Research Interests Research in our laboratory uses a multidisciplinary approach involving biochemistry, biophysics, chemistry, molecular biology and molecular virology in a variety of projects related to HIV/AIDS: · Studies of wild type and drug resistant mutant HIV reverse transcriptase (RT) structure and function. These include mechanistic analyses of the phenotypes arising from different mutations associated with resistance to nucleoside RT inhibitors, especially mutations associated with multidrug resistance, and the role of multiple mutations in resistance to tight-binding nonnucleoside RT inhibitors. · Development of new antiviral agents against novel HIV targets. Our primary focus is on the identification and characterization of “drug-like” compounds that inhibit HIV RT-associated ribonuclease H activity. · Evaluation of nonucleoside RT inhibitors for use in topical microbicide formulations to prevent sexual transmission of HIV. In addition to these HIV-related research projects, the laboratory is also involved in the development of new antisense oligonucleotide technologies. These studies focus on the role of nucleotide sugar conformation and flexibility in antisense action, especially in the ability of antisense to elicit ribonuclease H degradation of target mRNA. Techniques: Site-specific mutagenesis, transient (pre-steady state) kinetic analysis of enzyme function, biochemical probes of protein structure and function, molecular modeling of drug-receptor interactions, cell and virus culture, antiviral drug susceptibility assays, development and characterization of HIV resistance to novel antiviral agents.   Selected Publications Garforth SJ, Parniak MA, Prasad VR. Utilization of a deoxynucleoside diphosphate substrate by HIV reverse transcriptase. PLoS ONE. 2008 Apr 30;3(4):e2074. Ilina T, Parniak MA. Inhibitors of HIV-1 reverse transcriptase. Adv Pharmacol. 2008;56:121-67. Review. No abstract available. Han Q, Sarafianos SG, Arnold E, Parniak MA, Gaffney BL, Jones RA. Synthesis of AZTpSpCX2ppSA and AZTpSpCX2ppSAZT: hydrolysis-resistant potential inhibitors of the AZT excision reaction of HIV-1 RT. Org Lett. 2007 Dec 6;9(25):5243-6. Patton DL, Sweeney YT, Balkus JE, Rohan LC, Moncla BJ, Parniak MA, Hillier SL. Preclinical safety assessments of UC781 anti-human immunodeficiency virus topical microbicide formulations.Antimicrob Agents Chemother. 2007 May;51(5):1608-15. Dharmasena S, Pongracz Z, Arnold E, Sarafianos SG, Parniak MA. 3'-Azido-3'-deoxythymidine-(5')-tetraphospho-(5')-adenosine, the product of ATP-mediated excision of chain-terminating AZTMP, is a potent chain-terminating substrate for HIV-1 reverse transcriptase. Biochemistry. 2007 Jan 23;46(3):828-36. Complete Publication Listing   Grant Support NIH: HIV RNase H natural product inhibitors. Role: Principal Investigator NIH: Bisphosphonate inhibitors of HIV NRTI excision. Role: Principal Investigator NIH: Chain terminator excision in HIV drug resistance. Role: Principal Investigator NIH: Development of NNRTI’s as combination microbicides. (PI: Hillier) Role: Co-Director   Other Links Microbiology and Molecular Genetics University of Pittsburgh

Michael A Parniak, Ph.D., Professor Office:  W1142 BSTWR Lab: BSTWR W1116, W1117, W1109A Phone: 412-648-8884 Fax: 412-648-9653 map167@pitt.edu   Academic Affiliations Medicine (primary) Microbiology and Molecular Genetics Director, Molecular Virology & Microbiology Graduate Training Program   Education 1972 B.S. University of Waterloo 1978 Ph.D. University of Waterloo 1978 - 1982 Post-doc NIH   Lab Personnel Research Associates: Sanjeewa Dharmasena, PhD. Jason Newman, Ph.D. Postdoctoral Fellow: Tatiana Ilina, Ph.D. Laboratory Manager/Research Specialist IV: Eva Nagy Research Specialists III: Lena Miller, Ph.D.