My laboratory is dedicated to discerning molecular basis of hormone-dependent cancer development and progression, with a focus on cell cycle and transcriptional control in advanced prostate cancer. I serve as the Chair of the Hilary Koprowski Professor of Cancer Biology at the Thomas Jefferson University, with joint appointments in the Departments of Urology, Radiation Oncology, and Medical Oncology. I am also the Director of the NCI-designated Kimmel Cancer Center. My research interests are dedicated to understanding the mechanisms by which hormone receptor and cell cycle deregulation lead to prostate cancer progression and therapeutic bypass. The overall goal of our research is to utilize this information for successful development of precision medicine, to improve therapeutic outcome through rational therapy delivery. Our studies identifying tumor suppressor and hormone receptor alterations have uncovered new targets for treating advanced disease, and led to development of investigator-initiated, funded clinical trials. I collaborate closely with clinical, translational, and basic researchers.
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Schematic Highlighting the Translational Implications of the Dual Roles of PARP1 in DNA Repair and Transcriptional Regulation Multiple preclinical studies have demonstrated the dual roles of PARP-1 in facilitating DNA repair and in regulating transcription. The findings from these studies have resulted in the initiation of greater than 100 clinical trials. PARP-1 inhibitors have been utilized, as monotherapy or in combination with cytotoxic agents, to target DNA repair in the context of clinical trials aimed at improving cancer therapy. PARP-1 inhibitors have also been investigated as a strategy for suppressing transcriptional drivers of disease in the setting of both cancer and non-cancer conditions, such as stroke and myocardial infarction. Representative clinical trials are highlighted for each of these translational settings.
Chromatin to Clinic: The Molecular Rationale for PARP1 Inhibitor Function. Feng FY, de Bono JS, Rubin MA, Knudsen KE. Mol Cell. 2015 Jun 18;58(6):925-34. doi: 10.1016/j.molcel.2015.04.016.
Karen E Knudsen, PhD
Director of the Sidney Kimmel Cancer Center
Chair of Cancer Biology
Bluemle Life Science Building
233 South 10th Street
Philadelphia, PA 19107