Our Science – Durum Website

Scott K. Durum, Ph.D.

Laboratory of Molecular Immunoregulation Head, Immunological Cytokine Group Deputy Laboratory Chief Building 560, Room 31-71 NCI-Frederick Frederick, MD 21702-1201 Phone:   301-846-1545 Fax:   301-846-7042 E-Mail:   durums@mail.ncifcrf.gov

Biography

After receiving his Ph.D. in 1978, Dr. Durum received his postdoctoral training in immunology at the National Jewish Hospital in Denver and at Yale Medical School. Dr. Durum joined the Laboratory of Molecular Immunoregulation in 1984.

Research

Cytokines and T Cell Development

Our group has studied various aspects of cytokine function in T cell development. Lately we have focused on IL-7 because it has been clearly established in humans and mice that this cytokine is required for normal T cell development in the thymus, and for T cell survival and homeostatic proliferation of mature peripheral T cells. Our goal is to understand the basis of this IL-7 requirement.

We first showed that one requirement for IL-7 during T cell development is to promote VDJ recombination. This effect was based on IL-7 inducing the opening of chromatin at the T cell receptor gamma locus. Thus, Rag proteins can cleave DNA which subsequently rejoins, creating the active rearranged T cell receptor gamma gene.

Our principal focus in recent years has been the 'trophic' activity of IL-7 on T cells. This refers to the capacity of IL-7 to protect immature and mature T cells from spontaneous cell death. We have shown that withdrawal of IL-7 induces a new death pathway, beginning with stress kinases that induce alkalinization of the cytosol. This elevated pH in turn activates the death protein Bax to attack mitochondria, leading to cell death. We have shown that this new death pathway is common to withdrawal of a number of cytokines, suggesting that it is a basis of cellular dependency on extracellular trophic signals. Most of the cells in multicellular organisms depend on such trophic signals to regulate tissue size and understanding its mechanisms also has implications for metastatic cancer cells which lose this dependency.

We have also examined the mechanism by which IL-7 induces cell division in T cells. We found that this mechanism is distinct from that of conventional growth factors acting on other cell types. We showed that IL-7 stimulation affects the stability of two proteins, Cdc25a and P27kip1, and these in turn affect the Cdk4 enzyme which controls cell division.

We have collaborated in this research with many scientists at the NIH and universities.

This page was last updated on 6/11/2008.