233 S. Tenth Street
Room 1050
Philadelphia, PA 19107
(215) 503-5692
(215) 503-9334 fax
Most Recent Peer-reviewed Publications
- Dual fluorescent molecular substrates selectively report the activation, sustainability and reversibility of cellular PKB/Akt activity
- Erratum: ChIP sequencing of cyclin D1 reveals a transcriptional role in chromosomal instability in mice (J Clin Invest. (2013) 123:5 (2332) 10.1172/JCI70042)
- Compartment-specific activation of PPARγ governs breast cancer tumor growth, via metabolic reprogramming and symbiosis
- Cav1 suppresses tumor growth and metastasis in a murine model of cutaneous SCC through modulation of MAPK/AP-1 activation
- Nutrient restriction and radiation therapy for cancer treatment: When less is more
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