Physiology

Dr. Banek's research is focused on the neurophysiological underpinnings of cardiovascular and renal disease. He has a broad training background in cardio-renal physiology and neuroscience, and a specific expertise in neural-mediated essential hypertension and renal inflammation. His team is currently investigating the contributions of renal sympathetic and sensory nerves to hypertension, polycystic kidney disease, and chronic kidney disease development and maintenance. His previous and ongoing work in hypertension has laid the groundwork for the role of renal sensory nerves in renal and cardiovascular disease etiology, which he aims to expand to other renal disease models such as polycystic kidney disease. One current target is polycystic kidney disease (PKD) and developing a new line of treatment and research for this debilitating disease with limited treatment options. Dr. Banek is also very passionate about mentorship and teaching at all levels. Many of his trainees have gone on to careers in academic and industry, and his numerous undergraduate trainees have pursued higher-level MD and/or PhD degrees.

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.

Stephen Wright, PhD, is focused on understanding the molecular and cellular physiology of organic electrolyte transport in the kidney. The kidney, particularly the proximal tubule, actively secretes a wide array of organic ions, largely derived from dietary or pharmaceutical sources. Many of these compounds are toxic and renal secretion of these xenobiotic compounds plays a critical role in protecting the body from these agents. However, this task also places the kidney in harm's way, and the development of nephrotoxicity is one consequence of the renal secretion of what are typically referred to as organic anions and organic cations. Dr. Wright’s lab currently studies the renal transport of organic anions and cations at several different levels of biological organization.At the molecular level, they clone individual transport proteins for use in studies that gauge the effect of protein and substrate structure on the transport process. At the cellular level, Dr. Wright and his lab use cultured cells (including primary renal cells, continuous renal cell lines, and generic cells lines for the expression of cloned transport proteins) in studies of the activity and regulation of transport activity. At the tissue level, they use isolated, intact renal proximal tubules, including single non-perfused and perfused tubules, to study the process of organic electrolyte secretion as it occurs in the native renal epithelium.Studies employ a wide array of methodologies, including molecular cloning, site-directed mutagenesis, construction of fusion proteins, kinetic assessment of membrane transport in cultured cells, suspensions of isolated renal tubules and in single tubule segments using radiometric and real-time optical approaches, computationally-based assessment of transporter, and substrate structure and 3D distribution of cell type distribution along the renal nephron. Keywords: Membrane Transport; Kidney; Drug Clearance

Ron Lynch received a B.S. from the University of Miami (1978) with a dual major in Chemistry (Physical) and Biology, and a Ph.D. degree from the University of Cincinnati (1984) in Physiology and Biophysics. Dr. Lynch began training in optical imaging and MR spectroscopy of cardiac metabolism while at the NIH/NHLBI under the direction of Dr. Robert Balaban from 1984-1987. In 1987, Dr. Lynch moved to a staff position in the Biomedical Imaging Group with appointment in the Physiology Department at the University of Massachusetts Medical Center where he was involved in the development of approaches for 3-dimensional imaging including deconvolution and confocal microscopy. Dr. Lynch joined the faculty of the University of Arizona in 1990 with dual appointment in the Departments of Physiology and Pharmacology, and is currently a full professor, and director of the Arizona Research Institute for Biomedical Imaging. In 2000, Dr. Lynch was a visiting scientist at the Laboratory of Functional and Molecular Imaging and the Magnetic Resonance Imaging Center with Dr. Alan Koretsky at the NIH/NINDS. Dr. Lynch is a member of the Biophysical Society, the American Physiological Society and American Diabetes Association, and regularly serves on grant review panels for the JDRF, NIH/NIDDK, and NSF. Research in the Lynch lab focuses on second messenger signaling in vascular smooth muscle cells and nutrient sensing cells (e.g., Pancreatic Beta-cells) with emphasis on alterations in signaling that occur during development of Diabetes. We are developing methods to modify and analyze beta cell mass in order to evaluate the initiation of the pre-diabetic state, and efficacy of its treatment. Analyses of subcellular protein distributions, second messenger signaling, and ligand binding is performed in our lab using state of the art microscopy and analysis approaches which is our second area of expertise. Over the past 3 decades, our lab has been involved in the development of unique microscopic imaging and spectroscopy approaches to study cell and tissue function, as well as screening assays for cell signaling and ligand binding. Keywords: Diabetes, Cancer, Optical Imaging, Targeted Contrast Agents, Metabolism, Biomedical Imaging, Drug Development

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.

The broad goal of research in our laboratory is to understand how inhibitory inputs influence neuronal signaling and sensory signal processing in the healthy and diabetic retina. Neurons in the brain receive inputs that are both excitatory, increasing neural activity, and inhibitory, decreasing neural activity. Inhibitory and excitatory inputs to neurons must be properly balanced and timed for correct neural signaling to occur. To study sensory inhibition we use the retina, a unique preparation which can be removed intact and can be activated physiologically, with light, in vitro. Thus using the retina as a model system, we can study how inhibitory synaptic physiology influences inhibition in visual processing. This intact system also allows us to determine the mechanisms of retinal damage in early diabetes. Keywords: neuroscience, diabetes, vision, electrophysiology, light

Nicholas Delamere, Ph.D., studies how ocular pressure (pressure in the eye) is controlled and the way cells transport fluid, and seeks to find methods to regulate the mechanisms involved. His goal is to develop drugs that reduce intraocular pressure, thereby decreasing the severity of glaucoma and damage to the retina. His cataract research also offers a promising model for tissue preservation, which will delay the onset of cataracts. https://delamerelab.medicine.arizona.edu/

Dr. Brooks is a renal physiologist and has developed microarray technology to address in vivo signaling pathways involved in the hormonal regulation of renal function. Current areas of research in the Brooks Laboratory are focused on importance of sex differences in the onset of postmenopausal hypertension and diabetic kidney disease and identifying new therapies for polycystic kidney disease and lithium-induced nephropathy.

Dr. Scott Boitano Ph.D., is a Professor of Physiology, Cellular and Molecular Medicine, the BIO5 Institute and Associate Research Scientist of the Arizona Respiratory Center. Dr. Boitano received a B.S. in Plant Biology from University of California; Berkeley and a Ph.D. in Genetics & Cell Biology from Washington State University. Dr. Boitano’s primary research interest is in cell respiration. This encompasses the analysis and observation of cell physiology, cell-cell communications and cell-pathogen interactions. Dr. Boitano’s research pertains to the upper airway epithelium is an active cellular layer with ciliary movement to clear materials, the ability to secrete inflammatory effectors, and a biological barrier function that helps protect against pathogenic microorganisms, foreign insults and injury. Although much is known concerning the microbial genetics and microbial signaling of infection by Bordetella, relatively little is known about host cell pathology after exposure to Bordetella. Individuals have a primary tissue culture system that serves as an in vitro model of airway cell signaling and communication, and a battery of B. bronchiseptica strains, some of which are mutant in key factors shown to inhibit their ability to establish infection in animal models. His research goal is to define specific pathogen factors that alter host cell physiology to initiate or overcome host cell defense. The Boitano lab also analyzes the layers of the alveoli of the distal mammalian lung. Minimal information is known about this subject and Dr. Boitano believes that this model system for alveolar intercellular communication could expedite the formulating and testing of new medical treatments for dysfunctional alveolar cell physiology that underlies specific airway conditions following disease, insult and injury in the lung.