DENNIS M. PEFFLEY, JD, PHD
Department of Bio-Medical Sciences - Georgia
Assistant Professor of Physiology and Pharmacology


Contact

Email: dennispe@pcom.edu
Office: 678-225-7575

After completing his PhD in genetics at the Pennsylvania State University, Dr. Peffley did postdoctoral training in molecular biology at the University of Colorado School of Medicine in Denver, Colorado. His first faculty position was in the Department of Pharmacology at the University of Tennessee Health Sciences Center in Memphis, Tennessee. At this institution, Dr. Peffley obtained his first NIH grant that focused on cholesterol synthesis.

Dr. Peffley then moved to the Rosalind Franklin School of Medicine in North Chicago, Illinois where he was promoted to associate professor in the Department of Pharmacology and Molecular Biology. His research interests moved from cholesterol research to the dietary prevention of cancer. To support this research, Dr. Peffley received an NIH grant from the National Cancer Institute.

A promotion to full professor lead Dr. Peffley to the Kansas City University of Medicine and Bioscience in the Department of Pharmacology. At this institution he continued his research in dietary prevention of cancer as well as teaching pharmacology, genetics and biochemistry. While in Kansas City, Dr. Peffley finished his Juris Doctor in law at the University of Missouri Kansas City School of Law. He has also served as founding faculty at two medical schools including Edward Via College of Osteopathic Medicine and The University of South Carolina School of Medicine Greenville.

  • Education

    • Juniata College, BS, Biology
    • The Pennsylvania State University, Ph.D., Genetics
    • The University of Missouri Kansas City School of Law, J.D., Law
  • Courses

    • Pharmacology
    • Genetics
    • Biochemistry
  • Research

    Dr. Peffley's research interests focus on dietary prevention of cancer by plant-derived terpenes or isoprenoids derived from the plant mevalonate biosynthetic pathway. Terpenes have potent antitumor effects and it is believed that diets rich in plant products provide some degree of protection from cancer (chemopreventives). Research has established that terpene-mediated antitumor actions are due in part to suppression of the mechanistic target of rapamycin (mTOR). mTOR is a serine/threonine kinase belonging to the family of phosphatidyl-3-kinase (PI3K) related kinases (PIKK). The mTOR activity is elevated in many tumor cells and has been associated with elevated translation of proteins required for cell cycle regulation and other metabolic processes. Suppression of the mTOR pathway in tumor cells leads to cell death through autophagy.

  • Awards

    • Cora Louise Carson Award from the Tennessee Affiliate of the American Heart Association (In honor of receiving the highest research merit rating)
    • New Investigator Award - American Heart Association, Tennessee Affiliate
    • Travel Award ($500) from the Basic Science Council of the American Heart Association, presented to Jae Won Choi, a graduate student in my laboratory, for his presentation at the 65th Scientific Sessions of the American Heart Association (1993)
    • Travel Award ($500) from the Basic Science Council of the American Heart Association, presented to Robbie Buechler, a graduate student in my laboratory, for his presentation at the 71st Scientific Sessions of the American Heart Association (1998)
    • Travel Award ($500) presented to Seon H. Yuh, graduate student in my laboratory, for her poster presentation at the Aspen Lipid Conference (1998)
    • Grant preproposal on genistein/isoprenoid-mediated effects on prostate cancer submitted with Patricia Hentosh, Sc.D. to Soy Health Research Program selected as best proposal for $10,000 incentive award (2001)
    • Recipient of the University of Health Sciences Research Support Award (2002)
    • Recipient of the UHS Faculty Publication Award (2002)
    • 2nd Prize in the Nathan Burkan Memorial Competition (sponsored by the American Society of Composers, Authors and Publishers [ASCAP]) for paper entitled “Are Databases Adequately Protected by the 1976 Copyright Act in the Age of Bioinformatics?" (2003)
    • University of Missouri-Kansas City School of Law: Dean’s Honor List: Fall Semester 2004
    • Excellence Award in Molecular Medicine awarded at the Molecular Medicine: Applying Current and Emerging Technologies Conference, March 2008.
  • Publications

    • Nathaniel Tl, Williams-Hernandez A, Hunter LA, Liddy C, Peffley DM, Imeh-Nathaniel A. (2015) Tissue hypoxia during ischemic stroke: adaptive clues from hypoxia-tolerant animal models. Brain Res Bull. 114: 1-12.
    • Sundin T, Peffley DM, Hentosh P. (2013) Disruption of an hTERT-mTOR-RAPTOR protein complex by a phytochemical perillyl alcohol and rapamycin. Mol Cell Biochem. 375: 97-104.
    • Sundin, T, Peffley, D., Hentosh P. (2013) eIF4E-Overexpression imparts perillyl alcohol and rapamycin-mediated regulation of telomerase reverse transcriptase. Exp. Cell. Res. 319: 2103-12.
    • Sundin T, Peffley DM, Gauthier D, Hentosh P. (2012) The isoprenoid perillyl alcohol inhibits telomerase activity in prostate cancer cells. Biochimie. 9: 2639-48.
    • Peffley, D.M. and P. Hentosh (2012) Plant-derived isoprenoids mediate regulation of mTOR signaling in tumor cells. In “Natural compounds as inducers of cell death: Vol I”. (M. Diederich and K. Noworyta, eds.), pp 373 – 400. Springer Science+Business Media Dordrecht.S
    • Hentosh, P., Benjamin, T., Hall, L., Leap, S., Loescher, J., Poyner, E., Sundin, T., Whittle, M., Wilkinson, S. and Peffley, D.M. (2011) Xeroderma Pigmentosum Variant: Complementary molecular approaches to detect a 13 base pair deletion in the DNA polymerase eta gene. Experimental and Molecular Pathology. 91: 528-533.
    • Hentosh, P and D.M. Peffley (2010) The cladribine conundrum: deciphering the drug’s mechanism of action. Expert Opin Drug Metab Toxicol. 6: 75-81.
    • Peffley, D.M., C. Sharma, P. Hentosh, and R.D. Buechler (2007) Perillyl alcohol and genistein differentially regulate PKB/Akt and 4E-BP1 phosphorylation as well as eIF4E/eIF4G interactions in human tumor cells. Arch. Biochem. Biophys. 465:266-273.
    • Buechler, R. and D.M. Peffley (2004) Protooncogene/eukaryotic translation initiation factor (eIF) 4E attenuates mevalonate-mediated regulation of 3-hydroxy 3-methylglutaryl Coenzyme A (HMG-CoA) reductase synthesis. Molec. Carcinog. 41: 39-53.
    • Peffley, D.M. and A.K. Gayen (2003) Plant-derived monoterpenes suppress hamster kidney 3-hydroxy 3 -methylglutaryl coenzyme A reductase synthesis at the post-transcriptional level. J. Nutr. 133: 38 - 44.
    • Hentosh, P., S.H. Yuh, C.E. Elson, and D.M. Peffley (2001) Sterol-independent regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in tumor cells. Molec. Carcinog. 32: 154 - 166.
    • Mo, H., Peffley, D.M. and Elson, C.E. (1999) Targeting the action of isoprenoids and related phytochemicals to tumors. In "Nutritional Oncology" (D. Heber, G.L. Blackburn, and V.L.W. Go, eds.), pp. 379 - 391. Academic Press, San Diego.
    • Elson, C.E., Peffley, D., Hentosh, P. and Mo, H. (1999) Isoprenoid-mediated inhibition of mevalonate synthesis: Potential application to cancer. Proc. Soc. Exp. Biol. Med. 221: 294 - 311.
    • Mehtani, S., Q. Gong. J. Panella, S. Subbiah, D.M. Peffley, and A. Frankfater (1998) In vivo expression of an alternatively spliced human tumor message that encodes a truncated form of cathepsin B. J. Biol. Chem. 273: 13236 -13244.
    • Peffley, D.M., A.K. Gayen, and O. Morand (1998) Down-regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase mRNA levels and synthesis in Syrian hamster C100 cells by the oxidosqualene cyclase inhibitor [4'-(6-allyl-ethyl-amino-hexyloxy)-2'-fluoro-phenyl]-(4-bromophenyl)-methanone (Ro 48-8071): comparison to simvastatin. Biochem Pharm. 56: 439 - 449.
    • Peffley, D.M. and A.K. Gayen (1997) Inhibition of squalene synthase but not squalene cyclase prevents mevalonate-mediated suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase synthesis at a posttranscriptional level. Arch. Biochem. Biophys. 337: 251 - 260.
    • Gayen, A.K. and D.M. Peffley (1995) The length of 5'-untranslated leader sequences influences distribution of 3-hydroxy-3-methylglutaryl-coenzyme A reductase mRNA in polysomes: effects of lovastatin, oxysterols, and mevalonate. Arch. Bioch. Biophys 322: 475 - 485.
    • Peffley, D.M. and A.K. Gayen (1995) Mevalonate regulates polysome distribution and blocks translation-dependent suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase mRNA: relationship to translational control. Somatic Cell Molec. Genet. 21: 189 - 204.
    • Choi, J.W. and D.M. Peffley (1995) 3'-untranslated sequences mediate posttranscriptional regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase mRNA by 25-hydroxycholesterol. Biochem. J. 307: 233 - 238.
    • Choi, J., E. Lundquist, and D.M. Peffley (1993) Inhibition of protein synthesis in baby hamster kidney cells blocks oxysterol-mediated suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase mRNA at a post-transcriptional level. Biochem. J. 296: 859 -866.
    • Pullen, G.L., C.P. Barsano, D.M. Peffley, and K.R. Singh. (1994) The appearance, distribution, and longevity of receptor-[125I]T3 complexes within the nuclei of isolated rat hepatocytes. Thyroid 4: 305 - 312.
    • Peffley, D.M. (1992) Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase synthesis in Syrian Hamster C100 cells by mevinolin, 25-hydroxycholesterol and mevalonate: the role of posttranscriptional control. Somatic Cell Molec. Genet. 18: 19-32.
    • Peffley, D.M., J. Miyake, S. Leonard, C. von Gunten, and M. Sinensky (1988) Further characterization of a somatic cell mutant defective in the regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Somatic Cell Molec. Genet. 14: 527-539.
    • von Gunten, C., J. Leighton, D.M. Peffley, and M. Sinensky (1987) Progress in understanding mechanisms of the serum cholesterol risk factor in atherosclerosis. Somat. Cell Molec. Genet. 13: 469-477.
    • Dingermann, T., W. Bertling, T. Brechner, K. Nerke, D.M. Peffley and M. Sogin (1986) Structure of two tRNA genes from Dictyostelium discoideum. Nucleic Acids Res. 14: 1127
    • Peffley, D.M. and M. Sinensky (1985) Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase synthesis by a non-sterol mevalonate-derived product in Mev-1 cells: apparent translational control. J. Biol. Chem. 260: 9949-9952.
    • Hahn, W.E., N. Chaudhari, L. Beck, K. Wilber, and D. Peffley (1983) Genetic expression and postnatal development of the brain: some characteristics of nonpolyadenylated mRNAs. Cold Spring Harbor Symp. Quant. Biol. 48: 465-475.
    • Peffley, D.M. and M.L. Sogin (1981) A putative tRNATrp gene cloned from Dictyostelium discoideum: its nucleotide sequence and association with repetitive deoxyribonucleic acid. Biochem. 20: 4015-4021.

    Technical Publications:

    • Christiansen JR, Annas GJ, Bose HP, Kalay HN, Markey ML, Pahi, S, Peffley DM, Perkins NL, Sokolowski S, Thush M and Dowdell T. Comments on the Precision Medicine Initiative: Proposed Privacy and Trust Principles. Prepared by a working group of eHealth, Privacy, and Security Interest Group of the Health Law Section (American Bar Association Working Group) and Submitted to the White House Office of Science and Technology, August 4, 2015.
    • Peffley DM. Cancer Chemotherapy. Patient-Oriented Problem Solving (POPS) Exercises. 2015 Revision Author.
  • Memberships

    • American Association of Biochemistry and Molecular Biology
    • American Society for Pharmacology and Experimental Therapeutics
    • Missouri Bar Association
    • District of Columbia Bar Association
    • American Bar Association
  • Grants

    • Multi-investigator grant (ODU Internal Funding) – Modeling and Testing Complex Interactions of Chromatin-associated Proteins in Cancer Cells – Total Direct Funding, $78,000 (Co-principal Investigator).
    • Breeden Foundation  A New Combination Therapy for Cancer Treatment – Subnanosecond Electrical Pulse Treatment of Electro-Sensitized Tumors – Total Direct Funding, $35,000 (Co-investigator)
    • National Cancer Institute (RO1 CA81756)  Modulation of Mevalonate Synthesis by Dietary Isoprenoids: 04/01/99-03/30/06, Total Direct Funding, $621,566: Principal Investigator
    • National Cancer Institute (CA81756S), Minority Faculty Supplement
    • Kansas City Area Life Sciences Institute Research Development Grant, Proteomic Analysis of Isoprenoid and Isoflavone-mediated Regulation of Cap-dependent and Cap-independent Protein Translation in Human Prostate Tumor Cells, December 1, 2003-November, 2004; Principal Investigator, Total Direct Funding, $25,000.
    • American Health Assistance Foundation, The Translational Control of HMG-CoA Reductase in Mammalian Cells: April 01, 1988-March 31, 1989, Total Direct Funding, $25,000: Principal Investigator
    • American Heart Association – Tennessee Affiliate, The Translational Control of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase in Mammalian Cells: 7/01/88-6/30/90, Total Direct Funding, $55,000: Principal Investigator
    • American Health Assistance Foundation, Regulation of HMG-CoA Reductase Gene Expression: 04/01/89-06/30/90, Total Direct Funding, $25,000: Principal Investigator
    • American Heart Association (National Chapter), Regulation of HMG-CoA Reductase by Oxysterols and Mevalonate: 7/01/90-6/30/93, Total Direct Funding- $105,000 (awarded but declined): Principal Investigator
    • National Heart, Lung and Blood Institute (RO1 HL44006), Regulation of HMG-CoA Reductase in Mammalian Cells: 1/01/90-12/31/96, Total Direct Funding – $441,417: Principal Investigator
    • National Heart, Lung, and Blood Institute (HL 44006-O4S1), Minority Graduate Research Assistant Supplement, $49,000
    • American Heart Association (National Chapter), Regulation of 3 Hydroxy 3 methylglutaryl Coenzyme A Reductase by Mevalonate and Oxysterols: 07/01/96 – 06/30/00, Total Direct Funding, $120,000: Principal Investigator
    • National Cancer Institute (RO1 CA73418), Cancer Prevention by Isoprenoid Constituents of Plants: 9/01/96-8/31/00, Total Direct Funding, $250,000: Co-Investigator
    • National Cancer Institute (R03 CA72527) - Dietary Isoprenoid Regulation of Growth Related Genes: 12/01/96-11/30/99, Total Direct Funding, $50,000: Principal Investigator