Amy Gardiner, MD, PhD
Department of Neurosciences
Cellular and Molecular Oncology
University of Pittsburgh School of Medicine
My research interests include understanding the role of post-transcriptional mechanisms in embryonic development, substance abuse, and cancer. Cancer-related projects involve examining the function of the post-transcriptional regulator KSRP and its non-protein-coding RNA targets using cell culture and animal models of glioblastoma multiforme. Post-transcriptional regulators control the expression of a vast number of neuronal genes through the regulation of such processes as mRNA splicing, stability, localization, and translation. Many microRNAs (miRNAs) and RNA-binding proteins (RBPs) are therefore considered to be important regulators of gene expression. Much of my work has concentrated on defining the regulatory regions and mechanisms that direct post-transcriptional processes. Recent projects include describing the molecular competition between a miRNA and an RBP for control of genes important in synaptic plasticity and addiction, exploring the function of two RBPs, HuD and KSRP, in their control of genes critical for neuronal development, and identifying miRNAs in maternal serum that are associated with alcohol consumption. KSRP expression is significantly associated with prolonged survival of glioblastoma patients. Next-generation sequencing of KSRP targets in the cortex revealed novel long non-coding RNAs (lncRNAs) and miRNAs, many of which are altered in glioblastoma multiforme. Further studies will provide insight about the role of KSRP in glioblastoma and its potential as a therapeutic target. We also used next-generation sequencing to identify miRNAs in the plasma of pregnant dams that were indicative of alcohol exposure and effects on the fetus. Of particular interest was miR-150-5p, a negative regulator of angiogenesis, which was significantly increased in the developing cortices of animals prenatally exposed to alcohol. We also identified a novel target, vascular endothelial zinc finger 1 (Vezf1), an endothelial-specific transcription factor required for normal vascular development. Further investigation will provide insight about the role of miR-150-5p in regulating the structure and function of the cortical vasculature.