Gautron Lab
We investigate the neuro-hormonal basis for complex eating behaviors and blood glucose control, with the ultimate goal of designing new methods to prevent and treat extremes of body weight, blood glucose, and associated disorders of mood and metabolism.
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Some of our major ongoing thematic projects are listed here:
Eating, Obesity, and Exercise ↔ Diabetes and Hypoglycemia ↔ Secretion of Ghrelin and other Stomach Hormones ↔ Ghrelin, Stress, and Depression
Eating, Obesity, and Exercise
Diabetes and Hypoglycemia
Secretion of Ghrelin and other Stomach Hormones
Ghrelin, Stress, and Depression
Eating, Obesity, and Exercise
We have demonstrated key roles for the hormone ghrelin in reward-based eating, stress-induced comfort food eating, and responses to exercise. Ongoing studies aim to identify the CNS sites and mechanisms by which the ghrelin system affects eating, body weight, and exercise and how the components of the ghrelin system contribute to obesity, cachexia, and Prader-Willi Syndrome.
Diabetes and Hypoglycemia
Ghrelin is critical in defending against marked hypoglycemia and death under conditions of marked calorie restriction. Ongoing studies in the lab investigate the CNS and peripheral sites and pathways responsible for the ghrelin system’s blood glucose-related actions in conditions such as diabetes and hypoglycemia.
Secretion of Ghrelin and other Stomach Hormones
We are using a one-of-a-kind set of tools to study the mechanisms directing ghrelin secretion and the physiology of gastric endocrine cells in several different metabolic settings.
Ghrelin, Stress, and Depression
Our group has demonstrated protective, anti-depressant-like actions and food reward-stimulating actions for the ghrelin system under conditions of chronic psychosocial stress. We have identified adult hippocampal neurogenesis as a mechanism for this anti-depressant-like effect of ghrelin.
Gautron Lab
Details about Our Research
The autonomic nervous system comprises a network of sensory and motor neurons that connect the brainstem and spinal cord to thoracic and abdominal organs. A better understanding of the anatomical and functional plasticity of the autonomic nervous system will likely move forward our understanding of numerous chronic diseases including, but not limited to, obesity, diabetes, visceral pain, neuropathy, and eating disorders. We also have a long-standing interest in the neurobiology of inflammation-associated anorexia. Furthermore, the fact that autonomic nerves reside outside the blood-brain barrier makes them a particularly relevant target for pharmacological agents and device-assisted manipulations such as vagus nerve stimulation. Using the power of the Cre-LoxP technology combined with techniques of molecular neuroanatomy and metabolic physiology, our laboratory is trying to elucidate the role played by the autonomic nervous system including vagal sensory neurons in the pathophysiology of chronic metabolic diseases.
Milestones
We were first to define essential roles for ghrelin in mediating stress-induced comfort food eating and other complex eating behaviors, including operant responding and conditioned place preference for high-fat diet, also confirming a role for the ghrelin system in cue-potentiated feeding. We also have characterized the role of ghrelin in post-exercise eating.
We have contributed substantively to a body of work demonstrating an essential role for the ghrelin system in the regulation of blood glucose. We have demonstrated not only that ghrelin secretion is enhanced when ghrelin cells are exposed to low glucose, but also that when regulation of ghrelin secretion by the sympathetic nervous system is blocked, life-threatening falls in blood glucose ensue. We have also identified the arcuate nucleus, the caudal brainstem, and pancreatic alpha cells as targets for ghrelin’s glucoregulatory actions.
Consistent with our mission to understand the biological basis for the strong link between eating behavior and mood, our group was the first to demonstrate a role for the hormone ghrelin as a natural antidepressant, preventing exaggerated depressive-like behaviors following chronic stress and inducing an antidepressant-like behavioral response upon caloric restriction. We showed that ghrelin’s antidepressant actions rely on protection of adult hippocampal neurogenesis, leading us in collaborative work with Andrew Pieper to identify antidepressant-like efficacy for the P7C3 class of strong, rapid-acting neuroprotective compounds, and paving the way
We have identified key central and peripheral sites of ghrelin’s orexigenic, glucoregulatory and antidepressant actions by comprehensively determining the pattern of ghrelin receptor-expressing neurons in the rat and mouse brain, by using Cre-lox mouse genetics to target ghrelin receptor expression to selective cell-types, and by using chemogenetics to manipulate the activity of ghrelin receptor-expressing neurons in specific brain regions.
Using a collection of novel models to directly study isolated populations of ghrelin cells and to modify ghrelin cell gene expression, we have led the way in identifying direct modulators of ghrelin release and key elements of the ghrelin cell molecular machinery mediating ghrelin secretion.
We determined that circulating levels of the endogenous ghrelin receptor antagonist and inverse agonist LEAP-2 in humans are correlated with body weight, several metabolic parameters related to obesity, food intake, and weight loss.
We have generated a large toolbox of transgenic mouse models with which to investigate ghrelin action in the brain and periphery, ghrelin cell biology, and the biology of other gastric enteroendocrine cell types. These include ghrelin-Cre mice, GHSR-IRES-Cre mice, HDC-Cre mice, SF1-Cre mice, KISS1-Cre mice, “floxed”-β1AR mice, ghrelin-KO mice, GHSR-null mice, and ghrelin-hrGFP mice, to name a few. In collaboration with the Brown/Goldstein labs, we generated SG-1 and PG-1 immortalized ghrelin cell lines. These tools are now used in numerous metabolism and neuroscience research labs worldwide.
Current Lab Members
Jenny Lee
Research Technician II
Sherri Osborne-Lawrence, M.S.
Senior Research Scientist and Lab Manager
Sherri was born in Texas and has lived here all of her life. She received her B.A. degree in Biology from Austin College in Sherman, TX, and an M.S. degree in Molecular & Cell Biology from UT Dallas. She has worked in five laboratories at UT Southwestern Medical Center. Sherri's initial research projects involved positional cloning of genes involved in rheumatoid arthritis and early-onset familial breast cancer. After a few years assisting with the final stages of sequencing for the Human Genome Project, she focused on discovering how endothelial cell dysfunction leads to cardiovascular disease, with particular interests in estrogen modulation as well as the effects of C-reactive protein. Sherri joined the Zigman Lab in 2006 as Senior Research Scientist and Lab Manager, and has now expanded her interests to include ghrelin and its effects on metabolic pathways. Among many other contributions, Sherri has designed and generated several new mouse lines currently in use in the lab and by our collaborators.
Nathan Metzger, M.S.
Research Associate
Nathan Metzger, M.S.
Research Associate
Nathan was born and raised in Apple Valley, MN. He obtained his BS in Community Health (2012) and Biomedical Science (2012) and his MS in Cell and Molecular Biology (2014) from Saint Cloud State University in Saint Cloud, MN. His research background includes having studied the post-translational modifications of a family of proteins collectively known as PGC-1. Specifically, identifying modifiers, locating binding sites, and exploring their effects on PGC-1 expression and activity. He relocated to Fort Worth, TX in the summer of 2016, after which he joined Dr. Zigman's lab.
Deepali Gupta, Ph.D.
Postdoctoral Research Fellow
Deepali Gupta, Ph.D.
Postdoctoral Research Fellow
Deepali was born in Chhattisgarh, a tribal state in the central part of India. She received her Bachelor in Pharmacy from Rajiv Gandhi Technical University in 2008 and Master in Pharmacy from BITS-Pilani, Pilani Campus, India in 2011. During her Master’s dissertation program mentored by Prof. Mahesh, she studied the role of serotonin signaling and hypothalamic-pituitary-adrenal axis dysregulation in depression. Later, she enrolled in the doctoral program at BITS-Pilani and continued to work under the guidance of Prof. Mahesh . Her doctoral research project was aimed at investigating the role of serotonin type-3 (5-HT3) receptor signaling in the pathogenesis of type-1 diabetes-induced depression and the antidepressant activity of novel 5-HT3 receptor antagonists. Deepali joined the Zigman lab in January 2017 to further explore pathogenic pathways involved in depression, in particular, those modulated by the ghrelin system. When not in the lab, she likes cooking and chatting with her family and friends.
Kripa Shankar, Ph.D.
Postdoctoral Research Fellow
Kripa Shankar, Ph.D.
Postdoctoral Research Fellow
Kripa was born in a small city Kannauj, famous as a city of perfume, in Uttar Pradesh, India. Kripa completed his undergraduate education at CSJM University in Kanpur, India. Afterwards, Kripa received a Master of Science degree in Biotechnology at Babasaheb Bhimrao Ambedkar University in Lucknow, India. After obtaining Junior and Senior Research fellowships from the University Grant Commission, India, Kripa joined the lab of Dr. Anil N. Gaikwad at CSIR-Central Drug Research Institute in Lucknow, India. He earned his PhD degree in 2017. His PhD work focused on pathways involved in chronic hyperinsulinemia and high fat diet-induced insulin resistance. In June of 2017, Kripa joined the Zigman Lab to further enhance his expertise in the area of ghrelin-mediated effects on blood glucose regulation. Apart from science, Kripa loves watching cricket and listening to Bollywood music.
Former Lab Members
- Postdoctoral Fellows/Instructors
- Graduate Students
- Research Technicians & Research Associates
- Summer Students
Ichiro Sakata, Ph.D. – Postdoctoral Research Fellow 2007 – 2010 – Ichiro is currently Associate Professor in charge of his own lab at Saitama University in Japan.
Mario Perello, Ph.D. – Postdoctoral Research Fellow 2/2008 – 3/2010 – Mario is currently an associate investigator in charge of his own lab at the Laboratory of Neurophysiology, Multidisciplinary Institute of Cell Biology (IMBICE) in La Plata, Argentina
Jen-Chieh (Jay) Chuang, Ph.D. – Postdoctoral Research Fellow 8/2008 – 5/2011 – Jay is currently working as a Biomarker Scientist at Gilead in the San Francisco Bay Area.
Paul K. Piper Jr, M.D. – Postdoctoral Research Fellow/Clinical Fellow in Diabetes, Endocrinology, and Metabolism, 2009-2011 – Paul is currently in private practice as an endocrinologist in The Woodlands, TX.
Daniela Pereira Derderian, Ph.D., Pharm.D. – Postdoctoral Research Fellow 5/2010 – 7/2012 –Daniela is currently an assistant professor in biological sciences at the School of Math and Science at Wayland Baptist University in Plainview, TX.
Won-Mee Park, Ph.D. – Postdoctoral Research Fellow – 2011–2012 – Won-Mee is currently enjoying her role as a new mom.
Qian Wang, Ph.D. – Postdoctoral Research Fellow – 1/2012–12/2013 – Qian is currently working as a Data Scientist at AIG.
Aki Uchida, Ph.D. – Postdoctoral Research Fellow – 1/2012–3/2014 – Aki is currently a Senior Project Manager at Takeda.
Sun-Hyun Park, Ph.D. – Postdoctoral Research Fellow – 10/2015–9/2016 – Sun–Hyun has moved back to South Korea where he is pursuing a science-related business venture.
Emily Bruggeman, M.S., Ph.D. – Postdoctoral Research Fellow –7/2016 – 7/2017 – Emily is currently working as a neuroscientist at Emory University School of Medicine.
Shota Takemi, Ph.D. – Postdoctoral Research Fellow – 6/2019 – 12/2019 – Shota is an Assistant Professor at Saitama University, Japan
Bharath Mani, D.V.M., Ph.D. – Postdoctoral Research Fellow, Instructor – 5/2012 – 5/2020 – Bharath is currently working as a scientist at Novo-Nordisk in Indianapolis, IN
Angela Walker – Ph.D. student in the Neuroscience Graduate Program, 1/11–4/14 – Angela successfully defended her thesis entitled “From the ghrelin cell to ghrelin action: Assessing ghrelin’s influence on mood, cue-potentiated feeding, and ghrelin cell physiology.” She is performing basic and clinical research related to autism at UT Southwestern.
Siegfried Meier – Research Assistant II, 3/09–3/10
Sherry Rovinsky – Research Assistant, 2007-2009. Graduate Student, 2010–2011.
Chelsea Migura – Research Assistant I, 3/2010–7/2012
Brittany Mason, Ph.D. – Senior Research Associate, 6/2012–7/2013
Sydney Lawrence – Research Assistant, Summer 2013, Summer 2014, Summer 2015, Summer 2016
Connor Lawrence – Research Assistant, Summer 2015, Summer 2016
Jakub Woloszyn – 2008 UTSW Medical Student, Summer Research
Neha Chaudhary – 2009 UTSW Medical Student, Summer Research
Gregory Wallingford, Jr. – 2009 Summer Undergraduate Research Fellowship student
Anna Kuperman – 2010 Summer Undergraduate Research Fellowship student
Shloka Raghavan – 2011 Summer Undergraduate Research Fellowship student
Carolyn Chakuroff – 2012 Summer Undergraduate Research Fellowship student
Imikomobong (Micky) Ibia – 2012 MSTP Summer Undergraduate Research Fellowship student
Christina Mosher –2013 UTSW Medical Student, Summer Research
Madhu Karamsetty – 2013 Summer Undergraduate Research Fellowship student
Nicole Huang – 2014 Summer Undergraduate Research Fellowship student
Rachel Hodge – 2015 Summer Undergraduate Research Fellow
Hannah Viroslav –2016 UTSW Medical Student, Summer Research
Henry Roseman –2017 Undergraduate student, Summer Research
Anna Patterson –2019 Amgen scholar
Avi Burstein –2019, 2020 High School student, Summer Research
Available Positions
Available Student, Postdoctoral fellow, and Research Technician Positions
The Zigman lab is seeking motivated, hard-working, and imaginative student, postdoc, and technician researchers to join our team.
The Zigman lab investigates the neuronal/hormonal basis for eating, body weight, and blood glucose control with the goal of designing new methods to treat obesity, diabetes, hypoglycemia,
cachexia/anorexia, and associated disorders of mood. Most of our studies focus on the hormone ghrelin, which is made primarily by a distinct group of cells in the stomach, the ghrelin receptor (GHSR), which is highly expressed in the brain and pancreatic islets, and LEAP2, which decreases activity of the ghrelin receptor. Our past and ongoing studies have investigated how ghrelin and ghrelin receptors influence eating, blood glucose, body weight, and mood in the settings of high fat diet exposure, caloric restriction, exercise, chronic stress, weight loss surgery, insulin administration, and Prader-Willi Syndrome. We also study the mechanisms of ghrelin secretion. Newer projects investigate novel proteins involved in the body’s responses to obesity and caloric restriction.
Several graduate student and postdoctoral positions are available in the Zigman lab. There are also Research Assistant/Research Associate positions available. Projects will take advantage of our one-of-a-kind collection of transgenic mouse models targeting the ghrelin system, other endocrine cells, and neurons. These models allow us to characterize and manipulate gene expression and modulate cellular activity in specific cells and neurons of interest. Methods include mouse behavioral protocols, CRISPR-Cas9, transcriptomics, tissue clearing, cell culture, histology, glucose clamp techniques, stereotaxic brain surgery, chemogenetics, optogenetics, and in vivo fiber photometry, to name a few.
Candidates for the graduate student positions can come from any UT Southwestern Ph.D. Program, and most usually are from the Neuroscience Graduate Program or the Genetics Development and Disease Graduate Program. Students most often are also affiliated with the Molecular Metabolism and Metabolic Diseases (3MD) Track (chaired by Dr. Zigman). We would love to have you and your friends rotate through the lab!
Candidates for the postdoctoral positions must hold a Ph.D. and/or M.D. degree.
Graduate student and postdoctoral fellow candidates should be self-motivated and are expected to contribute substantively to the design, implementation, interpretation and reporting of their investigational studies. Prior experience with genetically-engineered mouse models and related breeding strategies, mouse behavioral studies, stereotaxic brain surgery and other neuroanatomical techniques such as chemogenetics and optogenetics, histology, cell culture, and/or bioinformatics leading to publication in peer-reviewed journals is recommended but not required.
Interested individuals should send a CV, statement of interests, and a list of three references to Jeffrey Zigman, M.D., Ph.D.
UT Southwestern Medical Center is an Affirmative Action/Equal Opportunity Employer. Women, minorities, veterans and individuals with disabilities are encouraged to apply.
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