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Abdul A. Waheed, Ph.D.

Portait Photo of Abdul Waheed
HIV DRP Retroviral Replication Laboratory
Virus-Cell Interaction Section
Staff Scientist
Center for Cancer Research
National Cancer Institute
Building 535, Room 108B
P.O. Box B
Frederick, MD 21702-1201
Phone:  
301-846-1739
Fax:  
301-846-6777
E-Mail:  
waheedab@mail.nih.gov

Biography

Dr. Abdul Waheed obtained his M.Sc. from Jawaharlal Nehru Technological University, Hyderabad, India, in 1993. He received his Ph.D. in Membrane Biochemistry from the University of the Ryukyus, Okinawa, Japan, in 1999. As a postdoctoral fellow under the guidance of Prof. Ohno-Iwashita at Tokyo Metropolitan Institute of Gerontology, Tokyo, Dr. Waheed showed the specific binding of theta-toxin (perfringolysin O) to cholesterol in the lipid rafts. He joined the National Institute of Diabetes and Digestive and Kidney Diseases in 2001, where he worked with Dr. Teresa Jones on the role of lipid rafts in G-protein signaling. In 2003 he joined Dr. Eric Freed's lab in the Virus-Cell Interaction Section, HIV Drug Resistance Program, NCI, where he was promoted to Staff Scientist in 2006. Dr. Waheed was appointed as Lead Guest Editor for a special issue of Molecular Biology International on Host-Pathogen Interactions of Retroviruses in 2012. He also serves as an Editorial Board member of Journal of Venereology and as a member of the Editorial Board (Virology domain) of The Scientific World Journal.

Research

Vpu Counteraction of Host Restriction Factor Tetherin

There are several host restriction factors that protect mammalian cells from viral infection. Tetherin (also known as CD317 or BST2) is an interferon-inducible type II transmembrane protein that prevents the release of a variety of enveloped viruses by directly tethering the virions on the cell surface. Viruses have evolved mechanisms to counteract these host restriction factors. HIV-1 accessory protein Vpu, an 81-amino-acid integral membrane protein, counteracts tetherin activity and enhances virus particle release by downregulation of tetherin. The antagonism of human tetherin by Vpu is associated with proteasome- and lysosomal-mediated degradation. The Vpu-mediated degradation of tetherin is cell type specific, as our recent studies show Vpu markedly increases tetherin expression in agm kidney (COS) cells, apparently by sequestering it in an internal compartment that bears lysosomal markers. To further understand the mechanism of Vpu-mediated tetherin regulation, we carried out yeast two-hybrid screening using full-length Vpu as bait to identify Vpu-interacting proteins. We have identified five Vpu-interacting proteins and are currently studying the role of these Vpu-interacting proteins in tetherin regulation.

High-Throughput Screening for Small-Molecule Inhibitors of HIV-1 Budding

Budding of viruses from the plasma membrane of infected cells is required for spreading infections, and expression of Pr55Gag is necessary and sufficient for the production of virus-like particles. For HIV-1, the budding process requires a direct interaction between the Pro-Thr-Ala-Pro (PTAP) motif in the p6 domain of Gag and the cellular endosomal sorting protein Tsg101. Mutation of the PTAP motif or depletion of Tsg101 severely disrupts HIV-1 budding. Thus, the Gag-Tsg101 interaction is essential for efficient HIV-1 release; disruption of this interaction could potentially serve as a therapeutic target for the development of novel drugs against HIV-1. We have developed a fluorescence polarization (FP)-based assay to monitor the interaction between PTAP-containing peptide and the ubiquitin E2 variant (UEV) domain of Tsg101. Using this PTAP-Tsg101 binding assay, we performed quantitative high-throughput screening (qHTS) of ~380,000 compounds from the Molecular Libraries Small Molecule Repository (MLSMR) and picked about 100 active compounds that inhibit PTAP-Tsg101 interaction. We are currently testing the activity of these compounds in cell-based assays to identify potential inhibitors of HIV-1 budding.

This page was last updated on 3/17/2014.