Catharine L Smith, PhD
Biography
I have worked in the areas of molecular endocrinology and cancer biology for 35 years. I received a doctorate in Biochemistry and worked as a postdoctoral fellow at the National Cancer Institute where I studied epigenetic mechanisms of transcriptional regulation by steroid receptors. I continued that work after moving to the University of Arizona in 2006. Since then I focus on the roles of lysine deacetylases in glucorticoid-regulated transcription. Because several lysine deacetylase inhibitors are now approved for clinical use, I began a translational line of research to investigate their mechanism of action in Diffuse Large B Cell Lymphoma, the most commonly-diagnosed type of non-Hodgkin Lymphoma.
Cancer Focus
My cancer focus is on mechanism of action of histone/lysine deacetylase inhibitors, five of which have been approved for clinical use. To study this we use a cell-based, preclinical model of Diffuse Large B Cell Lymphoma (DLBCL). Our goal is to use this mechanistic knowledge to achieve rational prediction of therapeutics which could be combined to deacetylase inhibitors for synergistic effect. This will allow more efficient use of these drugs against DLBCL and potentially other blood cancers. In addition, we are using clinical trial samples to identify potential predictive biomarkers of clinical response to deacetylase inhibitors through next generation sequencing methods.
Selected Publications
Griggs, C. A., S. W. Malm, R. Jaime-Frias, and C. L. Smith, "Valproic acid disrupts the oscillatory expression of core circadian rhythm transcription factors.", Toxicol Appl Pharmacol, vol. 339, pp. 110-120, 2018 01 15. PMID: 29229235
Patrick, N. M., C. A. Griggs, A. L. Icenogle, M. M. Gilpatrick, V. Kadiyala, R. Jaime-Frias, and C. L. Smith, "Class I lysine deacetylases promote glucocorticoid-induced transcriptional repression through functional interaction with LSD1.", J Steroid Biochem Mol Biol, vol. 167, pp. 1-13, 2017 03. PMCID: PMC5444329 PMID: 27645313
Havas, A. P., K. B. Rodrigues, A. Bhakta, J. A. Demirjian, S. Hahn, J. Tran, M. Scavello, A. A. Tula-Sanchez, Y. Zeng, M. Schmelz, et al., "Belinostat and vincristine demonstrate mutually synergistic cytotoxicity associated with mitotic arrest and inhibition of polyploidy in a preclinical model of aggressive diffuse large B cell lymphoma.", Cancer Biol Ther, vol. 17, issue 12, pp. 1240-1252, 2016 12. PMCID: PMC5199166 PMID: 27791595
Kadiyala, V., N. M. Patrick, W. Mathieu, R. Jaime-Frias, N. Pookhao, L. An, and C. L. Smith, "Class I lysine deacetylases facilitate glucocorticoid-induced transcription.", J Biol Chem, vol. 288, issue 40, pp. 28900-12, 2013 Oct 04. PMCID: PMC3789985 PMID: 23946490
Tula-Sanchez, A. A., A. P. Havas, P. J. Alonge, M. E. Klein, S. R. Doctor, W. Pinkston, B. J. Glinsmann-Gibson, L. M. Rimsza, and C. L. Smith, "A model of sensitivity and resistance to histone deacetylase inhibitors in diffuse large B cell lymphoma: Role of cyclin-dependent kinase inhibitors.", Cancer Biol Ther, vol. 14, issue 10, pp. 949-61, 2013 Oct 01. PMCID: PMC3926892 PMID: 23982416