Dr. Morrione Andrea Morrione, Ph.D.

Contact Dr. Morrione

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

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

Qualifications
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.

Publications

  • Marco Vanoni, Marina Vai, Andrea Morrione, Marina Venturini, Emanuela Lacanà, Enzo Martegani, Laura Popolo and Lilia Alberghina: Sequences promoting and preventing excretion in the growth medium of homologous and heterologous proteins in Saccharomyces cerevisiae. ECB6: Proceedings of the 6th European Congress on Biotechnology, 143-146, 1993.
  • Andrea Morrione, Tiziana DeAngelis and Renato Baserga: The GC factor regulates the expression of the Insulin-like Growth Factor 1 receptor. Cell Proliferation. 28:659-671, 1995.
  • Andrea Morrione, Tiziana DeAngelis and Renato Baserga: Failure of the bovine papilloma virus to transform mouse embryo fibroblast with a targeted disruption of the IGF-I Receptor Genes. Journal of Virology, vol. 69, 6:5300-5303, 1995
  • Consuelo D'Ambrosio, Susanne R. Keller, Andrea Morrione, Gustav E. Lienhard, Renato Baserga and Ewa Surmacz: Transforming Potential of the Insulin Receptor Substrate. Cell Growth and Differentiation 6:557-562, 1995.
  • Atsushi Hongo, Consuelo D'Ambrosio, Masahiko Miura, Andrea Morrione and Renato Baserga: Mutational Analysis and Transforming Activities of the Insulin-Like Growth Factor I Receptor. Oncogene 12:1231-1238, 1996.
  • Andrea Morrione, Barbara Valentinis, Shiwei Li, James Y. T. Ooi, Ben Margolis and Renato Baserga: Grb10: a new substrate of the Insulin-like Growth Factor Receptor I. Cancer Research 56:3165-3167, 1996.
  • Marina Venturini, Andrea Morrione, Patrizia Pisarra, Enzo Martegani and Marco Vanoni: In Saccharomyces cerevisiae a short amino acid sequence facilitates excretion in the growth medium of periplasmic proteins. Molecular Microbiology 23 (5) 997-1007, 1997.
  • Andrea Morrione, Barbara Valentinis, Shi-Qiong Xu, Gladys Yumet, Angeliki Louvi, Argiris Efstratiadis and Renato Baserga: IGF-II Stimulates Cell Proliferation through the Insulin Receptor. Proceedings of the National Academy of Sciences, U.S.A. 94:3777-3782, 1997.
  • Barbara Valentinis, Andrea Morrione, Stephen Taylor and Renato Baserga: IGF-I Receptor Signaling in Transformation by src Oncogenes. Molecular and Cellular Biology 17:3744-3754, 1997.
  • Andrea Morrione, Barbara Valentinis, Mariana Resnicoff, Shi-Qiong Xu and Renato Baserga: The Role of mGrb10a in IGF-I-Mediated Growth. Journal of Biological Chemistry 272:26382-26387, 1997.
  • Renato Baserga, Andrea Morrione, and Marco Prisco: Growth Factors, Cell Proliferation, and Apoptosis. Heart Failure Reviews 3, 5-14, 1998.
  • Barbara Valentinis, Andrea Morrione, Francesca Peruzzi, Krzysztof Reiss, RenatoBaserga: Anti-apoptotic Singaling of the IGF-I Receptor in Fibroblasts Following Loss of Matrix Adhesion. Oncogene 18:1827-1836, 1999.
  • Barbara Valentinis, Gaetano Romano, Francesca Peruzzi, Andrea Morrione, Marco Prisco, Silvia Soddu, Barbara Cristofanelli, Ada Sacchi and Renato Baserga: Growth and Differentiation Signals by the Insulin-like Growth Factor 1 Receptor in Hemopoietic Cells Are Mediated through Different Pathways. Journal of Biological Chemistry 274:12423-12430, 1999.
  • Andrea Morrione, Pamela Plant, Barbara Valentinis, Oliver Staub, Daniela Rotin, Sharad Kumar and Renato Baserga: mGrb10 interacts with Nedd4. Journal of Biological Chemistry 274:24094-24099, 1999.
  • Krzysztof Reiss, Gladys Yumet, Simei Shan, Ziwei Huang, Emad Alnemri, Srinivasa M. Srinivasula, Jin-Ying Wang, Andrea Morrione and Renato Baserga: A Synthetic Peptide Sequence from the C-Terminus of the IGF-I Receptor that induces Apoptosis and Inhibition of Tumor Growth. Journal of Cellular Physiology 181:124-135, 1999.
  • Renato Baserga and Andrea Morrione: Differentiation and Malignant Transformation: Two Roads Diverged in a Wood. Journal of Cellular Biochemistry, 32/33:68-75, 1999.
  • Andrea Morrione. Grb10 proteins in insulin-like growth factor and insulin receptor signaling. International Journal of Molecular Medicine. International Journal of Molecular Medicine 5:151-154, 2000.
  • Andrea Morrione, Gaetano Romano, Magali Navarro, Krzysztof Reiss, Barbara Valentinis, Michael Dews, Eva Eves, Marsha Rich Rosner, and Renato Baserga. Insulin-like Growth Factor-1 Receptor Signaling in Differentiation of Neuronal H19-7 Cells. Cancer Research 60:2263-2272, 2000.
  • Michael Dews, Marco Prisco, Francesca Peruzzi, Gaetano Romano, Andrea Morrione and Renato Baserga: Domains of the IGF-I Receptor Required for the Activation of Extracellular Signal-Regulated Kinases. Endocrinology 141:1289-1300, 2000.
  • Krzysztof Reiss, Jin-Ying Wang, Gaetano Romano, Frank B. Furnari, Webster K. Cavenee, Andrea Morrione, Xiao Tu and Renato Baserga: IGF-I receptor signaling in a prostate cancer cell line with a PTEN mutation. Oncogene19: 2687-2694, 2000.
  • Barbara Valentinis, Magali Navarro, Tommaso Zanocco-Marani, Pamela Edmonds, Jason McCormick, Andrea Morrione, Ada Sacchi, Gaetano Romano, Krzysztof Reiss and Renato Baserga: Insulin Receptor Substrate-1, p70S6K and Cell Size in Transformation and Differentiation of Hemopoietic Cells. Journal of Biological Chemistry 275: 25451-25459, 2000.
  • Slupianek, M. Nieborowska-Skorska, G. Hoser, A. Morrione, M. Majewski, L. Xue, S. W. Morris, M. A. Wasik, and T. Skorski. Role of PI-3k-Akt pathway in NPM/ALK-mediated lymphomagenesis. Cancer Research. 61:2194-2199, 2001. (view abstract)
  • Barbara Belletti, Marco Prisco, Andrea Morrione, Barbara Valentinis, Magali Navarro and Renato Baserga. Regulation of Id2 Gene Expression by the IGF-I Receptor Requires Signaling by Phosphatidylinositol-3 Kinase. Journal of Biological Chemistry. 276: 13867-13874, 2001. (view abstract)
  • Andrea Morrione, Magali Navarro, Gaetano Romano, Michael Dews, Krzysztof Reiss, Barbara Valentinis, Barbara Belletti and Renato Baserga: The Role of the Insulin Receptor Substrate-1 in the Differentiation of Rat Hippocampal Neuronal Cells. Oncogene. 20: 4842-4852, 2001. (view abstract)
  • Francesca Peruzzi, Marco Prisco, Andrea Morrione, Barbara Valentinis and Renato Baserga: Anti-apoptotic Signaling of the IGF-I Receptor by Mitochondrial translocation of c-Raf and Nedd4. Journal of Biological Chemistry. 276: 25990-25996, 2001. (view abstract)
  • Barbara Belletti, Robert Drakas, Andrea Morrione, Xiao Tu, Ivan Casaburi and Renato Baserga: Regulation of ID1 Protein Expression in Mouse Embryo Fibroblasts by the Type 1 Insulin-Like Growth Factor Receptor. Experimental Cell Research. 277: 107-118, 2002. (view abstract)
  • Agata Klejman, Lori Rushen,Andrea Morrione, Artur Slupianel and Tomasz Skorski: Phosphatidylinositol-3 kinase inhibitors enhance the anti-leukemia effect of STI571. Oncogene. 21: 5868-5876, 2002. (view abstract)
  • Andrea Vecchione, Adriano Marchese, Pauline Henry, Daniela Rotin and Andrea Morrione: The Grb10/Nedd4 complex regulates ligand-induced ubiquitination and stability of the IGF-I Receptor. Molecular and Cellular Biology. 23 3363-3372, 2003. (view abstract)
  • Andrea Morrione. Grb10 adapter protein as regulator of Insulin-like Growth Factor Receptor Signaling. Journal of Cellular Physiology. 197. 307-311, 2003. (view abstract)
  • Gustavo Baldassarre, Barbara Belletti, Milena Nicoloso, Monica Schiappacassi, Andrea Vecchione, Paola Spessotto, Andrea Morrione, Vincenzo Cerami, and Alfonso Colombatti: p27Kip1-stathmin interaction influences sarcoma cell migration and invasion. Cancer Cell. 7 51-63, 2005. (view abstract)
  • Shu-yue Ren, Elizabeth Bolton, M. Golam Mohi, Andrea Morrione, Benjamin G. Neel, and Tomasz Skorski: Phosphatidylinositol 3-kinase p85a subunit-dependent interaction with BCR/ABL-related fusion tyrosine kinases: molecular mechanisms and biological consequences. Molecular and Cellular Biology. 25(18) 8001-8008, 2005. (view abstract)
  • Giada Monami, Eva M. Gonzalez,Michelle Hellman, Leonard G. Gomella, Raffaele Baffa, Renato V. Iozzo and Andrea Morrione: Proepithelin promotes migration and invasion of 5637 bladder cancer cells through the activation of ERK1/2 and the formation of a paxillin/FAK/ERK complex. Cancer Research. 66(14)7103-7110, 2006.(view abstract)
  • Giada Monami, Velia Emiliozzi and Andrea Morrione: Grb10-/Nedd4-mediated multiubiquitination of the Insulin-Like Growth Factor Receptor regulates receptor internalization. Journal of Cellular Physiology. 216 426-437, 2008. (view abstract)
  • Andrea Vecchione, Matteo Fassan, Andrea Morrione, Silvia Goldoni, Gustavo Baldassarre, Dolores Byrne, Domenico D'arca, Juan Palazzo, J Lloyd, V Anesti, Luca Scorrano, Leonard G. Gomella, Renato V. Iozzo, Raffaele Baffa: Mitostatin, a Novel Mitochondrial Putative Tumor Suppressor Gene on Human Chromosome 12Q24.1, is Down-Regulated in Bladder and Breast Cancers. Oncogene. 2008 Jan 15;28(2):257-69. (view abstract)
  • Giada Monami, Velia Emiliozzi, Alessandro Bitto, Francesca Lovat, Xi-Qiong Xu, Silvia Goldoni, Matteo Fassan, Ginette Serrero, Leonard G. Gomella, Raffaele Baffa, Renato V. Iozzo and Andrea Morrione: Proepithelin Regulates Prostate Cancer cell Biology by Promoting Cell Growth, Migration and Anchorage-independent Growth. American Journal of Pathology. 2009 Mar;174(3):1037-47. (view abstract)
  • Francesca Lovat, Alessandro Bitto, Shi-Qiong Xu, Matteo Fassan, David Metalli, Vera Wubah, Silvia Goldoni, Peter McCue, Ginette Serrero, Leonard G. Gomella, Raffaele Baffa, Renato V. Iozzo and Andrea Morrione: Proepithelin is an autocrine growth factor for bladder cancer. Carcinogenesis. 2009 May;30(5):861-8. (view abstract)
  • David Metalli, Francesca Lovat, Farida Tripodi, Shi-Qiong Xu, Lilia Alberghina, Marco Vanoni, Leonard G. Gomella, Renato V. Iozzo and Andrea Morrione: The Insulin-Like Growth Factor Receptor I Promotes Motility and Invasion of Bladder Cancer Cells Through Akt- and Mitogen-Activated Protein Kinase-Dependent activation of Paxillin. Submitted.

 

Publications

Most recent Peer-reviewed Publications

  1. Growth of v-src-transformed cells in serum-free medium through the induction of growth factors
  2. β1 integrins mediate resistance to ionizing radiation in vivo by inhibiting c-Jun amino terminal kinase 1
  3. Dichotomy of decorin activity on the insulin-like growth factor-I system
  4. Proline-rich tyrosine kinase 2 (Pyk2) regulates IGF-I-induced cell motility and invasion of urothelial carcinoma cells
  5. Insulin and insulin-like growth factor II differentially regulate endocytic sorting and stability of insulin receptor isoform A
  6. Novel RasGRF1-derived Tat-fused peptides inhibiting Ras-dependent proliferation and migration in mouse and human cancer cells
  7. Decorin antagonizes IGF receptor I (IGF-IR) function by interfering with IGF-IR activity and attenuating downstream signaling
  8. Mitostatin is down-regulated in human prostate cancer and suppresses the invasive phenotype of prostate cancer cells
  9. Mutual interaction and reciprocal down-regulation between c-met and insulin receptor substrate-1
  10. The insulin-like growth factor receptor I promotes motility and invasion of bladder cancer cells through Akt- and mitogen-activated protein kinase-dependent activation of paxillin
  11. Proepithelin is an autocrine growth factor for bladder cancer
  12. Proepithelin regulates prostate cancer cell biology by promoting cell growth, migration, and anchorage-independent growth
  13. MITOSTATIN, a putative tumor suppressor on chromosome 12q24.1, is downregulated in human bladder and breast cancer
  14. Grb10/Nedd4-mediated multiubiquitination of the insulin-like growth factor receptor regulates receptor internalization
  15. Proepithelin promotes migration and invasion of 5637 bladder cancer cells through the activation of ERK1/2 and the formation of a paxillin/FAK/ERK complex
  16. Phosphatidylinositol 3-kinase p85α subunit-dependent interaction with BCR/ABL-related fusion tyrosine kinases: Molecular mechanisms and biological consequences
  17. p27Kip1-stathmin interaction influences sarcoma cell migration and invasion
  18. Grb10 Adapter Protein as Regulator of Insulin-Like Growth Factor Receptor Signaling
  19. The Grb10/Nedd4 complex regulates ligand-induced ubiquitination and stability of the insulin-like growth factor I receptor
  20. Regulation of Id1 protein expression in mouse embryo fibroblasts by the type 1 insulin-like growth factor receptor

View All Publications