email skowrons@cshl.edu, phone (516) 367-8407, fax (516) 367-8454

Research in my laboratory is focused on the mechanisms involved in induction of Acquired immune deficiency syndrome (AIDS) by human and simian immunodeficiency viruses (HIV and SIV). In particular, we study the function of accessory proteins, such as Nef, Vpr and Vpx of these two primate lentiviruses. These accessory proteins are important virulence factors, which modify the cellular milieu to disrupt adaptive and/or innate anti-viral responses and to provide a more conducive environment for virus replication.
We combine two complementary approaches to address the functions of these accessory factors. First, we use cell biology, molecular genetics, biochemistry and proteomics approaches to dissect how these proteins modulate normal functions of infected cells and to identify the cellular targets involved. Second, in collaborative experiments, we address the importance of these molecular interactions for AIDS pathogenesis by studying SIV-infected rhesus monkeys and by characterizing viral proteins isolated directly from HIV-1-infected people.
Together, our studies provide a molecular framework for understanding the functions of accessory virulence factors of immunodeficiency viruses and their importance in pathogenic processes, and could lead the rational design of drugs that control HIV-1 infection.

Janardhan, A., T. Swigut, B. Hill, M.P. Myers, and J. Skowronski. 2004. HIV-1 Nef binds the DOCK2–ELMO1 complex to activate Rac and inhibit lymphocyte chemotaxis. PLoS Biol. 2: 65–76.

Swigut, T., N. Shohdy, and J. Skowronski. 2001. Mechanism for downregulation of CD28 by Nef. EMBO J. 20: 1593–1604.

Greenberg, M.E., A.J. Iafrate, and J. Skowronski. 1998. The SH3 domain-binding surface and an acidic motif in HIV-1 Nef regulate trafficking of class I MHC complexes. EMBO J. 17: 2777–2789.

Lang, S.M., A.J. Iafrate, C. Stahl-Hennig, E.M. Kuhn, T. Nisslein, F.-J. Kaup, M. Haupt, G. Hunsmann, J. Skowronski, and F. Kirchhoff. 1997. Association of simian immunodeficiency virus Nef with cellular serine/threonine kinases is dispensable for the development of AIDS in rhesus macaques. Nat. Med. 3: 860–865.