Postdoctoral Position Available

Leslie Berg, Ph.D.

Academic Role: Professor

Faculty Appointment(s) In:
   Pathology

Other Affiliation(s):
   Biochemistry and Molecular Pharmacology
   Center for AIDS Research
   Interdisciplinary Graduate Program
   Program in Immunology and Virology

T lymphocyte development and activation

The research in my laboratory is aimed at understanding the signal transduction pathways important for T lymphocyte development and activation. For these studies, we use a combination of mouse genetics (transgenics and knockouts), biochemistry, and cellular immunology. Our current work focuses on three projects. First, we have identified a tyrosine kinase, Jak3, involved in cytokine receptor signaling, and have generated Jak3-deficient mice. These mice have severe defects in lymphocyte development and function. Second, we have identified a novel tyrosine kinase, Itk, involved in T cell receptor signaling. Using Itk-deficient mice generated in the lab we are currently examining the role of this protein in lymphocyte development and activation. Finally, we are examining the role of Eph receptor tyrosine kinases and their ligands, ephrins, in T lymphocyte maturation. This latter family of proteins is known to play a role in cell migration and tissue patterning during the development of many organ systems in the body; we are investigating a potential role for these receptor-ligand interactions during thymic development and T cell maturation.

Representative Publications

Thomis, D.C., C.B. Gurniak, E. Tivol, A.H. Sharpe, and L.J. Berg. (1995). Defects in B lymphocyte maturation and T lymphocyte activation in mice lacking JAK3, Science 270, 794-797.

Andreotti, A. H., S. C. Bunnell, S. Feng, L. J. Berg and S. L. Schreiber. (1997). Intramolecular association of two domains in a Tec family tyrosine kinase influences binding of signaling proteins, Nature 384, 93-97.

Thomis, D.C. and L.J. Berg. (1997). Peripheral expression of JAK3 is required to maintain T lymphocyte function. J. Exp. Med. 185, 197-206.

Liu, K.-Q., S.C. Bunnell, C.B. Gurniak, and L.J. Berg. (1998). TCR-initiated calcium release is uncoupled from capacitative calcium entry in Itk-deficient T cells, J. Exp. Med. 187, 1721-1727

Bunnell, S.C., M. Diehn, M.B. Yaffe, P.R. Findell, L.C. Cantley, and L.J. Berg. (2000). Biochemical interactions integrating Itk with the TCR-initiated signaling cascade, J. Biol. Chem. 275:2219-2230.

Gozalo-Sanmillan, S., J.M. McNally, M.Y. Lin, C. Chambers, and L.J. Berg. (2001). Cutting Edge: Two distinct mechanisms lead to impaired T cell homeostasis in Jak3- and CTLA4-deficient mice. J. Immunol. 166, 727-730.

Miller, A.T. and L.J. Berg. (2002). Defective FasL expression and activation-induced cell death in the absence of Itk, J. Immunol., in press.

Potential Rotation Projects

1. Our genetic and biochemical data indicate that Itk plays an important role in T cell antigen receptor (TCR) signaling.  However, T cells express two other Tec family tyrosine kinases in addition to Itk.  We would like to test the ability of RNAi-type approaches to generate T cells lacking expression of all three Tec kinases.  These Tec-deficient T cells would provide the most conclusive evidence concerning the role of these kinases in TCR signaling.
2. We are currently performing structure/function analysis of Jak3 by generating “knock-in” mice, in which the endogenous Jak3 gene is replaced with Jak3 genes carrying point mutations in individual protein domains or phosphorylation sites.  We would like to generate additional constructs and targeted ES cells for these studies.
3. We hypothesize that Eph receptor/ephrin interactions also play a role in the organization of secondary lymphoid organs into discreet T and B cell areas.  As a first test of this hypothesize, we would like to examine the expression patterns of Eph receptors and ephrins in lymph node and spleen, before and after immunization.

Office: S3-143B
Phone: 508-856-8371
E-mail: Leslie.Berg@umassmed.edu
Keywords: Genetic Systems, Signal Transduction, Immunology

More on Leslie Berg's Research Research | Publications | Rotations View All Sections on One Page

Postdoctoral Position Available A postdoctoral position is available to study in this laboratory. Contact Dr. Berg for additional details.