Profile of a Pathology Faculty Member

Pathology Faculty Photo

William Lewis, MD

Cardiovascular Biology
HIV Pathogenesis
Cardiac Pathology

Professor
Pathology & Laboratory Medicine

Other Appointments/Positions

  • Professor (tenured), Pathology, Director, Cardiovascular Pathology, Emory University School of Medicine, Atlanta GA

Pathology Division(s):
Anatomic Pathology
Experimental Pathology
Email Address:   wlewis@emory.edu

Education:

B.S.   University of Michigan, Ann Arbor, MI (Zoology), 1968 - 1971
M.D.   Boston University School of Medicine (M.D.), 1971 - 1975

Research Interests:

- Mitochondrial DNA replication in disease: AIDS, congestive heart failure, hepatitis, renal failure One classic biological teaching is that mitochondria are the "powerhouses of the cell", particularly in tissues that require significant energy, like heart, liver and muscle. The focus of the Lewis lab is the diverse effects of toxins on mitochondria structure and function. The primary focus is the untoward mitochondrial effects of a class of drugs called nucleoside reverse transcriptase inhibitors (NRTI) used to treat HIV infection, that are known to inhibit mitochondrial (mt-) DNA replication in vitro. These drugs are toxic to various tissues including heart, skeletal muscle, liver and kidney. Our overall goals are to (1) define the molecular mechanisms of how NRTIs change the abundance of precursors for mtDNA replication in vivo (2) define the effects of active NRTI triphosphates on the mitochondrial replicon in vivo (3) define the effects of specific polymerase mutants on the replication of mtDNA in vivo and (4) define the effects of the mtDNA template itself on its replication in vivo. The approach taken employs tissue specific targeting of genes involved in the processes and evaluation of structural and functional defects that result using state of the art biochemical, molecular, physiological, and pathological approaches. Conditional, tissue specific targeting also is addressed. The direct clinical benefits of these studies are twofold (1) the toxicity of important compounds is defined so that better therapeutics can be designed and administered and (2) mechanisms of organ specific changes in HIV disease and related illnesses are elucidated.

Clinical Focus:

Cardiovascular Disease, Heart Transplantation, HIV effects on the cardiovascular system

Honors / Awards:

  • Alpha Omega Alpha

    , 2006

  • Chartered Member, Contractility Congestive heart failure SS NIH, CSR, 2003-2007
  • Clinician-Investigator Award, 2001-2004
  • Honorary, Member, Italian Society, 2000
  • Award of Merit, Society for Cardiology, 1995
  • Mentor, Commonwealth Fund Scho, 1989-1990
  • Mount Sinai Journal of Medicine, 1984-1985
  • Sigma XI

    , 1984

  • Recipient, Clinical Investigation, 1982-1987

Specialty Boards:

  • Diplomate Anatomic and Clinical Pathology

Selected/Most Recent Publications:

Click here to view all publications

Published and Accepted Research Articles -

  • JJ Kohler, SH Hosseini, E Green, A Hoying-Brandt, CP Haase, R Russ, J Srivastava, K Ivey, T Ludaway, V Kapoor, R Santoianni, A Saada, O Elpeleg and W Lewis. "Cardiac targeted transgenic mutant mitochondrial enzymes: mtDNA antiretroviral toxicity and cardiomyopathy". Cardiovasc Toxicol 8(2):57-69. (2008). http://www.ncbi.nlm.nih.gov/pubmed/18446447
  • Kohler JJ, Hosseini SH, and Lewis W. "Mitochondrial DNA impairment in nucleoside reverse transcriptase inhibitor-associated cardiomyopathy." Chem Res Toxicol. May; 21(5):990-6, (2008). http://www.ncbi.nlm.nih.gov/pubmed/18393452
  • Kohler, J.J. and W. Lewis, "A brief overview of mechanisms of mitochondrial toxicity from NRTIs. " Environmental & Molecular Mutagenesis, 48(3-4):p166-72, (2007). http://www.ncbi.nlm.nih.gov/pubmed/16758472
  • SH Hosseini, JJ Kohler, CP Haase, N Tioleco, T Stuart, E Keebaugh, T Ludaway, R Russ, R Long, L Wang S Eriksson and W Lewis. "Targeted transgenic overexpression of mitochondrial thymidine kinase (TK2) regulates mtDNA and mitochondrial polypeptide abundance". AmJPath 170:865-874, (2007). http://www.ncbi.nlm.nih.gov/pubmed/17322372
  • Lewis,W., et al., "Decreased mtDNA, oxidative stress, cardiomyopathy, and death from transgenic cardiac targeted human mutant polymerase gamma." Lab Investigation, 87(4):p. 326-35, (2007). http://www.ncbi.nlm.nih.gov/pubmed/17310215
  • Lewis, William, Kohler, James J., Hosseini, Seyed H, Haase, Chad P., Copeland, William C., Bienstock, Rachelle, J., Ludaway, Tomika, McNaught, Jamie, Russ, Rodney, Stuart, Tamie and Santioianni, Robert. "Antiretroviral nucleosides, deoxynucleotide carrier and mitochondrial DNA: evidence supporting the DNA pol gamma hypothesis" AIDS 20: 675-684.(2006). http://www.ncbi.nlm.nih.gov/pubmed/16514297
  • Lewis, William "Nucleoside reverse transcriptase inhibitors, mitochondrial DNA and AIDS Therapy" Antiviral Therapy 10: (Suppl 2) M13-M27. (2005). http://www.ncbi.nlm.nih.gov/pubmed/16152703
  • Lewis, William, Yoon K. Miller, Chad P. Haase, Tomika Ludaway, Jamie McNaught, Rodney Russ, Jeffrey Steltzer, Andrew Folpe, Robert Long and John Oshinski. "HIV viral protein R causes atrial cardiomyocyte mitosis, mesenchymal tumor, dysrhythmias, and heart failure." Laboratory Investigation 85:182-192 (2005). http://www.ncbi.nlm.nih.gov/pubmed/15608661
  • Lewis, William, Haase, Chad P., Miller, Yoon Kim,; Ferguson, Brandy; Ludaway, Tomika; McNaught, Jamie; Russ, Rodney; Steltzer, Jeffrey; Long, Robert; Fieramonte, Giuseppe, and Palmieri, Ferdinando: "Transgenic expression of the deoxynucleotide carrier causes mitochondrial damage that is enhanced by NRTIs for AIDS" Laboratory Investigation, 85:972-981. (2005). http://www.ncbi.nlm.nih.gov/pubmed/15951836
  • Cheng, Lihong, Ding, Guoliang, Qin, Qianhong, Huang, Yao, Lewis, William, He, Nu, Evans, Ronald M., Schneider, Michael D., Brako, Florence A., Xiao, Yan Chen, Yuqing E. and Yang, Qinglin. "Cardiomyocyte-restricted peroxisome proliferator-activated receptor d perturbs myocardial fatty acid oxidation and leads to cardiomyopathy." Nature Medicine 10: 1245-1250. (2004). http://www.ncbi.nlm.nih.gov/pubmed/15475963
  • Lewis, William: "Cardiomyopathy, nucleoside reverse transcriptase inhibitors and mitochondria are linked through AIDS and its therapy." Mitochondrion 4:141-152. (2004). http://www.ncbi.nlm.nih.gov/pubmed/16120379
  • Velsor, Leonard W., Kovacevic, Miro, Goldstein, Mark, Leitner, Heather M., Lewis, William, and Day, Brian J. "Mitochondrial Oxidative Stress in Human Hepatoma Cells Exposed to Stavudine". Toxicology and Applied Pharmacology. (2004). http://www.ncbi.nlm.nih.gov/pubmed/15289086
  • Day, Brian J. and Lewis, William: "Oxidative Stress in NRTI-Induced Toxicity: Evidence from Clinical Experience and Experiments in vitro and in vivo." Cardiovascular Toxicology 4:207-216. (2004). http://www.ncbi.nlm.nih.gov/pubmed/15470269
  • Lewis, William: "Mitochondrial dysfunction and nucleoside reverse transcriptase inhibitor therapy: experimental clarifications and persistent clinical questions." Antiviral Res 58:189-197. (2003). http://www.ncbi.nlm.nih.gov/pubmed/14526384
  • Sutliff; Roy L., Haase, Chad, Russ, Rodney, Hoit, Brian D., Morris, Randal, Norman, Andrew B., and Lewis, William: "Cocaine increases mortality and cardiac mass in a murine transgenic model of Acquired Immune Deficiency Syndrome". Laboratory Investigation 83:983-989. (2003). http://www.ncbi.nlm.nih.gov/pubmed/12861038

Book Chapters -

  • Lewis, William, Dialogues in Cardiovascular Medicine; Vol. 12. No 1, 2007 "How does HIV/AIDS cause cardiomyopathy?" p. 27-36; (2007).
  • Lewis, William and Currie, Peter, F: "HIV/AIDS and the Cardiovascular System" in Hurst's: The Heart, Chapter 92 pp2118-2131.
  • Lewis, William, Reverse Transcriptase Inhibitors in HIV/AIDS Therapy, Humana Press, Inc.; Chapter 9, "Mitochondrial Dysfunction and Nucleoside Reverse Transcriptase Inhibitor Therapy" p. 267-279, (2006)
  • Lewis, William: "Toxic Heart Diseases" in Silver's Cardiovascular Pathology 3rd Edition, A gotlieb, F. Schoen, M. Silver, Editors Saunders, Philadelphia.
  • Lewis, William: "Clinical Laboratory Analysis of the Genetically Manipulataed Mouse" in "Cardiovascular Physiology in the Genetically Engineered Mouse" 2nd Edition, R. A. Walsh and B. D. Hoit, Editors Kluwer, Norwell, MA. pp 303-317.
  • Lewis, William "Pathologic changes in hearts of patients with AIDS in Cardiology in AIDS, S. Lipshultz, Editor; Chapman and Hall, New York
  • Lewis, William: "Mitochondrial toxicity of antiviral nucleosides used in AIDS: insights into mitochondrial cardiac and skeletal defects and changes in other tissues rich in mitochondria" in Cardiology in AIDS, S Lipshultz, Editor; Chapman and Hall, New York