Lab Research Focus
The Program in Epidemiology of Infection and Immunity and its laboratory, under the direction of Dr. James Tang, applies the combined disciplines of molecular genetics and epidemiology to examine how human gene variations determine the occurrence and outcome of infectious and other diseases of immunity. In individuals from populations carefully selected for their epidemiologic relevance, standard manual DNA amplification techniques as well as automated sequencing protocols are employed to produce profiles of genetic polymorphisms in the human major histocompatibility complex (HLA), chemokine receptor (CCR), tumor necrosis factor (TNF) and other genetic systems. Efforts have concentrated on HIV-1 infection but also include ongoing and planned studies of KSHV (HHV-8), mycobacterial, and hepatitis C virus infections and AIDS-associated lymphoma. These systems represent opportunities for studying gene sequence effects at the population and the molecular level. Examples of specific projects include:
-HIV Infection. Our early work demonstrated the strong influence of multiple combinations of polymorphic markers in the HLA region on the outcome of HIV-1 infection. Subsequent studies have identified chemokine receptor variants that determine both acquisition and progression of infection. Our Program is now engaged in a detailed exploration of the respective roles of HLA genes for transporters (TAP), the chemokine receptors variants and other markers in Caucasians of European origin and black Africans in order to quantify their effects on the development of infection and immunodeficiency.
- Disseminated mycobacterium avium complex (DMAC) infection. Previous indications that certain HLA class II markers are associated with tuberculosis and leprosy have suggested their role in determining the nature and severity of mycobacterial infection in general. We have found one class II haplotype associated with DMAC. Efforts to examine the role of HLA and other genes more comprehensively are underway in a large group of DMAC cases and unaffected control subjects from a cohort of homosexual men with HIV infection.
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