Zigman 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, Hypoglycemia, and Islet Size
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.
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.
Details about Our Research
The Zigman Lab is composed of Dr. Zigman, our lab manager and senior research scientist, Sherri Osborne-Lawrence, and a core group of talented instructors/postdoctoral fellows/students/research associates/technicians. We investigate how gastrointestinal hormones such as ghrelin and LEAP2 interact with the brain and peripheral nervous system to control eating, body weight, blood glucose, responses to exercise, and mood in an effort to devise better treatments for obesity, diabetes, eating disorders, depression, cancer cachexia, and neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS).
Our work spans the fields of molecular endocrinology, behavioral neuroscience, and neuroanatomy and includes mouse, human, and cell culture experiments.
Our studies employ a one-of-a-kind collection of Zigman Lab-generated novel transgenic mouse models including those made using recombineering and CRISPR-Cas9 approaches. We also design and use several animal behavioral models and cell culture models. We incorporate state-of-the-art techniques to characterize gene expression, manipulate gene expression, and modulate cellular activity in specific cells and neurons of interest, for instance by chemogenetic/DREADD technology. We use gold standard methodology such as glucose clamps to investigate glucose homeostasis. We also routinely utilize RNAseq technology (transcriptomics), tissue clearing, cell culture, traditional neuroanatomic techniques, microscopy of various types, and histochemistry to probe ghrelin and LEAP2 action, ghrelin and LEAP2 secretion, and the coordinated hormonal/neuronal response to conditions relevant to perturbed metabolic states.
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 and the mouse pancreas, by using Cre-lox mouse genetics to target ghrelin receptor expression to selective cell-types, by using chemogenetics to manipulate the activity of ghrelin receptor-expressing neurons in specific brain regions, and by characterizing GHSR expression using traditional in situ hybridization histochemistry techniques as well as reporter mouse lines.
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 also generated the first LEAP2-KO mouse line and have performed the initial metabolic characterization of those mice, confirming a suspected role for LEAP2 in mediating the phenomenon of ghrelin resistance.
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, floxed-GHSR mice, LEAP2-KO mice, and GH-IRES-Cre 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
Sherri Osborne-Lawrence, M.S.
Senior Research Scientist and Lab Manager
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.
Deepali Gupta, Ph.D.
Instructor
Deepali Gupta, Ph.D.
Instructor
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 as a postdoctoral research fellow to further explore pathogenic pathways involved in depression, in particular, those modulated by the ghrelin system. She was promoted to Assistant Instructor in September 2021 and to Instructor in September 2022. When not in the lab, she likes cooking and chatting with her family and friends.
Kripa Shankar, Ph.D.
Instructor
Kripa Shankar, Ph.D.
Instructor
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 as a postdoctoral research fellow to further enhance his expertise in the area of ghrelin-mediated effects on blood glucose regulation. He was promoted to Assistant Instructor in September 2021 and to Instructor in September 2022. Kripa received the Ethan Sims Young Investigator Award from The Obesity Society in 2021. He received an Endocrine Society Outstanding Abstract Award for travel to ENDO 2023. Apart from science, Kripa loves watching cricket and listening to Bollywood music.
Salil Varshney, Ph.D.
Postdoctoral Research Fellow
Salil Varshney, Ph.D.
Postdoctoral Research Fellow
Salil was born and raised in Chandausi, a large town in Sambhal district, Uttar Pradesh, India. Salil completed his undergraduate education at M.J.P. Rohilkhand University, S.M. Degree College, Chandausi India. Afterwards, Salil received a Master of Science degree in Microbiology at University of Lucknow, India while working with Dr. Anil N. Gaikwad. Afterwards, Salil worked as a research fellow in India, where he was engaged in an institutional drug discovery program. After obtaining Senior Research fellowships from the Indian Council of Medical Research (ICMR) New Delhi, India, Salil enrolled in the doctoral program at CSIR- Central Drug Research Institute and continued to work with Dr. Gaikwad. He earned his PhD degree in 2019 from the Academy of Scientific and Innovative Research New Delhi, India. His PhD work focused on Harnessing good of lipids for healthy lifestyle: lipid intervention from signalling to phenotype in adipocyte biology and insulin resistance. After completing his doctoral training in the field of diabetes and obesity, Salil was interested in advanced training in diabetes and obesity. This led him to join the Zigman Lab in Feb 2020. Outside the lab, Salil loves playing & watching cricket, listening to music, and spending time with family and friends.
Sepideh sheybani, Ph.D.
Postdoctoral Research Fellow
Sepideh Sheybani, Ph.D.
Postdoctoral Research Fellow
Sepideh was born in Tehran, the capital of Iran. She initially joined the MD program at Tehran University of Medical Sciences in 2008, but she left medical school to move to Canada with her family in 2010. She got her honors bachelor of science degree in human biology from the University of Toronto. She then completed her Master of Science in Physiology in the laboratory of Dr. Norman Rosenblum at SickKids Research Institute, where she studied the role of constitutive activity of hedgehog signaling in lineage decisions in early kidney development. She then joined Dr. CC Hui’s lab at Sickkids Research Institute, who had become interested in studying the role of Iroquois transcription factors in hypothalamic regulation of feeding behavior and energy homeostasis. During her PhD, she employed the relatively new single-cell multiomic assays (RNA+ATAC-seq) to study both embryonic development and neuroglial processes underlying obesity. Through her studies, she became interested in the emotional and motivational aspects of feeding. After finishing her PhD in Molecular Genetics at the University of Toronto, she joined the Zigman lab in 2023 to study the contribution of the ghrelin system to the pathogenesis of eating disorders, mood, and alcoholism. She has received major Canadian federal training awards at both master's and doctoral levels from the Natural Sciences and Engineering Research Council of Canada (NSERC). Outside of the lab, she enjoys exploring nature, and trying new coffee shops!
Omprakash Singh, Ph.D.
Postdoctoral Research Fellow
Omprakash Singh, Ph.D.
Postdoctoral Research Fellow
Om was born and raised in Ballia district, which is the easternmost city of Uttar Pradesh, India. He earned his master’s degree in Zoology at the University of Lucknow in 2011, and then he worked as a research fellow in the Biological Rhythm Research Laboratory, University of Lucknow, where he studied the regulation of circadian and seasonal responses in birds. In July 2013, Om joined Dr. Praful Singru’s lab at NISER-Bhubaneswar, India, and completed his Ph.D. degree in May 2020. In the Singru lab, he worked on two projects: (i) determining the significance of non-hypophysiotropic TRH in controlling food intake and energy balance in the mammalian brain and (ii) determining how the TRHergic neural circuitry is organized in the brain of non-mammalian vertebrates. He employed a teleost, reptile, and bird as model animals to trace the evolution of TRHergic modulation of energy balance. Om joined the Zigman lab in October 2020. In the lab, Om is using stereotaxic surgery, neuronal tract tracing, immunofluorescence, ICV drug administration, and behavioral analysis of mice to understand the role of ghrelin in the metabolic responses to exercise and exercise endurance. Om's project was selected for funding by the UTSW Peter O'Donnell Jr. Brain Institute (OBI) Sprouts Program in 2023. Om was awarded a Donald W. Seldin Research Symposium Award for Basic Science in 2023. Om was an Ethan Sims Young Investigator Award finalist for the Obesity Society 2023. Outside the lab, Om enjoys traveling, exploring nature, and playing + watching cricket.
Connor lawrence
Research Assistant
Connor Lawrence
Research Assistant
Connor was born in Texas. He is currently attending University of North Texas for a degree in Mathematics. He worked in the Zigman Lab as a Research Assistant in the Summers of 2015 and 2016, and now is back!! Outside of the lab, he enjoys hiking, video games, soccer, and spending time with his cat, Miko.
JEFFREY ZIGMAN, M.D., PH.D.
Professor
Jeffrey Zigman, M.D., Ph.D.
Professor
Jeff was given the amazing opportunity to start the Zigman Lab in September 2006 at UT Southwestern Medical Center. Jeff loves science and all his past and current lab members. Jeff's favorite hormone is ghrelin. His favorite endocrine organ to treat in the clinic is the thyroid. Jeff's hobbies include hangin' out with his doggy, growing fruit trees from pits, pixel art, antiquing, and gardening.
Research Associate
Corine Richard, M.S.
Research Associate
Corine was born and raised in Atlanta, GA. She obtained her B.S. in Biological Science in 2015 from Georgia Southern University and her M.S. in Neurobiology and Human Behavior in 2017 from Georgia State University in Atlanta, GA. Her M.S. thesis research includes having studied how various genetic factors (including a variety of common and rare genetic variants) and environmental factors interact as potential causes for onset of Schizophrenia. She also completed neuroendocrinological research on the effect of sex difference on stress hormone levels in juvenile convict cichlids (Amatitlania nigrofasciata) while at Georgia State University. She relocated to Dallas, TX in 2019 and in October 2020, joined Dr. Zigman’s lab.
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 a Professor at the Graduate School of Science and Engineering, Saitama University in Japan.
Mario Perello, Ph.D. – Postdoctoral Research Fellow 2/2008 – 3/2010 – Mario is currently Principal Investigator of the National Scientific and Technical Research Council, Head of the Neurophysiology lab at the Multidisciplinary Institute of Cell Biology (IMBICE), and Director of the 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 in New York City.
Aki Uchida, Ph.D. – Postdoctoral Research Fellow – 1/2012–3/2014 – Aki is currently Associate Director, Strategy and Business Planning – Global Patient Safety Evaluation at Takeda in the Greater Boston Area.
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 Medical Writer II at Nucleus Global in Atlanta.
Juan Rodriguez, Ph.D. – Postdoctoral Research Fellow – 6/2017 – 8/2019 – Juan is a Senior Research Associate in the lab of Steven Gray at UTSW.
Shota Takemi, Ph.D. – Postdoctoral Research Fellow – 6/2019 – 12/2019 – Shota is an Assistant Professor in the Graduate School of Science and Engineering, Saitama University, Japan
Bharath Mani, D.V.M., Ph.D. – Postdoctoral Research Fellow, Instructor – 5/2012 – 5/2020 – Bharath is currently a Senior Scientist at Novo Nordisk Research Center Indianapolis
Subhojit Paul, Ph.D. – Postdoctoral Research Fellow – 7/2021 – 7/2021 – Subhojit is currently performing a second postdoctoral fellowship in another UT Southwestern lab.
Sean Ogden, Ph.D. – Postdoctoral Research Fellow – 7/2020 – 3/2023 – Sean is currently a Medical Writer at EBSCO Information Services.
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
Julia Klavon – Research Assistant I, 7/2021-10/2021
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, Summer Research
Francisco PiÑon – 2021 STEP-UP program, Summer Research
Soumya Kulkarni – 2022 UTSW MSTP student, Summer Research
Hassan Baig – 2022 Summer Undergraduate Research Fellow and 2023 UTSW Green Fellows Program student, Spring Research
Jake Tessnow – 2023 UTSW STARS Program student, Summer Research
Avi Burstein – 2019 – 2023 High School Student Intern
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, associated disorders of mood, and amyotrophic lateral sclerosis. Most lab studies focus on the stomach-derived “hunger” hormone ghrelin, LEAP2, a liver- and intestine-derived hormone that decreases ghrelin action, and ghrelin’s and LEAP2’s receptor GHSR (growth hormone secretagogue receptor), which is highly expressed in the brain and pancreatic islets. Our past and ongoing studies have investigated how ghrelin, LEAP2, and GHSR 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, new obesity and diabetes treatments, amyotrophic lateral sclerosis, and Alzheimer’s Disease.
Several graduate student and postdoctoral positions are available in the Zigman lab. There are also occasionally 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, cell culture, histology, glucose clamp techniques, stereotaxic brain surgery, single cell RNAseq, and chemogenetics, to name a few.
Candidates for the graduate student positions can come from any UT Southwestern Ph.D. Program, including but not limited to the Neuroscience Graduate Program and the Genetics Development and Disease Graduate Program, both of which Dr. Zigman is affiliated with. Students most often are also affiliated with the Molecular Metabolism and Metabolic Diseases (3MD) Track (chaired by Dr. Zigman). During rotations, we hope students can learn about the techniques we use, the research questions and disease states that interest us, and the personalities comprising the lab. We would love to have you and your friends rotate through the lab and other labs in the Center for Hypothalamic Research!
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.
Insulin receptors directly regulate feeding-induced dips in plasma ghrelin
A recent study by the Zigman lab, spearheaded by Dr.
Dr. Shankar is the recipient of the 2021 Ethan Sims Young Investigator Award
The Obesity Society recently selected Dr. Kripa Shankar, an Assistant
Study shows hunger-blocking hormone levels change with eating, obesity.
DALLAS – The hormone LEAP2, which naturally blocks the “hunger”