Current Research Directions

Dr. David Giovannucci:

Work in the Giovannucci lab uses a variety of electrophysiological, optical and biochemical methods to define the cellular and molecular mechanisms that underlie the cytosolic calcium dynamics that control salt, peptide and protein secretion.  The exocytotic secretion of neuropeptide has profound consequences for neuronal function, cardiovascular homeostasis and GI tract regulation in health and disease. This work has significance for human health concerns such as GI cancer, hypertension and dry mouth. The lab also leads a multidisciplinary/multi-PI project advancing the use of biomarkers in saliva that correlate with neural stress, brain trauma and human performance. The Giovannucci lab has been continually supported by government, military, intramural or private grant funding.

Dr. Marthe Howard:

Work in the Howard laboratory focuses on deciphering the molecular mechanisms of specification and differentiation of autonomic neurons.  We use modern molecular biology and cell biology techniques to assess gene regulation in avian and mouse embryos. The overall goal of our studies is: 1) to identify genetic regulatory networks involved in neurogenesis and expression of neurotransmitter molecules, 2) to identify cell extrinsic signaling molecules involved in neurogenesis, and 3) to understand the interplay between cell extrinsic cues and cell intrinsic patterns of gene regulation resulting in differentiation of autonomic neurons. To this end, we identified and cloned the basic helix-loop- helix DNA binding protein Hand2 and have shown that it is both necessary and sufficient for neurogenesis and cell type-specific gene expression of sympathetic ganglion neurons, is necessary for development of the enteric nervous system, as well as having a central role in heart and cranio-facial development.  Howard's lab is funded by the National Institute of Health (NIDDK, NINDS).

Dr. Joseph Margiotta:

Our laboratory is engaged in two research projects designed to better understand fundamental biological properties relevant to excitable cells.  Both projects have been research-training venues for postdoctoral scholars as well as PhD, MD, and undergraduate students.  One long-standing project involves cell autonomous and synaptic signaling meditated by nicotinic acetylcholine receptors (nAChRs).  With NIH support, ours was the first US laboratory to document the single channel properties of nAChRs on neurons and we later aligned these properties with defined molecular subtypes.  We also gained decades long-experience in studying the influences of developmental interactions and G-protein coupled receptor (GPCR) signaling on nAChR properties and localization.  Over the last 10 years our interests broadened to address the role of nAChRs in mediating non-synaptic signaling functions such as survival in neurons and endothelial cells.  With additional support from NSF we gained further experience in studying the molecular basis of nAChR localization in neurons and with a recent NSF award we are currently focused on nAChR-mediated synaptic transmission and its regulation by GPCR signaling.   Our experience in these areas has resulted in several collaborations, most recently with Dr Marthe Howard with whom we will examine synapse formation in the enteric nervous system as part of her newly acquired NIH grant.  A second project involves photomechanical transduction mechanisms in iris muscle.  This project is supported by a University of Toledo Research Innovation award and, while still evolving, is yielding exciting results.

 Dr. Joshua Park:

Our first research project is to develop a new drug for the treatment of neurodegenerative diseases. Over 5 million people in the US and 35 million worldwide suffer from Alzheimer's disease (AD), a devastating disease that costs the US over $100 billion every year. Enormous efforts have been poured on the development of therapeutic agent(s) that can slow AD while current treatments only address symptoms without disease-modifying effect and have side effects. Conversely, increasing evidence points to the effectiveness of neurotrophic agents for AD treatment. However, the BBB-impermeability and short half-life of protein neurotrophic factors limit their use for AD treatment. Hence, neurotrophic agent that overcomes those shortcomings should be a better neurotrophic treatment of AD. We discovered a neuroprotrophic polysaccharide named ‘midi-GAGR’ that has good BBB-permeability, strong neuroprotective and neurotrophic effects in primary neurons and in animals, and >12-h half life. Our current research focuses on the examination of the efficacy of midi-GAGR in slowing pathogenesis in AD animals. Achieving our goal will provide a strong scientific basis for the clinical development of midi-GAGR.

Our second research project is to develop a stem cell-based treatment that can modify osteoarthritis (OA). OA is a disease caused by degradation of extracellular matrix at the cartilage of inflamed synovial joints, resulting in joint deformation and dysfunction. An estimated 27 million Americans, especially aged people, suffer from OA and the population is expected to reach 67 million in USA by 2030. Traditional OA treatments including non-steroidal anti-inflammatory drug, joint replacement, etc., have no disease-modifying effect. Given most OA treatments cannot overcome synovial inflammation that decreases cartilage formation and increases cartilage breakdown, OA-modifying treatment should suppress inflammation and increase cartilage formation. In collaboration with NWO Stem Cure, LLC, we have developed an innovative stem cell-based OA therapy device named CHAMP (chondrogenic hyaluronic acid-mesenchymal stem cells-PPAR-delta agonist) that is designed to enhance cartilage formation and decrease inflammation. In our study, CHAMP could generate type II collagen-containing chondrocytes in human inflammatory OA synovial fluid while current MSC-based OA therapy could not, showing that CHAMP is superior to current MSC-based OA therapy. Given that all three CHAMP components are already used for human treatment or in clinical trial, it is expected to take a short regulatory process to obtain the approval of the use of CHAMP for human OA treatment. The current goal of our research is to examine the efficacy of CHAMP in treating OA in anterior cruciate ligament transaction (ACLT) animal model. Achieving our goal will provide solid pre-clinical and clinical bases for the clinical development of CHAMP for OA treatment.

Dr. John Wall:

A traditional doctrine of neuroscience was that human cortex changes as it develops, but then becomes stable during adulthood.  Contrasting with this doctrine, it has become clear that adult human cortex can change functionally due to normal life experiences.  Until recently, it was not possible to test if cortical structure in an individual adult person also changes over time, but recently developed MRI techniques now make this possible.  One main research focus of our human brain imaging group is to test if cortical structure in an individual adult person is static over short periods, as current thinking suggests, or whether structure is dynamic and fluctuates over short periods. We are addressing this issue with longitudinal structural MR imaging at week and longer intervals in an individual adult during normal living. In parallel with longitudinal cortical structural measurements, we are also testing whether cortical structural state is related to body state as indicated by longitudinal cardiovascular, blood glucose, and other body measures in the same individual.  Our goal is to use recent advances in techniques for noninvasive longitudinal tracking of brain structure and body states to explore concepts of how the brain and body of an adult person are continuously maintained.

Dr. Ruili Xie:

I am interested in the neural mechanism of hearing loss due to aging and noise trauma.  The processing of sound information is degraded in the auditory system under hearing loss conditions, which leads to difficulties in performing auditory tasks like pitch identification and speech recognition.  Among the changes is the synaptic transmission within the neural network.  Utilizing electrophysiological technique (whole-cell patch clamp recording in slice), my lab is currently focused on identifying the changes and the underlying mechanisms of synaptic transmission during age related and noise induced hearing loss.  We use mouse as our animal model and target cochlear nucleus as our site of interest.

Last Updated: 8/17/17