupta RK, Banks AS, Cohen P, Khandekar MJ, Boström P, Mepani RJ, Laznik D, Kamenecka TM, Song X, Liedtke W, Mootha VK, Puigserver P, Griffin PR, Clapham DE, Spiegelman BM. TRPV4 is a regulator of adipose oxidative metabolism, inflammation, and energy homeostasis. Cell. 2012,Sep 28;151(1): 96-110. PMID:23021218

Solt LA, Kumar N, He Y, Kamenecka TM, Griffin PR, Burris TP. Identification of a selective RORy ligand that suppresses T(H)17 cells and stimulates T regulatory cells. ACS Chem Biol. 2012 Sep 21;7(9):1515-9. Epub 2012 Jul 9. PMID:22769242

Pascal BD, Willis S, Lauer JL, Landgraf RR, West GM, Marciano D, Novick S, Goswami D, Chalmers MJ, Griffin PR. HDX workbench: software for the analysis of H/D exchange MS data. J Am Soc Mass Spectrom. 2012 Sep;23(9):1512-21. Epub 2012 Jun 13. PMID: 22692830

Chalmers MJ, Wang Y, Novick S, Sato M, Bryant HU, Montrose-Rafizdeh C, Griffin PR, Dodge JA. Hydrophobic Interactions Improve Selectivity to ERalpha for Ben-zothiophene SERMs. ACS Med Chem Lett. 2012, Mar 8;3(3): 207-210. PMID: 22582136

Musille PM, Pathak MC, Lauer JL, Hudson WH, Griffin PR, Ortlund EA. Antidiabetic phospholipid-nuclear receptor complex reveals the mechanism for phospholipid-driven gene regulation. Nat Struct Mol Biol. 2012 Apr 15;19(5):532-7, S1-2. PMID 22504882

Kumar N, Lyda B, Chang MR, Lauer JL, Solt LA, Burris TP, Kamenecka TM, Griffin PR. Identification of SR2211: a ptent synthetic RORy-selective modulator. ACS Chem Biol. 2012 Apr 20;7 (4):672-7. Epub 2012 Feb 13. PMID: 22292739

Burris TP, Busby SA, Griffin PR. Targeting orphan nuclear receptors for treatment of metabolic diseases and autoimmunity. Chem Biol. 2012 Jan 27;19(1):51-9. Review.19, 51-9. PMID:22284354

Hughes TS, Chalmers MJ, Novick S, Kuruvilla DS, Chang MR, Kamenecka TM, Rance M, Johnson BA, Burris TP, Griffin PR, Kojetin DJ. Ligand and receptor dynamics contribute to the mechanism of graded PPARy agonism. Structure. 2012 Jan 11;20(1):139-50. PMID:22244763

Mizwicki MT, Menegaz D, Zhang J, Barrientos-Durán A, Tse S, Cashman JR, Griffin PR, Fiala M. Genomic and nongenomic signaling induced by 1a,25(OH)2-vitamin D3 promotes the recovery of amyloid-beta phagocytosis by Alzheimer's disease macrophages. J Alzheimers Dis., 2012; 29(1):51-62. PMID:22207005

Ng LM, Soon FF, Zhou XE, West GM, Kovach A, Suino-Powell KM, Chalmers MJ, Li J, Yong EL, Zhu JK, Griffin PR, Melcher K, Xu HE. Structural Basis for basal activity and autoactivation of abscisic acid (ABA) signaling SnRK2 kinases. Proc Natl Acad Sci U S A. 2011 Dec 27; 108(52):21259-64. Epub 2011 Dec 12. PMID:22160701

Landgraf RR, Chalmers MJ, Griffin PR. Automated hydrogen/deuterium exchange electron transfer dissociation high resolution mass spectrometry measured at single-amide resolution. J Am Soc Mass Spectrom. 2012 Feb 23(2):301-9. Epub 2011 Dec 1. PMID: 22131230

Soon FF, Ng LM, Zhou XE, West GM, Kovach A, Tan MH, Suino-Powell KM, He Y, Xu Y, Chalmers MJ, Brunzelle JS, Zhang H, Yang H, Jiang H, Li J, Yong EL, Cutler S, Zhu JK, Griffin PR, Melcher K, Xu HE., Molecular Mimicry Regulates ABA Signaling by SnRK2 Kinases and PP2C Phosphatases., Science, 2011 Nov 24. PMID:22116026

Canny SA, Cruz Y, Southern MR, Griffin PR. PubChem promiscuity: a web resource for gathering compound promiscuity data from PubChem.Bioinformatics. 2012 Jan 1;28(1):140-1. Epub 2011 Nov 13. PMID: 22084255

Devarakonda S, Gupta K, Chalmers MJ, Hunt JF, Griffin PR, Van Duyne GD, Spiegelman BM., Disorder-to-order transition underlies the structural basis for the assembly of a transcriptionally active PGC-1α/ERRγ complex. Proc Natl Acad Sci U S A., 2011 Nov 15; 108(46):18678-83. 18678-83. doi: 10.1073/pnas.1113813108. Epub 2011 Nov 2. PMID: 22049338

Malapaka RR, Khoo S, Zhang J, Choi JH, Zhou XE, Xu Y, Gong Y, Li J, Yong EL, Chalmers MJ, Chang L, Resau JH, Griffin PR, Chen YE, Xu HE. J Biol Chem. 2012 Jan 2;287(1):183-95. Epub 2011 Oct 28. PMID: 22039047

Choi JH, Banks AS, Kamenecka TM, Busby SA, Chalmers MJ, Kumar N, Kuruvilla DS, Shin Y, He Y, Bruning JB, Marciano DP, Cameron MD, Laznik D, Jurczak MJ, Schürer SC, Vidović D, Shulman GI, Spiegelman BM, and Griffin PR., Anti-Diabetic Actions of a Non-Agonist PPARγ Ligand Blocking Cdk5-Mediated Phosphorylation, Nature, 2011 Sep 4;477(7365):477-81.doi 10.1038/nature10383. PMID:21892191

West GM, Chien EYT, Katritch V, Gatchalian J, Chalmers MJ, Stevens RC, Griffin PR., Ligand-dependent perturbation of the conformational ensemble for the GPCR beta2 adrenergic receptor revealed by HDX, Structure, 2011 Oct 12;19(10): 1424-32. Epub 2011 Sep 1. PMID:21889352

Lee JM, Lee YK, Mamrosh KL, Busby SA, Griffin PR, Pathak MC, Ortlund EA and Moore DD, Antidiabetic Effects of a Novel Agonist Ligand for the Nuclear Receptor LRH-1, Nature, 2011 May 25;474(7352):506-10. PMID: 21614002

Chalmers MJ, Pascal BD, Willis S, Zhang J, Iturria SJ, Dodge JA, Griffin PR. Methods for the Analysis of High Precision Differential Hydrogen Deuterium Exchange Data. Int J Mass Spectrom. 2011 Apr 30;302(1-3):59-68. PMID:21528013

Solt LA, Kumar N, Nuhant P, Wang Y, Lauer JL, Liu J, Istrate MA, Kamenecka TM, Roush WR, Vidovic D, Schurer S, Xu J, Wagoner G, Drew PD, Griffin PR, and Burris TP, Suppression of TH17 differentiation and autoimmunity by a synthetic ROR ligand, Nature, 2011, Apr 28;472(7344): 491-4. Epub 2011 Apr 17. PMID: 21499262

Zhang J, Chalmers MJ, Stayrook KR, Burris LL, Wang Y, Busby SA, Pascal BD, Garcia-Ordonez RD, Bruning JB, Istrate MA, Kojetin DJ, Dodge JA, Burris TP and Griffin PR, DNA binding alters coactivator interaction surfaces of the intact VDR–RXR complex, Nat Struct Mol Biol, 2011 May 18(5): 556-63. Epub 2011 Apr 10. PMID:21478866

Heidebrecht T, Christodoulou E, Chalmers MJ, Jan S, Ter Riet B, Grover RK, Joosten RP, Littler D, van Luenen H, Griffin PR, Wentworth P Jr, Borst P, Perrakis A., The structural basis for recognition of base J containing DNA by a novel DNA binding domain in JBP1, Nucleic Acids Res., 2011 Jul 39(13): 5715-28. doi: 10.1093/nar/gkr125.Epub 2011 Mar 16. PMID: 21415010

Willis S and Griffin PR, Mutual Information identifies sequence positions conserved within the nuclear receptor superfamily: approach reveals functionally important regions for DNA binding specificity, NURSA, 2011 Feb 25;9:e001. PMID: 21383938

Busby SA, Kumar N, Kuruvilla DS, Istrate MA, Conkright JJ, Wang Y, Kamenecka TM, Cameron MD, Roush WR, Burris TP, Griffin PR., Identification of a Novel Non-retinoid Pan Inverse Agonist of the Retinoic Acid Receptors, ACS Chem Biol., 2011 Jun 17;6(6):618-27. Epub 2011 Mar 17. PMID: 21381756

Chalmers MJ, Busby SA, Pascal BD, West GM and Griffin PR, Differential hydrogen/deuterium exchange mass spectrometry analysis of protein-ligand interactions, Expert Rev Proteomics, 2011 Feb 8(1):43-59. Review. PMID: 21329427

Istrate MA, Spicer TP, Wang Y, Bernard JA, Helvering LM, Bocchinfuso WP, Richardson TI, Zink R, Kumar N, Montrose-Rafizadeh C, Dodge JA, Hodder P and Griffin PR, Development of an HTS-Compatible Assay for Discovery of RORα Modulators Using AlphaScreen Technology, J Biomol Screen, 2011 Feb16(2):183-91. PMID: 21297105

Wright E, Busby SA, Wisecarver S, Vincent J, Griffin PR, Fernandez EJ, Helix 11 dynamics is critical for constitutive androstane receptor activity, Structure, 2011,Jan 12;19(1):37-44. PMID:21220114

Southern MR and Griffin PR, A Java API for working with PubChem datasets, Bioinformatics, 2011, Mar 1;27(5):741-2. Epub 2011 Jan 6. PMID: 21216779

Vidović D, Busby SA, Griffin PR, Schürer SC, A combined ligand- and structure-based virtual screening protocol identifies submicromolar PPARγ partial agonists, ChemMedChem, 2011, Jan 3;6(1);94-103. PMID: 21162086

Kumar N, Kojetin DJ, Solt LA, Kumar KG, Nuhant P, Duckett DR, Cameron MD, Butler AA, Roush WR, Griffin PR, Burris TP., Identification of SR3335 (ML-176): A Synthetic RORα Selective Inverse Agonist, ACS Chem Biol. 2011 Mar 18;6(3):218-22. Epub 2010 Dec 6. PMID: 21090593

Zhang J, Chalmers MJ, Stayrook KR, Burris LL, Garcia-Ordonez RD, Pascal BD, Burris TP, Dodge JA and Griffin PR, Hydrogen/Deuterium Exchange Reveals Distinct Agonist/Partial Agonist Receptor Dynamics within the intact Vitamin D Receptor/Retinoid X Receptor Heterodimer, Structure, 2010,Oct 13;18(10): 1332-41. PMID: 20947021

Wang Y, Kumar N, Nuhant P, Cameron MD, Istrate MA, Roush WR, Griffin PR, Burris TP. Identification of SR1078, a synthetic agonist for the orphan nuclear receptors RORalpha and RORgamma, ACS Chemical Biology, 2010 Nov 19;5(11):1029-34. PMID: 20735016

Kumar N, Solt LA, Conkright J, Wang Y, Istrate MA, Busby SA, Garcia-Ordonez RD, Nuhant P, Burris T, Mercer BA, Hodder P, Roush WR, Rosen H, Griffin PR. Campaign to identify novel modulators of the Retinoic acid receptor-related Orphan Receptors (ROR). Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010.

Choi JH, Banks AS, Estall JL, Kajimura S, Boström P, Laznik D, Ruas JL, Chalmers MJ, Kamenecka TM, Blüher M, Griffin PR, Spiegelman BM, Anti-diabetic drugs inhibit obesity-linked phosphorylation of PPARgamma by Cdk5, Nature, 2010, Jul 22; 466(7305):451-6. PMID: 20651683

Solt LA, Griffin PR and Burris TP Ligand regulation of retinoic acid receptor-related orphan receptors: implications for development of novel therapeutics, Current Opin Lipidol, 2010,Jun 21;(3):204-11. doi:10.1097/MOL.0b013e328338ca18. Review. PMID: 0463469

Kumar N, Solt LA, Wang Y, Rogers PM, Bhattacharyya G, Kamenecka TM, Stayrook KR, Crumbley C, Floyd ZE, Gimble JM, Griffin PR and Burris TP Regulation of adipogenesis by natural and synthetic REV-ERB ligands, Endocrinology, 2010, Jul;151(7): 3015-5. Epub 2010 Apr 28. PMID: 20427485

Wang Y, Kumar N, Crumbley C, Griffin PR and Burris TP A second class of nuclear receptors for oxysterols: Regulation of RORalpha and RORgamma activity by 24S-hydroxycholesterol (cerebrosterol), Biochim Biophys Acta. 2010 Aug; 1801(8):917-923. Epub 2010 Mar 6. PMID: 20211758

Zhang X, Chien EYT, Chalmers MJ, Pascal BD, Gatchalian J, Stevens RC, and Griffin PR, Dynamics of the beta2-adrenergic G-protein coupled receptor revelaed by hydrogen/deuterium exchange, Analytical Chem. 2010 Feb 1;82(3):1100-8. PMID: 20058880

Wang Y, Kumar N, Solt LA, Richardson TI, Helvering LM, Crumbley C, Garcia-Ordonez RD, Stayrook KR, Zhang X, Novick S, Chalmers MJ, Griffin PR, Burris TP., Modulation of retinoic acid receptor-related orphan receptor alpha and gamma activity by 7-oxygenated sterol ligands., J Biol Chem., 2010 Feb 12;285(7):5013-25. Epub 2009 Dec 4. PMID: 19965867

Kumar N, Solt LA, Conkright JJ, Wang Y, Istrate MA, Garcia-Ordonez R, Burris TP, and Griffin PR, The benzenesulfoamide T0901317 is a novel RORalpha/gamma inverse agonist, Mol Pharmacol. 2010, Feb;77(2):228-36. Epub 2009 Nov 3. PMID: 19887649

Dai S., Burris TP, Dodge JA., Montrose-Rafizadeh C., Wang Y., Pascal B., Chalmers MJ, and Griffin PR, Unique ligand binding patterns between estrogen receptor α and β revealed by hydrogen/deuterium exchange, Biochemistry, 2009 Oct 13;48(40): 9668-76. PMID: 19739677

Noël R, Song X, Jiang R, Chalmers MJ, Griffin PR, Kamenecka TM., Efficient methodology for the synthesis of 3-amino-1,2,4-triazoles, J Org Chem, 2009 Oct 2;74(19):7595-7. PMID: 19731897

Avvaru BS, Busby SA, Chalmers MJ, Griffin PR, Venkatakrishnan B, Agbandje-McKenna M, Silverman DN, McKenna R, Apo-human carbonic anhydrase II revisited: implications of the loss of a metal in protein structure, stability, and solvent network, Biochemistry, 2009 Aug 11;48(31):7365-72. PMID: 19583303

Lauer-Fields JL, Chalmers MJ, Busby SA, Minond D, Griffin PR, Fields GB., Identification of specific hemopexin-like domain residues that facilitate matrix metalloproteinase collagenolytic activity, J Biol Chem., 2009 Sep 4;284(36):24017-24. Epub 2009 Jul 1. PMID: 19574232

Pascal BD, Chalmers MJ, Busby SA, Griffin PR, HD desktop: an integrated platform for the analysis and visualization of H/D exchange data, J Am Soc Mass Spectrom. 2009 Apr;20(4):20, 601-10. Epub 2008 Dec 6. PMID: 19135386

Dai, S.Y., Chalmers, M.J., Bruning, J., Bramlett, K.S., Osborne, H.E., Montrose-Rafizadeh, C., Barr, R.J., Wang, M., Burris, T.P., Dodge, J.A., Griffin, P.R., Prediction of the tissue-specificity of selective estrogen receptor modulators using a single biochemical method. Proc. Natl. Acad. Sci. U. S. A., 2008 May 20;105(20):7171-6. Epub 2008 May 12. PMID: 18474858

Madoux F, Li X, Chase P, Zastrow G, Cameron MD, Conkright JJ, Griffin PR, Thacher S, Hodder P., Potent, selective and cell penetrant inhibitors of SF-1 by functional ultra-high-throughput screening, Mol Pharmacol, 2008 Jun;73(6):1776-84. Epub 2008 Mar 11. PMID: 18334597

Bruning JB, Chalmers MJ, Prasad S, Busby SA, Kamenecka TM, He Y, Nettles KW, Griffin PR., Partial agonists activate PPARgamma using a helix 12 independent mechanism, Structure, 2007 Oct;15(10):1258-71. PMID: 17937915

Chalmers MJ, Busby SA, Pascal BD, Southern MR, Griffin PR. A two-stage differential hydrogen euterium exchange method for the rapid characterization of protein/ligand interactions. J Biomol Tech. 2007 Sep;18(4): 194-204. PMID:17916792

Hamuro Y, Coales SJ, Morrow JA, Molnar KS, Tuske SJ, Southern MR, Griffin PR. Hydrogen/deuterium-exchange (HD-Ex) of PPARgamma LBD in the presence of various modulators. Protein Sci. 2006 Aug;15(8):1883-92. Epub 2006 Jul 5. PMID: 16819819

Quint P, Ayala I, Busby SA, Chalmers MJ, Griffin PR, Rocca J, Nick HS, Silverman DN. Structural mobility in human manganese superoxide dismutase. Biochemistry.2006 Jul 11;45(27):8209-15. PMID: 16819819

Chalmers MJ, Busby SA, Pascal BD, He Y, Hendrickson CL, Marshall AG, Griffin PR. Probing protein ligand interactions by automated hydrogen/deuterium exchange mass spectrometry. Anal Chem. 2006 Feb 15;78(4):1005-14. PMID: 16478090

Hamuro Y, Weber PC, Griffin PR. High-throughput analysis of protein structure by hydrogen
/deuterium exchange mass spectrometry. Methods Biochem Anal. 2005;45:131-57. Review.
PMID: 19235294

Links

Company Ember is launched and website is live.

Nat Struct Mol Biol. 2012 Apr 15. doi: 10.1038/nsmb.2279. [Epub ahead of print]

Scientists Establish New Class of Anti-Diabetic Compound

NIH Research Matters: Designing New Diabetes Drugs

Patrick Griffin and Paul Kenny Awarded Grant to Create National Anti-Addiction Network

Scripps Florida is Awarded Grant to Create National Anti-Addiction Network

Bicoastal Team Pinpoints Shape-Shifting Mechanism Critical to Protein Signaling

Building a Bridge from Basic Science to New Therapies

The Scripps Research Molecular Screening Center