Scripps Research Logo

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: R. D. Garcia-Ordonez, D. Marciano, G. West, D. Goswami, D. Kuruvilla, S. Novick, B. Pascal, M. Chang, A. Corzo, Vinh Lam, Venkat Dharmarajan, Yelenis Mari, Tanya Khan, Rebecca Leon (former members of the lab: 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).

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 present
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

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 ActivitiesStructure, 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. doi: 10.1016/j.bmci.2012.11.025. Epub 2012 Nov 22.

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. doi: 10.1093/ntr/nts201. 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. doi: 10.1016/j.cell.2012.08.034. 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. doi: 10.1007/s13361-012-0419-6. 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. doi: 10.1038/nsmb.2279. 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. doi: 10.1021/cb200496y. 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.doi:10.1016/j.chembiol.2011.12.011. 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. DOI:10.1016/j.str.2011.10.018. 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. doi: 10.3233/JAD-2012-110560. 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. doi 10.1073/pnas.1118651109. Epub 2011 Dec 12. PMID:22160701

Landgraf RR, Chalmers MJ, Griffin PRAutomated 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. doi 10.1007/s13361-11-0298-2. 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 PRPubChem promiscuity: a web resource for gathering compound promiscuity data from PubChem.Bioinformatics. 2012 Jan 1;28(1):140-1. doi: 10.1093/bioinformatics/btr622.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. doi: 10.1074/jbc.M111294785. 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. doi:10.1016/j.str.2011.08.001. 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. doi:10.1038/nature 10111. PMID: 21614002

Chalmers MJ, Pascal BD, Willis S, Zhang J, Iturria SJ, Dodge JA, Griffin PRMethods 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. doi: 10.1038/nature10075. 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. doi: 10.1038/nsmb.2046. Epub 2011 Apr 10.

        PMID:21478866 [PubMed - indexed for MEDLINE]

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 [PubMed - indexed for MEDLINE]

        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. DOI: 10.1621/NRS.09001.

        PMID: 21383938 [PubMed - indexed for MEDLINE]

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. doi:10.1021/cb100396s. Epub 2011 Mar 17.

PMID: 21381756 [PubMed - indexed for MEDLINE]

        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. doi: 10.1586/epr.10.109.Review.

        PMID: 21329427 [PubMed - indexed for MEDLINE]

        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. doi: 10.1177/1087057110389040.

        PMID: 21297105 [PubMed - indexed for MEDLINE]

        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. doi:
        10.1016/j.str.2010.11.008.

        PMID:21220114 [PubMed - indexed for MEDLINE]

        Southern MR and Griffin PR, A Java API for working with PubChem datasets, Bioinformatics,
          2011, Mar 1;27(5):741-2. doi: 10.1093/bioinformatics/btq715.Epub 2011 Jan 6.

        PMID: 21216779 [PubMed - indexed for MEDLINE]

        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. doi: 10.1002/cmdc.201000428.

        PMID: 21162086 [PubMed - indexed for MEDLINE]

        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. doi: 10.1021/cb1002762.
        Epub 2010 Dec 6.

        PMID: 21090593 [PubMed - indexed for MEDLINE]

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. doi: 10.1016/jstr.2010.07/007.

PMID: 20947021 [PubMed - indexed for MEDLINE]

        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. doi:10.1021/cb100223d. 

        PMID: 20735016 [PubMed - indexed for MEDLINE]

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. doi: 10.1038/nature09291.

PMID: 20651683 [PubMed - indexed for MEDLINE]

        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: 20463469 [PubMed - indexed for MEDLINE]

        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): 3015-25. doi: 10.1210/en.2009-0800.
        Epub 2010 Apr 28.

        PMID: 20427485 [PubMed - indexed for MEDLINE]

        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. doi: 10.1016/j.bbalip.
        2010.02.012. Epub 2010 Mar 6.

        PMID: 20211758 [PubMed - indexed for MEDLINE]

        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. doi: 10.1021/ac902484p.

        PMID: 20058880 [PubMed - indexed for MEDLINE]

        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. doi: 10.1074/jbc.M109.080614. Epub 2009 Dec 4.

        PMID: 19965867 [PubMed - indexed for MEDLINE] 

        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. doi: 1124/mol.109.060905. Epub 2009 Nov 3.

        PMID: 19887649 [PubMed - indexed for MEDLINE]

        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. doi: 10.1021/bi901149t.

        PMID: 19739677 [PubMed - indexed for MEDLINE]

        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. doi:10.1021/jo9016502.

        PMID: 19731897 [PubMed - indexed for MEDLINE]

        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. doi: 10.1021/bi9007512.

        PMID: 19583303 [PubMed - indexed for MEDLINE]

        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. doi: 10.1074/jbc.M109.016873.
        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. doi: 10.1016/j.jasms.2008.11.019. Epub 2008 Dec 6.

        PMID: 19135386 [PubMed - indexed for MEDLINE]

        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. doi:10.1072/pnas.0710802105.
        Epub 2008 May 12.

        PMID: 18474858 [PubMed - indexed for MEDLINE]

        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. doi: 10.1124/mol.108.
        045963. Epub 2008 Mar 11.

        PMID: 18334597 [PubMed - indexed for MEDLINE]

        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 [PubMed - indexed for MEDLINE]

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

        PMID:17916792 [PubMed - indexed for MEDLINE]

        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 [PubMed - indexed for MEDLINE]

        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 [PubMed - indexing for MEDLINE]

        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 [PubMed - indexed for MEDLINE]

        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 [PubMed - indexed for MEDLINE]

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