• Associate Professor of Microbiology & Immunology
• Associate Member of the Walther Oncology Center

• Campus Address: MS 415 C
• Telephone: (317) 278-3698
• E-mail: galkhati@iupui.edu

Hal Broxmeyer named distinguished professor at IUSM (click here for more details)

Janice Blum discusses Immunology & Infectious Diseases (click here for more details)

Training:
• B.Sc., 1979: Pahlavi (Shiraz) University, Shiraz, Iran
• Ph.D., 1988: McGill University, Montreal, Quebec
• PostDoctoral, 1988-1990: Mammalian Cell Genetics Group,
  Genetic Engineering Section, Biotechnology Research Institute,
  National Research Council Canada, Montréal, Québec, Canada
• PostDoctoral, 1990-1993 Department of Molecular Immunology &
  Neurobiology, Mount Sinai Hospital Research Institute, Toronto, Canada
• PostDoctoral, 1995-1998 Laboratory of Viral Diseases, NIAID, National
  Institutes of Health, Bethesda, Maryland, Supervisor: Dr. Ed Berger.

Summary of the focus of the research of Dr. Alkhatib:
Studies in this laboratory are focused on the molecular determinants involved in retrovirus infection. Our research is directed at understanding how interactions of HIV-1 (AIDS virus) and HTLV-1 (human T cell leukemia virus) envelope glycoproteins with host cell receptors lead to membrane fusion and viral entry. Analyzing the mechanisms of retroviral entry is a key step in the development of anti-viral agents.

Description and summary of research focus of the laboratory:
The AIDS project focuses on the mechanisms of genetic resistance to HIV-1 infection. HIV-1 requires CD4 and a coreceptor (CCR5 or CXCR4) for entry into susceptible host cells. CCR5 and CXCR4 belong to the family of seven transmebrane spanner proteins. A naturally occurring frame-shift mutation caused by a 32 base pair deletion (D32) in the human CCR5 gene is highly associated with protection against HIV-1. CCR5D32 is a loss-of-function mutation that abolishes cell surface expression of the HIV coreceptor CCR5 and provides genetic resistance to HIV-1 infection and disease progression. Our results suggest that at least two distinct mechanisms may account for genetic resistance to HIV-1 conferred by CCR5D32: loss of wild type CCR5 surface expression, and generation of CCR5D32 truncated protein, which functions as a scavenger of both CCR5 and CXCR4. Understanding how CCR5D32 interacts with the HIV coreceptors will lead to novel findings concerning coreceptor structure-function that may be utilized for the design of drugs that mimic CCR5D32 activity.  

We employed a functional cDNA screening strategy to isolate the erythrocyte glucose transporter protein (GLUT-1) as an obligate receptor for HTLV-1.   Studies are underway to analyze the molecular determinants involved in HTLV-1 tropism and infection. The GLUT-1 receptor is a membrane multispanner protein that crosses the plasme membrane 12 times. The common use by HIV-1 and HTLV-1 of these membrane multispanning proteins may lead to the identification of common retroviral entry mechanisms and may lead to design of drugs that inhibit retroviral entry.

Publications
Agrawal, L., and Alkhatib, G.   2001.    Chemokine receptors:   Emerging opportunities for new anti-HIV therapies, Exp. Opin. Ther. Targets 5(3): 303-326.

Agrawal, L., VanHorn-Ali, and Alkhatib G.   2002.   Multiple factors are involved in HIV coreceptor usage as determined by CCL22 (MDC)/CCR4 interaction in peripheral blood mononuclear cells (PBMCs).   Journal of Leukocyte Biology 72:1063-1074.

Agrawal, L., VanHorn-Ali, Berger, EA and Alkhatib G.   2004. Specific Inhibition of HIV-1 Coreceptor Activity by Synthetic Peptides Corresponding to the Predicted Extracellular Loops of CCR5.   BLOOD 103(4): 1211-1217.

Agrawal, L., Lu, X., Qingwen, J., VanHorn-Ali, Z., Nicolescu, IV., David H. McDermott, Murphy, P., and Alkhatib G.   2004. Role For CCR5D32 Protein In Resistance To R5, R5X4, and X4 HIV-1 In Primary CD4+ Cells.   Journal of Virology 78 (5): 2277-2287.

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