Lin Chang, MD
Director, Functional GI Disroders Program, UCLA G. Oppenheimer Center for Neurobiology of Stress and Resilience; Vice-Chief, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA
Lin Chang is a gastroenterologist and physician scientist who serves as Co-Director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience, an interdisciplinary center with a research and clinical focus on the interactions of pain, stress and emotions in health and disease. She has served as Co-Director of the Administrative Core of our Center’s NIH Specialized Centers of Research (SCOR), which has been funded for the past 16 years. Our SCOR has focused on sex differences in brain-gut interactions mainly with regard to irritable bowel syndrome (IBS). She has served as PI of one of the projects for each cycle. For this SCORE renewal, she will serve as Multi-PI, Co-Lead of Project 1, Co-Lead of the Career Enhancement Core (CEC), and Co-Lead of the Administrative Core. As Co-Lead of the CEC, she will oversee the collaboration with the pilot and feasibility programs to provide seed grant funding, oversee the recruitment and mentoring of young investigators, and organization of educational conferences. She has been performing clinical and translational research studies, including clinical treatment trials for 25 years. Her research has focused on brain-gut interactions, specifically pathophysiologic mechanisms, clinical symptoms, health outcomes, and treatment in IBS. She has mentored 3 gastroenterology research fellows on the UCLA Gastroenterology T32 training grant in addition to 10 clinical GI fellows, 11 medical residents, 3 post-docs, 8 visiting scientists, 10 medical students, and 5 pre-med students. Her leadership positions include Vice-Chief of the Division of Digestive Diseases at UCLA, Program Director of the UCLA GI Fellowship Program, Clinical Research Councilor of the AGA Governing Board, President of the American Neurogastroenterology and Motility Society (ANMS), member of the Rome Foundation Board of Directors. She currently serving a 4-year term on the NIH Clinical, Integrative and Molecular Gastroenterology Study Section and FDA GI Advisory Committee.
Arpana Gupta, PhD
Co-Director, Neuroimaging and Bioinformatics Core, G. Oppenheimer Center for Neurobiology of Stress and Resilience; Assistant Professor, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA
Arpana Gupta is an Assistant Professor and Director of the Neuroimaging Core at the UCLA G. Oppenheimer Center of Neurobiology of Stress and Resilience (CNSR); where she specializes in research that investigates the interactions between environmental and biological factors in shaping neurobiological phenotypes associated with stress-based diseases such as obesity and metabolic syndrome. Her current program of research, broadly defined, is based on developing a model that aims to understand the bidirectional interaction of the brain with those in the periphery (immune cells, gut microbiota-related metabolites), and the modification of these interactions by vulnerability or protective factors (adverse life events, sex, race, socioeconomic status [SES], resilience, diet) related to obesity and ingestive behaviors. More recently she has been investigating diet interventions in altering the brain-gut microbiome axis on health and disease. Another main area of interest is sex differences in central responses related to the brain-gut microbiome axis, as well as its relationship to various disease states. She applies advanced multivariate analytic techniques in order to integrate data from multiple neuroimaging sources, inflammatory markers, microbiome and metabolite profiles, and behavioral data, in order to determine the unique variance associated with altered brain gut microbiome axis in specific disorders. In 2016, she received a mentored K23 grant and in 2020 a R03 grant from the NIH NIDDK to investigate the brain-gut microbiome influences in obesity. She has also received funding from the AGA Rome Foundation, Biocodex, and pilot funds from the UCLA CURE/CTSI program.
Elaine Hsiao, PhD
Assistant Professor, Department of Integrative Biology and Physiology, De Logi Chair in Biological Sciences, Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA
Dr. Elaine Y. Hsiao is an Assistant Professor in the Department of Integrative Biology & Physiology at UCLA, where she leads a laboratory studying fundamental interactions between the microbiome, brain and behavior, and their applications to neurological disorders. Her studies on the relationships between the microbiota, immune system and nervous system led her to discover that the microbiota can regulate behavioral, metabolic and gastrointestinal abnormalities relevant to autism spectrum disorder (ASD). Her work in this area, and on neuroimmune interactions in autism, has led to several honors, including the National Institutes of Health Director’s Early Independence Award, distinction as Forbes’ 30 Under 30 in Science and Healthcare, National Geographic’s Emerging Explorer Award and fellowships from the National Institute of Mental Health and Autism Speaks. Inspired by this interplay between the microbiota and nervous system, the Hsiao laboratory is mining the human microbiota for microbial modulators of host neuroactive molecules, investigating the impact of microbiota-immune system interactions on neurodevelopment and examining the microbiome as an interface between gene-environment interactions in neurological diseases.
Yano JM, Yu K, Donaldson G, Shastri G, Ma L, Ann P, Nagler C, Ismagilov RF, Mazmanian SK, Hsiao EY (2015) Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell, 161:264-76.
Hsiao EY, McBride SW, Hsien S, Sharon G, Hyde ER, McCue T, Codelli JA, Chow J, Reisman SE, Petrosino JF, Patterson PH*, Mazmanian SK* (2013) The microbiota modulates behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell, 155:1451-1463.
Hsiao EY, McBride SW, Chow J, Mazmanian SK, Patterson PH (2012) Modeling an autism risk factor in mice leads to permanent immune dysregulation. PNAS 109:12776-81
Jonathan Jacobs, MD, PhD
Assistant Professor-in-Residence, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA
Dr. Jacobs’ research program focuses on characterizing host-microbiome interactions in patients with gastrointestinal, metabolic, and inflammatory disorders using a combination of human association studies and animal models, including humanized gnotobiotic mice. This evolved initially from several translational microbiome studies he performed investigating the mucosal microbiome and metabolome of inflammatory bowel disease patients compared to healthy family members or unrelated controls, stratified by genetic traits. These studies required the development and refinement of efficient pipelines for 16S ribosomal RNA sequencing, metabolomics, and bioinformatics analysis of multi’omics datasets. He established the Microbiome Core for the UCLA Microbiome Center to offer a range of microbiome-related services to the local research community. This core became affiliated with the UCLA Specialized Center of Research (SCOR) in Neurovisceral Sciences and Women’s Health led by Emeran Mayer and Lin Chang. Through this collaboration, his laboratory assumed responsibility for sample processing, 16S ribosomal RNA sequencing, and bioinformatics analysis for initial SCOR studies on sex differences in the brain-gut-microbiome axis of irritable bowel syndrome (IBS) patients and healthy controls, and their relationship to symptom severity and psychological parameters. This research led to a publication in Microbiome linking microbiome features to brain structural parameters and unpublished work was presented at last year’s Digestive Diseases Week showing that the gut microbiome predicts response of IBS patients to cognitive behavioral therapy.
The current proposal would build upon these collaborations to establish a unique research program within the UCLA Center for Neurovisceral Sciences and Women’s Health dissecting sex differences in brain-gut-microbiome pathways underlying IBS. He serves as co-lead of the Data Processing and Analysis Core, with primary responsibility for microbiome analyses across all three projects and joint responsibility with his co-Leads, Jennifer Labus and Arpana Gupta, for integrative bioinformatics analyses bridging the microbiome, metabolome, neuroimaging, and clinical parameters. This exciting research would draw upon his extensive background in microbiome bioinformatics and experience as Director of the UCLA Microbiome Core.
Lisa Kilpatrick, PhD
Assistant Researcher, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA; Oppenheimer Center for Neurobiology of Stress
Lisa Kilpatrick’s research has focused on brain signatures related to brain-body dysregulation in stress-sensitive disorders, including irritable bowel syndrome. In addition, she has a long-standing interest in the influence of sex on these signatures, and she regularly attends and contributes to the annual meeting of the Organization for the Study of Sex Differences. The exploration of sex differences in the mechanisms of treatment response is an important step towards optimizing cost-effective treatments for both men and women. In her role as a co-Investigator in the Bioinformatics Core, she will apply her advanced expertise on the analysis of resting state fMRI data, as well as other neuroimaging modalities, to implement the proposed neuroimaging analyses. She maintains this expertise through regular attendance at the Biennial Resting State Conference and Organization for Human Brain Mapping annual meeting, and she can quickly adapt to new developments in the rapidly-changing field of neuroimaging. In addition, she will lend her expertise in sex differences during the interpretation of the findings. She has collaborated with Drs. Gupta, Labus, and Mayer over the years and looks forward to contributing to this ambitious project.
Jennifer Labus, PhD
Director, Biostatistics and Bioinformatics Core, G. Oppenheimer Center for Neurobiology of Stress and Resilience; Adjunct Professor, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA
Dr. Labus is an Adjunct Professor in the Vatche and Tamar Manoukian Division of Digestive Diseases in the Department of Medicine at University of California, Los Angeles (UCLA). She is the Director of the Integrative Biostatistics and Bioinformatics Core in the G. Oppenheimer Center for Neurobiology of Stress at UCLA and the UCLA Microbiome Center.
Dr Labus is an applied statistician with expertise in biostatistics, bioinformatics, treatment-outcome research, pain neuroscience, multimodal brain imaging, microbiome, metabolomics, and multi-omics integrative analysis. Her current research focused is on determining biological markers of disease, including chronic pain, obesity and Alzheimer’s disease. Using state-or-the-art computational, biostatistical, and bioinformatics approaches, she assesses the interaction between various levels of biological data (e.g., microbiome, metabolomics, immune markers, multimodal brain imaging data) with clinical data. The overall goal of her systems-based approach is to identify and target the key regulators of multi-omics-biological disease-interaction networks in order to understand the underlying pathophysiological mechanisms and provide new targets for treatment.
Dr Labus has made seminal contributions to mapping neural networks underlying visceral pain and elucidating brain-gut –microbiome axis in humans. As a result, she was the recipient of the 2011 Master’s Award for Outstanding Achievement in Basic or Clinical Digestive Sciences, American Gastroenterology Association. Dr Labus has been the recipient of a K08 Career Development award, Effective connectivity of central response in irritable bowel disorder, from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). She has served as the primary investigator on two grants funded by the National Institute of Childhood Health and Human Development (NICHD): R01HD076756 Profiling vulvodynia subtypes based on neurobiological and behavioral endophenotypes and R21HD086737 Deriving novel biomarkers of localized provoked vulvodynia through metabolomics: A biological system-based approach. Labus is a co-investigator on several NIH funded grants, international research collaborations, and is actively involved in mentoring graduate students and postdoctoral fellows.
Emeran A. Mayer, MD
Director, UCLA G. Oppenheimer Center for Neurobiology of Stress and Resilience; Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA
Emeran Mayer is the director of the G Oppenheimer Center for the Neurobiology of Stress and Resilience (CNSR) at UCLA and co-director of the P30 funded CURE Digestive Diseases Research Center at UCLA. The CNSR is a NIH-funded, interdisciplinary and translational research center focused on brain gut microbiome interactions in 4 areas: Functional GI Disorders, Inflammatory Bowel Disorders, Ingestive Behavior/Eating Disorders, Chronic Visceral Pain Disorders. Within the CNSR, he has been the PI of a P50 SCOR grant from ORWH/NIDDK on sex-related differences in brain gut interactions with an emphasis on the effects of early adverse life effects on adult stress responsiveness and related brain circuits for the past 15 years. This grant has been successfully renewed over a total of three 5 year funding cycles under hisleadership. He is also the Co-PI of a UO1 grant focused on studying mechanisms of chronic pelvic pain (MAPP), now in its third 5 year funding cycle, and he leads the neuroimaging efforts within the consortium. Under his leadership, CNSR investigators have done pioneering work in applying psychophysiological and advanced brain imaging techniques to study the response of the brain to visceral stimuli in rodent models and human subjects with persistent visceral pain disorders, including IBS, IBD, IC/PBS and vulvodynia, to identify sex related differences in these brain responses, and to evaluate the effectiveness of pharmacologic and mind-based (including cognitive behavioral therapy) therapeutic approaches to some of these disorders. During the last 5 years, they have expanded their research efforts into the role of the gut microbiome in bidirectional brain gut interactions. They have pursued studies looking at the effect of altered autonomic nervous system output to the gut in altering gut microbial composition and function, and have been testing the hypothesis that gut microbial metabolites and inflammatory mediators in vulnerable patients can lead to neuroplastic changes in the central nervous system manifesting in persistent visceral hypersensitivity, cognitive decline and symptoms of autism spectrum disorders.
Bruce Naliboff, PhD
Director, Pain Research Program, UCLA Oppenheimer Family Center for Neurobiology of Stress; Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA
My research has focused on psychological and psychophysiological mechanisms of stress and pain, including sex differences, utilizing a variety of methodologies and with particular emphasis on visceral pain disorders such as IBS. The development and assessment of nonpharmacological treatments targeted at chronic pain has also been a significant focus of my research. These include cognitive behavioral therapies as well as alternative medicine treatments of yoga and meditation. An important theme of this research is the use of both psychological and physiological measures (including autonomic assessment and brain imaging) to better understand the mechanism of change from non-pharmacological interventions and use of this information to guide better targeting of treatments to specific problems and individual phenotypes. My role Project Co-Leader for Project 3 in the current application involves working on the overall design, assessment protocols and application of the CBT treatment to interventional phenotyping. I have a long and close collaboration with Dr. Mayer, Dr. Chang and the other Investigators who will have my extensive background in behavioral, perceptual, psychophysiological and intervention research applied to chronic pain at their disposal throughout the study.
Catia Sternini, MD
Professor, Department of Medicine Digestive Diseases/Gastroenterology, Neurobiology, David Geffen School of Medicine, UCLA
The “Brain in the Gut” and Taste Receptors
My research program is concerned with the neuronal circuits that control gastrointestinal motility and the mechanisms that govern receptor-mediated responses in the enteric nervous system, the “brain in the gut”, and with chemosensing in the gastrointestinal tract. Currently, the main lines of my research include: (1) trafficking and signaling of G protein-coupled receptors induced by physiological and pathophysiological events with an emphasis on µ opioid receptor, the target of opioid analgesics used for pain control, which mediates opioid bowel syndrome and tolerance, and (2) role of taste signaling molecules in the regulation of gastrointestinal functions and feeding behavior. My group was the first to demonstrate that opioids differing in their ability to induce tolerance also differ in their efficiency to induce µOR trafficking, a process that regulates receptor signaling and function. The findings of ligand-selective and stimulation-dependent µOR internalization in enteric neurons are of importance for understanding the mechanisms underlying intracellular adaptations induced by prolonged activation of µORs, which hamper the use of opioids as analgesics. Furthermore, we have shown that µOR activation exerts a protective effect on acute intestinal inflammation through cytokine and NF-KB modulation. Another focus of my research is on the role of taste signaling molecules as chemosensory receptors in the gut mucosa, which are likely to modulate gut function and food intake through the release of signaling molecules by enteroendocrine cells, with emphasis on bitter taste receptors, a putative side of defense from potentially toxic substances, drugs and pathogens. The recent discovery that taste receptors for sweet and bitter are expressed throughout the body and not only in the tongue has given rise to the concept of a broader role for these receptors beyond “taste”. My lab has shown that taste signaling molecules are expressed by distinct populations of mucosal cells, including enteroendocrine cells, which synthesize peptides affecting motility, secretion, satiety and hunger, and that bitter taste receptors are regulated by feeding and different diets, suggesting they participate in the functional detection of intraluminal content and they serve as regulators of diet-induced responses by detecting changes in the microbiota.
Kirsten Tillisch, MD
Director, Mind Body Research Program, G. Oppenheimer Center for Neurobiology of Stress and Resilience; Associate Professor, Department of Medicine, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA
Dr. Kirsten Tillisch completed her undergraduate work at the Otis Institute of Parsons School of Design, earning a Bachelor of Fine Arts with Honors. She obtained her medical degree from the David Geffen School of Medicine at UCLA and was elected to the medical honor society Alpha Omega Alpha. She continued on at UCLA to complete her training in internal medicine and gastroenterology, graduating in 2003. Her clinical interests are functional bowel disorders such as irritable bowel syndrome, functional dyspepsia, and cyclic vomiting syndrome. Her research interests include brain-gut interactions , the effects of nonpharmacological therapies on functional gastrointestinal disorders, and pharmacological treatment of irritable bowel syndrome. Her recent research projects include defining resting state brain dysfunction in irritable bowel syndrome patients, evaluating the role of gut microbiota modulation on emotional processing in the brain, and assessment of neurokinin-1 receptor antagonists effects on the gut and brain in irritable bowel syndrome. She is a member of the Neuroimaging Program of the Gail and Gerald Oppenheimer Family Center for Neurobiology of Stress.
Mayer EA, Tillisch K, Gupta A. Gut/brain axis and the microbiota. J Clin Invest. 2015 Mar 2;125(3):926-38. doi: 10.1172/JCI76304. Epub 2015 Feb 17. Review. PubMed PMID: 25689247; PubMed Central PMCID: PMC4362231.
Mayer EA, Knight R, Mazmanian SK, Cryan JF, Tillisch K. Gut microbes and the brain: paradigm shift in neuroscience. J Neurosci. 2014 Nov 12;34(46):15490-6. doi: 10.1523/JNEUROSCI.3299-14.2014. Review. PubMed PMID: 25392516; PubMed Central PMCID: PMC4228144.
Mayer EA, Padua D, Tillisch K. Altered brain-gut axis in autism: comorbidity or causative mechanisms? Bioessays. 2014 Oct;36(10):933-9. doi: 10.1002/bies.201400075. Epub 2014 Aug 22. Review. PubMed PMID: 25145752.
Tillisch K, Labus JS. Neuroimaging the microbiome-gut-brain axis. Adv Exp Med Biol. 2014;817:405-16. doi: 10.1007/978-1-4939-0897-4_18. Review. PubMed PMID: 24997044.
Tillisch K. The effects of gut microbiota on CNS function in humans. Gut Microbes. 2014 May-Jun;5(3):404-10. doi: 10.4161/gmic.29232. Epub 2014 May 16. Review. PubMed PMID: 24838095; PubMed Central PMCID: PMC4153780.
Tillisch K, Labus J, Kilpatrick L, Jiang Z, Stains J, Ebrat B, Guyonnet D, Legrain-Raspaud S, Trotin B, Naliboff B, Mayer EA. Consumption of fermented milk product with probiotic modulates brain activity. Gastroenterology. 2013 Jun;144(7):1394-401, 1401.e1-4. doi: 10.1053/j.gastro.2013.02.043. Epub 2013 Mar 6. PubMed PMID: 23474283; PubMed Central PMCID: PMC3839572.