Brain

Chandrasekaran (Arun) received his doctorate from University of Hyderabad, India. He worked on the molecular and immunological aspects of Leishmania donovani infection. He joined the Koshy lab as Postdoctoral research associate and will be working on transcriptional profiling of individual neurons which have interacted with Type II and Type III Toxoplasma parasites.

Dr. Vitali's research currently focuses on the development of bioinformatics analysis to advance the prevention and treatment of age-associated neurodegenerative diseases. Dr. Vitali is an Assistant Professor of Neurology at the University of Arizona and work with the research group of Dr. Roberta Diaz Brinton where is the Director of Bioinformatics and a faculty member of the Center for Innovation in Brain Science (CIBS). She is a doctor of bioinformatics and bioengineering from the University of Pavia, Italy.

Dr. Rodgers’ research over the last 30 years has evaluated the ability of angiotensin peptides and small molecule Mas agonists to mitigate injury and regenerate injured tissues and product development. Stimulation of Mas through endogenous peptides, analogues and peptidomimetics has been shown to increase stem cells/progenitors in a number of disease states with a deficit regenerative cells and to reduce oxidative stress and inflammation. By targeting these three fundamental processes, a platform leading to clinical development from laboratory observations has led has been generated. Current disease targets include vascular dementia, Alzheimer’s Disease and multiple sclerosis. Dr. Rodgers has deep domain knowledge in therapeutic development that spans discovery, IND-enabling pharmacology and toxicology, clinical trial design and regulatory submissions. She has designed and conducted numerous clinical trials and holds over 50 US patents with expanded coverage in major therapeutic indications.

Research in Dr. Pires's laboratory follows his training and expertise in the cerebral microcirculation, and focuses on investigating the role of ion permeable molecular sensors expressed in endothelial cells, both arteriolar and capillary, in the control of localized blood perfusion in the brain, physiologically induced by neuronal stimulation. This interest is coupled with his long-standing scientific passion in elucidating the molecular mechanisms underlying cerebrovascular disorders related to the development of dementia, such as aging, cerebral amyloid angiopathy, Alzheimer's disease and traumatic brain injury. To progress in these projects the Pires lab have developed and is systematically characterizing a mouse strain with endothelial cell-specific knockout of the N-Methyl-D-Aspartate receptor (cdh5:Grin1-/-). Further, the lab has established aging colonies of different mouse models of hypercholesterolemia, cerebral amyloid angiopathy and Alzheimer’s disease, together with respective wild-type littermates, including ApoE3 / ApoE4 knock-in, Tg-SwDI (a model of cerebral amyloid angiopathy), and the 5x-FAD (a model of early-onset Alzheimer’s Disease with prevalence of parenchymal amyloidosis). Further, the Pires lab has a colony of mice expressing the genetically encoded calcium indicator GCaMP8 in endothelial cells (cdh5:GCaMP8), acquired from Dr. Michael Kotlikoff at Cornell University. Lastly, we have successfully implemented AAV-BR1 viral transfection of cerebral endothelial cells using a GFP reporter, we are currently expanding the use of this tool to perform cerebral artery endothelial cells-specific knock-in / knock-out of targets of interest. In recent years the Pires laboratory has started studying the function of the waste clearance system of the brain (the glymphatic system), and its impact and potential therapeutic potential in neurodegenerative diseases. This is an exciting novel area of research involving highly integrative studies, starting at the molecular / cellular signaling level and expanding to whole animal physiology and behavior. Taken together, the long-term goal of the Pires laboratory is to perform translational, clinically relevant scientific investigation of how chronic neurodegenerative diseases, as well as acute traumatic events, affect the cerebral circulation and increase the risk of developing severe dementia, with the hopes of identifying novel therapeutic targets to improve the lives of the affected population.

Our research focuses applying engineering methods to problems in biology with the goal of improving human health. In particular we aim to understand the underlying mechanisms of traumatic brain injury in order to better prevent and diagnose. We also research on the cerebral hemodynamics and the effect it can have on neurodegenerative diseases and stroke. We use an array of computational and experimental approaches including finite element modeling, magnetic resonance imaging and impact biomechanics. https://www.engr.arizona.edu/~klaksari/

Linda L. Restifo, MD, PhD, has an overarching interest in the genetics of brain development, ranging from the control of large-scale morphogenetic movements to the remodeling of individual neurons. Her lab uses the fruit fly model system, Drosophila melanogaster, in part because of its phylogenetic similarities to mammals. In particular, they are using fruit flies to understand human developmental brain disorders, such as mental retardation and autism, and as a drug-discovery tool. Methods include genetic manipulations, primary neuron cell culture, immunostaining and confocal microscopy, expression profiling (with Affymetrix microarrays), bioinformatics, and software development for neuron-image analysis.In order to study genetic pathways that control brain morphogenesis and neuronal plasticity, the focus pertains to the metamorphosis portion of development because the nervous system undergoes dramatic changes, including neuronal remodeling. These changes are under the control of a steroid hormone, 20-hydroxyecdysone (20E), whose receptor subunits are members of the nuclear receptor superfamily. At the cellular level, steroid hormone-induced changes in neuronal structure and function are very similar in mammals and insects.Many of our studies deal with a fascinating brain region known as mushroom bodies. They are remodeled during metamorphosis and mediate complex adult behaviors, including some forms of learning and memory. Using dissociated cell culture methods, the lab group demonstrated that 20E promotes neurite outgrowth of mushroom body neurons harvested early in the metamorphic interval. Dr. Restifo’s group also found a number of neuronal morphology phenotypes in vitro, which suggested that cell culture could provide a sensitive assay system for identifying neuronal defects.Broad Complex transcription factors play a pivotal role in mediating 20E-regulated nervous system metamorphosis. This family of BTB-zinc-finger proteins (BRC-Z1 through -Z4) is generated by alternative splicing of transcripts from a large gene directly induced by 20E in the CNS and other tissues. Transgenic-rescue and spatial expression studies support a model of BRC function in coordinating cell-cell interactions that underlie central nervous system morphogenetic movements.Hundreds of human genes can mutate to a mental retardation (MR) phenotype, either in isolation or as part of a syndrome. Bioinformatics methods show that 75% of human MR genes have a candidate functional ortholog in Drosophila. To date, four of the Drosophila genes have been shown by others to have learning or memory phenotypes, and we predict that this will be true for many more of them. Dr. Restifo has shown that mutants of Drosophila fragile X mental retardation 1 (dfmr1) have defects in mushroom body development during metamorphosis. A major new initiative uses mushroom body cell culture methods to search for neuronal phenotypes of MR gene mutants in vitro. Her long-term goal is to use the Drosophila system as a stepping stone for discovery of drugs that will benefit human MR patients... :)

Dr. Lifshitz is the Director of the Translational Neurotrauma Research Program through the College of Medicine - Phoenix, which brings together clinicians and scientists as faculty to address the pathophysiology and recovery from animal models of acquired neurological injury (e.g. stroke, hemorrhage, concussion). These studies are guided by gaps in clinical knowledge to empower healthcare providers to improve quality of life for survivors. To this end, they use public databases, biorepositories, and animal models to address questions across the lifespan. Specific strengths include inflammation, rehabilitation, puberty, sleep, and neuronal morphology.

Charles Higgins, PhD, is an Associate Professor in the Department of Neuroscience with a dual appointment in Electrical Engineering at the University of Arizona where he is also leader of the Higgins Lab. Though he started his career as an electrical engineer, his fascination with the natural world has led him to study insect vision and visual processing, while also trying to meld together the worlds of robotics and biology. His research ranges from software simulations of brain circuits to interfacing live insect brains with robots, but his driving interest continues to be building truly intelligent machines.Dr. Higgins’ lab conducts research in areas that vary from computational neuroscience to biologically-inspired engineering. The unifying goal of all these projects is to understand the representations and computational architectures used by biological systems. These projects are conducted in close collaboration with neurobiology laboratories that perform anatomical, electrophysiological, and histological studies, mostly in insects.More than three years ago he captured news headlines when he and his lab team demonstrated a robot they built which was guided by the brain and eyes of a moth. The moth, immobilized inside a plastic tube, was mounted on a 6-inch-tall wheeled robot. When the moth moved its eyes to the right, the robot turned in that direction, proving brain-machine interaction. While the demonstration was effective, Charles soon went to work to overcome the difficulty the methodology presented in keeping the electrodes attached to the brain of the moth while the robot was in motion. This has led him to focus his work on another insect species.

Dr. Hay is internationally known for her work in cardiovascular neurobiology and her current studies on the role of sex and sex hormones in the development of hypertension. She has been continuously funded by the NIH and other sources for the past 26 years. She has extensive experience in central renin angiotensin mechanisms, neurophysiology and reactive oxygen and cytosolic calcium neuroimaging and in advancing knowledge related to central mechanisms of neurohumoral control of the circulation. She is a Professor of Physiology at the University of Arizona College of Medicine and maintains active participation in the American Physiological Society, the Society of Neuroscience, AAAS, and has served on numerous editorial boards of prestigious scientific journals and grant review panels for the National Institutes of Health and the National American Heart Association. The primary focus of Dr. Hay’s laboratory is the understanding of the biophysical and cellular mechanisms underlying neurotransmitter modulation of sympathetic outflow and ultimately arterial blood pressure. The scientific questions being asked are: 1) What central neurotransmitter mechanisms are involved in the normal regulation of cardiovascular function? 2) Does the development of some forms of hypertension involve biophysical or molecular alteration in the neurotransmitter mechanisms regulating cardiovascular control? 3) Can these central signal transduction systems, which control sympathetic outflow and ultimately arterial blood pressure, be altered in order to prevent or attenuate the development of some forms of hypertension? 4) Are there gender related differences in some of these mechanisms?Dr. Hay has extensive national experience in university-wide administration and interdisciplinary research program development. Prior to coming to the University of Arizona in 2008 as Executive Vice President and Provost, Dr. Hay was the Vice President for Research for the University of Iowa, where she worked with state and federal lawmakers, private sector representatives, and local community groups to broaden both private and public support for research universities. Dr. Hay, a Texas native, earned her B.A. in psychology from the University of Colorado, Denver, her M.S. in neurobiology from the University of Texas at San Antonio, and her Ph.D. in cardiovascular pharmacology from the University of Texas Health Sciences Center, San Antonio. She trained as a postdoctoral fellow in the Cardiovascular Center at the University of Iowa College of Medicine and in the Department of Molecular Physiology and Biophysics at Baylor College of Medicine in Houston. She was a tenured faculty member of the University of Missouri-Columbia from 1996-2005. Prior to Missouri, she was a faculty member in the Department of Physiology at the University of Texas Health Science Center- San Antonio.

The broad goal of my research is to understand the neural basis of emotion and social behavior in non-human primates. Our laboratory pioneered multichannel neural recordings from the amygdala of monkeys engaged in naturalistic social interactions. Neural activity was monitored simultaneously with cardiovascular and other autonomic parameters of emotion to capture unique, coordinated brain-body states. These states, and the transitions between them, are the neural underpinnings of our emotional experiences and the memory thereof. I bring to BIO5 expertise from a broad and diverse range of sources. I earned a medical in Romania in 1988, followed by postgraduate training in neurosurgery, and a Ph.D. in Neuroscience in 1996 at the University of Arizona. As a student, I explored the neural dynamics of spatial learning and memory in rats and determine the interaction of multiple spatial reference frames during navigation. I completed by postdoctoral studies at the UC Davis in primate socio-emotional behavior and the neurophysiological basis of communication with facial expressions. While at Davis, I received a K01 career development award that allowed me to assemble the largest existent annotated video library of macaque social behavior. I used this library to probe the behavioral and neural events that are the basic building blocks of social behavior (e.g., eye contact, the reciprocation of facial expressions, and gaze following). We discovered a specialized class of cell in the monkey brain that are active exclusively in the context of natural social behaviors and respond selectively to eye contact. We have developed techniques of precisely targeted bilateral microinjections in the primate brain and implemented successfully neural recording and parallel with microinjections of drugs and hormones. Currently we are testing the effect of various drugs in the activity of eye cells in the amygdala.