Philadelphia University + Thomas Jefferson University

Pestell, Richard G.

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Richard G. Pestell, MD, PhD

Contact Dr. Pestell

233 South 10th Street
Room 1050
Philadelphia, PA 19107

(215) 503-5692
(215) 503-9334 fax

Education

Executive MBA, New York University, Leonard N. Stern School of Business, New York, NY
PhD, University of Melbourne, Australia
MD, University of Melbourne, Australia
MB, BS, University of Western Australia, Australia

Expertise & Research Interests

Molecular mechanisms and gene therapy of breast and prostate cancer.

Our research activities focus o­n understanding the mechanisms governing cell-cycle regulated gene transcription and the role of these proteins in tumorigenesis and differentiation. The cyclin D1 gene encodes a regulatory subunit of a holoenzyme that phosphorylates and inactivates the tumor suppressor protein pRB (retinoblastoma protein) resulting in release of the pRB binding proteins and transcription factors, E2Fs. Several cyclin dependent kinase inhibitors (CDKI), p16/p19 block this activity of cyclin D1. Cyclin D1 plays a critical role in tumorigenesis and differentiation.

Because the abundance of the cyclin D1 gene is rate-limiting in progression through the cell-cycle in cells that contain the pRB protein, we have delineated the molecular mechanisms regulating the cyclin D1 gene. We demonstrated that cyclin D1 kinase (CDK) activity and cyclin D1 promoter activity is induced by o­ncogenes (p21ras, Rac, dbl, v-src, Neu-also known as ErbB-2), growth factors and G-protein coupled receptors. The transcription factors (E2Fs,JUN/Fos, CREB, ATF2/ETS), coactivators (p300/CBP,Brg/Brm1) and scaffolding proteins (JIP1, caveolins) coordinate this induction.

Using retroviral and lentiviral expression systems we are examining the requirement for specific cyclins and CKI for induction and progression of breast and prostate tumors induced by o­ncogenes. These systems are used to examine treatment synergy with conventional therapies.

We have developed tissue-specific inducible transgenic expression systems and are using this transgenic approach to examine the role of cyclin D1, the CDKI in breast and prostate cancer.

Using knockout mice we are examining the role of CDKI in breast cancer induced by specific o­ncogenes and synergy with conventional therapies.

Keywords

cyclin d1; signal transduction; breast cancer; prostate cancer; gene therapy

Publications

Most Recent Peer-Reviewed Publications

  1. The dialyzable leukocyte extract TransferonTMinhibits tumor growth and brain metastasis in a murine model of prostate cancer
  2. DACH1 antagonizes CXCL8 to repress tumorigenesis of lung adenocarcinoma and improve prognosis
  3. CCR5 Governs DNA damage repair and breast cancer stem cell expansion
  4. Cyclin D1-mediated microRNA expression signature predicts breast cancer outcome
  5. DACH1 suppresses breast cancer as a negative regulator of CD44
  6. Recent advances of bispecific antibodies in solid tumors
  7. Cyclin D1 restrains oncogene-induced autophagy by regulating the AMPK–LKB1 signaling axis
  8. Recent advances of highly selective CDK4/6 inhibitors in breast cancer
  9. Small RNA zippers lock miRNA molecules and block miRNA function in mammalian cells
  10. Cell cycle-related kinases
  11. Biological functions of CDK5 and potential CDK5 targeted clinical treatments
  12. Hormone-induced DNA damage response and repair mediated by cyclin D1 in breast and prostate cancer
  13. Cancer metabolism: A therapeutic perspective
  14. Cytochalasin B-induced membrane vesicles convey angiogenic activity of parental cells
  15. Stromal cyclin D1 promotes heterotypic immune signaling and breast cancer growth
  16. v-Src oncogene induces Trop2 proteolytic activation via cyclin D1
  17. Hepatocyte DACH1 Is Increased in Obesity via Nuclear Exclusion of HDAC4 and Promotes Hepatic Insulin Resistance
  18. Cancer stem cell metabolism
  19. Time-lapse video microscopy for assessment of EYFP-Parkin aggregation as a marker for cellular mitophagy
  20. A direct quantification method for measuring plasma MicroRNAs identified potential biomarkers for detecting metastatic breast cancer