Our Science – Birchenall-Roberts Website

Maria Birchenall-Roberts, Ph.D.

Laboratory of Experimental Immunology Leukocyte Biology Section Staff Scientist (Contr) LEI, CIP, CCR, NCI Bldg. 567, Room 2259 PO Box B Frederick, MD 21701-1201 Phone:   301-846-1442 Fax:   301-846-1673 E-Mail:   birchena@ncifcrf.gov

Biography

Dr. Maria C. Birchenall-Roberts obtained her Ph.D. in Molecular Biology at Illinois State University, Normal, Illinois in 1981. She was a Visiting Research Fellow in the Laboratory of Molecular Immunoregulation, Biological Response Modifiers Program. Division of Cancer Treatment, National Cancer Institute, NCI-Frederick from 1984-1990. Dr. Birchenall-Roberts is currently a Senior Scientist and works with Dr. Frank W. Ruscetti in the Basic Research Program, Science Applications International Corporation-Frederick, Frederick, Maryland 21702, USA. Laboratory of Experimental Immunology, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute-Frederick, Frederick, Maryland 21702, USA.

One major objective of her research is to define the physiological relevance of TGF-beta as a regulator of hematopoiesis and to determine the mechanisms by which it exerts its complex effects in a physiologically relevant context. Her focus at this moment is the identification of the interplay between tumor suppressors like TGF-beta, TSC2 and SPA-1 in the myeloid cells. This work opens new avenues for resolving important questions of cancer development and leukemogenesis.

Research

Molecular signaling of TGF-beta in myeloid cell development
Our laboratory has previously identified TGF beta as a regulator of all stages of hematopoiesis. The importance of TGF beta is underscored by the observation that TGF beta -/- mice have a significant increase in mature myeloid cells and rapidly die due to inflammation. We have focused our research on the role of TGF-beta in myeloid cell development and the molecular mechanisms by which it exerts its complex effects.

TGF beta has pleiotropic and often opposing effects on cellular processes. We reasoned that the varying effects were dependent on cell context and controlled by additional signaling mechanisms and accessory factors that are specific to the cell cycle and differentiation state of the cell. Accordingly, we have focused our work on understanding the interaction of TGF beta signaling pathway with other signaling networks.

We recently discovered that the tuberous sclerosis gene product 2 (TSC2), a tumor suppressor gene which causes growth arrest in G1, directly interacts with SMAD2 and SMAD3 to increase transcriptional activation mediated by TGF beta. The laboratory continues investigating the role of TSC2 in myeloid cell growth. In particular, TSC2 is a component of the mTOR/Akt signaling pathway that has been implicated in an increasing number of cancers. PI3K and AKT are striking markers for cancer treatment seeing that they lay in a central position of the oncogenic pathway where it separates and connects with signals from other critical pathways.

More recently, we have identified the participation of the important GTP-binding protein Rap1 in TGF beta signaling pathway in myeloid cells. We have shown that the Rap1A protein physically associates with the TGF-beta receptor complex and augments Smad-dependent signaling of TGF-beta responsive reporter constructs. Furthermore, we have found that in human myeloid leukemic cells, the fate of differentiation is regulated by the intracellular Smad pathway in conjunction with MAPK pathway, and identified Rap1A as a likely mediator of the cross-talk between these two pathways. Thus, a better understanding of how these signaling pathways are interconnected is likely to reveal new therapeutic opportunities in disease states.

This page was last updated on 3/4/2009.