I. Frogs, Clams, Yeast & Human Cancer: Historical Perspective on Cell Cycle Regulation
II. Translating Fundamental Cell Cycle Principles to Targeted Cancer Therapies
Part I: Frogs, Clams, Yeast & Human Cancer: Historical Perspective on Cell Cycle Regulation
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In her first talk, Dr. Helen Piwnica-Worms provides a historical perspective on cell cycle regulation and outlines important experiments in frogs, clams, and yeast that revealed crucial mediators of the cell cycle. Scientists observed that there were factors that allowed cell cycle progression, while there were other factors that prevented the cell from going backward. Using these model organisms, scientists were able to characterize the activation of the inducer of mitosis, the M-Phase promoting factor, which is a heterodimer between cyclin-dependent kinase (Cdc2/Cdk1) and cyclin B.
In her second talk, Piwnica-Worms explains how scientists have used their understanding of the cell cycle regulation to generate targeted cancer therapies. The cell has proteins that serve as cell cycle checkpoints, which allows the cell to respond appropriately to DNA damage. Although not all of the checkpoints are functional in a cancer cell, these cells still need the checkpoint proteins to respond to DNA damage. Piwnica-Worms’ laboratory studies the use of combining DNA damaging agents with checkpoint inhibitors to selectively kill cancer cells. Her laboratory developed a patient-derived xenograft mouse model to study Triple Negative Breast Cancer (TNBC), and predict how the genotype of the tumor affects treatment.
Dr. Helen Piwnica-Worms is professor of experimental radiation oncology at the University of Texas MD Anderson Cancer Center. She completed her bachelor’s degree in Biology at St. Olaf College in 1979, a doctoral degree in microbiology and immunology at Duke University Medical School in 1984, and a postdoctoral fellowship in pathology at the Dana-Farber Cancer Institute in 1988. In 1989, Piwnica-Worms joined the faculty of Tufts University Medical School, and in 1992 she moved to the Microbiology and Molecular Genetics department at Harvard Medical School. In 1994, she joined the faculty at Washington University School of Medicine in St. Louis, where she was the chair of Cell Biology and Physiology. Since 2013, Piwnica-Worms assumed the role of Vice Provost of Science and Professor of Experimental Radiation Oncology at the University of Texas MD Anderson Cancer Center.
As a basic research scientist, she was interested in understanding how the cell cycle was regulated. She showed how basic research discoveries allow for a better understanding of molecular underpinnings that opens new strategies to treat diseases, like cancer. Using immunocompromised mice, her laboratory developed a mouse model to perform preclinical studies using breast cancer cells from patients. For her scientific contributions, she was an Investigator of the Howard Hughes Medical Institute from 1994 to 2011 and was elected as a member of the National Academy of Medicine in 2013. Learn more about Piwnica-Worms’ research at her lab website.
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Parker LL & Piwnica-Worms H (1992) Inactivation of the p34cdc2-cyclin B complex by the human WEE1 tyrosine kinase. Science 257(5078):1955-7
Peng CY, et al. (1997) Mitotic and G2 checkpoint control: regulation of 14-3-3 protein binding by phosphorylation of Cdc25C on serine-216. Science 277(5331):1501-5
Ma CX, et al. (2012) Targeting Chk1 in p53-deficient triple-negative breast cancer is therapeutically beneficial in human-in-mouse tumor models. J Clin Invest 122(4):1541-52
Ma CX, Janetka JW, Piwnica-Worms H (2011) Death by releasing the breaks: CHK1 inhibitors as cancer therapeutics. Trends Mol Med. 17(2):88-96