Anthony J. Capobianco, Ph.D.
Professor of Surgery
Description of Research
Dr. Capobianco's laboratory is directed toward the elucidation of the Notch signaling pathway and how deregulation of this pathway drives cancer. The deregulation of the Notch pathway is common in many human cancers and contributes to properties that guide resistance to therapy and metastasis. Therapeutic targeting of this pathway is a clear objective in the era of precision medicine. Research in his lab is centered on three main projects. The most important project in the lab is the dissection of the biochemical signaling mechanism of Notchic proteins, as this serves as the foundation for his translational projects.
Dr. Capobianco and his colleagues have discovered that Notch exists in the nucleus in a large multi-component transcriptional regulatory complex, and are working to define the role of this complex in Notch signaling. This projects has defined key regulatory mechanisms that guide with the activation and repression of gene expression. Furthermore, information derived from these studies will uncover other draggable targets. A second major area of research is related to the role Notch plays in human cancer. In this regard, Dr. Capobianco’s lab has demonstrated a role for Notch in driving stemless and tumorgenicity in esophageal adenocarcinoma. This cancer has a devastating disease with an increasing incidence and poor outcome. Research from the lab has demonstrated that Notch activity in the cancer underlies resistance to chemotherapy and has led to a clinical trial hypothesis which is currently being evaluated. The third major area of research in the Capobianco lab is focused on the discovery and development of novel notch pathway specific inhibitors and drugs. Currently, the lab has discovered two specific inhibitors of the Notch regulatory complex and is currently developing these inhibitors towards clinical candidates.
- Dr. Capobianco and his colleagues have discovered that Notch exists in the nucleus in a large multi-component complex, and are working to define the role of this complex in Notch signaling
- Dr. Capobianco's lab has discovered that Jagged1, in addition to signaling through Notch, can signal via a PDZ-dependent mechanism
- His studies provide direct evidence that the Notch/DSL signaling pathway is, in fact, bi-directional
Selected Cancer-Related Publications
- Licciulli S, Avila JL, Hanlon L, Troutman S, Cesaroni M, Kota S, Keith B, Simon MC, Pure E, Radtke F, Capobianco AJ, Kissil JL. Notch1 is required for Kras-induced lung adenocarcinoma and controls tumor cell survival via p53. Cancer Res :,2013 Read more »
- Azzam DJ, Zhao D, Sun J, Minn AJ, Ranganathan P, Drews-Elger K, Han X, Picon-Ruiz M, Gilbert CA, Wander SA, Capobianco AJ, El-Ashry D, Slingerland JM. Triple negative breast cancer initiating cell subsets differ in functional and molecular characteristics and in ?-secretase inhibitor drug responses. EMBO Mol Med :,2013 Read more »
- Rodriguez-Blanco J, Schilling NS, Tokhunts R, Giambelli C, Long J, Liang Fei D, Singh S, Black KE, Wang Z, Galimberti F, Bejarano PA, Elliot S, Glassberg MK, Nguyen DM, Lockwood WW, Lam WL, Dmitrovsky E, Capobianco AJ, Robbins DJ. The Hedgehog processing pathway is required for NSCLC growth and survival. Oncogene :,2012 Read more »
- Fei DL, Sanchez-Mejias A, Wang Z, Flaveny C, Long J, Singh S, Rodriguez-Blanco J, Tokhunts R, Giambelli C, Briegel KJ, Schulz WA, Gandolfi AJ, Karagas M, Zimmers TA, Jorda M, Bejarano P, Capobianco AJ, Robbins DJ. Hedgehog Signaling Regulates Bladder Cancer Growth and Tumorigenicity. Cancer Res :,2012 Read more »
- Ranganathan P, Weaver KL, Capobianco AJ. Notch signalling in solid tumours: a little bit of everything but not all the time. Nat Rev Cancer 11:338-51,2011 [JIF 37.184] Read more »
- Singh S, Wang Z, Liang Fei D, Black KE, Goetz JA, Tokhunts R, Giambelli C, Rodriguez-Blanco J, Long J, Lee E, Briegel KJ, Bejarano PA, Dmitrovsky E, Capobianco AJ, Robbins DJ. Hedgehog-Producing Cancer Cells Respond to and Require Autocrine Hedgehog Activity. Cancer Res 71:4454-4463,2011 [JIF 8.234] Read more »
- Vasquez-Del Carpio R, Kaplan FM, Weaver KL, Vanwye JD, Alves-Guerra MC, Robbins DJ, Capobianco AJ. Assembly of a notch transcriptional activation complex requires multimerization. Mol Cell Biol 31:1396-408,2011 [JIF 6.188] Read more »
- Demarest RM, Dahmane N, Capobianco AJ. Notch is oncogenic dominant in T-cell acute lymphoblastic leukemia. Blood 117:2901-9,2011 [JIF 10.558] Read more »
- Negorev DG, Vladimirova OV, Kossenkov AV, Nikonova EV, Demarest RM, Capobianco AJ, Showe MK, Rauscher FJ 3rd, Showe LC, Maul GG. Sp100 as a Potent Tumor Suppressor: Accelerated Senescence and Rapid Malignant Transformation of Human Fibroblasts through Modulation of an Embryonic Stem Cell Program. Cancer Res 70:9991-10001,2010 [JIF 7.543] Read more »
Collaborating in the Multidisciplinary Research Program(s):