Alcohol Research Training in Neuroscience

MSC 08 4740
1 University of New Mexico
Albuquerque, NM 87131

Phone: (505) 272-4411
Fax: (505) 272-8082

Faculty

Andrea Allan, Ph.D. (Professor, Department of Neurosciences)  

Dr. Allan's laboratory has focused on exploring the mechanisms through which prenatal exposures to alcohol produce developmentally imprinted modifications in stress responding and stress pathways.  Stress and steroid hormones have been shown to affect synaptic receptors and ion channels and thus regulate synaptic transmission, neuronal plasticity and neurogenesis.  Dr. Allan is exploring the developmental alterations within the hypothalamic-pituitary-adrenal (HPA) axis including steroidal regulation within the hippocampus, amygdala and the medial frontal cortex in an effort to link these modifications to fetal alcohol-induced changes in impulsive behavior, learning and memory, depression, anxiety and stress responding (Component 4 of the P50 NMARC in collaboration with Dr. Caldwell).  A collaborative research project between her laboratory and Dr. Cunningham’s laboratory has found that prenatal ethanol modifies adult neurogenesis.  Dr. Allan is investigating epigenetic changes that may underlie the pathophysiology of FASD. Techniques employed are related to basic and behavioral pharmacology, molecular biology and epigenetics, behavior, and protein biochemistry. In addition to the research on FASD, Dr. Allan studies the epigenetic effects of prenatal arsenic exposure on stress responding in both placenta and brain.


Jonathan Brigman, Ph.D. (Associate Professor, Department of Neurosciences)

Prior to joining the faculty at UNM he completed postdoctoral work with Drs. Andrew Holmes and David Lovinger at the NIAAA Intramural Research Program.  His research focuses on the biological basis of maladaptive behavioral changes that accompany alcohol abuse, drug addiction and numerous neuropsychiatric disorders.  Dr. Brigman’s laboratory integrates genetic, pharmacological and in vivo electrophysiological recording techniques with behavioral assays and newly developed touch-screen based asks. He is currently investigating the role of corticostriatal networks and glutamatergic systems in mediating habitual and executive control behaviors as PI of Component 5 of the P50 NMARC together with Dr. Valenzuela.  In addition, he is investigating commonality of neural mechanisms in cross species tasks of Research Domain Criteria utilizing rodent EEG and depth recording approaches. He is also Associate Director of the Preclinical Core of the Center for Brain Recovery and Repair, focused on making access to sophisticated instrumentation for behavioral and anatomical assessment available to the research community at UNM.


Kevin Caldwell, Ph.D.  (Professor, Department of Neurosciences)

The primary area of research in Dr. Caldwell’s laboratory is the study of signal transduction systems that underlie learning and memory and their roles in cognitive dysfunction resulting from developmental exposure to environmental factors, with a focus on alcohol and arsenic.  These studies are conducted in collaboration with the Valenzuela lab and aim to test the hypothesis that errors in the integration of cellular signaling are important components of the neurochemical imbalances that underlie the cognitive abnormalities associated with prenatal alcohol exposure.   In collaborations with the Allan Lab, Dr. Caldwell’s laboratory studies the associations between prenatal ethanol exposure and emotional disorders, with a focus on depression and stress disorders (Component 4 of the P50 NMARC).  In addition, in collaboration with the Allan Lab, Dr. Caldwell’s laboratory studies the transcriptional, posttranscriptional and posttranslational regulation that underlie the effects of prenatal arsenic exposure on learning and memory and stress responding.  Results from these studies will facilitate the development of targeted therapeutics for the treatment of learning and behavioral disorders that are associated with prenatal exposures to alcohol and environmental toxins.


Benjamin Clark, Ph.D., (Assistant Professor, Department of Psychology)

Studies in Dr. Clark’s laboratory are aimed at better understanding the circuit level mechanisms underlying how the mammalian brain generates neural signals reflecting an animal’s spatial orientation. His work has focused on a class of limbic system and hippocampal neurons that behave much like a neural “map” and “compass”, called head direction cells, grid cells, and place cells. A broad aim of his research program is to apply this model system of spatial orientation to further understand the structural and functional loss in prenatal alcohol exposure (supported by a Pilot Project from the P50 NMARC and an NIAAA R21) and Alzheimer’s disease, both of which are marked by symptoms of spatial disorientation and memory impairment, and to evaluate treatments promoting brain recovery and repair. He uses a combination of techniques to map the functional connectivity of neural circuits including high-density electrophysiology recordings in behaving rodents, neuroanatomical tracing, and immediate early gene expression to identify neural activity and plasticity within circuits during behaviorally relevant events.  Dr. Hamilton will be the senior mentor for Dr. Clark.


Lee Anna Cunningham, Ph.D. (Professor, Department of Neurosciences)

Dr. Cunningham’s laboratory studies neural stem cell function in mouse models of CNS plasticity and repair.  Current research in her laboratory is focused on understanding the long-term impact of developmental alcohol exposure on postnatal hippocampal neurogenesis, utilizing a combination of genetic, anatomical, electrophysiological and behavioral approaches. She is particularly interested in how gestational or early postnatal alcohol exposure results in long-lasting changes in the survival and integration of adult-generated hippocampal dentate granule neurons under conditions of enriched environment (Component 3 of the P50 NMARC in collaboration with Dr. Valenzuela).  More recently, her laboratory has also begun studies to investigate mechanisms by which developmental alcohol impairs oligodendrogenesis and causes long-term white matter injury. She is also investigating neural stem cell function in plasticity and repair mechanisms following ischemic stroke.


Derek Hamilton, Ph.D. (Professor, Department of Psychology) 

Dr. Hamilton utilizes basic behavioral, pharmacological, anatomical, and electrophysiological methods to investigate the neurobiological foundations of learning, memory, and behavior. His work includes investigations in humans and rats with an emphasis on the role of the frontal cortex and hippocampus in complex behavior and cognition. He is currently investigating the effects of moderate prenatal ethanol exposure on frontal cortex function and hippocampal function, in relation to social behavior and spatial memory deficits, respectively (supported by an R21 from NIAAA). These studies are being performed in collaboration with the laboratories of Drs. Savage, Valenzuela, and Clark.


Erin Milligan, Ph.D. (Associate Professor, Department of Neurosciences)

Dr. Milligan’s research focuses on the role of spinal cord glial-derived factors such as proinflammatory cytokines and chemokines in generating pathological pain states. She has been examining how adverse in utero conditions alter spinal sensory signaling that predisposes one to developing neuropathy following minor peripheral nerve insults. Given the profound neuroimmune overlap that exists with animal models of prenatal alcohol exposure (PAE) and chronic neuropathic pain that includes immune proinflammatory cytokines, she has been studying the effects of PAE on spinal neuroimmune function and the susceptibility to developing neuropathic conditions such as allodynia (pathological sensitivity to light mechanical touch).  Dr. Milligan has been supported by a pilot project from the P50 NMARC and an R21 from NIAAA (in collaboration with Dr. Savage).  She currently has a pending NIAAA R01 that is being considered for funding.


Nora Perrone-Bizzozero, Ph.D. (Professor, Department of Neurosciences) 

Dr. Perrone-Bizzozero’s program is focused on the post-transcriptional control of neuronal gene expression during normal nervous system development and in neurodevelopmental disorders, particularly in animal models of prenatal alcohol exposure. She is interested in defining how prenatal alcohol exposure affects the levels of growth- and plasticity-associated proteins such as GAP-43, BDNF and the RNA-binding proteins HuD and KSRP, and microRNAs (miRNAs) that affect their expression. She is also studying the genetic contributions to brain imaging alterations in patients with schizophrenia.  More recently, she has begun to examine the role of RBPs and miRNAs in the context of cocaine addiction. She is currently collaborating with Drs. Andrea Allan, Dan Savage and Ludmila Bakhireva on the identification of biomarkers of maternal alcohol consumption in serum samples from pregnant women and mouse dams that consume alcohol during pregnancy (Component 7 of the P50 NMARC). Throughout these studies, Dr. Perrone-Bizzozero’s group employs a variety of in vitro molecular, cellular and in vivo techniques as well as bioinformatics approaches for the analysis of genome-wide gene expression and genetic data. Trainees in her laboratory are exposed to several state-of-the-art methodologies ranging from RNA-sequencing, qRT-PCR and microarray studies to lentiviral-mediated gene transduction, and in situ hybridization for both mRNAs and miRNAs, together with immunocytochemistry.


Daniel D. Savage II, Ph.D. (Regents' Professor & Chair, Department of Neurosciences)

Dr. Savage’s laboratory was the first to report that the consumption of moderate quantities of ethanol during pregnancy causes persistent changes in markers of glutamatergic neurotransmission in rats.  These changes were associated with decreased dentate gyrus long-term potentiation (LTP) as well as hippocampal-sensitive learning deficits in prenatal alcohol-exposed (PAE) rats.  He is the PI of a NIAAA R01 award (AA019884) examining the impact of PAE on histaminergic regulation of glutamatergic neurotransmission (in collaboration with the Valenzuela and Hamilton Labs).  This work has led to the observation that PAE increases histamine H3 receptor-mediated inhibition of glutamate release.  Currently, Dr. Savage is applying his moderate PAE paradigm towards two translational research endeavors.  First, he is conducting preclinical screening of novel therapeutic interventions for PAE-induced behavioral and neurophysiological deficits.  In this project, he has shown that histamine H3 receptor inverse agonists ameliorate the LTP and learning deficits observed in PAE rats.  Second, he is using the moderate PAE to develop novel biomarkers for identifying offspring with functional brain damage as a consequence of PAE.  This work has begun to span from basic to clinical research on biomarkers for FASD.  Dr. Savage serves as the Director of the NIAAA P50-funded New Mexico Alcohol Research Center (AA022534).  He is the 2011 recipient of the Henry Rosett Award for excellence in FASD research and was a member of the RSA Board of Directors)


C. Fernando Valenzuela, M.D., Ph.D. (Director of T32 Alcohol Research Training Program in Neurosciences.  Professor, Department of Neurosciences) 

Research in the Valenzuela lab has focused on the modulation of synaptic transmission and plasticity by alcohol in the central nervous system.  A major area of research interest is the effects of ethanol on developing neuronal circuits in several brain regions (cerebral cortex, hippocampus, cerebellum and amygdala).  A multidisciplinary approach is used in the Valenzuela lab, which includes electrophysiological, histological, Ca2+ imaging, and behavioral techniques.  Dr. Valenzuela is currently investigating the impact of developmental ethanol exposure on the function of GABAergic interneurons.  He is also characterizing the role of a BDNF gene polymorphism in determining the severity of developmental effects of alcohol.  He is also working on several collaborative projects with P50 investigators (Cunningham, Brigman, and Savage).


 Julia Stephen, Ph.D. (Associate Professor of Translational Neurosciences, MIND Research Network).

Dr. Stephen specializes in applying functional neuroimaging techniques in humans to investigate both sensory and cognitive functioning.  She uses the unique spatial and temporal precision afforded by magnetoencephalography (MEG) to better understand normal and abnormal brain function. MEG is a completely noninvasive technique which allows us to study brain development in children across the age spectrum, without confounds related to changes in skull anatomy. Dr. Stephen is currently using MEG to characterize sensory functioning in preschool and adolescent children with FASD to identify reliable markers of atypical brain development in individuals with prenatal alcohol exposure (Component 6 of the P50 NMARC). Furthermore, Dr. Stephen is using multimodal neuroimaging (MEG, EEG and MRI) to better characterize structural and functional deficits with the goal of identifying sensitive and specific markers for developmental brain disorders.


Jason Weick, Ph.D. (Assistant Professor, Department of Neurosciences)

Work in the Weick lab centers on understanding multiple aspects of the development of functional neural circuits, from how individual neurons acquire functional properties to how groups of neurons generate patterns of information. Using neurons differentiated from pluripotent stem cells he studies development both under normal conditions and in the context of developmental disorders. First, he recently identified an uncharacterized protein that is strongly upregulated as neuroepithelial cells differentiate to post-mitotic neurons, but is subsequently downregulated in adults. It is part of a family of proteins, the other members of which are known to associate with, and aid in the shuttling of receptors within post-synaptic compartments. He hypothesizes that this protein plays a central role in delivering molecular components involved with neurotransmission to the plasma membrane during a critical period of development. Secondly, new projects are focusing on aberrant development of neural circuits caused by genetic or environmental abnormalities that result in intellectual disabilities. For instance, he has identified an abnormal pattern of activity in in vitro cultures of neurons that carry trisomy 21. Current investigations seek to understand the molecular cause of this abnormality. Lastly, we are investigating the effects of ethanol on developing neurons during early stages of synapse formation (supported by a pilot project from the P50 NMARC).  Dr. Cunningham will be the senior mentor for Dr. Weick.


Additional Faculty

UNM-ARTN trainees will also have access to other investigators with complementary scientific expertise to that of the core training faculty. Although these individuals will not serve as primary mentors of our trainees, they will significantly contribute to the training of our students by, for example, serving on dissertation committees.  These individuals will also regularly attend student presentations at Student Data Blitzes, training grant retreats, and Journal Clubs, and will provide feedback on manuscripts and fellowship applications.  They will also be available for consultation regarding experimental design and technical issues.  Some of these faculty members work with human samples or patients in the clinical and/or community settings, bringing a broader perspective to the animal model studies conducted by our trainees. The following is a brief summary of the expertise of these investigators.  

Nikolaos Mellios, M.D., Ph.D. (Assistant Professor, Department of Neurosciences)  Dr. Mellios utilizes novel methodologies to elucidate the unexplored role of non-coding RNAs in both prenatal brain development and postnatal neuronal integration with the long-term goal of better understand and potentially treating neuropsychiatric disorders.  He is currently the PI of a pilot project funded by the P50 center where he will carry out systematic profiling of circular RNA expression in response to ethanol exposure in human stem cell-derived neuronal cultures and examine the role of ethanol-induced circular RNAs on synaptic plasticity and neuronal excitability.  He is collaborating with Dr. Jason Weick (member of the training faculty) on this project.

Lauren Jantzie, Ph.D. and Jessie Maxwell, M.D. (Assistant Professors, Division of Neonatology, Department of Pediatrics)  These investigators are studying the pathophysiology of encephalopathy of prematurity, and pediatric brain injury common to infants and toddlers. Dr. Jantzie is dedicated to understanding disease processes in the developing brain as a means to identifying new therapeutic strategies and treatment targets for perinatal brain injury. Her lab studies neural substrates of cognition and executive function, inhibitory circuit formation, the role of an abnormal intrauterine environment on brain development, mechanisms of neurorepair and microglial activation and polarization. Using a diverse array of clinically relevant techniques such as MRI, cognitive assessment, and biomarker discovery, combined with traditional molecular and cellular biology, their research is on the front lines of translational pediatric neuroscience.  Importantly, Drs. Maxwell and Jantze are co-PIs on a pilot project funded by the P50 center grant focused on the interaction of placental insufficiency and prenatal ethanol exposure on brain development.

Nathan Pentkowski, Ph.D. (Assistant Professor, Department of Psychology) Dr. Pentkowski’s research interests include the neurobiology of drug addiction, including cocaine, amphetamines, alcohol, and nicotine.  He is particularly interested in the behavioral and neurobiological consequences of adolescent exposure to nicotine, ethanol, and cocaine and social influences on drug self-administration and relapse, including prosocial interactions and chronic social stress. He is also examining serotonin (e.g., 5-HT1B, 5-HT2C, 5-HT2A) and corticotrophin-releasing factor (CRF1) receptors as novel targets for treating drug addiction and affective disorders. Moreover, Dr. Pentkowski is investigating the impact of prenatal ethanol exposure on conditioning place preference.

C. William Shuttleworth, Ph.D. (Regent’s Professor, Department of Neurosciences)  Dr. Shuttleworth leads a very successful translational research program that focuses on the pathophysiology of stroke.  He is a world-renowned expert in optical and fluorescence microscopy imaging techniques, who has been and will continue to be an important resource for our trainees.  He also serves as Associate Director for the Clinical & Translational Science Center.  Dr. Shuttleworth is also the Director of the Brain and Behavioral Institute.