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------------------------------------------------------------------------------------------------- Curriculum Vitae B.A.,
Northwestern University, 1976
------------------------------------------------------------------------------------------------- Research Interests Our research is focused on understanding the molecular mechanisms underlying the regulation and function of the actin cytoskeleton in oncogenesis. The actin cytoskeleton plays a central role in the regulation of cellular processes linked to cancer including cell proliferation, apoptosis, anchorage-independent cell growth, cell migration and invasion. Alterations in the actin-based cytoskeleton are an established part of the neoplastic phenotype. These alterations result from activation of specific signaling pathways that are part of the oncogenic program. Oncogene-mediated changes in actin filament dynamics and associated adhesive interactions contribute to enhanced motility and invasiveness of tumor cells. These changes in the cytoskeleton are a result of changes in both the expression of specific cytoskeletal proteins and signaling proteins, e.g., small GTPases and kinases. The changes in the expression of cytoskeletal proteins are more than simply a generic consequence of cell reorganization characteristic for oncogenic transformation. For example, work by our lab and others has shown that ectopic expression of specific cytoskeletal proteins can suppress many features of transformation including disruption of microfilament bundles and focal adhesions, enhanced cell motility, loss of contact-inhibited cell growth, ability to grow in soft agar, and tumorigenicity in nude mice, indicating the loss of specific cytoskeletal proteins plays a direct role in oncogenesis. We are investigating the mechanisms by which specific components of actin structures are targeted and de-regulated by oncogenes, and, more importantly, how the accompanying changes in actin filament organization contribute mechanistically to oncogenic processes including cell proliferation and ability to cancer cells to evade apoptosis. These studies are providing valuable new insights into the regulation of the actin cytoskeleton by oncogenes and how changes in the actin cytoskeleton contribute to inreased cell motility and signaling of cancer cells. Furthermore, specific components of the cytoskeleton might serve as a target for the development of prognostic and therapeutic targets in cancer. ------------------------------------------------------------------------------------------------- Selected Publications Connell L and Helfman DM. (2006) Myosin light chain kinase plays a role in the regulation of epithelial cell survival. J Cell Sci 119:2269-2281. Helfman DM, Kim EJ, Lukanidin E, and Grigorian M. (2005) The metastasis associated protein S100A4: role in tumor progression and metastasis. British J Cancer 92:1955-1958. Helfman DM and Pawlak G. (2005) Myosin light chain kinase and acto-myosin contractility modulate activation of the ERK cascade downstream of oncogenic Ras. J Cell Biochem 95:1069-1080. Helfman, D.M., Kim, E.J., Lukanidin, E., Grigorian, M. The metastasis associated protein S100A4: role in tumor progression and metastasis. British J Cancer, 92, 1955-1958, 2005. Lee, S., and Helfman, D.M. Cytoplasmic p21Cip1 is involved in Ras-induced inhibition of the of the ROCK/LIMK/COFILIN pathway. J. Biol. Chem 279, 1885-1891, 2004. Pawlak, G, McGarvey, T.W., Nguyen, T.B., Malkowicz, S.B., Helfman, D.M. Alterations in tropomyosin isoform expression in human transitional cell carcinoma (TCC) of the urinary bladder. International Journal of Cancer, 110, 368-373, 2004. Dhawan, J and Helfman, D.M. Modulation of acto-myosin contractility in skeletal muscle myoblasts uncouples growth arrest from differentiation. J Cell Science, 117, 3735-3748, 2004. Bakin, A.V., Rinehart. C., Safina, A., Daroqui, C., D., Darbary, H., and Helfman, D.M. A critical role of tropomyosins in TGF-b regulation of the actin cytoskeleton and cell motility in epithelial cells. Mol Biol. Cell 15, 4682-4694, 2004. Kim, E. and Helfman, D.M. Characterization of the metastasis associated protein, S100A4: Roles of calcium-binding and dimerization in cellular localization and interaction with myosin. J. Biol. Chem. 278, 30063-30073, 2003. Pawlak, G. and Helfman, D.M. Post-transcriptional down-regulation of ROCKI/Rho-kinase through an MEK-dependent pathway leads to cytoskeleton disruption in ras-transformed fibroblasts. Mol. Biol. Cell 13, 336-347, 2002. Pawlak, G. and Helfman, D.M. MEK mediates v-Src-induced disruption of the actin cytoskeleton via inactivation of the Rho-ROCK-LIM-kinase pathway. J. Biol. Chem. 277, 26927-26933, 2002. Pawlak, G. and Helfman, D.M. Cytoskeletal changes in cell transformation and tumorigenesis. Curr. Opin. Gen. Devel. 11, 41-47, 2001.
View published research articles by Dr. Helfman in the National Library of Medicine ------------------------------------------------------------------------------------------------- |
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