Clifford Stains

Education

NIH Postdoctoral Fellow - MIT
Ph.D., Chemistry - University of Arizona
B.S., Chemistry - Millersville University

Research Overview

Research activities in the Stains laboratory are focused on three core areas: 1) the development and application of chemosensors for phospho-regulatory enzymes, 2) new methodologies for constructing designer signaling networks, and 3) fundamental studies of protein misfolding. As part of the CIBC, the Stains laboratory is applying chemical approaches to define longitudinal signaling perturbations associated with the development of non-alcoholic fatty liver disease (NAFLD) and its progression to metastatic hepatocellular carcinoma (HCC). HCC is the third leading cause of cancer worldwide. Moreover, rates of HCC have been steadily increasing in the United States. One explanation for this observation is the alarming trend in obesity. Indeed, a positive correlation between the development of NAFLD and HCC has been identified in the clinic, supporting a link between obesity and HCC. However, little is known about the molecular mechanisms of NAFLD development and progression to HCC. In order to provide insight into this critical problem, the Stains laboratory will utilize a panel of direct protein phosphatase and kinase activity sensors to interrogate signaling changes associated with disease development and progression. To complement this initiative, this project will leverage a multidisciplinary approach to correlate observed changes in signaling with changes in RNA and metabolite production. This multipronged approach will permit the identification of regulators, as well as effectors, of altered signaling enzyme activity observed in disease models. Taken together, the proposed project will provide a quantitative picture of signaling perturbations in NAFLD and establish factors that contribute to progression to more aggressive disease phenotypes such as HCC. In the long-term, this work will provide a basis for the development of clinical diagnostics and identify potential new targets for therapeutic intervention in the development and progression of HCC.

Selected Publications

1. Kelly, M. I.; Bechtel, T. J.; Reddy, D. R.; Hankore, E. D.; Beck, J. R. & Stains, C. I. A Real-Time, Fluorescence-Based Assay for Rho-Associated Protein Kinase Activity. Anal. Chim. Acta In Press, DOI: 10.1016/j.aca.2015.07.058.
2. Zhou, X.; Lai, R.; Li, H. & Stains, C. I. The 8-Silyloxyquinoline Scaffold as a Versatile Platform for the Sensitive Detection of Aqueous Fluoride. Anal. Chem. 87, 4081-4086 (2015).
3. Szalewski, D. A.; Beck, J. R. & Stains, C. I. Design, Synthesis, and Evaluation of a Selective Chemosensor for Leucine-Rich Repeat Kinase 2. Bioorg. Med. Chem. Lett. 24, 5648-5651 (2014).
4. Beck, J. R.; Peterson, L. B.; Imperiali, B. & Stains, C. I. Quantification of Protein Kinase Enzymatic Activity in Unfractionated Cell Lysates Using CSox-Based Sensors. Curr. Protoc. Chem. Biol. 6, 135-156 (2014).