Pestell, Richard G.
Richard G. Pestell, MD, PhD
Philadelphia, PA 19107
(215) 503-9334 fax
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.
cyclin d1; signal transduction; breast cancer; prostate cancer; gene therapy
Most Recent Peer-Reviewed Publications
- DACH1 suppresses breast cancer as a negative regulator of CD44
- Recent advances of bispecific antibodies in solid tumors
- Cyclin D1 restrains oncogene-induced autophagy by regulating the AMPK–LKB1 signaling axis
- Recent advances of highly selective CDK4/6 inhibitors in breast cancer
- Small RNA zippers lock miRNA molecules and block miRNA function in mammalian cells
- Biological functions of CDK5 and potential CDK5 targeted clinical treatments
- Cancer metabolism: A therapeutic perspective
- Hormone-induced DNA damage response and repair mediated by cyclin D1 in breast and prostate cancer
- Cytochalasin B-induced membrane vesicles convey angiogenic activity of parental cells
- Stromal cyclin D1 promotes heterotypic immune signaling and breast cancer growth
- v-Src oncogene induces Trop2 proteolytic activation via cyclin D1
- Hepatocyte DACH1 Is Increased in Obesity via Nuclear Exclusion of HDAC4 and Promotes Hepatic Insulin Resistance
- Cancer stem cell metabolism
- Time-lapse video microscopy for assessment of EYFP-Parkin aggregation as a marker for cellular mitophagy
- A direct quantification method for measuring plasma MicroRNAs identified potential biomarkers for detecting metastatic breast cancer
- Cyclin D1 promotes androgen-dependent DNA damage repair in prostate cancer cells
- Breast cancer stem cell isolation
- The retinal determination gene network: From developmental regulator to cancer therapeutic target
- Cyclin D1 silencing suppresses tumorigenicity, impairs DNA double strand break repair and thus radiosensitizes androgen-independent prostate cancer cells to DNA damage
- Correction: Cyclin D1 silencing suppresses tumorigenicity, impairs DNA double strand break repair and thus radiosensitizes androgen-independent prostate cancer cells to DNA damage [Oncotarget., 7, 5, (2016) (5383-400)] DOI: 10.18632/oncotarget.6579