Judy Meinkoth
Associate Professor, Dept of Pharmacology

Cell Biology and Physiology Program

Address
1251 BRB I/II(Office)
1243-1246 BRB II/III (Lab)
421 Curie Blvd.
Philadelphia, PA 19104-6084

Office tel.: 215 898-1909
Lab tel.: 215 898-1719
Fax: 215 573-2236
E-mail: meinkoth@pharm.med.upenn.edu


EDUCATION

Miami University, Oxford, Ohio: (Zoology), 1973.

University of Calif, San Diego: PhD (Gene amplification, cancer), 1985.

RESEARCH INTERESTS

• Signal transduction, proliferation, differentiation, apoptosis.

Key words: signal transduction, proliferation, differentiation, apoptosis, Ras, Rap1, cAMP.

Search PubMed for articles

DESCRIPTION OF RESEARCH

My laboratory is interested in normal and aberrant growth regulation in thyroid follicular cells, specialized epithelial cells that synthesize, secrete and store thyroid hormone. Thyrotropin or TSH, the physiological regulator of thyroid cell proliferation, differentiation and survival, elicits many of its effects through the ubiquitous second messenger, cAMP. In addition to activating PKA, cAMP activates small G proteins, specifically Ras and Rap1 in thyroid cells. The contributions of PKA, Ras and Rap1 to the regulation of cell proliferation, differentiation and survival are under investigation.

Ras mutations occur at high frequency in thyroid tumors where alterations in H-, K- and N-Ras have been identified. B-Raf mutations are also prevalent in thyroid tumors. Stable expression of oncogenic Ras in thyroid cells confers TSH-independent proliferation, induces dramatic morphological alterations and extinguishes differentiated gene expression. In contrast, acute expression of oncogenic Ras stimulates aberrant cell cycle progression and apoptosis. The molecular mechanism through which Ras deregulates cell cycle progression and stimulates apoptosis is under investigation. Identifying the secondary changes that transpire to allow the survival of cells expressing activated Ras is an area of active interest.

RECENT PUBLICATIONS

Dworet, J.H. and Meinkoth, J.L. (2006). Interference with CREB stimulates apoptosis through aberrant cell cycle progression and checkpoint activation. Molec. Endocrinol. 20, 1112-1120.

Abulaiti, A., Fikaris, A.J., Tsygankova, O.M., and Meinkoth, J.L. (2006). Ras induces chromosome instability and abrogation of the DNA damage response. Canc. Res. 66, 10505-10512.

Fikaris, A.J., Lewis, A.E., Abulaiti, A., Tsygankova, O.M. and Meinkoth, J.L. (2006). Ras triggers ATR activation and apoptosis through sustained mitogenic signaling. J. Biol. Chem. 281, 34759-34767.

Tsygankova, O.M., Prendergast, G.P., Puttaswamy, K., Wang, Y., Feldman, M.D., Wang, H., Brose, M.S., and Meinkoth, J.L. (2007). Downregulation of Rap1GAP contributes to Ras transformation. Molec. Cell. Biol. in press.

Lab

ROTATION PROJECTS

Ras induces aberrant cell cycle progression, checkpoint activation and apoptosis in thyroid epithelial cells. The mechanism through which Ras elicits effects on the cell cycle machinery is under investigation.

Rap1GAP, a negative regulator of RapGTPases, is highly expressed in normal human thyroid cells and downregulated in thyroid tumors. Experiments are underway to assess whether Rap1GAP is a tumor suppressor gene

Personnel:

Oxana Tsygankova, PhD (Research Associate)
Greg Prendergast (Research Specialist)
Lisa Vuchak (Graduate Student