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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. 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.
Brigman is a new faculty member in the Neurosciences Department and a
new member of the Core Training Faculty. 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
tasks. He is currently investigating the role of corticostriatal
networks and glutamatergic systems in mediating habitual and executive
control behaviors. He has initiated a collaborative project on
FASD with Dr. Valenzuela.
Kevin Caldwell, Ph.D. (Associate 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 prenatal exposure to alcohol. These studies are performed 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 addition, Dr. Caldwell’s laboratory studies the associations between prenatal ethanol exposure and emotional disorders, with a focus on depression and stress disorders. These studies are performed in collaboration with the Allan Lab. Results from these studies will facilitate the development of rational strategies for the treatment of alcohol-induced learning and behavioral disorders in humans.
DDr. Cunningham’s research interests are in mechanisms of cell death and repair in the adult CNS. Current research in her laboratory is focused on neurogenesis in the adult mammalian brain in mouse models of stroke and prenatal alcohol exposure. Using both in vitro and in vivo models of ischemic injury, Dr. Cunningham’s laboratory is also investigating the contribution of neuronal stem cells to revascularization and repair processes following stroke. Together with Drs. Allan and Valenzuela, Dr. Cunningham is studying the effects of moderate prenatal alcohol exposure on neurogenic responses in the adult hippocampus. In particular, she has been investigating the effect of prenatal alcohol exposure on the neurogenic response to an enriched environment in the dentate gyrus of adult mice.
Dr. Hamilton utilizes basic behavioral, pharmacological, anatomical, physiological, and computational methods to investigate the psychological and neurobiological foundations of learning, memory, and behavior. His work includes investigations in humans and rats with an emphasis on spatial (place) learning/navigation and nonspatial associative learning. He is currently investigating the effects of prenatal ethanol exposure on social behavior, experience, and learning in relation to structural plasticity and experience-dependent gene expression in frontal cortex. These studies are being performed in collaboration with the Savage and Valenzuela labs.
Dr. Perrone-Bizzozero’s program involves studies 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 GAP-43, BDNF and the RNA-binding proteins (RBPs) and microRNAs (miRNAs) that affect their expression, both during development and adult mechanisms of synaptic plasticity. She is also studying the genetic contributions to brain imaging alterations in patients with schizophrenia and children with FASD. More recently, she has begun to examine the role of RBPs and miRNAs in the context of cocaine addiction, a new research initiative soon to be funded by NIDA. In the future, she is planning to continue her collaboration with Drs. Dan Savage and Ludmila Bakhiereva on the identification of biomarkers of maternal alcohol consumption in placental and serum samples from animals and patients. Throughout these studies, Dr. Perrone-Bizzozero’s group employs a variety of molecular, cellular and in vivo techniques, ranging from qRT-PCR and microaarray studies to lentiviral mediated gene transduction, in situ hybridization for both mRNAs and miRNAs and immunocytochemistry and behavioral paradigms in animals exposed to different drugs of abuse, including alcohol.
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 that have been associated with deficits in hippocampal synaptic plasticity and learning in rats. More recently, Dr. Savage has applied his prenatal ethanol exposure paradigm in two novel translational research endeavors: 1) Preclinical screening of therapeutic interventions for fetal ethanol-induced behavioral deficits and, 2) As a system for developing novel biomarkers for identifying offspring with functional brain damage as a consequence of prenatal ethanol exposure. Currently, he is the PI of a NIAAA R01 award examining the impact of prenatal ethanol exposure on histaminergic regulation of glutamatergic neurotransmission (in collaboration with the Valenzuela and Hamilton Labs). In addition, his work has begun to span from basic to clinical science in the area of biomarkers for fetal alcohol exposure detection. Dr. Savage serves as the Director of the NIAAA P20-funded New Mexico Developmental Alcohol Research Center. He is the 2011 recipient of the Henry Rosett Award for excellence in FASD research.
Research in the Valenzuela lab has focused on the modulation of synaptic transmission by alcohol in the central nervous system. A major area of research interest is the effects of ethanol on developing neuronal circuits. His studies have demonstrated that ethanol can potently affect oscillatory activity and plasticity required for the refinement of neuronal connections. Studies have also shown that neurotransmitter release and neurotransmitter receptors have unique sensitivity to ethanol in developing neurons in comparison to mature neurons. Another major area of research interest is the impact of ethanol on the mature and developing cerebellum. Studies from his laboratory indicate that ethanol alters GABAergic and glutamatergic neurotransmission and plasticity at different synapses throughout the cerebellar cortex. A multidisciplinary approach is used in the Valenzuela lab, which includes electrophysiological, histological, Ca2+ imaging, and behavioral techniques. He is also working on several collaborative projects with the Caldwell, Cunningham, Savage, and Hamilton labs.
Stephen is a new member of the Core Training Faculty, who 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. 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. Dr. Stephen is working on collaborative projects
with several investigators of the P20 Alcohol Research Center.
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. Two of these faculty members work with human populations in the clinical and/or community settings, bringing a broader perspective to the animal model studies conducted by our trainees. Moreover, senior members of the advisory faculty will also contribute to mentoring junior faculty. The following is a brief summary of the expertise of these investigators.
Ludmila Bakhrieva, M.D., Ph.D., M.P.H. (Assistant Professor, School of Pharmacy). Dr. Bakhireva’s primary research interests are in the area of pharmacoepidemiology, perinatal and reproductive epidemiology, and drug safety in pregnancy. She is a member of the Teratology Society. Dr. Bakhireva is a co-investigator on a multi-disciplinary and cross-cultural Collaborative Initiative on Fetal Alcohol Syndrome Disorders funded by the NIAAA and conducted in six countries around the world. She is also conducting research in the area of biomarkers of prenatal ethanol exposure. She has collaborated extensively with members of the Core Faculty (Savage, Stephen, Perrone-Bizzozero) and is a member of the P20 NM Alcohol Research Center. She was the recipient of the Society for Teratology-Young Investigator Award in 2011.
Piyadasa Kodituwakku, Ph.D. (Associate Professor, Department of Pediatrics). Dr. Kodituwakku has conducted studies aimed at investigating executive control functioning, attention, memory, language, and motor functioning in children with FASD. His current research is concerned with probing early stages of information processing in alcohol-affected children and investigating plasticity of the motor system in children with FASD using a combination of behavioral and neuroimaging methods. He has collaborated extensively with members of the Core Faculty (Savage; Stephen) and is a member of the P20 NM Alcohol Research Center.
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 a co-investigator in the Alcohol and Cerebellar Circuits grant (P.I. Dr. Valenzuela).