Skip to Content

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.

Find us on Twitter @ZigmanLab

Read About us in the news

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.

Zigman Lab

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

READ BIO

Deepali Gupta, Ph.D.

Instructor

READ BIO

Kripa Shankar, Ph.D.

Instructor

READ BIO

Salil Varshney, Ph.D.

Postdoctoral Research Fellow

READ BIO

Sepideh sheybani, Ph.D.

Postdoctoral Research Fellow

READ BIO

Omprakash Singh, Ph.D.

Postdoctoral Research Fellow

READ BIO

Connor lawrence

Research Assistant

READ BIO

JEFFREY ZIGMAN, M.D., PH.D.

Professor

READ BIO
Corine Richard, M.S.

Research Associate

READ BIO

Former Lab Members

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 KlavonResearch 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.

In the News