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Faculty
 David
I. Dorsky
Associate Professor of Medicine
Division of Infectious Diseases
dorsky@nso2.uchc.edu
Areas of Interest:
Anti-herpesvirus and anti-HIV chemotherapy mechanisms. The
biology and biochemistry of the heterodimeric herpesvirus DNA
polymerases have been studied through the functional analysis of
heterologously expressed site-directed mutants. We have identified and
continue to study functional domains of the polymerase accessory protein
BMRF1 involved in nuclear localization, phosphorylation, dsDNA-binding,
polymerase processivity, and functional interaction with the BZLF-1
lytic origin-binding protein.
An HIV-1 LTR-GFP retrovector was constructed to develop indicator
cell assays for HIV based on the activation of HIV-1 LTR-driven GFP gene
expression by the viral tat gene product. The indicator cell assay is
being used to study interactions of the antiviral drug ribavirin with
antiretroviral drugs, to screen candidate antiviral agents, and to
develop a method for the recovery of primary clinical isolates.
Gene Transfer and Bioengineering. The Center for Molecular
Tissue Engineering at UCONN Health Center is working to overcome the
problem of biofouling in the development of an implantable glucose
biosensor through the induction of neovascularization. Gene transfer
strategies involving adenovectors and retrovectors are being employed to
test the effects of neovascularization on implanted sensor function in
animal models.
Antigen Presentation. Gene transfer is being used to study the
T cell response to genetically engineered and matured dendritic cells
(DC), a type of antigen presenting cell. Adenovectors and retrovectors
are used to express melanoma tumor-associated antigens altered by
protein trafficking signals in DC to study the generation of CTL and
CD4+ responses to specific epitopes. In particular, we are studying
cross-presentation of souble antigens mediated by the protein
translocation domain of HSV VP22 protein.
Selected Publications:
Klueh U, Dorsky DI, Kreutzer DL. (2004). Enhancement of implantable
glucose sensor function in vivo using VEGF gene transfer-induced
neovascularization. Biomaterials. In press.
Mehrotra S, Chhabra A, Chakroborty A, Chattopadhyay, Stevens R,
Zengou R, Mathias C, Butterfield LH, Dorsky DI, Economou JS, Mukherji B,
Chakraborty NG. (2004) Antigen presentation by MART-1 adenovirus
transduced IL-10 polarized human monocyte derived dendritic cells.
Immunology, 113:472-81.
Mehrotra S, Stevens R, Zengou R, Chakraborty NG, Butterfield LH,
Economou JS, Dorsky DI, Mukherji B. (2004) Regulation of melanoma
epitope specific cytolytic T lymphocyte response by dendritic cells, in
vitro. Cancer Research 2003; 63:5607-5614.
Chhabra AC, Mehrotra S, Chakraborty NG, Mukherji B, Dorsky, DI.
(2004). Cross-presentation of a tumor-associated-but-self-antigen
delivered to dendritic cells by intercellular spreading. European
Journal of Immunology. Journal of Immunology, 34:2824-2833.
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