Dr. Kravitz is an Investigator in the Eating and Addiction Section, Diabetes, Endocrinology, and Obesity Branch of the National Institute of Diabetes and Digestive and Kidney Diseases. His work focuses on the study of basal ganglia circuits and how their function changes in disease states such as obesity, addiction, and depression. Under normal conditions, the basal ganglia drives animals toward the selection of specific behavioral outcomes. Learning can bias this selection process toward specific behavior by altering synapses within and outside the basal ganglia. In extreme cases, these synaptic alterations can produce pathological behavioral selection, as in obesity or addiction. Using behavioral testing, optogenetics, and in vivo electrophysiology and optical measurements, the lab characterizes changes in behavior following learning in a feeding context and attempts to understand the neural correlates and causes of these changes in behavior.
See more of his work: Kravitz Lab
Jennifer Kern and Katherine Flynt are two speech-language pathologists at Duke University who work with many autistic children. They shared their insights into autism and its relationship to eating abnormalities!
Lawrence David is an Assistant Professor in GCB and the Department of Molecular Genetics & Microbiology. His Lab is particularly interested in how commensal microbes help resist, and ultimately respond to, colonization by human pathogens. An active area of research is the longitudinal study of cholera infections among residents of Dhaka, Bangladesh. Primary research questions include: Can enteric microbial communities predict an individual’s susceptibility to cholera? Why do bacterial ecological successions follow cholera infection? What long-term effects do infection and treatment have on commensal gut microbes? The David Lab is also broadly interested in developing new modeling and visualization tools for time-series of complex microbial communities, as well as exploring the ecology of human microbiota in the developing world.
See more of his work: David Lab
Dr. Scott Magness is an Associate Professor in the Department of Cell Biology at UNC. His research is focused on the basic biology of intestinal stem cells, the genes that control their behavior, and translational approaches to stem cell based therapies for human disease and injury of the intestine. Furthermore his research focuses on elucidating genetic mechanisms underlying stemness and developing translational models to establish a finer understanding of stem cell-driven regeneration dynamics in homeostasis and injury. Using a combination of genetic mouse models and micro-frabricated bioengineered platforms, Dr. Magness’ team is exploiting the self-renewal capacity and multipotency of ISCs to develop long-term ex vivo models of the intestine and colon with primary tissues. These biomimetic models offer new solutions for compound screening and cell-based therapies.
See more of his work: Magness Lab.
Dr. Jenna McHenry, Assistant Professor of Psychology and Neuroscience at Duke University, starting Fall 2018
Hormonal regulation of a hypothalamic social reward circuit
Dr. Jenna McHenry was recently hired as an Assistant Professor of Psychology and Neuroscience at Duke University starting Fall 2018. She is currently completing her post-doctoral fellowship at the University of North Carolina- Chapel Hill in Dr. Garret Stuber’s laboratory. Her post-doctoral work has focused on investigating the neural circuitry that links social and emotional processing within the brain. As evident in reproductive mood disorders such as post-partum depression and premenstrual dysphoric disorder, hormonal flux can cause affective disorders. Dr. McHenry’s post-doctoral work has focused on studying the neural circuits—specifically the circuits involving the medial preoptic area (mPOA)— that regulate hormone mediated reward programming and sex specific behavior. In work published in Nature Neuroscience in 2017, Dr. McHenry used in vivo two-photon imaging in awake mice to identify a subset of neurotensin-expressing mPOA neurons that interface with the ventral tegmental area (VTA) to form a socially engaged reward circuit. By recording from these neurons both at different times in the female reproductive cycle and after ovariectomy, she found this subset of neurons is steroid-responsive, indicating steroids modulate social encoding. As an extension of her post-doctoral work, Dr. McHenry’s central research question in her laboratory will be to understand how social processing neurons are intertwined with or embedded into positive and negative valence systems. Further, her lab will investigate the interplay between social and non-social reward circuits. Her lab will use a combination of advanced techniques including freely moving calcium imaging and optogenetics to investigate these questions. We look forward to the exciting research that Dr. McHenry will bring to Duke as a new faculty member.
See Dr. McHenry’s work here.
“Microbiome-immune crosstalk in neurodevelopmental disease”
Dr. John Lukens is an Assistant Professor at the University of Virginia. His research aims to understand how immunologic pathways and interactions contribute to neurodevelopmental diseases. During his talk, he focused on his lab’s work related to the microbiome-immune crosstalk influencing autism and multiple sclerosis. Significant research exists implicating the microbiome in the pathogenesis of autism spectrum disorders. Dr. Lukens and his team found that microbiome differences between Jackson and Taconic mice change the TH17 response and the expression of an autistic phenotype. Further, they showed microbiota transfer of the maternal microbiome of susceptible, Taconic mice induces autism susceptibility in Jackson mice. They then asked what metabolites are affected by changes in the microbiome. They found that Taconic dam’s injected with Poly-IC have increased IL-17a compared to Jackson mice. Inhibiting IL-17 in pregnant dams rescued the mice from an autistic phenotype. Further work will investigate additional metabolic mediators and identify protective commensal bacteria. Dr. Lukens then shared his work on inflammasome biology, specifically with relation to experimental autoimmune encephalomyelitis (EAE), a mouse model for multiple sclerosis. Caspase 1 in inflammasomes is thought to be required to cleave IL-1β into active IL-1. However, research from the Lukens lab suggests inflammasome-independent cleavage of IL-1 is important in driving EAE. They found that reduced levels of IL-1 receptor correlate with a reduced disease burden; knocking out caspase 1 does not confer protection, but knocking out the IL-1 receptor does. Further research will seek to better define the pathways and pharmaceutical targets involved in this phenomenon.
Check out Dr. Lukens’s work here: Lukens Lab
Speaker: Dr. Alban Gaultier, Ph.D. from University of Virginia
Title: “Effect of gut microbes on mood and anxiety”
Dr. Alban Gaultier is an Assistant Professor at the University of Virginia. To study the effect of the microbiome on depression and anxiety, Dr. Gaultier’s lab used the unpredictable chronic mild stress (UCMS) protocol to induce a depressive phenotype in mice. In work published in Scientific Reports this year, they showed the UCMS protocol does not change the total amount of microbiota present in the gut. Rather, it drives dysbiosis, reducing the population of Lactobacillus species in the gut across multiple strains of mice. Further, they found that replacing the lost species with Lactobacillus reuteri improved the depressive phenotype. They then delved into the pathogenesis of these findings.
Using metabolomics, they found an increase in products of the tryptophan kynurenine pathway in depressed mice. They reasoned that Lactobacillus generate reactive oxygen species, and these reactive species inhibit the enzyme IDO1, responsible for converting tryptophan to kynurenine. They hypothesized that reduced Lactobacillus species can cause increased levels of kynurenine, which is able to cross the blood brain barrier and contribute to depressive symptoms. To confirm this hypothesis, they found that augmenting kynurenine levels abolished the beneficial effect of Lactobacillus supplementation. Since the publication of their paper this year, Dr. Gaultier’s lab has been asking the question: how does the UCMS protocol change the microbiome?
Their first hypothesis was that the adaptive immune system could be contributing to this change, but they observed the same decrease in Lactobacillus in mice without an adaptive immune system. Further investigation showed that stressed mice have increased colonic motility; and because Lactobacillus are scavengers, they hypothesized that the reduced transit time in the colon caused the Lactobacillus to be outcompeted. Their data show that not only does administering a laxative reduce Lactobacillus species, but also it drives depressive behavior in mice.
Finally, they have been investigating the effect of the kynurenine pathway on oligodendrocytes, the glial cells of the CNS, as a reduction of glial cells can be found in the brains of depressed patients. Preliminary data shows that increased levels of kynurenine reduces the survival of oligodendrocyte progenitor cells and inhibits their differentiation. In summary, Dr. Gaultier and his lab has revealed a mechanism by which the microbiome, specifically Lactobacillus species, can contribute to anxiety and depression.
Speaker: Dr. Ivan de Araujo, D.Phil from Yale University
Dr. de Araujo is an Associate Professor from Yale University in the John B. Pierce Laboratory. The goal of his lab is to define the sensorimotor circuitry that controls feeding programs. In 2008 work published in Neuron, Dr. de Araujo showed that taste alone is not enough to communicate the reward value of sugar; he knocked out the trpm5 taste receptor in mice to create a taste blind mouse, but found that mice still tend to prefer sugar after a few hours.
From there, he studied the brain regions that encode for this reward. He found that reward behavior can be abolished by inhibiting the mesolimbic and nigrostriatal brain dopamine pathways. He found that intake of sweeteners activates the ventral striatum while D-glucose activates the dorsal striatum, and that the infusion of nutrients into the gut increases dopamine levels proportional to the amount of calories infused. He then went about delineating the neural circuit driving this response.
Initially, he found that energy is transmitted to the substantia nigra pars compacta to the dorsal striatum to the substantia nigra. Meanwhile, sweetness, in the form of non-nutritive sweeteners, takes a different pathway; it is transmitted to the ventral tegmental area to the ventral striatum to the ventral pallidum. In summary, Dr. Ivan de Araujo has greatly impacted the way we understand the neurobiology of feeding and the reward pathways it elicits.
Speaker: Dr. Adam Gracz, Ph.D from UNC Chapel Hill
Title: “Stem Cell Dynamics in Intestinal and Biliary Epithelia.”
Dr. Gracz is an Assistant Professor at UNC Chapel Hill and started his independent laboratory in July 2016 after completing his postdoctoral fellowship in intestinal stem cell biology in Dr. Scott Magness’s lab at UNC Chapel Hill. His collective work has explored how cells pattern to form functional tissues.
In his post-doctoral work, Dr. Gracz studied how stemness is regulated in the intestine. He and his colleagues found that SOX9 EGFP is expressed in variable levels in intestinal crypts, specifically finding that the level of expression marks distinct cell populations including progenitor cells, intestinal stem cells, and enteroendocrine cells. They used various novel and state-of-the-art techniques in their work; specifically, they collaborated with biomedical engineers to use microraft arrays (MRAs) to facilitate genetic screening of organoids. After his successful postdoctoral fellowship, Dr. Gracz started his independent laboratory based on the central question “How does epigenetic regulation drive functional outcomes in cell and tissue biology?”
His lab focuses on two areas of research: the chromatin structure of intestinal stem cell biology and the cellular dynamics of biliary epithelium. In his talk, Dr. Gracz focused on his lab’s work in biliary epithelial populations. He is using SOX9 EGFP to study the sub-populations of biliary epithelial cells and to identify potential biliary stem cells. In summary, Dr. Gracz is continuing to further the field’s understanding of stem cell dynamics in GI epithelial tissues.