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. Targeting androgen receptor and DNA repair in metastatic castration-resistant prostate cancer: Results from NCI 9012
  2. Role of genetic testing for inherited prostate cancer risk: Philadelphia prostate cancer consensus conference 2017
  3. Differential impact of RB status on E2F1 reprogramming in human cancer
  4. Response and resistance to paradox-breaking BRAF inhibitor in melanomas in vivo and Ex vivo
  5. Detection of activating estrogen receptor gene (ESR1) mutations in single circulating tumor cells
  6. Posttranscriptional regulation of PARG mRNA by HuR facilitates DNA repair and resistance to PARP inhibitors
  7. Analysis of circulating cell-free DnA identifies multiclonal heterogeneity of BRCA2 reversion mutations associated with resistance to PARP inhibitors
  8. Androgen Receptor Deregulation Drives Bromodomain-Mediated Chromatin Alterations in Prostate Cancer
  9. PARP Inhibitors in Prostate Cancer
  10. Sigma1 targeting to suppress aberrant androgen receptor signaling in prostate cancer
  11. Not So Fast: Cultivating miRs as Kinks in the Chain of the Cell Cycle
  12. Cell cycle-coupled expansion of AR activity promotes cancer progression
  13. RB loss promotes prostate cancer metastasis
  14. Potential Impact on Clinical Decision Making via a Genome-Wide Expression Profiling: A Case Report
  15. There and back again: The middle earth of DNA repair
  16. Linking DNA Damage and Hormone Signaling Pathways in Cancer
  17. Patient-level DNA damage and repair pathway profiles and prognosis after prostatectomy for high-risk prostate cancer
  18. Downregulation of critical oncogenes by the selective SK2 Inhibitor ABC294640 hinders prostate cancer progression
  19. Development and Validation of a Scalable Next-Generation Sequencing System for Assessing Relevant Somatic Variants in Solid Tumors
  20. Analysis of 13 cell types reveals evidence for the expression of numerous novel primate- And tissue-specific microRNAs