The Schwartz laboratory investigates the role of the brain in the control of both energy balance and glucose homeostasis with a focus on how defects in these systems contribute to the pathogenesis of obesity and diabetes. Our lab, in collaboration with the lab of Greg Morton, has shown that circulating hormones (such as leptin) can act in the brain to normalize elevated blood glucose levels in diabetic animals by powerfully activating insulin-independent processes. Specifically, our work centers on the concept that when the brain senses that body energy content and nutrient availability are in sufficient supply, further increases of stored energy (in the form of fat) and circulating nutrients (e.g., glucose) are resisted. Consequently, a decrease in neuronal input from one or more of these afferent signals alerts the brain to a current or pending deficiency of stored energy or nutrient availability. In turn, the brain activates responses that increase food intake, reduce energy expenditure, and raise circulating levels of glucose and other nutrients. Under normal circumstances, the resultant increase of body fat content and plasma levels of glucose, leptin, insulin, and free fatty acids are sensed in the brain, such that the adaptive response to nutritional deprivation is terminated upon the return of body fat mass and blood glucose levels to their original values. However, defects in the ability to mount, sense or respond to these humoral signals by neurocircuits in the mediobasal hypothalamus are proposed to be highly prevalent in human populations, and these defects collectively can set in motion a vicious cycle of weight gain, insulin resistance and impaired insulin secretion that can lead to type 2 diabetes.
In addition to our work investigating the central actions of leptin on energy balance and glucose metabolism over >2 decades, our lab focuses on the anti-diabetic effects of members of the FGF family, including FGF19, FGF21 and FGF1. In each case, the brain has emerged as a key target for these beneficial effects. Of particular interest is that in both rat and mouse models of T2D, a single injection of FGF1 into the brain induces diabetes remission that is sustained for weeks or months. We have subsequently localized this unprecedented effect to the mediobasal hypothalamus, and our current work investigates the hypothesis that defective glucose sensing in this brain area contributes to diabetes pathogenesis, and that this defect is ameliorated by the action of FGF1 in this brain area. Accordingly, ongoing studies aimed at delineating the cellular and molecular underpinnings of this effect have important implications at both a basic science and translational level. A key long-term goal is to translate these findings into novel approaches to the treatment of T2D.
Another area of active research pertains to perineuronal nets (PNNs), extracellular matrix (ECM) specializations that enmesh key neurons in a circuit and thereby regulate their function. We recently showed that neurons crucial for metabolic homeostasis located at the junction of the arcuate nucleus and median eminence (a mediobasal hypothalamic area specialized for sensing humoral signals) are enmeshed by PNNs. Our ongoing studies seek to determine the role played by these PNN-enmeshed neurons in how the brain senses glucose and other relevant humoral signals.
Members of the Laboratory
Kimberly Alonge, PhD
Research ScientistDr. Kimberly Alonge completed her Bachelor of Science at Salisbury University before completing a PhD in Biochemistry and Molecular Biology in the laboratory of Dr. Hillgarter at West Virginia University. In 2017, she accepted a post-doctoral fellowship in the laboratory of Dr. Schwartz at the University of Washington within the Division of Metabolism, Endocrinology and Nutrition. Dr. Alonge's work focuses on elucidating the functional role of hypothalamic perineuronal net extracellular matrix structures in central blood glucose regulation. Dr. Alonge was awarded UW's SLU trainee of 2018 for her dedication and scientific advancements to the field of diabetes and metabolism.
Marie Bentsen, PhD
Research ScientistDr. Marie A. Bentsen completed her Master of Science at the University of Copenhagen, Denmark, before completing a PhD in the laboratory of Thue W. Schwartz at the University of Copenhagen. In 2017, she accepted a 1-year bridging post-doctoral fellowship in the laboratory of Dr. Tune H. Pers at the University of Copenhagen and received additional independent funding to pursue a postdoctoral fellowship in the laboratory of Dr. Michael W. Schwartz at the University of Washington within the Division of Metabolism, Endocrinology and Nutrition. Her work focuses on understanding the brains role in metabolic disorders by studying the transcriptional signatures of rodent brains in health and disease.
Jenny Brown, BS
Graduate StudentJenny completed her BS in Biology from Cal State Monterey Bay. She subsequently moved to Seattle, where she matriculated in the Molecular Medicine and Mechanisms of Disease (M3D) PhD program at the University of Washington. She elected to conduct her thesis work under the mentorship of Dr. Michael Schwartz within the Division of Metabolism, Endocrinology and Nutrition. The goal of her research work is to examine the mechanisms whereby FGF1 action in the brain regulates glucose homeostasis.
Research Scientist, Engineer 3, & Lab ManagerSarah has completed a BS in Neurobiology as well as both a BS and MS in Electrical Engineering at the University of Washington. Sarah previously worked in the laboratory of Dr. Steiner, examining neuroendocrine mechanisms that govern reproduction before recently joining the lab in 2019. Sarah works with investigators to examine the neuroendocrine control of feeding and blood sugars by implementing new technologies into their neuroendocrine research, including the use of wireless optogenetics; a tool for stimulating and inhibiting neurons, fiber photometry; a method to monitor endogenous neural activity in real time and a thermal gradient; an assay for thermoregulatory studies.
Kayoko Ogimoto, PhD
Research ScientistKayoko completed a Doctor of Philosophy in Exercise Physiology with an integrated minor of Biochemistry, Nutrition and Veterinary Physiology at the Oregon State University She joined the lab in 2002 and is a Research Scientist 4. Kayoko works with investigators to streamline the study implementation for the UW Medicine Energy Balance Core. She oversees the data collection and is responsible for the organization, formatting, processing and biostatistical data analysis of indirect calorimetry and related service for rodents.
Research ScientistJarrell Nelson joined the lab in 2010 and is a Research Scientist 1. He completed his Bachelor of Science in Zoology at Washington State University and is responsible for the performance of indirect calorimetry, ambulatory activity, body temperature, running wheel studies and insulin/glucose tolerance tests.
Research ScientistVincent Damian graduated with a B.A. Philosophy, B.S. Biochemistry, University of Washington and joined the lab in 2011 as a Research Scientist 1. He is a Colony Manager and his research responsibilities include: Murine Genetics, Gene Expression Technologies, Operation Management, Project Management
Bao Anh Phan
Research ScientistBao Anh Phan joined the laboratory in 2017. She completed a Bachelor of Science in Biochemistry at the University of Washington. She is an expert in histology, with the performance of cryostat sectioning, immunohistochemical staining and western blot analysis
UW Undergraduate StudentTammy's research interests include studying the role of the brain in maintaining glucose homeostasis and the impact of FGF1 on diabetes remission.
UW Undergraduate StudentSarwesh is a current undergraduate at the University of Washington double majoring in molecular biology and mathematics. His interests include cell signaling proteins and mitogens in cellular processes, specifically focusing on fibroblast growth factors. He is passionate about leading his own independent research project and plans to pursue an MD-PhD dual degree in the near future
UW Undergraduate StudentI am currently going into my sophomore year at UW and studying molecular biology and computer science. In general. I am very interested in the cross of research and the biological sciences. Specifically, I am interested in how energy homeostasis and glucoregulatory neurocircuits are linked and how they can be disrupted by the development of obesity. I love science and I look forward to being part of the team!"
UW Medicine Diabetes Institute
750 Republican Street, Box 358062
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Jarrell Nelson: firstname.lastname@example.org
To inquire about Postdoctoral and Graduate Student Openings click on: mschwart.uw.edu