Research / Clinical Summary

Jack Dixon, PhD Dean for Scientific Affairs and Professor, Pharmacology / Cellular & Molecular Medicine / Chemistry & Biochemistry Cancer Biology Program Contact by Email

Jack Dixon, PhD, serves as Dean for Scientific Affairs, Health Sciences, and also holds faculty appointments as Professor of Pharmacology, and of Cellular and Molecular Medicine. A National Academy of Sciences member, Dixon has been a pioneer in the study of proteins and their function, with a focus on a family of proteins called phosphotases that play a key role in cellular response to molecular signals. His work has helped define a broad range of signaling actions, including the role of specific phosphotases in cancer and tumor suppression, and in cellular response to bacterial toxins, which has direct implications for biological warfare research. In his administrative role, Dixon oversees research initiatives of the Health Sciences, supporting ongoing programs and leading the design and implementation of new initiatives both internally and with partners outside of the university.

In addition to his NAS membership, Dixon is a member of the Institute of Medicine, the American Academy of Arts and Sciences, and the American Association for the Advancement of Science. He is also former president of the American Society for Biochemistry and Molecular Biology, which has awarded him the 2003 William Rose Award for outstanding contributions to biochemical and molecular biological research and a demonstrated commitment to training younger scientists.

Cells are highly responsive to signals from their environment. These signals include growth factors, neuronal firing, or even the presence of a bacteria or pathogen that has invaded the body. The sensing and processing of these signals are carried out by molecular circuits within the cell which detect, amplify and integrate these signals into a specific response. One of the most widely utilized cellular responses to environmental signals is to change the phosphorylation state of specific proteins. The level of protein phosphorylation is controlled by two families of enzymes known as protein kinases and phosphatases. My laboratory is interested in deciphering the role of the phosphatase in various cellular paradigms, including the ontogeny of cancer.

We have cloned, expressed and characterized a number of Protein Tyrosine Phosphatases (PTPases) showing that this entire family of enzymes proceeds via a unique phosphoenzyme intermediate. Our laboratory also identified the first dual specific phosphatase which dephosphorylates Ser/Thr as well as Tyr phosphoproteins. This family now includes major regulators of growth cycle such as p80cdc25 as well as phosphatases which regulate the mitogen-activated protein kinase pathway. In collaboration with Mark Saper, we have determined the X-ray structure of a PTPase and a dual specific phosphatase. Several projects in the laboratory focus on further defining the structures and functions of PTPases.

Because PTPases can potentially reverse the action of oncogenes such as v-src, several research projects currently under investigation in the laboratory focus on the anti-transformation activity of the phosphatases and their role in cancer. We have demonstrated that a tumor suppressor gene known as PTEN, which has sequence identity to the PTPases, specifically dephosphorylates phosphatidylinositol 3,4,5-triphosphate. This was the first reported example of a PTPase which functions to dephosphorylate a lipid second messenger and it also established the biological function of PTEN. Understanding the function of PTEN also provides a rationale for why the loss of this gene plays a key role in oncogenesis.

Keywords: Protein Tyrosine Phosphatase, Dual=specific Phosphatase, PTEN

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