Overview

Lab Members
Ian Whitehead, Ph.D.
Email: whiteip@umdnj.edu

Research: Our laboratory conducts research in the field of mammalian signal transduction, with a particular interest in small G proteins and their contribution to human cancer. More specifically, we have focused our research efforts on the identification and analysis of those signaling pathways that are regulated by members of the RhoGEF family.

Aikins Anthea, PhD
Email: aikinsaa@umdnj.edu

Ilona Tala
Email: talail@umdnj.edu

Education

PHD, 1993, University of British Columbia
B.S., 1987, University of British Columbia

Relevant Publications

Liu, Z., Adams, H.C. 3rd, and Whitehead, I.P. (2009) The Rho-specific Guanine Nucleotide Exchange Factor Dbs Regulates Breast Cancer Cell Migration. J Biol Chem. 284(23):15771-80.

Sahay, S., Pannucci, N.L., Mahon, G.M., Rodriguez, P.L., Megjugorac, N.J., Kostenko, E.V., Ozer, H.L., and Whitehead, I.P. (2008) The RhoGEF domain of p210 Bcr-Abl activates RhoA and is required for transformation. Oncogene. 27(14):2064-71.

Rodriguez, P.L., Sahay, S., Olabisis, O., and Whitehead I.P. (2007) ROCK I-mediated activation of NF-kB by RhoB. Cell. Signal. 19(11) 2361-9.

Kostenko, E., Olabisi, O., Sahay, S., Rodriguez, P., and Whitehead, I.P.. (2006) Ccpg1, a novel scaffold protein that regulates the activity of the Rho guanine nucleotide exchange factor Dbs. Mol Cell Biol, 26(23):8964-75.

Olabisi, O.O., Mahon, G.M., Kostenko, E., Liu, Z., Ozer, H.L. and Whitehead, I.P. (2006) Bcr interacts with components of the ESCRT-I complex and is required for epidermal growth factor receptor turnover. Cancer Res. 66(12):6250-7.

Liu Z., Kostenko E.V., Mahon G.M., Olabisi O.O., Whitehead, I.P. (2006) Transformation by the Rho-specific guanine nucleotide exchange factor Dbs requires ROCK-I-mediated phosphorylation of MLC. J Biol Chem. 281(23):16043-51

Martinez, S.E., Yuan, L., Lacza, C., Ransom, H., Mahon, G.M., Whitehead I.P. and Hake, LE (2005) XGEF mediates early CPEB phosphorylation during xenopus oocyte meiotic maturation. Mol. Biol. Cell. 16:1152-64.

Kostenko, E., Mahon, G.M., Cheng, L. and Whitehead, I.P. (2005) The Sec14 homology domain regulates the cellular distribution and transforming activity of the Rho-specific guanine nucleotide exchange factor, Dbs. J Biol Chem. 280:2807-17.

Oh, H.S., Moharita, A., Potian, J.G., Whitehead, I.P., Livingston, J.C., Castro, T.A., Patel, P.S.,and Rameshwar, P. (2004) Bone marrow stroma influences TGF-B production in breast cancer cells to regulate c-myc activation of the preprotachykinin-1 gene in breast cancer cells. Canc. Res. 64:6327-36.

Cheng, L., Mahon, G.M., Kostenko, E., and Whitehead, I.P. (2004) PH domain-mediated activation of the Rho-specific guanine nucleotide exchange factor Dbs by Rac1. J. Biol. Chem. 279: 12786-93.

Areas Of Interest

Bioinformatics

Drug Design

Molecular Mechanisms of Cancer

Proteomics

Signal Transduction

Stem Cells

Technology Solutions

Therapeutics

Our laboratory conducts research in the field of mammalian signal transduction, with a particular interest in small G proteins and their contribution to human cancer. More specifically, we have focused our research efforts on the identification and analysis of those signaling pathways that are regulated by members of the RhoGEF family. The RhoGEFs are a structurally-related family of oncoproteins that share an approximately 200 amino acid stretch of sequence similarity with Dbl, a transforming protein that was isolated from a diffuse B cell lymphoma. The important role that RhoGEF controlled signaling pathways play in multiple aspects of oncogenic transformation has been well documented. Deregulation of these pathways will trigger a variety of parameters of cell transformation including uncontrolled proliferation, motility, invasiveness and angiogenesis. At least two members of the RhoGEF family, LARG and Bcr, contribute directly to rearrangements that are the causative agents of human leukemias, and a third member of the family has been identified at a common provirus integration site in murine B cell and myeloid leukemias. Additional disorders attributed to disruptions in members of this family include the developmental disorder faciogenital dysplasia, sporadic X-linked mental retardation, and amyotrophic lateral sclerosis.


Bcr and Dbs are two members of the RhoGEF family that are studied extensively in this laboratory. Bcr is a contributing partner to a fusion protein (p210 Bcr-Abl) that is the causative agent of chronic myelogenous leukemia. It is has now been demonstrated in a number of studies that biological activities that are contained within both Bcr, and its fusion partner Abl, are required for full transforming activity. Dbs is a RhoGEF that was identified in a screen for cDNAs whose expression cause deregulated growth in mice. Subsequent analysis revealed that this protein harbored substantial oncogenic activity as measured by focus formation, growth in low serum, anchorage independent growth and tumorigenicity. We have been developing both Dbs and Bcr as model systems to study how the deregulated expression of a mammalian RhoGEFs can trigger oncogenic signaling pathways. Central to our understanding of Dbs and Bcr mediate oncogenicity will be our ability to determine how they interact with regulatory factors, and our ability to identify downstream signaling pathways that are responsible for the transformed phenotype.