Paul J. Davis, M.D.

Education

American Board of Internal Medicine, Diplomate  
Harvard Medical School, M.D., cum laude
Westminster College (MO), B.A. magna cum laude

PREVIOUS POSITION

Director, Ordway Research Institute, Inc.

Research Interests

Dr. Davis directs a group of scientists who have defined molecular mechanisms for many nongenomic, plasma membrane-initiated actions of thyroid hormone, including actions on plasma membrane ion transporters, intracellular protein trafficking, phosphorylation of nuclear hormone receptors and of p53 and on transcription of specific genes. They have described the cell surface receptor for thyroid hormone on integrin avb3 and the actions of tetraiodothyroacetic acid (tetrac) and reformulated (nanoparticulate) tetrac initiated at this plasma membrane receptor that are anti-angiogenic and anti-cancer by multiple cell surface and intracellular pathways.

Books

Editorship

  • SA Mousa, PJ Davis (eds). 2013. Angiogenesis Modulations in Health and Disease. Springer Publishers
  • Calkins E, Davis PJ, Ford AB (eds). 1986. The Practice of Geriatrics. Philadelphia: WB Saunders Co
  • Calkins E, Davis PJ, Levitt J (eds). 1982. Primary Care, vol 9 no 1: Geriatric Medicine. Philadelphia: WB Saunders Co.

Book Section Editorship

  • Davis PJ (ed). 1992. Endocrine System Pharmacology. In Smith CM, Reynard AM (eds). Textbook of Pharmacology. Philadelphia: WB Saunders Co.

Publications

Selected from 215 co-authored published scientific articles are a limited number of articles relevant to the tetrac-Nanotetrac pharmaceutical platform.

Lin HY, Nu YF, Hsieh MT, Lin S, Meng R, London D, Lin C, Tang HY, Hwang J, Davis  FB, Mousa SA, Davis PJ.  2013. Nuclear monomeric integrin av in cancer cells is a co-a activator regulated by thyroid hormone.  FASEB J, in press.

Yalcin M, Lin HY, Sudha T, Bharali DJ, Meng R, Tang HY, Davis FB, Stain SC, Davis PJ,  Mousa SA.  2013. Response of human pancreatic cell xenografts to tetraiodothyroacetic acid nanoparticles. Hormones Cancer, in press.

Davis PJ, Glinsky GV, Lin HY, Incerpi S, Davis FB, Mousa SA, Tang HY, Hercbergs A, Luidens MK.  2013.  Molecular mechanisms of actions of formulations of the thyroid hormone analogue, tetrac, on the inflammatory response.  Endocr Res, in press.

Bharali DJ, Yalcin M, Davis PJ. Mousa SA.  2013.  Tetraiodothyroacetic acid (tetrac) conjugated PLGA nanoparticles: a nanomedicine approach to treat drug-resistant breast cancer.  Nanomedicine (London), in press.

Lin HY, Tang HY, Davis FB, Mousa SA, Incerpi S, Luidens MK, Meng R, Davis PJ. 2012.  Nongenomic regulation by thyroid hormone of plasma membrane ion and small molecule pumps. Discov Med 14:199-206.

Freindorf M, Furlani T, Kong J, Cody V, Davis FB, Davis PJ. 2012.  Combined QM/MM study of thyroid and steroid hormone analogues interactions with avß3 integrin. J Biomed Biotechnol 2012:957057.

Hercbergs AH, Davis FB, Lin HY, Luidens MK, Meng R, Ashur-Fabian O, Mousa SA, Davis, PJ. 2012.  Integrin-mediated actions of thyroid hormone analogues on tumor cell chemosensitivity, integrin-growth factor receptor crosstalk and inflammatory gene expression. Cancer Clin Oncol 1:32-40.  Ashur-Fabian O, Blumenthal DT, Bakon M, Nass D, Davis PJ, Hercbergs A. 2012. Long-term disease response in glioblastoma multiforme treated with medically-induced  hypothyroidism and chemotherapy. Anti-Cancer Drugs, in press.

Davis PJ, Davis FB, Mousa SA, Lin HY.  2011.  Membrane receptor for thyroid hormone: physiologic and pharmacologic implications. Ann Rev Pharmacol Toxicol 51:99-115.

Lin HY, Landersdorfer CB, London D, Meng R, Lim CU, Lin C, Lin S, Tang HY, Brown  D, Van Scoy B, Kulawy R, Queimado L, Drusano GL, Louie A, Davis FB, Mousa SA, Davis PJ.  2011.  Pharmacodynamic modeling of anti-cancer activity of tetraiodothyroacetic acid in a perfused cell culture system.  PLoS Comput Biol 7(2):e1001073.

De Vito P, Incerpi S, Pedersen JZ, Luly P, Davis FB, Davis PJ.  2011. Thyroid hormones as modulators of immune activities at the cellular level. Thyroid 21:879-890.

Mousa SA, Yalcin M, Bharali D, Meng R, Tang HY, Lin HY, Davis FB, Davis PJ. 2011. Tetraiodothyroacetic acid and its nano-derivative inhibit thyroid hormone stimulation of non-small cell lung cancer cells in vitro and growth of NSCLC xenografts. Lung Cancer 76:39-45.

Cohen K, Ellis M, Hercbergs A, Davis PJ, Ashur-Fabian O. 2011. Thyroid hormone is a MAPK-dependent growth factor for human myeloma cells acting via v3 integrin. Mol Cancer Res 9:1385-1394.

Hercbergs AH, Lin HY, Davis FB, Davis PJ, Leith JT. 2011. Radiosensitization and  production of DNA double-strand breaks in U87MG brain tumor cells induced by tetraiodothyroacetic acid (tetrac). Cell Cycle 10:352-357.

Lin HY, Cody V, Davis FB, Hercbergs AA, Luidens MK, Mousa SA, Davis PJ.  2011. Identification and functions of the plasma membrane receptor for thyroid hormone  analogues. Discov Med 11:337-347.

Cheng SY, Leonard JL, Davis PJ. 2010. Molecular aspects of thyroid hormone actions. Endocr Rev 31:139-170.

Yalcin M, Dyskin E, Lansing L, Bharali DJ, Mousa SS, Bridoux A, Hercbergs, AH, Lin HY, Davis FB, Glinsky GV, Glinskii A, Ma J, Davis PJ, Mousa SA.  2010. Tetraiodothyroacetic acid (tetrac) and nanoparticulate tetrac arrest growth of human medullary carcinoma of the thyroid. J Clin Endocrinol Metab 95:1972-1980.

Lin HY, Sun M, Tang HY, Lin C, Mousa SA, Incerpi S, Davis FB, Davis PJ. 2009.  L-Thyroxine vs. 3, 5, 3’-triiodo-L-thyronine and cell proliferation: activation of mitogen-activated protein kinase and phosphatidylinositol 3-kinase. Am J Physiol Cell Physiol 296:C980-C991.

Lin HY, Davis PJ, Mousa SA, Tang HY, Hercbergs AH, Davis FB.  2009.  The pro-apoptotic action of stilbene-induced COX-2 in cancer cells. Convergence with the  anti-apoptotic effect of thyroid hormone.  Cell Cycle 8:1877-1882.

Hercbergs A, Davis PJ, Davis FB, Cieslieski M, Leith JT. 2009. Radiosensitization of GL261 glioma cells by tetraiodothyroacetic acid (tetrac). Cell Cycle 8:2586-2591.

Mousa SS, Davis FB, Davis PJ, Mousa SA. 2009. Human platelet aggregation and de-granulation is induced in vitro by L-thyroxine, but not by 3, 5, 3’-triiodo-L-thyronine or diiodothyropropionic acid (DITPA).  Clin Appl Thromb Hemostasis  16:287-292.

Davis PJ, Davis FB, Lin HY, Mousa SA, Zhou M, Luidens MK. 2009. Translational implications of nongenomic actions of thyroid hormone initiated at its integrin receptor. Am J Physiol Endocrinol Metab 297:E1238-E1246.

Yalcin M, Bharali DJ, Dyskin E, Dier E, Lansing L, Mousa SS, Davis FB, Davis PJ, Mousa SA. 2009.  Tetraiodothyroacetic acid (tetrac) and tetrac nanoparticle effectively inhibit  growth of human follicular thyroid cell carcinoma. Thyroid 20:281-286.

Glinskii AB, Glinsky GV, Lin HY, Teng HY, Sun M, Davis FB, Luidens MK, Mousa SA, Hercbergs AH, Davis PJ.  2009.  Modification of survival pathway gene expression in human breast cancer cells by tetraiodothyroacetic acid (tetrac). Cell Cycle 8:3554-3562.

Yalcin M, Bharali DJ, Lansing L, Dyskin, Mousa SS, Davis FB, Davis PJ, Mousa SA. 2009.  Tetraiodothyroacetic acid (tetrac) and tetrac nanoparticles inhibit growth of human renal cell carcinoma. Anticancer Res 29:3825-3831.

Lin H-Y, Tang H-Y, Keating T, Wu Y-H, Shih A, Hammond D, Sun M, Hercbergs A, Davis FB, Davis PJ.  2008.  Resveratrol is pro-apoptotic and thyroid hormone is anti- apoptotic in glioma cells: both actions are integrin- and ERK-mediated. Carcinogenesis 29:62-69.

Mousa SA, Bergh JJ, Dier E, Rebbaa A, O’Connor LJ, Yalcin M, Aljada A, Dyskin E, Davis FB, Lin H-Y, Davis PJ. 2008. Tetraiodothyroacetic acid, a small molecule integrin ligand, blocks angiogenesis induced by vascular endothelial growth factor and basic fibroblast growth factor. Angiogenesis 11:183-190.

Rebbaa A, Chu F, Davis FB, Davis PJ, Mousa SA. 2008. Novel function of the thyroid hormone analog tetraiodothyroacetic acid: a cancer chemosensitizing and anti-cancer agent. Angiogenesis 11:269-276.

Lin H-Y, Tang H-Y, Shih A, Keating T, Cao J, Davis PJ, Davis FB.  2007. Thyroid  hormone is a MAPK-dependent growth factor for thyroid cancer cells and is anti-apoptotic. Steroids 72:180-187.

Cody V, Davis PJ, Davis FB. 2007. Molecular modeling of thyroid hormone interactions with avß3 integrin. Steroids 72:165-170.

Davis FB, Tang H-Y, Shih A, Keating T, Lansing L, Hercbergs A, Fenstermaker RA, Mousa A, Mousa S, Davis PJ, Lin H-Y. 2006. Acting via a cell surface receptor, thyroid hormone is a growth factor for glioma cells.  Cancer Res 66:7270-7275.

Lin H-Y, Lansing L, Merillon J-M, Davis FB, Tang H-Y, Shih A, Vitrac X, Krisa S, Keating T, Cao HJ, Bergh J, Quackenbush S, Davis PJ.  2006.  Integrin avß3 contains a receptor site for resveratrol. FASEB J 20:1742-1744.

Mousa SA, Feng X, Davis FB, Mohamed S, Scanlan TS, Davis PJ. 2006. Pro-angiogenesis action of the thyroid hormone analog GC-1 in a 3-dimensional in vitro microvascular endothelial sprouting assay. Int Angiology 25:407-413.

Bergh JJ, Lin H-Y, Lansing L, Mohamed SN, Davis, FB, Mousa S, Davis PJ.  2005.  Integrin avß3 contains a cell surface receptor site for thyroid hormone that is linked to activation of MAPK and induction of angiogenesis. Endocrinology 146:2864-2871 (subject of an Endocrinology editorial by S Incerpi).

Mousa SA, O’Connor LJ Bergh JJ, Davis FB, Scanlan TS, Davis PJ. 2005. The pro-angiogenic action of thyroid hormone analogue GC-1 is initiated at an integrin. J Cardiovasc Pharmacol 46:356-360.

Shih A, Lin H-Y, Cao J, Davis FB, Davis PJ. 2004. Disparate effects of thyroid hormone on EGF and TGF-alpha are mediated by cyclic AMP-dependent protein kinase II. Endocrinology 145:1708-1717.

Zhang S, Lin H-Y, Tang H-Y, Davis FB, Davis PJ. 2004. Thyroid hormone causes mitogen-activated protein kinase-dependent phosphorylation of the nuclear estrogen receptor. Endocrinology 145:3265-3272.

Davis FB, Mousa SA, O’Connor L, Mohamed S, Lin H-Y, Davis PJ. 2004. The pro-angiogenic action of thyroid hormone is fibroblast growth factor-dependent and is  initiated at the cell surface. Circ Res 94:1500-1506.

D’Arezzo S, Incerpi S, Davis FB, Aconcia F, Marino M, Farias RN, Davis PJ. 2004. R Rapid non-genomic effects of 3,5,3’-triiodo-L-thyronine on the intracellular pH of  L-6 myoblasts is mediated by intracellular calcium mobilization and kinase pathways. Endocrinology 145:5694-5703.

Davis PJ, Shih A, Lin H-Y, Davis FB. 2000. Thyroxine promotes association of mitogen-activated protein kinase (MAPK) and nuclear thyroid hormone receptor (TR) and causes serine phosphorylation of TR. J Biol Chem 275:38032-38039.

Lin H-Y, Shih A, Davis FB, Davis PJ. 1999. Thyroid hormone promotes phosphorylation of STAT3 and potentiates the action of EGF in cultured cells. Biochem J 338:427-432.

Lin H-Y, Davis FB, Gordinier JK, Martino LJ, Davis PJ. 1999. Thyroid hormone induces activation of mitogen-activated protein kinase in cultured cells.  Am J Physiol 276:C1014-C1024 (subject of an AJP editorial by GR Brent).

Lin H-Y, Martino LJ, Wilcox BD, Davis FB, Gordinier J, Davis PJ. 1998. Potentiation by thyroid hormone of human interferon-gamma-induced HLA-DR expression. J Immunol 161:843-849.

Bernardis LL, Benedict MR, Deziel MR, Davis FB, Davis PJ. 1996. Increased plasma IGF-1 levels, but lack of changes in adipocyte glucose transport, in weanling rats with dorsomedial hypothalamic nucleus lesions 1 year after lesion production.  Physiol Behav 59:689-697.

Lawrence WD, Deziel MR, Davis PJ, Schoenl M, Davis FB, Blas SD. 1993. Thyroid hormone stimulates release of calmodulin-enhancing activity from human erythrocyte membranes in vitro. Clin Sci 84:217-223.

Sundquist J, Blas SD, Hogan JE, Davis FB, Davis PJ. 1992. The a1-adrenergic receptor in human erythrocyte membranes mediates interaction in vitro of epinephrine and thyroid hormone at the membrane Ca2+-ATPase.  Cell Signal 4:795-799.

Davis FB, Smith TJ, Deziel MR, Davis PJ, Blas SD. 1990. Retinoic acid inhibits calmodulin-binding to human erythrocyte membranes and reduces membrane Ca2+-ATPase activity.  J Clin Invest 85:1999-2003.

Mylotte KM, Cody V, Davis PJ, Davis FB, Blas SD, Schoenl M.  1985.  Milrinone and  thyroid hormone stimulate myocardial membrane Ca2+-ATPase activity and share  structural homologies.  Proc Natl Acad Sci USA 82:7974-7978.

Patents

Five issued, 25 U.S. and international applications pending, the majority concerned with the Nanotetrac platform.

Issued

  • US 7,276,514 B2.  Pyrroloquinolone quinone drugs for treatment of cardiac injury and methods of use thereof  (issued October 2, 2007).
  • Australia 2004273986 Thyroid hormone analogs and methods of use in angiogenesis (issued  April, 2010)
  • US 7,785,632. Thyroid hormone analogs and methods of use (angiogenesis) (filed September 5, 2004) (issued Aug. 31, 2010).
  • US National Phase Patent Application no. 11/920,910. Inhibitors of PGHS-2 transactivator activity (notice of allowance, November, 2010).

Pending

  • US 60/856,450. Thyroid hormone analogs and method of use (cancer) (filed November 2, 2006).
  • US  60/831,740. Thyroid hormone analog nanopolymer formation and methods of synthesis and use (filed July 17, 2006).
  • US  60/876,770. Arg-Gly-Asp Peptides and novel actions of thyroid hormone (filed December 22, 2006).  
  • US  11/786,723. Nanoparticle and polymer formulations of thyroid hormone analogs, antagonists and formulations thereof (filed April 11, 2007).
  • US  61/219,993. Radiosensitization by tetrac (filed June 24, 2009).
  • US  61/165,119. Combination treatment of cancer with cetuximab and tetrac (filed March 31,  2009).

Awards

  • American Thyroid Association, Distinguished Service Award
  • American College of Physicians, Laureate Award, New York Chapter
  • Alumni Achievement Award, Westminster College
  • Outstanding Teaching Award from medical student body, SUNY at Buffalo School of Medicine and Biomedical Sciences
  • White Coat Award from medical house staff, SUNY at Buffalo School of Medicine and Biomedical Sciences

Professional Organizations

  • Endocrine Society
  • American Thyroid Association
  • American Society for Biochemistry and Molecular Biology, Membership Committee 
  • American College of Physicians, Fellow
  • American Diabetes Association
  • Alpha Omega Alpha Alpha Omega Alpha Honor Medical Society
  • American Association for Cancer Research

National Organizations

Below is a partial listing:

  • American Thyroid Association, President, 1997-1998; multiple committees, through 2011
  • American Board of Internal Medicine, Board of Directors, 1993-1997; multiple committees through 2004
  • American College of Physicians, Governor, New York State, 1997-2001; multiple  committees through 2009; Mastership, 2004
  • Chernobyl Tissue Bank (CTB), European Commission (EU), Extramural Review Panel,  2010-
  • Endocrine Society, Self-Assessment (ESAP) Steering Committee, 2007-2012
  • Faculty of 1000 Medicine, U.S. Faculty Head, Endocrinology, 2007-

Professor of Pharmacy

Pharmaceutical Research Institute (PRI)

E-mail:  pdavis.ordwayst@gmail.com
Tel: (518) 694-7589