Dennis J. Templeton, MD, PhD

Dennis J. Templeton, MD, PhD

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Mechanisms of physical stress and inflammatory cytokine signaling

The Templeton lab is interested in the control of signaling processes that are involved in cancer. They have three major interests.

Redox control of signal transduction. they have identified cysteine oxidation events that silence both SAPK and MEKK elements of the stress activated protein kinase pathways. As part of this effort, they developed a mass spectroscopic means of isolating and fingerprinting targets of cell oxidation, and hope to identify pathways of redox controlled signal transduction that operate through reversible oxidation of cysteine residues.  As part of this effort, they identified a novel oxidative modification of the p53 tumor suppressor protein, and are pursuing this work in collaboration with Dr. Alex Zaika, who is a Cancer Center member and who discovered the mitochondrial lifecycle of p53.

The MIF cytokine in cancer. While MIF is held to be principally involved in transcriptional control of inflammatory response (for example by regulating expression of TLR4), several groups have also characterized it as being able to override the cell death response manifested by normal p53. They have identified a small molecule inhibitor of the enzymatic activity of MIF, and are applying this to both cell models of cancer and to an animal model in which the carcinogenic properties of helicobacter infection result in gastric cancer.  MIF1 expression is required for the induction of inflammation by helicobacter, and they hope that this small molecule could reduce the impact of this infection, that afflicts the majority of adults in third world countries. They are collaborating on this effort with Dr. Peter Ernst, a Cancer Center member in the division of gastroenterology.

Methods for discovery of protein biomarkers of cancer. Beginning with their interest in redox proteomics, they have developed some unique analytical methods and reagents for isotope tagging of proteins to enable quantitative comparison of two complex mixtures. They are applying these techniques to a biomarker discovery program collaboratively with Dr. David Brenin, a breast surgeon and Cancer Center member.  This effort compares nipple aspirates from the involved and uninvolved breast from women with newly diagnosed cancers, with the hope of making this facile method a diagnostic tool.