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Dr. Smith is a molecular endocrinologist with 30 years of research experience in the area of steroid receptors and epigenetic mechanisms of transcription. Her current research focuses on two areas involving lysine (histone) deacetylases. The first area involves the role of histone deacetylases in glucocorticoid-regulated transcription. They have determined that these enzymes play important roles in both activation and repression of transcription by glucocorticoid receptor. Dr. Smith is the PI on an NSF grant that is focused on defining the mechanism by which lysine deacetylases cooperate with glucocorticoid receptor to activate transcription. Small molecule inhibitors of deacetylases (HDACi) are used clinically in the treatment of cancer, epilepsy, and bipolar disorder. Their work strongly indicates that these drugs could act as endocrine disruptors in vivo and should be used with care in humans.
The second area of deacetylase research is focused on developing effective anti-lymphoma therapies that incorporate drugs such as deacetylase inhibitors, which target the epigenome. Recent next generation sequencing studies have revealed significant epigenetic deregulation during lymphomagenesis that might be circumvented with epigenome-targeted drugs. She has attracted funding from multiple sources to fund this research.
Dr. Smith was recently informed that she would receive a two year grant from the Hope Foundation to use next generation sequencing techniques to identify potential biomarkers of clinical response to histone deacetylase inhibitors using patient tumor samples collected during a clinical trial that incorporated treatment with the deacetylase inhibitor, vorinostat. She collaborates with two University of Arizona Cancer Center members to conduct the lymphoma studies: Daniel Persky, MD (Dept. of Medicine) and Monika Schmelz, PhD (Dept. Pathology). In addition, this work is supported by a translational group of scientists that form the Lymphoma Consortium at the cancer center.