Neurology

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.

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... :)

My laboratory studies neurogenetic mechanisms which underlie normal and abnormal motor speech using the zebra finch songbird. My particular focus is to investigate molecular and cellular pathways altered by speech disorders associated with natural aging and neurological diseases such as Parkinson’s Disease. To carry out these investigations, we use a combination of behavioral, genetic, biochemical and electrophysiological approaches that enable us to link changes at the molecular/cellular levels to alterations in neural circuits for birdsong/human speech. We also have collaborations with researchers working in mouse models to understand shared molecular pathway for vocal function. The end goal is to leverage the advantages offered by each species and an array of biological tools to further advance our understanding of how the brain controls vocalizations. Our laboratory website, including an updated publication list, can be found at: https://julieemiller.lab.arizona.edu/content/publications-abstracts

Dr. Madhavan M.D., PhD, is an Assistant Professor of Neurology at the University of Arizona. She is also a member of the Arizona Cancer Center and the Evelyn F. McKnight Brain Institute, and is affiliated with the Neuroscience, Physiology and Molecular, Cellular Biology graduate programs at UA. Dr. Madhavan’s research centers on stem cells and neurological diseases. The ultimate goal of the work is to devise brain repair strategies for neural disorder using stem cells, and other alternate approaches. Currently, her lab is focused on Parkinson’s Disease, and is engaged in three main endeavors: (1) Understanding the therapeutic potential of stem cells in the context of aging, (2) Creating patient-specific induced pluripotent stem cells to study the etiology of Parkinson’s Disease, and (3) Testing the therapeutic feasibility of various types of adult stem cells in preclinical Parkinson’s Disease models. These projects are united by a common goal, which is to investigate core problems hindering the development of effective stem cell-based therapies for Parkinson’s Disease. In addition, the work represents a novel path of research for not only Parkinson’s Disease therapy, but has broad implications for developing treatments for several other age-related neurodegenerative disorders. Visit the Madhavan Lab website to learn more.

Anita Koshy, MD is an Associate Professor in the Department of Neurology and the Department of Immunobiology, and an affiliate of the Clinical Translational Science Institute and the Evelyn F. McKnight Brain Institute. Clinically, Dr. Koshy is a recognized expert in the area of Infectious Diseases of the Nervous System, and has co-authored 4 chapters on this subject. Dr. Koshy’s lab focuses on understanding how a common human parasite, Toxoplasma gondii, is able to persist in the mammalian brain (including in up to 1/3 of the human population.) The goals of this work are to: 1) improve treatments for patients with symptomatic toxoplasmosis (there are no drugs to cure patients of Toxoplasma) and 2) use the co-evolution between the parasite and the mammalian CNS to better understand how immune responses in brain can be triggered and aborted. The latter research may have broad applicability to disorders of the brain in which the immune response is dysfunctional; these disorders include Multiple Sclerosis, traumatic brain injury, and neurodegenerative diseases such as Alzheimer’s disease. Keywords: Neuroscience, Infectious Disease, Parasitology

Fabian-Xosé Fernandez, PhD, Departments of Psychology and Neurology, McKnight Brain InstituteCircadian timekeeping is fundamental to human health. Unfortunately, under many clinical circumstances, the temporal organization of our minds and bodies can stray slowly from the Universal Time (UT) that is set with the Earth’s rotation. This disorganization has been linked to progression of several age-related and psychiatric diseases. Non-invasive phototherapy has the potential to improve disease outcomes, but the information that the brain’s clock tracks in twilight (or any electric light signal) to assure that a person entrains their sleep-wake cycles to the outside world is not understood. The central theme of my research program is to fill in this blank and to usher in an era where therapeutically relevant “high-precision” light administration protocols are institutionalized at the level of the American Medical and Psychiatric Associations to change the standard of care for a wide variety of conditions that impair quality of life. Of the conditions my lab is currently studying, we are particularly interested in how chronic and quick, sequenced light exposure can be designed to: 1. promote normal healthy aging and 2. strengthen adaptive cognitive/emotional responses to being awake in the middle of the night (12-6AM), a key interval of the 24-h cycle that we have associated with increased suicidal ideation and mortality. Our circadian work on suicide is done in very close partnership with the University of Arizona Sleep Health and Research Program directed by Dr. Michael A. Grandner.