Research conducted in the organ systems biology area includes investigations in reproduction, bone biology, cardiovascular function, lung biology, bladder physiology, anatomy, and immunology. Specific areas of interest include periodontitis, neuroendocrine tumors, epigenetics, and endocrinology. These areas are actively investigated using several techniques and model systems.
Faculty involved in organ systems physiology:
Skeletal effects of bisphosphonates and bone anabolic agents/drugs for the prevention and treatment of local osteopenias (e.g., jaw) and postmenopausal osteoporosis. Pathophysiology of osteonecrosis of the jaw (ARONJ), and other side effects of antiresorptive drugs. Small animal models of periodontitis. Extended half-life of RANK Ligand antagonists for preclinical testing of osteoporosis treatments in small animals. Comparative medicine.
Cough is the most common reason why sick patients visit physicians in the US. This defensive reflex is the most common manifestation of tobacco- and non-tobacco-related pulmonary diseases. Furthermore, cough suppressant (also called antitussive) drugs are among the most commonly prescribed in the world. Significant gaps exist in our understanding of how cough is produced and how this defensive reflex is inhibited by antitussive drugs. The long-range goal of research in our laboratory is to delineate the how the nervous system produces and regulates cough. We use antitussive drugs as tools to determine how the cough system is controlled. As such, our work also will expand our knowledge of the mechanisms by which these drugs inhibit cough. Our current approach incorporates the use of multiple extracellular electrode array technology to investigate the behavior of spontaneously active and recruited neurons in the brainstem during cough. Determination of the identity and functional relationships between these neurons will allow modeling of the configuration of the brainstem cough network. Perturbation of the behavior of these neurons with antitussive drugs will allow us to identify the mechanism by which cough suppressants act to inhibit this behavior.
My research team investigates the afferent and efferent mechanisms involved in the behavioral control of breathing pattern, respiratory defensive reflexes, respiratory response to exercise and the neural mechanisms of respiratory perception. Our research focus is on the physiological mechanisms of central neural behavioral control of respiratory pattern. We investigate the role of pulmonary and respiratory muscle afferents in activating cognitive centers of the brain, behavioral control of breathing pattern and respiratory muscle strengthening rehabilitation of disorders in swallow (dysphagia) and cough (dystussia). Our patient studies have focused on the control of breathing pattern in individuals with neuromuscular disease, spinal injury, stroke and asthma. My research laboratory has also studied the sense of respiratory breathing effort for load compensation in humans and experimental animals. I am also studying high frequency oscillation of the airways of humans and experimental animals which increases the concentration of exhaled molecules and decreases the sense of respiratory breathing effort. My lab is also investigating the effect of respiratory muscle strength training on exercise performance in healthy sedentary individuals and athletes.
We study how environmental contaminants impact a broad range of biological systems such as the nervous system, endocrine system, and gut-microbiome axis. We use neuronal cell models (dopaminergic rat and human cells) and zebrafish in vivo toxicity assays to determine the mechanisms of environmental toxicants, focusing on pesticides that have been associated with neurodegenerative diseases and the mitochondria. We are also using CRISPR gene editing approaches to understand the functional significance of genes during pesticide exposures. Specialties: Molecular toxicology, omics, environmental science, neurodegeneration, high throughput in vitro screening, neurotoxicology
Development of technology to study visceral diseases and refine current/develop new analgesic technologies – Our lab works closely with material, chemical and electrical engineers to develop new tools to study the nervous system with the end goal using these tools to study the changes that occur in these systems during and after the development of chronic pain, as well as the hopeful end goal of implementing these strategies in patients.
Urothelial cell-to-sensory afferent signaling in bladder pain and function – Urothelial cells, the endothelial cells that line the bladder wall, were classically thought to function as a passive barrier. However, evidence collected over the last decade has shown them to be a much more active component of bladder physiology and pathophysiology. The fact that urothelial cells express many different types of sensory receptors, ion channels, signaling peptides and neurotransmitters, along with their close proximity to nerve fibers suggest that they could communicate and/or receive input from neuronal cells. Our lab is using innovative techniques to isolate these signaling mechanisms to specific cell types with the goal of understanding how these cells communicate under normal physiologic conditions as well as how the signaling may be altered under disease conditions.
The role of immune cell signaling in interstitial cystitis/ bladder pain syndrome (IC/BPS) pain – IC/BPS is idiopathic in nature, however over the past two decades mounting evidence suggests alterations to the innate immune response may play a role in the symptomology and progression of the disease. Our lab aims to study the involvement of different immune cells in pain and bladder dysfunction associated with models of IC/BPS
The research interests of my lab are centered on the interface of the nervous system and the airway. Using multidisciplinary approaches, we aim to answer three big picture questions: 1) Is dysfunction of the nervous system sufficient to induce airway disease? 2) What are the neural substrates that detect airway insults? 3) Can targeting the nervous system prevent airway disease?
To answer these questions, we use models of asthma and cystic fibrosis, with a special emphasis on early stage life. We perform in vitro and in vivo studies in parallel, and utilize numerous techniques ranging from basic molecular biology to microscopy to ion transport studies to whole animal physiology. We are keenly interested in the communication of the nervous system with the airway, and the processes governing transmission of that information to target tissues (i.e. epithelia, smooth muscle, submucosal glands). The goal of all our efforts is to improve human health and discover new mechanisms of airway disease.
The main focus of my research has been on regenerative medicine approaches to improve skin wound healing and regeneration. My training as both veterinary doctor and molecular, developmental, and cell biologist gives me a singular set of skills and a unique research perspective. As a veterinarian scientist, I follow the One Heath concept —the multidisciplinary collaborative efforts to attain optimal health for people, animals, and our environment—so my research program aims to benefit both human and animal health. My expertise includes cell and molecular biology techniques – such as cell cultures, immunohistochemistry, western blotting, qPCR, flow cytometry and cell sorting, various animal models (mouse, rat, rabbits) and histopathology. In addition, I have experience with transgenic mouse models (conditional knockouts and lineage tracing).
- Biology of reproduction
- Mesenchymal stem cells
- Regenerative medicine
- Skin wound healing