Paula Monaghan-Nichols, PhD
Professor and Chair, Department of Biomedical Sciences
Associate Dean of Research Administration
University of Missouri, Kansas City
PhD, Medical Research Council, Edinburgh
Postdoctoral Fellowship, Medical Research Council, Edinburgh
Prenatal basis of neurological and behavioral abnormalities
My laboratory focuses on understanding the molecular and developmental basis of emotional and cognitive behavior and psychiatric illness. The long-term goal of my research is to identify both intrinsic and environmental factors that specifically alter the development of areas in the brain that are essential for emotion and cognition. My laboratory has identified a number of transcriptional repressors (Tlx, Sall1, Sall2, Sall3 and Sall4) that are expressed in the developing forebrain.
This research has shown that these genes are express in stem and progenitor cells in the cerebral cortex, and are required to regulate the rate of stem/progenitor cell proliferation and neuronal differentiation. Using both conditional and classical knockout experiments and in-utero electroporation studies in mice, my laboratory has shown that altering the levels of these proteins during development leads to emotional, behavioral and cognitive abnormalities in adult animals.
Our most recent studies focus on identifying the cellular and biochemical targets of glucocorticoid action on the developing brain in-utero. Synthetic glucocorticoids are administered to mothers at risk for pre-term labor, to stimulate lung maturation and to reduce the risk of intraventricular hemorrhage and necrotizing enterocolitis. Clinical follow up studies indicate that children exposed to steroid in-utero have cognitive abnormalities and an altered stress response. My laboratory is using a combination of molecular, cellular, proteomic, RNA-Seq. and genome wide DNase hypersensitive site mapping to identify the cellular targets of steroid action. These studies have shown that prenatal exposure to glucocorticoids leads to changes in neuronal number and density in the cerebral cortex at birth coupled to long-term alterations in neurite complexity in the prefrontal cortex and hippocampus in adolescents. These anatomical abnormalities are associated with changes in anxiety and depressive like behaviors in adults.
Follow up studies include validating our identified targets in human brain and in umbilical cord blood cells. These findings will for a framework for modifying current clinical dosing regiments in preterm labor to reduce the adverse consequences of premature exposure to corticosteroids in-utero.