cmbn contributing faculty and research
In addition to the investigation shown here, read about clinical trials now in progress at the Center.
Twum Ansah, Ph.D.
Department of Neuroscience and Pharmacology
The research in Dr. Twum Ansah's laboratory seeks to understand the neurobiological mechanisms that mediate neurological disorders, such as Parkinson's Disease as well as psychiatric disorders such as depression and drug abuse, all of which involve the dopaminergic system and its regulation by other systems, such as the serotonergic system. His major research efforts are being devoted to systematically investigate alterations in the serotonergic system and to understand its role in the hypokinesia produced by lesioning of the dopaminergic system with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The objective is to understand the role of serotonin in the neurobiology of Parkinson's Disease and how manipulating the serotonergic system might alter the course of the disease, as a prelude to identification of novel therapeutic targets for the disease.
Clivel George Charlton, Ph.D.
Professor and Chairman
Department of Neurobiology and Neurotoxicology
Dr. Charlton's laboratory is exploring the possible causal relationship between excess methylation in the brain and Parkinson's disease. Methylation depletes the amount of the essential neurotransmitter dopamine and increases levels of lyso-phosphatidyl choline, which disrupts the structure of biological membranes in the microcompartment where this occurs. Dr. Charlton and his colleagues have observed that injection of the methyl donor, S-adenosyl-methionine (SAM), into the brain of rodents results in extensive brain methylation and causes transient tremor, hypokinesia, rigidity, and abnormal posture, changes that resemble the motor deterioration that accompanies Parkinson's. Consistent with their hypothesis of a role of methylation in the pathway leading to Parkinson's disease is the finding that MPP+, a toxic metabolite linked to Parkinson's disease development in human beings, increases SAM-dependent methylation in the brain. The laboratory is exploring possible therapeutic interventions to alter these methylation processes. Interestingly, a current Parkinson's therapy, L-dopa, diminishes the Parkinson's-like symptoms in SAM-injected rats. However, there are considerable side effects and loss of effects of L-dopa when given therapeutically. Dr. Charlton and his colleagues are also exploring the molecular basis for these unwanted treatment sequelae.
Darryl B. Hood, Ph.D.
Department of Neuroscience and Pharmacology
The research program of Dr. Hood is in the area of Environmental Health and Toxicology with a particular interest in the effects of exposure to environmental toxicants during critical periods of CNS development and the subsequent effects on behavioral learning in offspring. The specific compounds of interest are polycyclic aromatic hydrocarbons (PAHs). The environmental contaminants of immediate concern to minority communities are released as emission by-products from industrial environmental polluters. Dr. Hood's laboratory has been investigating and characterizing the health effects of polycyclic aromatic hydrocarbon exposure using various exposure regimens for over a decade. The long-term goal is to determine the mechanistic connection between environmental insults to experience-dependent neural activity and alterations in gene expression during the postnatal period when synapses are forming for the first time (PND7-14). The recent finding by a group at Vanderbilt [Morrow et al., (2008)] has illuminated the fact that deletions of certain genes that are regulated by neuronal activity or that certain regions of these genes are potentially involved in regulation of gene expression in environmental exposure-induced disease. This work has served to spotlight Dr. Hood's studies where he is testing hypotheses of prenatal toxicant-induced insult to activity-dependent gene expression as a cause of behavioral deficits in the neuropathology of at least a subset of environmental exposure-induced behavioral learning disorders.
Sukhbir Mokha, Ph.D.
Professor, Meharry Department of Neuroscience and Pharmacology
Adjunct Professor of Pharmacology, Vanderbilt University
Director of Graduate Studies, Neuroscience Program
Dr. Mokha's laboratory is investigating the neurobiology of pain and analgesia in normal and pathological states using electrophysiological, behavioral, cellular, and molecular techniques. Many painful syndromes/disorders such as migraine, trigeminal neuralgia, temporomandibular joint disorder (TMJ/TMD), and irritable bowel syndrome (IBS) are more prevalent in women than in men. Dr. Mokha and his colleagues are interested in understanding the biological mechanisms that generate the higher prevalence of painful syndromes in women. Specifically, the laboratory is investigating whether activation of endogenous noradrenergic or serotonergic pathways involving G protein–coupled receptors (opioid, noradrenergic, and serotonergic) produce estrogen-dependent, sex-specific inhibition of pain mechanisms , in both spinal and trigeminal systems. Estrogen-dependent decreased inhibition in the female could contribute to the higher prevalence of painful syndromes in women. They have already provided evidence that estrogen decreases the analgesic effects produced by activation of α₂-adrenoceptors and opiod or opiod-like receptors (ORL1) in the spinal cord and trigeminal system and have shown that estrogen alters the expression of the gene encoding ORL1.
Mitchell Parks, M.D.
Assistant Professor, Department of Psychiatry & Behavioral Sciences
Dr. Parks's research examines the nexus of two health disparities in African-American women: their documented increased incidence of alcohol use disorders and their prevalence of HIV infection. The technique employed to address the question of why these two disparities occur in this population is functional magnetic resonance imaging (fMRI). fMRI utilizes hemoglobin as a natural tracer to differentially determine activity in brain areas. Dr. Parks's previous work with chronic alcoholic patients determined their different utilization of frontal and parietal regions in response to simple motor tasks. The objective in the work with African-American women is to use fMRI to determine whether routine or binge ingestion of alcohol incurs changes in brain physiology that might lead to HIV infection risk.
Eun-Sook Lee, Ph.D.
Department of Physiology
Impairment of astroglial glutamate transporters is associated with various neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and manganism, which is caused by chronic manganese (Mn) exposure. Since tamoxifen (TX) and 17B-estradiol (E2) have been shown to be neuroprotective in various neurodegenerative diseases, Dr. Lee is testing whether E2/SERMs can exert neuroprotective effects by attenuating Mn-induced impairment of astroglial glutamate transporters. Moreover, Dr. Lee's team is testing whether growth factors, TGF-a/B, mediate E2/TX-induced restoration of glutamate transporters.