Andrea Morrione, PhD

Contact Dr. Morrione

233 S. 10th Street
Room 620, Bluemle Life Sciences
Philadelphia, PA 19107

(215) 503-4519
(215) 923-0249 fax

Publications for this author are currently unavailable.


1992: Ph.D., University of Milan, Italy, Biological Sciences.
1992-1993: Research Fellow, Biochemistry, University of Milan, Italy.
1993-1997: Post-Doctoral Fellow, Department of Microbiology and Immunology, Thomas Jefferson University in the laboratory of Dr. Renato Baserga.

University Appointment

Research Associate Professor
Director of Urology Research

Research and Clinical Interests

The tyrosine kinase type 1 insulin-like growth factor receptor (IGF-IR) plays a significant role in a variety of cellular processes including mitogenesis, differentiation and increased cell motility. Aberrant IGF-IR signaling contributes toward tumor progression through its antiapoptotic action and the induction of prometastatic pathways. Targeted depletion of the IGF-IR reverses the transforming phenotype and sensitizes cells to anticancer treatments in several cancer cell models, suggesting that the IGF-IR plays a broad role in cancer. The adaptor protein Grb10 interacts with the IGF-IR in a ligand-dependent manner serving as an important regulator of IGF-IR signaling. Grb10 functions as an adaptor protein by binding the E3 ubiquitin ligase Nedd4 serving to bring the ligase into close proximity to the IGF-IR such that ubiquitination occurs upon ligand stimulation. The ubiquitinated IGF-IR is subsequently targeted for degradation, giving rise to long-term attenuation of signaling, a process known as down-regulation. However, the precise molecular details by which Grb10 and Nedd4 serve to contribute to down-regulation of the IGF-IR remain poorly understood. We have recently shown that Grb10/Nedd4complex mediates multiubiquitination (monoubiquitination at multiple sites) of the IGF-IR, which is required for receptor internalization in clathrin-dependent and independent pathways. We are now focusing on the identification of novel proteins involved in IGF-IR sorting/recycling.

Proepithelin is a secreted pluripotent growth factor that plays a significant role in cell proliferation and cell cycle progression in many cellular systems. Proepithelin is highly expressed in several aggressive tumors, where the malignancy grade correlates with its expression levels. Proepithelin is also promoting cell migration, and it is important in wound healing and tissue repair. Given its critical role in wound repair and cancer progression, proepithelin may prove a useful clinical target for prognosis and therapy. Despite the strong connections with growth control and cancer, proepithelin's mode of action is not well understood. Furthermore, the proepithelin receptor and/or proteins that mediate the early stages of proepitelin signaling from the plasma membrane have not been identified. We are now investigating the role of proepithelin and novel proepithelin-binding trans-membrane proteins, which we hypothesize are either the proepithelin receptor or proteins involved in proepithelin signaling, in proliferation, migration and transformation of bladder and prostate cancer cells.

For additional information, please see Dr. Morrione's faculty interest page.