DEPARTMENT OF PATHOLOGY

 

Dwayne Stupack, Ph.D.

Dwayne Stupack, Ph.D.

  • Associate Professor of Reproductive Medicine and Pathology
  • Cancer Biology Program
  • Ph.D. -  University of Manitoba, 1996

Research Interests

A principle objective of our laboratory is to understand the basic cell biology of neuroblastoma. Neuroblastoma is the most common pediatric solid tumor, accounting for 7-10% of all childhood cancer. Malignant (stage IV) Neuroblastoma manifests as an aggressive, disseminated disease characterized by widespread dissemination of the tumor in vivo. These events are facilitated by modifications in gene expression associated with aggressive disease. Among these are the down regulation of the "suicide protein" caspase 8, and alterations to cellular receptors for extracellular matrix proteins such as collagens.

We have found that these systems and others collaborate to promote a metastatic phenotype in these cells. The receptors for extracellular matrix - "Integrins" act to promote apoptosis when they are unbound (or antagonized) via the activation of caspases. The system is not unique to neuroblastoma, but also appears to regulate survival in many other invasive cells.

A secondary interest of the Stupack lab include ongoing investigations into the regulation of angiogenesis, the growth of new blood vessels which nourish tumors and permit their growth. We are also very interested in developing new methods to attack tumors, and have substantial interactions in the Moores Cancer Center Chemical Biology program as well as the Nanotechnology Center.

Representative Publications

  1. Stupack,D.G., Teitz,T., Potter,M., Mikolon,D., Kidd,V.J., Lahti,J.M., Cheresh,D.A. Potentiation of neuroblastoma metastasis by loss of caspase 8. Nature 439:95-99, 2006.
  2. D.A. Cheresh and D.G. Stupack. Integrin-mediated death: An explanation for integrin knockout mice? Nat Medicine. 2002 8(3):193-194
  3. D.G. Stupack. X.S. Puente, S. Boutsaboulaouy, C.M. Storgard, D.A. Cheresh. Apoptosis induced by the recruitment of caspase 8 to unligated integrins. J Cell Biol 2001 155(3) 459-470
  4. .M. Storgard & D.G. Stupack, A. Jonczyk, S. Goodman, R.I. Fox, D.A. Cheresh. Decreased angiogenesis arthritic disease in rabbits treated with ?v?3 antagonist. J Clin Invest. 103:47-54, 1999.
  5. D.G. Stupack, E. Li, S. Silletti, J.A. Kehler, R.L. Geahlen, K. Hahn, G.R. Nemerow, D.A. Cheresh. Matrix valency regulates integrin-mediated lymphoid adhesion through Syk kinase. J Cell Biol. 144:777-788, 1999.
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Biography

Dr. Stupack received his Bachelors of Science degree, with honors/ valedictorian, in Genetics from the university of Manitoba, Winnipeg, Canada. From 1989 to 1996, Dr. Stupack conducted his Ph.D. graduate research at the Health Sciences Center in the University of Manitoba, in the Department of Medical Microbiology and within the Rheumatic Disease Unit Laboratory. He completed a brief fellowship in Pharmacology in Canada before joining The Scripps Research Institute as a post-doctoral research associate. At TSRI, Dr. Stupack was promoted to senior research associate in 2001, and to Assistant professor in 2004.

Dr. Stupack has been a pioneering advocate of integrins as Dependence Receptors, a class of molecules that transmit very different signals into the cell. The nature of these signals depending upon whether their target ligand is present or not, and what form it is in. He has presented numerous lectures across the US as well as internationally in Europe, South America and Asia, and has received numerous academic honors and awards, including the 2004 Junior Investigator Lectureship of the American Society for Matrix Biology.

Dr. Stupack has a substantial publication record with more than thirty papers in first-rate, peer-reviewed journals, and several book chapters. Dr. Stupack currently lectures in several courses at UCSD. He is the organizer of the Moores Cancer Center Basic and Translational Rounds as well as an Organizer of the Annual La Jolla Cell Signaling Conference, and participates in numerous inter and intramural programs related to apoptosis and metastasis. Dr. Stupack has trained several physician-scientists in scientific approach, and continues to train both basic and clinician scientist in his lab. , Dr. Stupack maintains a significant community involvement participates in a number of outreach programs that train high school students (and teachers) fundamental principles of science, as well as providing access to (and explanation of) his work to the public and the media.

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