News and Publications

2002 DEPARTMENT HIGHLIGHTS

A number of Immunology faculty participate in the National Institutes of Health (NIH) grant review process. This activity helps support efforts of the broader scientific community, insures that NIH research dollars go to the best scientists, and reinforces the image of excellence that is the hallmark of TSRI's faculty. NIH Review Group members include Professor Gary Bokoch, Ph.D., Professor David Cheresh, Ph.D., Professor Linda Curtiss, Ph.D., Associate Professor Ann Feeney, Ph.D., Associate Professor Wendy Havran, Ph.D., Associate Professor Jonathan Kaye, Ph.D., Associate Professor Dwight Kono, M.D., Associate Professor Nigel Mackman, Ph.D., Professor David Nemazee, Ph.D., Professor Nora Sarvetnick, Ph.D., Professor Linda Sherman, Ph.D., and Associate Professor Peter Tobias, Ph.D.

Immunology faculty hold key positions with consortiums or foundations focused on solving major heath problems worldwide. For example, Professor Dennis Burton, Ph.D., directs the International AIDS Vaccine Initiative Neutralizing Antibody Consortium. Professor Ian Wilson, D.Phil., is also a member. The consortium is investigating the interaction of broadly neutralizing antibodies with the virus at the molecular level in an effort to further the development of an HIV vaccine.

TSRI Professor Argyrios Theofilopoulos, M.D., was awarded an honorary doctorate of medicine from the University of Athens in Greece.

2002 RESEARCH HIGHLIGHTS

Research Associate T. Zal, Ph.D., and his colleagues in the laboratory of Associate Professor Nicholas Gascoigne, Ph.D., are using real-time fluorescence resonance energy transfer (FRET) to study molecular interactions at the cell surface during T-lymphocyte activation. The use of biophysical techniques to measure real-time changes in living cells provides a new level of molecular detail about crucial processes in the immune response.

Additional studies of the structure of key molecules of the immune system at the molecular level are being undertaken by Associate Professor Luc Teyton, M.D., Ph.D., and his collaborators, including long-standing collaborators in the Wilson laboratory.

Understanding the function of specific genes and defining genetic disposition to disease continues to be a major department focus. It involves the study of both B and T lymphocytes and is exemplified in the work of Theofilopoulos and Kono. They have defined a paradigm of tumor immunotherapy involving T-cell homeostatic proliferation whereby a broad anti-tumor response is induced. This work, published in the Journal of Clinical Investigation, may lead to new approaches to tumor therapy.

The biochemical signals that lead to homeostatic proliferation and survival of naïve T cells have also been the subject of studies in the laboratory of Associate Professor Charles Surh, Ph.D. A recent study published in Proceedings of the National Academy of Sciences highlights a key role for cytokine IL-7 in this process.

The function of a unique subset of T cells in epithelial tissues are the subject of intense efforts in the Havran laboratory. During the past year, this laboratory's newest findings have appeared in Science and in Proceedings of the National Academy of Sciences, documenting a key role for this T-cell subset in wound healing and providing new paradigms to study the immune system's role in this process.

Nemazee and colleagues demonstrated the role of receptor editing in B-cell development. Nemazee is recognized as having made the key observations that support the role of receptor editing in a number of processes related to B-cell development and function. A recent study in Science describes the contribution of receptor editing to the antibody repertoire.

The Department of Immunology continues to be recognized for its studies defining intracellular signaling pathways. Milestones from the past year include:

• Studies published in Science from the laboratory of Associate Professor J. Han, Ph.D., that define an entirely new paradigm for MAP kinase activation not involving the classical upstream MAP kinases.

• A key role for a coagulation protein, Protein C, was established for the treatment of septic shock. Recent studies by Associate Professor Wolfram Ruf, M.D., and Research Associate Mathias Riewald, M.D., appearing in Science document a key role for activated Protein C, its receptor on the surface of endothelial cells, and one of the Protease Activated Receptors (PAR1) in induction of anti-apoptotic and anti-inflammatory genes.

• Understanding cell migration at the molecular level is essential to controlling a number of human diseases, including malignancy and autoimmune disease. The laboratory of Associate Professor David Schlaepfer, Ph.D., has approached this problem by investigating how focal adhesion kinase (FAK) integrates multiple extracellular signals to control cell migration. A publication in Nature Cell Biology highlights one of its most recent efforts, in which signals from growth factor receptors and integrins are shown to be mediated by FAK.

• Two studies by Bokoch and his collaborators published in Nature Cell Biology provide a better understanding of the role of RAC and Cdc42, two low molecular weight GTP binding proteins, in regulating cell signaling to the actin cytoskeleton. These studies help define the complex process of cell movement at the molecular level.