Physician Profile

David I. Dorsky, M.D., Ph.D.

Associate Professor of Medicine
Division of Infectious Diseases
Overview:

1975 B.A. in Biochemistry, Brandeis University
1982 M.D. Harvard Medical School
1982 Ph.D. in Experimental Pathology, Harvard University
1982-1985 Residency in Internal Medicine, Beth Israel Hospital, Boston
1985-1988 Fellowship in Infectious Diseases, Beth Israel-Brigham and Women's Hospital, Boston
1988-1989 Instructor in Medicine, Harvard Medical School, Beth Israel Hospital, Boston
1989-2007 Assistant Professor of Medicine, Division of Infectious Diseases, UConn Health Center, Farmington
2007-Present Associate Professor of Medicine, UConn Health Center, Farmington

Specialties:
Office Locations:

Infectious Diseases
UConn Health
Dowling North Medical Building
263 Farmington Avenue
Farmington, CT 06030
860-679-4225
Directions

Board Certifications:
  • Internal Medicine
Education and Training:
TrainingInstitutionMajor/Specialty
Undergraduate SchoolBrandeis UniversityBiochemistry
Medical SchoolHarvard Medical SchoolMedicine
Graduate SchoolHarvard UniversityExperimental Pathology
InternshipBeth Israel Deaconess Medical CenterInternal Medicine
ResidencyBeth Israel HospitalInternal Medicine
PostdoctoralNational Foundation for Infectious DiseasesLilly Postdoctoral Fellowship
FellowshipBeth Israel Hospital-Brigham and Women's HospitalInfectious Diseases
Hospital Affiliation:
  • John Dempsey Hospital
Honors and Awards:
Name of Award/HonorAwarding Organization
Young Investigator AwardNational Foundation for Infectious Diseases
Rishon M. Bialer Memorial PrizeBrandeis University
A.B., Magna cum laudeBrandeis University
Highest Department Honors in Biochemistry and BiologyBrandeis University
Elected to Phi Beta KappaBrandeis University Chapter
Julian and Helen Behr Scholarship PrizeBrandeis University
Clinical Interests:

Infectious Diseases Liaison to Bone Marrow Transplantation Unit, UConn Health Center, 1989-2002
Inpatient Consultations in Infectious Diseases, UConn Health Center
Clinical Staff at Newington VAMC, 1989-2004
Outpatient Consultations in Infectious Diseases, UConn Health Center
Longitudinal Management of HIV Patients, UConn Health Center

Research Interests:

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.

Detection and Characterization of HIV Isolates Using GFP-based Indicator Cell Assays

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.

Engineered Adaptive Immunity

Naive human T cells, both CD8+ and CD4+, may be reprogrammed to recognize target epitopes by transduction with vectors encoding TCR genes specific for HLA class I-restricted epitopes, melanoma and HIV antigens in our case. TCR-engineered CD8+ cells become epitope-specific CTLs that are cytotoxic for the appropriate tumor or target cells in vitro and have even begun to be used for clinical tumor immunotherapy; however, in vivo, the potent anti-tumor effect soon diminishes. We are studying the effects of certain TCR mutations that should alter the cell-death signaling associated with antigen-induced activation and may have translational value. With current transduction protocols, TCR engineered CD4+ cells develop into Th1 effectors, exhibiting tumor target cytotoxicity and antigen-induced Th1 cytokine release. We are trying to understand and control this process to engineer cognate help for CTL generation. Also, through systematic alteration of activation conditions prior to tranduction and by knocking-down expression of T-bet and JNK2, which control Th1-type differentiation, we are attempting to obtain antigen-specific Th2 and Treg.

Antigen Presentation

Melanoma tumor-associated antigens and HIV antigens altered by protein trafficking signals, including the HSV VP22 protein translocation domain, are introduced into antigen-presenting cells using viral vectors and protein transduction to study the in vitro generation of human CTL and CD4+ responses by these cross-presentation systems. The aim is to develop a better understanding of the basic processes associated with cross presentation that may be applicable to vaccine design and adaptive immunotherapy.



Selected Publications:


Peer Reviewed Publications

The HIVToolbox 2 web system integrates sequence, structure, function and mutation analysis. Sargeant, David P; Deverasetty, Sandeep; Strong, Christy L; Alaniz, Izua J; Bartlett, Alexandria; Brandon, Nicholas R; Brooks, Steven B; Brown, Frederick A; Bufi, Flaviona; Chakarova, Monika; David, Roxanne P; Dobritch, Karlyn M; Guerra, Horacio P; Hedden, Michael W; Kumra, Rma; Levitt, Kelvy S; Mathew, Kiran R; Matti, Ray; Maza, Dorothea Q; Mistry, Sabyasachy; Novakovic, Nemanja; Pomerantz, Austin; Portillo, Josue; Rafalski, Timothy F; Rathnayake, Viraj R; Rezapour, Noura; Songao, Sarah; Tuggle, Sean L; Yousif, Sandy; Dorsky, David I; Schiller, Martin R. (2014). PloS one, 6, (9), e98810.

MHC-I-restricted melanoma antigen specific TCR-engineered human CD4+ T cells exhibit multifunctional effector and helper responses, in vitro. Ray, Swagatam; Chhabra, Arvind; Chakraborty, Nitya G; Hegde, Upendra; Dorsky, David I; Chodon, Thinle; von Euw, Erika; Comin-Anduix, Begonya; Koya, Richard C; Ribas, Antoni; Economou, James S; Rosenberg, Steven A; Mukherji, Bijay. (2010). Clinical immunology (Orlando, Fla.), 3, (136), 338-47.

CD4+CD25- T cells transduced to express MHC class I-restricted epitope-specific TCR synthesize Th1 cytokines and exhibit MHC class I-restricted cytolytic effector function in a human melanoma model. Chhabra, Arvind; Yang, Lili; Wang, Pin; Comin-Anduix, BegoƱa; Das, Raja; Chakraborty, Nitya G; Ray, Swagatam; Mehrotra, Shikhar; Yang, Haiguang; Hardee, Cinnamon L; Hollis, Roger; Dorsky, David I; Koya, Richard; Kohn, Donald B; Ribas, Antoni; Economou, James S; Baltimore, David; Mukherji, Bijay. (2008). Journal of immunology (Baltimore, Md. : 1950), 2, (181), 1063-70.

Activation-induced cell death of human melanoma specific cytotoxic T lymphocytes is mediated by apoptosis-inducing factor. Chhabra, Arvind; Mehrotra, Shikhar; Chakraborty, Nitya G; Dorsky, David I; Mukherji, Bijay. (2006). European journal of immunology, 12, (36), 3167-74.

Enhancement of implantable glucose sensor function in vivo using gene transfer-induced neovascularization. Klueh, Ulrike; Dorsky, David I; Kreutzer, Don L. (2005). Biomaterials, 10, (26), 1155-63.