Philadelphia University + Thomas Jefferson University

Knudsen, Karen

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Karen E. Knudsen, PhD

Contact Dr. Knudsen

233 South 10th Street
Suite 1008
Philadelphia, PA 19107

(215) 503-8574

Research and Clinical Interests

Translational prostate cancer research, cell cycle control, hormonal control of gene transcription, chromatin remodeling. Prostate cancer is the most commonly diagnosed malignancy in the Unites States and the second leading cause of cancer death in men. Early prostate cancers require androgen to survive and proliferate; this dependence is exploited in treatment for disseminated disease. Wherein androgen ablation in the first line of therapeutic intervention. Although these regimens are initially effective, tumors ultimately recur due to reactivation of androgen receptor (AR) signaling, causing treatment failure and patient morbidity.

Despite the importance of understanding androgen action in the prostate, little is understood about the mechanisms underlying androgen dependence, and the means by which the androgen requirement is bypassed in relapsed tumors. My lab is dedicated to delineating the molecular mechanisms that govern these events. We currently have four main projects in the lab:

1. Regulation of AR dependent gene expression and cellular proliferation by cell cycle crosstalk in prostate cancer

2. Impact of SWI/SNF chromatin remodeling factors on AR function and prostate tumorigenesis

3. Impact of cell cycle deregulation on therapeutic efficacy

4. Role of endocrine disrupting compounds in circumventing the androgen requirement

Publications

Most Recent Peer-Reviewed Publications

  1. Detection of activating estrogen receptor gene (ESR1) mutations in single circulating tumor cells
  2. Posttranscriptional regulation of PARG mRNA by HuR facilitates DNA repair and resistance to PARP inhibitors
  3. Analysis of circulating cell-free DnA identifies multiclonal heterogeneity of BRCA2 reversion mutations associated with resistance to PARP inhibitors
  4. Androgen Receptor Deregulation Drives Bromodomain-Mediated Chromatin Alterations in Prostate Cancer
  5. PARP Inhibitors in Prostate Cancer
  6. Sigma1 targeting to suppress aberrant androgen receptor signaling in prostate cancer
  7. Not So Fast: Cultivating miRs as Kinks in the Chain of the Cell Cycle
  8. Cell cycle-coupled expansion of AR activity promotes cancer progression
  9. Potential Impact on Clinical Decision Making via a Genome-Wide Expression Profiling: A Case Report
  10. There and back again: The middle earth of DNA repair
  11. Linking DNA Damage and Hormone Signaling Pathways in Cancer
  12. Patient-level DNA damage and repair pathway profiles and prognosis after prostatectomy for high-risk prostate cancer
  13. Downregulation of critical oncogenes by the selective SK2 Inhibitor ABC294640 hinders prostate cancer progression
  14. Development and Validation of a Scalable Next-Generation Sequencing System for Assessing Relevant Somatic Variants in Solid Tumors
  15. Novel actions of next-generation taxanes benefit advanced stages of prostate cancer
  16. Models of neuroendocrine prostate cancer
  17. Chromatin to Clinic: The Molecular Rationale for PARP1 Inhibitor Function
  18. Cell-cycle-dependent regulation of androgen receptor function
  19. Consequence of the tumor-associated conversion to cyclin D1b
  20. Hormone whodunit: Clues for solving the case of intratumor androgen production