Neuromodulation Disorders Cluster

A number of health disparities exist within the predominantly Hispanic population of the U.S./Mexico border region served by the University of Texas at El Paso, including higher incidences of mental health disorders, obesity and type II diabetes, cervical and colon cancers, and cirrhosis of the liver. Environmental, genetic, biological, behavioral and socioeconomic factors all contribute significantly to these problems.

Research conducted within the Neuromodulation Disorders Cluster of the Border Biomedical Research Center is focused on developing specific treatment strategies for these maladies, and improving health measures and education throughout the area. The proposed studies range from investigations into the biochemical mechanisms of cellular function to the assessment of behavioral responses to addiction and stress. A core group of nine investigators in the Departments of Biological Sciences and Psychology will perform the majority of the research. The scope of the Cluster will be further extended, however, through collaborations with six additional researchers from the Departments of Biological Sciences and Mechanical Engineering. The translation of basic research into clinical correlates is a major aim of the Cluster, and will be more readily achieved through the continued support of our collaborators. To broaden the methodologies employed by the Cluster and increase collaborations with other groups, we hope to hire two additional faculty members who focus on neuroimmune interactions and developmental neurobiology. The research activities within and beyond the Cluster will generate a productive environment for training young scientists from underrepresented groups. Through research, education and training, the Neuromodulation Disorders Cluster will contribute substantially to the health and education of people in the El Paso/Cuidad Juarez community as well as the mission of the NIH and NCRR.

Mission

To contribute substantially to the health and education of people in the El Paso/Cuidad Juarez community as well as the mission of the NIH and NCRR

To contribute to the development of specific treatment strategies for neurological and metabolic disease states that are particularly relevant to border health.

Research Initiatives and Future Goals

The Neuromodulation Disorders Cluster of the Border Biomedical Research Center (BBRC) will undertake an integrated research program to address public health concerns of primary importance to the El Paso/Ciudad Juarez region of the U.S./Mexico border. This program will cross departmental boundaries to involve scientists with a wide range of skill sets, with the goal of generating interdisciplinary research results that will support the development of new therapeutic strategies for intervention. Each investigator will gain individually from their interactions with colleagues and collaborators who have shared goals but utilize different approaches, and the function of the Cluster as a whole will be enhanced by the broadening of perspective that will arise in this environment. In this way, the ability to translate basic research into clinical applications will be strengthened, and a diverse and productive research setting will contribute to the successful training of young scientists. Pursuant to these goals, continued enhancement of the infrastructure of the Cluster is required, including the acquisition of equipment, hiring of additional faculty, and support for research-related activities. Facilitation of these needs will sustain the momentum of all investigators toward securing extramural funding for future research and providing a vibrant research and educational environment for our students , consistent with the mission of the University of Texas at El Paso (UTEP) and the Research Centers in Minority Institutions (RCMI) program.  Research within the Neuromodulation Disorders Cluster contributes to six primary initiatives that are highly interrelated.

The "Mental Health" and "Metabolic Pathways and Disease " initiatives broadly address the two major divisions of the Project, share overlapping pathways and mechanisms with the other initiatives, and are relevant to public health in the El Paso/Ciudad Juarez region. Sustaining or improving mental health involves multiple neurological variables; this initiative focuses primarily on central nervous system mechanisms involved in addiction and affective disorders. Similarly, disruptions to cellular and systemic metabolic pathways contribute to numerous disease states, and research under this initiative investigates mechanisms of diabetes, cancer, and heavy metal toxicity.

NMD research projects:

• Mapping neural circuits critical for social interaction, monogamy, feeding control, sensory gating (attention), motivation, impulsivity, voluntary movement, learning and memory
• Sex differences in the mechanisms that promote nicotine reward and withdrawal
• Stem cell, prosthetic neural stimulation and neural tissue engineering for neuroregeneration
• Neural, cellular and molecular mechanisms underlying gene x environment x social interactions in behavioral plasticity and cognition
• Autonomic Regulation

NMD research expertise:

• Substance/alcohol abuse and addiction, Alzheimer’s disease, Parkinson’s Disease, obesity, diabetes, schizophrenia, epilepsy & neurodevelopmental disorders including ADHD and autism
• Attention, motivation, movement, learning, memory & neurodevelopment
• Behavioral, genetic, epigenetic, optogenetic, electrophysiological, imaging, brain mapping, neuroengineering, 3D printing, nanoparticle, stem cell, computational, molecular, cellular, biochemical and pharmacological approaches

Other research initiatives within the project include:

a) "Learning and Memory" , which seeks to understand the mechanisms behind the deficits in learning and memory that occur in response to age or insult;

b) "Neurogenetics and Development" , which is tightly linked with the Learning and Memory initiative, but with a view toward understanding how combinations of contributing factors can affect normal and pathological outcomes;

c) "Environmental Stress and Toxicology" , which considers the neurological and other consequences of exposure to environmental toxins and physiological challenges; and

d) "Recovery and Repair ", which focuses on recovery of function following conditions of neurological or metabolic dysregulation.

Within these frameworks, investigators in the NEUROMODULATION DISORDERS Project operate in a highly integrative and collaborative manner. The goals of this research are to increase our basic knowledge of the function of neurological and metabolic systems under normal and pathological states, and to improve the treatments for disorders of these systems through the identification of drug targets and enhancement of tissue transplantation strategies.

Faculty Research Interests

Faculty

Project Director

Dr. Kyung-An Han is an Associate Professor and Director of the Neuroscience and Metabolic Disorders Project. The major interest of her research is the molecular, biochemical, cellular and neural basis of behavioral plasticity. Monoamines such as dopamine, serotonin and norepinephrine affect numerous physiological and behavioral processes including emotion, attention, motivation, reward, learning, memory and motor control. Anomalous dopamine functions in particular underlie various neurological and psychiatric disorders such as Parkinson’s disease, schizophrenia, ADHD and drug addiction. Dr. Han’s research aims at elucidating the mechanisms by which dopamine and octopamine (an invertebrate counterpart of mammalian norepinephrine) mediate behavioral plasticity induced by natural stimuli and addictive drugs and reproduction in the fruit fly Drosophila melanogaster. Drosophila is a powerful model organism due to its well-characterized genetics with the fully sequenced genome and relatively simple nervous system mediating numerous versatile behaviors. The molecules important for development, synaptic transmission and plasticity, and behavioral plasticity are conserved from Drosophila to mammals including humans. Thus, knowledge obtained from her study in Drosophila provides insights into neural mechanisms underlying behavioral plasticity and related disorders in humans.

Project Members

Dr. Edward Castañeda, Professor in the Department of Psychology at UTEP brings senior leadership and experience along with his scientific background that meshes exceptionally well with the Neuromodulation Disorder Cluster. His research interests focus on the extrapyramidal motor systems, with special attention to the role of dopamine in functional behavioral recovery following brain damage and in amphetamine-induced psychosis. Recently, his work has sought to address the mechanisms of drug abuse and addiction in Hispanic populations, with a view toward gaining a better understanding of health disparities in this ethnic group.

Dr. Manuel Miranda is an Assistant Professor and the most recent hire in the Department of Biological Sciences. Interested in the regulation of intracellular trafficking of neurotransmitter transporters, Dr. Miranda’s Cellular and Molecular Neuroscience laboratory investigates the pathological trafficking of dopamine and glycine transporters that may contribute to Parkinson’s disease and schizophrenia, respectively. In addition, a more thorough understanding of transporter activity and the resulting effects on the duration of synaptic signaling may provide new information about the mechanisms of drug addiction and withdrawal. Dopaminergic mechanisms, in general, are heavily involved in mental health disorders that are prevalent in the U.S./Mexico border region, including substance abuse and depression.

Dr. Laura E. O’Dell is  a Professor and PI of the Behavioral Neuroscience Laboratory in the Department of Psychology.

Dr. Sukla Roychowdhury is a Research Assistant Professor in the Department of Biological Sciences, with interests in the ultrastructural and biochemical aspects of intracellular signaling. Specifically, she studies the role of G proteins in microtubule assembly and disassembly through their interactions with tubulin in the cytosol. This research contributes to our basic understanding of cell growth and motility, especially in the nervous system where plasticity in neuronal connectivity can take the form of rapidly remodeling projections and contacts that must be supported and stabilized by cytoskeletal mechanisms. Another important focus of this work relates to cell division and the regulation of the mitotic spindle apparatus which is composed of microtubules. Pharmacological blockers of microtubule assembly can serve as anti-cancer agents and may lead to new treatments for cervical or colon cancer which occur at a higher rate in people of Hispanic origin.

Dr. Rachid Skouta is a Research Assistant Professor in the Department of Biological Sciences. His research interests and activities span many traditional and emerging disciplines of chemistry and biology, with noteworthy focuses on the use of organic chemistry, medicinal chemistry and computational chemistry as tools to solve biological problems. Currently, Dr. Skouta is developing new catalytic reactions to synthesize interesting compounds, including natural products, with biological properties. These compounds will be tested in neurodegenerative and cancer disease models toward drug discovery and new treatments.

Dr. Christina Sobin , Professor, Public Health Sciences investigates how selected brain mechanisms alter behavior during development. She does so by studying low-level lead exposure and other physiologic conditions of childhood that disrupt glutamate/GABA pathways. She characterizes and quantifies the neurocognitive and behavioral deficits associated with these conditions, and then develops mouse models to explore the neuropathologic mechanisms that might account for observed behavioral and learning deficits. Dr. Sobin's work is translational and integrates methods from the fields of neuropsychology, neuroendocrinology, and neuroscience. The range of conditions studied in her laboratory is intentionally broad, and ranges from toxicant exposure to genetic disorders (22q11deletion syndrome). By studying diverse conditions with shared neuropathologic mechanisms, she is developing a unified model of how behavior is affected over time by cumulative damage in particular brain pathways.

Collaborators

Dr. Ellen C. Dengler is an Assistant Professor in Physical Therapy. Her research interest includes the neuro-immune signaling in neurodegenerative disease and chronic neuropathic pain. Most recently, along with collaborators at the Universities of New Mexico and Kentucky, I have been developing a novel in vivoelectrochemical methodology to measure real time glutamate neurotransmission the spinal cord of a live anesthetized animal. We are making these measurements the SOD (G93A) transgenic rat model of ALS, a fatal disease of human motor neurons for which there presently is no cure. Specialized ceramic–based, multi-site electrodes are being used for rapid, second by second measures of the release and uptake of the neurotransmitter glutamate. High glutamate levels have been implicated as one of several mechanisms responsible for onset of this disease. This new technology allows measurements directly in the ventral horn, a part of the spinal cord that houses neurons that dying in ALS. This research may shed new light on our current understanding of how this disease begins, progresses and responds to potential therapeutic medication.

Dr. Jeannie B. Concha is an Assistant Professor in the Department of Public Health Sciences. She received her PhD in public health from the University of Illinois at Chicago and her MPH from the University of Texas Health Science Center. Her research focuses on psychological well-being and diabetes prevention in ethnic minority and marginalized populations. Specifically, she investigates the impact of psychological distress on diabetes development, prognosis, and outcomes. Her previous work experience includes academic quantitative and qualitative mixed-methods research, managing non-profit community oriented diabetes education and prevention efforts in New Mexico, and conducting diabetes community resource and needs assessments. Her strength as a researcher is the ability to identify and garner cultural and community assets for reframing the public health messaging. She is currently working on an interdisciplinary Community Based Participatory Research (CBPR) diabetes awareness and management project tailored specifically for men in the El Paso, Texas community.

Dr. Kristine M. Garza is an Associate Professor in the Department of Biological Sciences and PI of the Cellular Immunology laboratory. Her interests lie in the activation and responses of T lymphocytes following their interaction with macrophages and dendritic cells. Current studies are focusing on the effects of leptin, a blood-borne signal related to fat stores and metabolic function in the body, on dendritic cell function. Enhancing T-cell immunity in type II diabetes is a major goal of this research, and will contribute to border health where obesity and type II diabetes are significant concerns.

Dr. Robert A. Kirken is Principle Investigator of the RCMI grant that supports the BBRC, Full Professor and Dean of the College of Science. His research interests are in cytokine signaling and the regulation of T-cell responses. Specifically, his Molecular Immunoregulation laboratory examines the role of interleukin-2-induced activation of intracellular Jak/Stat signal transduction pathways that may serve as drug targets for immunomodulation. Pharmacological manipulation of these pathways may translate directly into greater successes in organ or tissue transplantation, and improvements in the treatment of autoimmune disorders, both of which are key health concerns for the border region and beyond.

Dr. Ryan B. Wicker is a Full Professor in the Department of Mechanical Engineering and Director of the Keck Laboratories. Research in Dr. Wicker’s laboratory includes the use of biocompatible polymer scaffolds as structural support for live cells that contribute to tissue repair following injury or disease. For peripheral nerve injury, implanted scaffolds are placed at the site of transection and serve as a conduit for nerve regrowth. Seeding of the scaffold with support cells and bioactive factors further promotes regeneration and may alleviate the pain and sensory or motor deficits often experienced by patients with this type of injury. Similarly, hepatocyte-seeded scaffolds can enhance survival and metabolic function in conditions of liver failure, and increase lifespan and quality of life in patients awaiting transplant. Increases in liver and nerve function may improve health outcomes in people with toxicity-induced liver damage or diabetic neuropathy, both of which are prevalent in the border community. In addition, functional improvement through nerve or liver regrowth may be useful within the military sector of the El Paso area, where injuries to these tissues are regularly sustained.