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. |
