See more of his work here.
Season 2 Transcripts
Episode 7: Developing Our Creativity (Gary Wu, UPenn)
Dr. Wu shares his experiences as both a physician and scientist and how we can develop the skills to think creatively and communicate effectively.
Gary J. Schwartz, Ph.D., is a professor of medicine, neuroscience, and psychiatry at the Albert Einstein College of Medicine. His lab studies how the gut and the brain interact with each other to regulate food intake and associated metabolic processes. Their research focuses on the sensory neural controls of energy homeostasis in health and disease. They have identified the type of food stimuli that activate vagal and splanchnic sensory fibers supplying the gut, and have revealed the extent to which these stimuli influence gut-brain communication.
Their most recent efforts involve the analysis of gut-brain communication in the control of energy homeostasis in mouse models of obesity and diabetes.We have identified neurons in the periphery, brainstem and hypothalamus that integrate food-elicited signals with peptide signals that have profound effects food intake and metabolism. Data from these studies reveal that central hypothalamic and brainstem neuropeptides affect food intake and body weight by modulating the neural potency of food stimulated signals from the mouth and gut. This novel, synthetic conceptual framework is critical because it links forebrain hypothalamic structures, long known to be involved in the control of energy balance, to the sensory and motor systems in the brainstem that control ingestion, digestion, and metabolic processing of food. Future studies will use genetic mouse models of obesity and diabetes with targeted conditional neuropeptide/ receptor knockdown or replacement to determine how central neuropeptide signaling affects the neural processing of metabolic sensory signals critical to energy homeostasis.
See some of his work here.
Dr. James Bayrer is an Assistant Professor of Pediatrics at the University of California, San Francisco. As a practicing pediatric gastroenterologist and physician scientist, his work focuses on the mechanisms underlying diseases like inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). IBD is a multisystem problem, sitting at the intersection of the immune system, the microbiome, and the intestinal epithelium—he has focused his career on studying the latter. During his early work, he studied Liver Receptor Homolog-1 (LRH-1), a nuclear hormone receptor. He found that LRH-1 is critical for GI development and epithelial renewal. His team discovered that LRH-1 knockout in mice induces intestinal inflammation due to increased apoptosis and decreased Notch signaling. Using mouse and human organoids, he found this is a conversed mechanism. He further showed that overexpression of LRH-1 is protective against harsh chemotherapeutics and inflammatory molecules. To further investigate the role of the intestinal epithelium in health and disease, he collaborated with Dr. Nick Bellono on a landmark paper establishing that enterochromaffin cells form functional synapses with sensory nerve fibers, and that enterochromaffin cell activation triggers visceral mechanical hypersensitivity— a feature of IBS. Interestingly, in looking again at LRH-1, he found LRH-1 knockout mice have disrupted enteroendocrine and enterochromaffin cell development. In fact, his preliminary data show LRH-1 knockout mice demonstrate visceral hyposensitivity despite no change in mechanical compliance or GI transit time. By continuing to investigate this and other molecular pathways, he aims to discover targets to improve the clinical syndromes of IBD and IBS.
See his lab’s webpage here.
Dr. Wu is the Ferdinand G. Weisbrod Professor in Gastroenterology at the Perelman School of Medicine at the University of Pennsylvania where he is the Associate Chief for Research in the Division of Gastroenterology and is also the Associate Director of the Center for Molecular Studies in Digestive and Liver Disease. He is currently Director and Chair of the Scientific Advisory Board for the American Gastroenterological Association Center for Gut Microbiome Research and Education and is an elected member of both the American Society for Clinical Investigation and the American Association of Physicians. The research programs in the Wu laboratory focus on the mutualistic interactions between the gut microbiota and the host with a particular focus on metabolism. Growing evidence suggests that diet impacts upon both the structure and function of the gut microbiota that, in turn, influences the host in fundamental ways. Current areas of investigation include the effect of diet on the composition of the gut microbiota and its subsequence effect on host metabolism related to nitrogen balance as well as its impact on metabolic pathways in the intestinal epithelium, principally fatty acid oxidation. Through a UH3 roadmap initiate grant, he is helping to direct a project investigating the impact of diet on the composition of the gut microbiome and its relationship to therapeutic responses associated with the treatment of patients with Crohn’s disease using an elemental diet. Finally, Dr. Wu is leading a multidisciplinary group of investigators using phosphorescent nanoprobe technology to examine the dynamic oxygen equilibrium between the host and the gut microbiota at the intestinal mucosal interface.
During his Gastronauts seminar, he shared some of his most recent findings on the role of the microbiota in interacting with three key components: Molecular oxygen, Urea, and bile acids.
See some of his work here.
Dr. Costa-Mattioli is the Cullen Foundation Endowed Chair of Neuroscience at Baylor College of Medicine. His laboratory’s primary aim is to understand the neurobiological basis of long-term memory formation. They seek to understand what happens in the brain when a memory is formed and more specifically how a labile short-term memory becomes a stable long-term memory. Disorders of learning and memory can strike the brain of individuals during development (e.g., Autism Spectrum Disorder or Down syndrome), as well as during adulthood (e.g., Alzheimer’s disease). They are also interested in understanding the specific circuits and/or molecular pathways that are primarily targeted in cognitive disorders and how they can be restored. To tackle these questions, they use a multidisciplinary, convergent and cross-species approach that combines mouse and fly genetics, molecular biology, electrophysiology, imaging, stem cell biology, optogenetics and behavioral techniques.
See his work here.
Dr. Neunlist visited us on April 2nd, 2019. He earned his PhD in electrophysiology in 1994 at University Louis Pasteur in Strasbourg, France. In his postdoctoral position in the laboratory headed by Michael Scheman in Hannover, Germany, he worked in the field of neurogastroenterology. Since 2007, he has directed a laboratory devoted to the study of enteric nervous system and enteric neuropathies. During his visit, he shared the importance of the enteric nervous system in the gut and some exciting new techniques using optical coherence tomography to image the ENS in the intestine. Finally, he shared some interesting new findings implicating the gut in Parkinson’s disease.
See his work here.Join us! Apr 2 @ 4PM in MSRB3 1125
Re-engineering Rabies Virus
Dr. Wickersham elaborates on his lab’s work regarding the creation of a second-generation rabies virus. This second-generation rabies virus was created through the replacement of the G and L genes of the virus with Cre. This virus was found to be able to spread trans-synaptically, and the survival of cells infected with this virus was greater than cells infected with the first-generation virus. However, this second-generation virus did not come without its limitations. It was not as effective as the first-generation virus and more complex. This led to the creation of the third-generation rabies virus. This virus was created by replacing only the L gene with Cre, as opposed to both the G and L genes. The Wickersham lab proved that this third-generation virus does not kill cells and is able to spread trans-synaptically. Additionally, Wickersham’s lab proved that coating with EnvA also works with this third-generation virus.
See his work here.
Dr. Cheryl Nickerson is a professor at the Biodesign Center for Immunotherapy, Vaccines and Virotherapy at Arizona State University. Her lab studies the effects of biomechanical forces on living cells (microbial and human), how this response is related to normal cellular homeostasis or infectious disease, and its translation to clinical applications. She and her lab have developed several innovative model systems to study these processes including 3-D organotypic models of human tissues that mimic the structure and function of in vivo tissues and their application to study the host-pathogen interaction that leads to infectious disease.
Dr. Cheryl Nickerson’s lab’s aim to bridge the gap between current intestinal models and the real intestine. Her laboratory has pioneered the uses of Rotating Wall Vessels, which can model low fluid shear in mucosal tissues in the intestine. Her past work involved determining if the characteristic of Salmonella Typhimurium would change under low fluid shear conditions as compared to high fluid shear conditions. She also talked about her recent advancement in creating 3D intestinal models, which have been shown to have better tight junctions and specialized epithelial cell types such as M cells and goblet cells. This intestinal model can also differentiate between various Salmonella strains, such as a GI strain and a deadly bloodborne strain, and can model different effects of Salmonella infection on the small intestine and colon. She looks to advance her model by adding commensal microbes and the patient fecal microbiome, as infections occur in these specific environments.
See her work here.