Our Science – Howard Website

O.M. Zack Howard, Ph.D.

Laboratory of Molecular Immunoregulation Cellular Immunology Group Staff Scientist National Cancer Institute at Frederick Building 560, Room 31-19 P.O. Box B Frederick, MD 27102-1201 Phone:   301-846-1348 Fax:   301-846-6789 E-Mail:   howardz@ncifcrf.gov

Biography

Dr. Howard graduated for the University of Oklahoma in 1983 with a B.S. in chemistry and earned a Ph.D. in biochemistry from the University of South Carolina in 1987 with a Ph.D. dissertation entitled 'Determination of the primary structure of the subunit of human complement protein C8'. Following graduate school, Dr. Howard joined the University of Texas MD Anderson Cancer Center Molecular Hematology Program moving quickly from postdoctoral fellow to Project Investigator. While at the UT-MD Anderson Cancer Center Dr. Howard investigated the molecular escape of chronic myelogenous leukemia (CML) cells from interferon mediated growth suppression. In 1989, Dr. Howard moved to the National Cancer Institute-Frederick where she has remained. During her time with the NCI-Frederick, Dr. Howard has investigated the molecular regulation of growth factor receptors, IL-2Rbeta, prolactin receptor, and more recently the roles of chemokines and their receptors in cell migration, tumor metastasis and proliferation.

Research

Chemokines are structurally related endogenous chemotactic proteins secreted by most cell types. They mediate their responses by binding to and activating seven transmembrane G-protein coupled receptors (GPCR). Recent work has shown that other endogenous proteins or self-antigens can be chemotactic and they also use chemokine GPCRs to mediate their effects. However, these self-antigens, which are also known as autoantigens and tumor antigens, are not structurally related to chemokines and appear to differ from chemokines in that they associate with different domains of the receptor and activate different receptor mediated signaling. The differences in signaling and receptor domain usage are currently being investigated at the structure/function and immune consequence levels.

A second area of interest is targeting chemokine receptors in preclinical tumor models. The fact that chemokine receptors are also used by HIV and malaria as cellular entry ports lead to the evaluation of several discrete anti-HIV or anti-malarial chemicals as chemokine antagonists. These are being evaluated for their efficacy in metastatic tumor models. Dr. Howard has also characterized a number of natural products associated with the field of complementary and alternative medicine with anti-inflammatory activity. One of these compounds has shown in vivo efficacy limiting the growth of human glioma cells murine models. Future studies will focus on the development of stronger tumor models to predict the ability of a chemokine antagonist to have in vivo efficacy.

This page was last updated on 9/9/2008.