Dr. Jeffrey Frost
The University of Texas Health Science Center at Houston
Department of Integrative Biology & Pharmacology
- Small G proteins
- Signaling complexes
- Cell cycle regulation
Research in my laboratory is focused on identifying signaling pathways regulated by Rho GTPases that contribute to breast cancer initiation and progression. Rho GTPases are small GTP binding proteins that function as molecular switches to control various aspects of cell motility and proliferation, including actin cytoskeletal organization, cell cycle progression and mitosis. Current studies in the lab center on the role of a guanine nucleotide exchange factor for RhoA, known as Net1, in breast cancer initiation and progression. Net1 is a RhoA activating protein that shuttles between the nucleus and plasma membrane and is overexpressed in a number of human cancers, including breast cancer. We have shown that Net1 is required for breast cancer cell motility and invasive activity, and that co-expression of Net1 with the ?4 integrin predicts increased metastasis and reduced survival in breast cancer patients. Ongoing projects in the lab include: a) identifying post-translation modifications and novel interacting proteins that control Net1 activity; b) defining the molecular mechanism by which Net1 controls breast cancer cell motility and metastasis; c) characterization of the role of Net1 in regulating mitotic progression; d) understanding the role of Net1 in controlling DNA damage responses; and e) elucidating the role of Net1 in mouse mammary gland development.
A tutorial in my laboratory will provide a student with experience in basic molecular, biochemical, and cell biological techniques applicable to the study of cellular growth control and oncogenesis.
Guerra, L., Carr, H., Richter-Dahlfors, A., Thelestam, M., Masucci, M.G., Frost, J.A., and Frisan, T. (2008) A Bacterial Cytotoxin Identifies the RhoA Exchange Factor Net1 as a key effector in the response to DNA damage. PLoS ONE, 3(5), e2254.
Gilcrease, M.Z., Kilpatrick, S.K., Woodward, W.A., Zhou, X., Nicolas, M.M., Corley, L.J., Fuller, G.N., Tucker, S.L., Diaz, L.K., Buchholz, T.A., and Frost, J.A. (2009) Co-Expression of Beta4 Integrin and Guanine Nucleotide Exchange Factor Net1 Identifies an Aggressive Subgroup of HER2-Positive Breast Cancer. Cancer Epidemiology, Biomarkers and Prevention, 18, 80-86.
Pichot, C.S., Hartig, M., Xia, L., Lee, F.Y., Frost, J.A., and Corey, S.J. (2009) Dasatinib Synergizes with Doxorubicin to Block Growth, Migration, and Invasion of Breast Cancer Cells, British Journal of Cancer, 101(1), 38-47.
Carr, H.S., Cai, C., Keinanen, K., and Frost, J.A. (2009) Interaction of the RhoA exchange factor Net1 with Dlg1 protects it from proteasome mediated degradation and potentiates Net1 activity, J.Biol.Chem., 284, 24269-24280.
Pichot C.S., Hartig S.M,. Arvanitis D., Jensen S., Bechil J., Marzouk S., Scita G., Frost J.A., Corey S.J. (2010) Cdc42 Interacting Protein 4 promotes breast cancer cell invasion and formation of invadopodia through activation of N-WASp, Cancer Res., 70, 8347-8356.
Program in Cell and Regulatory Biology (Pharmacology Track)