Effect of Cellular Stress on the Cancer Protein, Retinoblastoma

Document Type



Under the Eugene M. Lang Student/Faculty research fellowship, Biology major Vivienne Tedesco and her Professor, Dr. Nancy Krucher, engaged in cancer research that focused on cell cycle controls. The cell cycle is a highly regulated process that is controlled by many different types of proteins. Related proteins that are mutated or dysfunctional can lead to uncontrolled proliferation, a hallmark of cancer cells. Their focus was the pRb, a growth suppressive protein involved with a major checkpoint in the cell cycle. pRb binds to various entities throughout the cell cycle and is modulated by a vast array of proteins.

Information about the Student Author

Class of 2001, Major: Biology

Summary of Research Experience

As a recipient of the Eugene M. Lang Student/Faculty Research Fellowship I was given the opportunity to perform cancer research with Dr. Nancy Krucher that focuses on the control of cell division, particularly the Rb protein. Under Dr. Krucher's guidance, I have become proficient in cell culture, western blotting, immunoprecipitation, and transfection. As research is accomplished through trial and error, it is avantageous to work on several projects simultaneously. While working under this grant, Dr. Krucher and I have maneuvered through four projects that are described below: #1 The goal of this project was to determine the mechanism by which cdk4 activity is inhibited toward Rb in hypoxic conditions. Through the efforts of Dr. Krucher, her former student and Pace graduate Adam Zygmunt, and myself, we found that the inhibition of cdk4 activity in hypoxic cells is due to a marked increase in p16 expression and concomitant association with cdk4. This work has led to the publication of a paper entitled "Hypoxia Stimulates p16 Expression and Association with cdk4" which appeared in the journal Experimental Cell Reasearch, 278, 53-60 (2002). #2 The goal of this project is to investigate the effect of Rb dephosphorylation under hypoxic conditions. My work with Dr. Krucher has shown that the hypophosphorylated form of Rb associates with the transcription factor E2F-1 in hypoxia. This project resulted in a poster presentation and publication of an abstract entitled "Rb Dephosphorylation and Association with E2F-1" at the annual meeting for the American Society for Cell Biology in Washington D.C. in December 2001. #3 The goal of this project is to investigate the mechanism of Rb dephosphorylation under hypoxic conditions. Fellow student Eshwar Udho, Dr. Krucher, and I have chartered the mechanism in which PNUTS (PP1 Nuclear Targeting Subunit) inhibits PP1 (Protein Phosphatase 1) activity toward Rb. This has recently been published in Biochemical and Biophysical Research Communications. #4 In collaboration with Dr. Ana Krtolica (Berkeley Laboratories) we have initiated an intensive study of Rb in differentiation. Although this work is in its preliminary stages, it has introduced me to an area of cell biology that I will be pursuing in Canada when I, as a Fulbright scholar, focus on establishment of a cell culture system for studying Rb in cellular differentiation. As mentioned above, I was awarded a Fulbright Scholarship for the academic year 2002-2003. The Fulbright will send me to Canada, where I will continue my work in cancer research. Working with Dr. Peter Whyte, Associate Professor in the Department of Pathology and Molecular Medicine at McMaster University located in Hamilton, Ontario, I will examine the retinoblastoma gene, RB, and the protein it encodes for while also enrolling in advanced Biology courses. The Eugene M. Lang Student-Faculty Research Fellowship has effectively launched me into the world of research, and I believe that being the recipient of this prestigious grant contributed considerable weight to my Fulbright application. After my year of Fulbright research in Canada, I intend to proceed to graduate school, pursuing a Ph.D. in Cell and Molecular Biology.

Faculty Mentor

Nancy A. Krucher, Ph.D., Biology, Dyson College of Arts and Sciences

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