Emory Pathology Research Lab Page: Dr. William Lewis
 

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  • Laboratory of:

    William Lewis, MD
    Pathology & Laboratory Medicine
    Emory University School of Medicine
    Woodruff Memorial Research Building
    101 Woodruff Circle, 7th Floor
    Atlanta, GA 30322, USA

    Dr. William Lewis' Lab Team

    Mitochondrial (mt) DNA replication in disease:
    HIV/AIDS, congestive heart failure, hepatitis, renal failure


    William Lewis, MD Dr. William Lewis Lewis Lab: Figure 1

    Proposed mechanism of nucleoside analog toxicity to mtDNA

    Proposed mechanism of nucleoside analog toxicity to mtDNA (small double circle), with attached DNA pol (in block) in which analog triphosphates serve as inhibitors of mtDNA replication (panel A, B). Details of interaction of mtDNA with DNA pol : Fialuridine (FIAU) -TP serves as an alternate substrate for dTTP with DNA pol and is incorporated (inserted into mtDNA as F) into the nascent chain because it possesses a 3'-OH. Panel C, D: In contrast, analog triphosphates (like AZT-TP) that lack 3'-OH compete with dTTP as substrates of DNA pol . Additionally, the latter analog monophosphates terminate mtDNA synthesis (inserted into DNA as Z) because nascent chain cannot be extended unless AZT is recognized as erroneous. Oxidative stress and mtDNA mutation are included in the "mitochondrial dysfunction hypothesis" 8,9,56

    Active Grants:

    ·2R01HL 059798-06 (Lewis) 07/01/1997-06/30/2010
    NHLBI/NIH
    Cardiomyopathy in AIDS. At present, there is an amended application under review. This application's initial goal was to define TG transgenic effects of selected HIV gene products and mammalian DNA-pol-? in AIDS CM.
    ·1R01 HL079867-01 (Lewis) 09/01/06-08/31/11
    Acquired mtDNA Depletion and Nucleoside Reverse Transcriptase Inhibitors
    Goals: This project dissects the roles of enzymes involved in the second phosphorylation of NRTIs to diphosphates. Using transgenic mice with conditional, targeted expression, overexpression of native and mutant TMPK is evaluated in NRTI treatment protocols

    Recent Funding:

    ·1R01 HL 072707 (Lewis) 9/01/02-08/31/07
    NHLBI/NIH
    Nucleoside Analogs, Mitochondria, and AIDS Cardiomyopathy
    Goals: To define mechanisms of mitochondrial defects of NRTIs in cardiac mitochondria. This model examines effects of NRTIs on HIV Tat, Vpr, Vpu, Nef and cardiac myocyte apoptosis in HIV. Competitive continuation submitted.
    ·CFAR03 Small Grant Award (Kohler) 09/01/06-08/31/07
    AIDS Nephropathy and Antiretroviral (Tenofovir) Renal Toxicity
    Goals: This project evaluates mechanisms of renal tubular epithelial mitochondrial damage associated with tenofovir disoproxil fumare (TDF, Viread) treatment.

    Laboratory Members:

    James J. Kohler, PhD
    Instructor, Pathology & Laboratory Medicine
    Rm 7126 WMRB
    404-712-9013

    Seyed H. Hosseini, PhD
    Research Specialist Supervisor
    Rm 7120 WMRB
    404-727-1258

    Ioan Cucoranu, MD
    Post-Doctoral Fellow
    Rm 7231 WMRB

    Earl Fields, MS
    Research Specialist
    Lab 7205 WMRB

    Elgin Green, MS
    Research Specialist Lead
    Lab 7207 WMRB

    Chad Haase, BS
    Research Specialist Lead
    Lab 7127 WMRB

    Amy Hoying Brandt, MS
    Research Specialist Lead
    Lab 7207 WMRB

    David Johnson, BS
    Research Specialist
    Lab 7207 WMRB

    Rodney Russ
    Animal Technician III
    Lab 7127 WMRB

    Bree Wittich, MS
    Research Specialist Lead
    Laba 7205 WMRB