Project Summary Preeclampsia, a hypertensive disorder of pregnancy, can advance to eclampsia, when the mother displays novel seizures. The mechanisms that cause some preeclampsia patients to advance to eclampsia are unknown. The long-term goals are to identify therapeutic targets to prevent seizures in pregnancy and preeclampsia and to pursue a career as an academic scientist.
PROJECT SUMMARY The cerebellum has long been thought to solely process motor information. Yet, there is a growing literature that points to a role of the cerebellum in processes across multiple domains. Individuals with cerebellar lesions classically have motor deficits but, in some instances, also have problems with executive functioning, emotion processing, language, and social cognition. Multiple psychiatric disorders, including autism spectrum disorders (ASD), have been linked to structural and functional differences in the cerebellum.
Project Summary Primate species frequently use social information to inform their decisions, for instance, to help make inferences about potential threats or rewards in the environment. The Diagnostics and Statistical Manual for Mental Disorders (DSM) has labeled social impairments, including social cognition, as a primary characteristic of many mental health-related disorders, including Autism Spectrum Disorder and Schizophrenia. Therefore, understanding the neurobiology surrounding social cognition and decision-making is of critical importance.
PROJECT SUMMARY: Behavioral dysfunction in neurodevelopmental diseases often arises from aberrant neural circuit assembly. However, the developmental logic that dictates circuit organization, function, and ultimately behavior remains unresolved due to the complexity of most circuits.
Project Summary Mutation of HCFC1 causes a multiple congenital anomaly syndrome characterized by inborn errors of cobalamin metabolism, intractable epilepsy, intellectual disability, and motor dysfunction. Despite an implication for HCFC1 in these neurological impairments, a mechanism describing the function of HCFC1 during brain development has not been completely elucidated. HCFC1 encodes for a transcriptional co-factor protein known to regulate cellular proliferation of various progenitor cells including neural precursor cells (NPC).
PROJECT SUMMARY Stress and addiction are intricately linked neural processes. Acute stress can serve as a stimulus for relapse to compulsive drug seeking following abstinence, and chronic stress can induce escalated drug intake to multiple classes of drugs. The Jones lab and others have shown that the chronic psychosocial stressor of adolescent social isolation (aSI) leads to impairments in dopamine (DA) function in the nucleus accumbens (NAc) and increased vulnerability to stimulant drug and alcohol taking that persists into adulthood.
PROJECT SUMMARY Charcot-Marie-Tooth (CMT) disease is a genetically and clinically heterogeneous group of inherited peripheral neuropathies that is characterized by damage to long motor and sensory axons. The overall goal of this project is to identify the molecular and cellular processes that are shared between different CMT genes to help address a common target for treatment for this currently incurable disease.
Optical voltage imaging analysis of the cellular and network mechanisms of deep brain stimulation Deep brain stimulation (DBS) directly stimulates brain tissue via implanted electrodes. DBS has emerged as a well-established therapy, FDA approved for several neurological and psychiatric disorders, and is increasingly explored for a variety of brain diseases. However, the neurophysiological mechanisms of DBS remain largely unknown. DBS therapeutic outcomes and time courses are diverse and depend on the specific disease conditions targeted.
The underlying mechanisms of brain stimulation in humans are poorly understood, especially at the level of gene expression. To address this gap in knowledge, we propose a series of three experiments that take advantage of the opportunity to obtain high-quality human neural tissue from neurosurgical patients in order to measure the impact of brain stimulation on gene expression. Our experiments will generate data to explicate changes at the level of gene expression that underlie brain circuit changes elicited by stimulation.
ABSTRACT Perturbations in redox signaling are associated with multiple neurological disorders, ranging from neurodegenerative diseases to brain tumors. The brain tumor glioblastoma (GBM) is a devastating disease and improved understanding of its altered bioenergetics and redox status is likely to improve treatment options. GBM is highly heterogeneous and includes cells that have altered redox states and similarities to neural stem cells, called brain tumor initiating cells (BTICs), that cause tumor recurrence.
