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Jonathan Braun, MD, PhD
Chair and Professor, Pathology and Laboratory Medicine; Molecular & Medical Pharmacology, UCLA
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Address UCLA MRL Building, 4525 MC: 173216 Los Angeles CA 90095 Phone: (310) 794-7953Fax: (310) 267-4486Website: UCLA Pathology & Laboratory Medicine

Dr. Jonathan Braun is Professor and Chair of Pathology and Laboratory Medicine, and Professor of Molecular and Medical Pharmacology at the David Geffen School of Medicine, and Chair of Pathology and Laboratory Medicine. A distinguished pathologist and mucosal immunologist , his 30 year career has been devoted to mucosal host-microbial interaction and the immune cell biology of chronic inflammatory disease (IBD and HIV) and lymphoma pathogenesis. With a long-standing commitment to inflammatory bowel disease, in recent years he has focused on the relationship of the intestinal microbiome and function to human genetic disease variation in IBD disease pathogenesis, penetrance, and phenotype. He has innovated in the detection and bioinformatics analysis of microbiome, metabolites, and peptides, through participation in the NIDDK IBD Genetics Consortium and NIH HMP2 projects, and as PI of the CCFA Microbiome Initiative.

Relevant Recent Publications

  1. Tong M, McHardy I, Ruegger P, Goudarzi M, Kashyap PC, Haritunians T, Li X, Graeber TG, Schwager E, Huttenhower C, Fornace AJ Jr, Sonnenburg JL, McGovern DP, Borneman J, Braun J. Reprograming of gut microbiome energy metabolism by the FUT2 Crohn’s disease risk polymorphism. ISME J. 2014 Nov;8(11):2193-206. doi: 10.1038/ismej.2014.64. PMID: 24781901
  2. McHardy IH, Goudarzi M, Tong M, Ruegger PM, Schwager E, Weger JR, Graeber TG, Sonnenburg JL, Horvath S, Huttenhower C, McGovern DP, Fornace AJ Jr, Borneman J, Braun J. Integrative analysis of the microbiome and metabolome of the human intestinal mucosal surface reveals exquisite inter-relationships. Microbiome. 2013 Jun 5;1(1):17. doi: 10.1186/2049-2618-1-17. PMCID: 3971612
  3. McHardy IH, Li X, Tong M, Ruegger P, Jacobs J, Borneman J, Anton P, Braun J. HIV Infection is associated with compositional and functional shifts in the rectal mucosal microbiota. Microbiome. 2013 Oct 12;1(1):26. doi: 10.1186/2049-2618-1-26. PMID: 24451087

Active Funding in Microbiome-Related Research

Funding Agency/Grant Number:NIH U54 DK102557
Title:“Characterizing the gut microbial community for diagnosis and therapy of IBD”
Goals:To identify the relationship of microbial composition, microbial genes, and their metabolite and peptide products in the intestinal mucosa of IBD patients
Funding Agency/Grant Number:CCFA Microbiome Consortium/323814 Crohn’s and Colitis Foundation of America
Title:“Establishing Mechanistically Validated Targets and Lead Molecules for Microbiome-based Therapy in IBD”
Goals:To mechanistically validate candidate microbiota and their products that determine IBD disease state and activity; to identify lead molecules for targeting these validated candidates; and, to expand the prospective candidates via longitudinal multi’omic human analyses.

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Lin Chang, MD
Director, Functional GI Disroders Program, UCLA Oppenheimer Family Center for Neurobiology of Stress; Division of Digestive Diseases, David Geffen School of Medicine at UCLA
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Lin Chang, MD, is a Professor of Medicine in the Department of Medicine, Division of Digestive Diseases, at the David Geffen School of Medicine at UCLA. She serves as the Co-Director of the Center for Neurobiology of Stress at the David Geffen School of Medicine at UCLA. She is also Director of the Digestive Health and Nutrition Clinic at UCLA. Dr. Chang’s clinical expertise is in functional gastrointestinal disorders which include irritable bowel syndrome (IBS), chronic constipation, and functional dyspepsia. Dr. Chang’s research is focused on the pathophysiology of IBS related to stress, sex differences, and neuroendocrine alterations and the treatment of IBS. She is a funded NIH-investigator studying the central and peripheral mechanisms underlying IBS.

She is the recipient of the Janssen Award in Gastroenterology for Basic or Clinical Research and the AGA Distinguished Clinician Award, Dr. Chang has authored more than 70 original research articles, 48 review articles, and 19 book chapters on her specialty interests and is a frequent speaker at national and international meetings. She is a fellow of the American Gastroenterological Association and American College of Gastroenterology, and a member of the Society for Neuroscience. Dr. Chang serves as an Associate Editor of the American Journal of Gastroenterology. She is a member of the Rome Foundation Board of Directors, the Rome IV Editorial Board and the Rome IV Functional Bowel Disorders Committee. She is President of the American Neurogastroenterology and Motility Society (ANMS). She served on the FDA GI Advisory Committee from 2005-2010 which she also chaired.

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Arpana Gupta, PhD
Adjunct Assistant Professor, Division of Digestive Diseases, David Geffen School of Medicine at UCLA; Oppenheimer Center for Neurobiology of Stress
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Address 10833 Le Conte Avenue Center for Health Sciences 42-210 MC:737818 Los Angeles CA 90095 Phone: (310) 206-0192Fax: (310) 825-1919Website: UCLA Oppenheimer Center for Neurobiology of Stress

Dr. Arpana (Annie) Gupta completed a PhD degree in Psychology from the University of Tennessee, Knoxville, followed by an APA accredited clinical internship at Massachusetts General Hospital/Harvard Medical Center. After coming to UCLA she joined the neuroimaging and psychophysiological cores at the Center for Neurobiology of Stress in 2012. She is currently Adjunct Assistant Professor, where she specializes in research that investigates the influence of environmental factors on shaping neurobiological phenotypes associated with stress and pain-based diseases such as obesity and functional gastroenterological disorders (FGIDs) [vuvlodynia, irritable bowel syndrome]. Her programmatic line of research broadly defined focuses on the bidirectional interactions between the brain and peripheral factors (in particular immune factors and gut microbiota-related metabolites) and how these interactions are modified by vulnerability (early adversity, race, adult stress, socioeconomic status [SES], diet) and protective (resilience, exercise) factors in contributing to the underlying pathophysiology of these disorders. She is dedicated to using advanced automated and mathematical analytic techniques, which allows her to integrate information from multiple data sources, while accounting for sex and race differences. Her goal is to develop a comprehensive model that provides a powerful and sensitive biomarker that will increase biological readouts of these stress and pain-based disorders, thus bringing to the forefront those individuals who are at increased risk as a result of disadvantaged backgrounds.

Relevant Recent Publications

  1. Gupta A, Mayer EA, Sanmiguel CP, Van Horn JD, Woodworth D, Ellingson BM, Fling C, Love A, Tillisch K, Labus JS. Patterns of Brain Structural Connectivity Differentiate Lean from Overweight Subjects. Neuroimage-Clinical, 2015. 13(7): 506-17. doi:10.1016/j.nicl.2015.01.005 [Epub Ahead of Print]. PMCID: PMC4338207.
  2. Mayer EA, Tillisch K, Gupta A. Gut-Brain Axis and the Microbiota. Journal of Clinical Investigation. 2015; 125(3): 926-38. doi: 10.1172/JCI76304. [Epub ahead of Print]. PMID: 25689247.
  3. Sanmiguel CP, Gupta A, Mayer EA. Gut Microbiome and Obesity: A Plausible Explanation for Obesity. Current Obesity Reports. 2015. In press.

Active Funding in Microbiome-Related Research

Funding Agency/Grant Number:American Psychological Fellowship – Visionary Grant
Title:“Mind Altering Microorganisms: Sex and Race Differences in the Influence of Gut Microbiota on Brain Signatures in Obese Healthy Control Subjects”
Goals:The goal of the proposed study is to assess sex (males versus females) and race (African Americans versus non-Hispanic White Americans) differences in the influence of gut-microbiota on brain signatures in obese subjects

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Xuesong He, DDS., PhD
Assistant Adjunct Professor, UCLA School of Dentistry
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Address UCLA School of Dentistry 10833 Le Conte Avenue 20-118 CHS Los Angeles CA 90095-1668 Phone: (310) 825-9748

Dr. Xuesong He is an Adjunct Assistant Professor in School of Dentistry at UCLA. Dr. He received his D.D.S. from Peking University Health Science Center in 1999, and his PhD in Microbiology from Indiana University in USA in 2006. Dr. He’s research interest includes: 1) Interspecies interaction between oral microbes; 2) culturing and studying “yet-to-be” cultivated oral microbes; and 3) studying the oral microbial ecology and its impact on human oral health and diseases. He is currently the co-principle investigator of a NIH RO1 grant on studying the unique epibiotic parasitic relationship between two oral commensal bacteria that could be involved in oral mucosal infectious disease. The international impact of his research can be proved by his over 30 well-cited publications in peer-reviewed leading scientific journals including: PNAS, ISME Journal, Advance in Dental Research, Microbiology and Molecular Biology Reviews, Journal of dental research, Journal of Endodontics, Molecular Microbiology, Microbiome Journal, Scientific Reports, Frontiers in Microbiology, Molecular Oral Microbiology, Microbial Ecology, Plos One, International Journal of Oral Science, FEMS Microbiology Letter and Journal of Bacteriology, etc.

Relevant Recent Publications

  1. Guo, L., JS. McLean, Y.Yang, R. Eckert, C.W. Kaplan, P.Kyme, O. Sheikh, B. Varnum, R. Lux, W. Shi and X. He*. 2015 A precision guided antimicrobial peptide as a targeted modulator of human microbial ecology. Proc Natl Acad Sci USA 112(24): 7569-7574
  2. He, X., JS. McLean, A. Edlund, S. Yooseph, A.P. Hall, SY. Liu, P. Dorrestein, E. Esquenazi, R. Hunter, G. Cheng, KE. Nelson, R. Lux and W. Shi. 2015. Domestication of a human-associated TM7 reveals a reduced genome and parasitic lifestyle. Proc Natl Acad Sci USA 112(1):244-9. PMCID:PMC4291631
  3. Wu, T., L. Cen, C. Kaplan, X. Zhou, R. Lux, W. Shi and X. He*. 2015. Cellular components mediating co-aggregation of Candida albican and Fusobacterium nucleatum. Journal of Dental Research. DOI:10.1177/0022034515593706

Active Funding in Microbiome-Related Research

Funding Agency/Grant Number:NIH NIDCR 1R01DE023810
Title:“Domestication and characterization of TM7-the most elusive oral phylum”

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Elaine Y. Hsiao, PhD
Assistant Professor, Department of Integrative Biology and Physiology, De Logi Chair in Biological Sciences, Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA
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Website: Hsiao Lab

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.

Relevant Recent Publications

  1. 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.
  2. 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.
  3. 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

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Jonathan Jacobs, MD, PhD
Assistant Professor-in-Residence, Division of Digestive Diseases, David Geffen School of Medicine at UCLA
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Phone: (310) 825-9333Website: Jacobs Laboratory

Dr. Jonathan Jacobs is an Assistant Professor-in-Residence in the Division of Digestive Diseases within the UCLA Department of Medicine. His research background is in immunology and the intestinal microbiome. He originally trained under Diane Mathis and Christophe Benoist at Harvard, where he published three first author papers on the immunopathological mechanisms of arthritis in an autoantibody-mediated model. He later joined Jonathan Braun’s lab at UCLA to investigate the interactions of the mucosal immune system and the intestinal microbiome in inflammatory bowel disease (IBD). He utilized human cohorts and transgenic mice to demonstrate that the IBD-associated genes RORC and TL1A, both involved in mucosal immunity, garden the intestinal microbiome. This raises the possibility that genetic risk factors promote IBD through their effects on the microbiome. An ongoing human cohort study with Dr. Braun aims to define the microbial and metabolomics features of IBD in the colonic mucosa and to characterize their relationship to IBD-associated genetic polymorphisms. In a separate translational study, he found that healthy relatives of pediatric IBD patients could be classified by their intestinal microbial and metabolomics profiles into “enterotypes” and “metabotypes” that may predict their future risk for IBD. He has authored a review article, a commentary, and two textbook chapters on intestinal host-microbiome interactions. His current research employs in vivo models and multi’omics analysis of IBD cohorts to define the role of IBD-associated genes in shaping the intestinal microbiome and to identify microbial products that promote IBD.

Relevant Recent Publications

  1. Jacobs JP, Lin L, Goudarzi M, Ruegger P, McGovern DPB, Fornace AJ, Borneman J, Xia L, Braun J. Microbial, metabolomic, and immunologic dynamics in a relapsing genetic mouse model of colitis induced by T-synthase deficiency. Gut Microbes. 2017 Jan; 8(1):1-16.
  2. Jacobs JP, Goudarzi M, Singh N, Tong M, McHardy IH, Ruegger P, Asadourian M, Moon B, Ayson A, Borneman J, McGovern DPB, Fornace AJ, Braun J, Dubinsky M. A Disease-associated Enterotype and Metabotype in Healthy Relatives of Pediatric Inflammatory Bowel Disease Patients. Cellular and Molecular Gastroenterology and Hepatology. 2016 Nov; 2(6):750-66.
  3. Jacobs JP, Braun J. Immune and genetic gardening of the intestinal microbiome. FEBS Letters. 2014 Nov; 588(22):4102-11.

Complete Publications List

http://www.ncbi.nlm.nih.gov/myncbi/browse/collection/48438874/

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Hon Wai Koon, PhD
Assistant Professor, Division of Digestive Diseases, David Geffen School of Medicine at UCLA
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Phone: (310) 825-9742Fax: (310) 825-3542

Dr. Koon’s research is focused on the synthetic mechanism and roles of the antimicrobial peptide Cathelicidin in inflammatory bowel disease, intestinal infections, colorectal cancer, obesity, and diabetes. Cathelicidin is a natural endogenous anti-microbial peptide that is protective to its host as a part of innate immune system. Our laboratory was the first to show that endogenous cathelicidin ameliorates dextran sulfate (DSS) colitis via bone marrow-derived immune cells. We also found increased expression of cathelicidin in monocytes/macrophages in the colonic mucosa of ulcerative colitis patients. Cathelicidin-deficient mice develop more severe bacterial penetration into intestinal mucosa and associated intestinal inflammation than wild-type mice. Therefore, we understand that endogenous cathelicidin may be a protective response to intestinal infection and inflammation. Moreover, intracolonic administration of the cathelicidin peptide ameliorates C. difficile-mediated colitis in mice. We are now studying the role of cathelicidin in the change of intestinal microflora in the development of obesity and diabetes. Dr. Koon is now investigating the role of a non-peptide cathelicidin-mimic, Ceragenin CSA13, in the protection against intestinal inflammation, C. difficile infection, obesity, and diabetes. This protection may be related to change of intestinal microflora. CSA13 is more chemically stable than natural cathelicidin and may be suitable for clinical use. Our research establishes a new direction of research in digestive diseases using microflora study, clinically relevant human primary cells, fresh intestinal biopsies, biologically induced colitis animal models, and system biology approaches.

Recent Relevant Publications

  1. Koon HW, Shih DQ, Chen J, Bakirtzi K, Hing TC, Law I, Ho S, Ichikawa R, Zhao D, Xu H, Gallo R, Dempsey P, Cheng G, Targan SR, Pothoulakis C. Cathelicidin signaling via the Toll-like receptor protects against colitis in mice. Gastroenterology. 2011 Nov;141(5):1852-63.e1-3. PubMed PMID: 21762664; PubMed Central PMCID: PMC3199285.
  2. Hing TC, Ho S, Shih DQ, Ichikawa R, Cheng M, Chen J, Chen X, Law I, Najarian R, Kelly CP, Gallo RL, Targan SR, Pothoulakis C, Koon HW. The antimicrobial peptide cathelicidin modulates Clostridium difficile-associated colitis and toxin A-mediated enteritis in mice. Gut. 2013 Sep;62(9):1295-305. PubMed PMID: 22760006; PubMed Central PMCID: PMC3737259.

Active Funding in Microbiome-Related Research

Funding Agency/Grant Number:NIH 1R03DK103964-01A1
Title:“Role of cathelicidin in obesity and diabetes”

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Jennifer Labus, PhD
Director, Neuroimaging and Biostatistics Core, Oppenheimer Center for Neurobiology of Stress; Associate Professor, Division of Digestive Diseases, David Geffen School of Medicine at UCLA
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Address 10833 Le Conte Avenue Center for Health Sciences 42-210 MC:737818 Los Angeles CA 90095 Phone: (310) 206-0738

Dr. Jennifer S. Labus is an Associate Professor in the David GeffenSchool of Medicine at University of California, Los Angeles. She is an investigator and Director for the Neuroimaging and Bioinformatics Core in the Oppenheimer Family Center for Neurobiology of Stress at UCLA. Her research is focused on the interface of stress, pain and emotions and its influence on the role of dysregulation in the pathophysiology of common chronic pain disorders. She has unique expertise in applying advanced statistical and computational technologies to analyze multimodal brain imaging data. She has made seminal contributions to mapping neural networks underlying visceral pain. Dr. Labus’ current research focus lies in applying a biological system based approach using bioinformatics, network analyses, supervised and unsupervised machine learning tools to integrate multimodal brain imaging data with other large scale biological data sets including genetics and metabolomics. This research provides the means to integrate and decipher large amounts of multivariate neuroimaging data to subgroup patients based on objective biological markers, and characterize central nervous system alterations for further pathophysiological investigations targeting treatment of chronic pain and obesity. She 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) as well as a RO3 award examining the role of altered attention and emotional arousal networks in IBS. Recently, acting as lead Co-Primary investigator she was awarded R01 funding by the National Institute of Childhood Health and Human Development (NICHD) to use brain imaging data, along with genetic, physiological and biological data, to extensively phenotype women with vulvodynia. Dr. Labus is a co-investigator on several NIH funded grants, international research collaborations, and is actively involved in mentoring graduate students and postdoctoral fellows. As a result of her work she was awarded the Master’s Award in Gastroenterology in 2010 for her outstanding achievements in Basic and Clinical Digestive Sciences. Dr. Labus was also the recipient of the American College of Neuropsychopharmacolgy Travel Award in 2013.

Relevant Recent Publications

http://www.ncbi.nlm.nih.gov/sites/myncbi/labusjs

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Huiying Li, PhD
Assistant Professor, Department of Molecular & Medical Pharmacology; Faculty, Crump Institute for Molecular Imaging, UCLA
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Address 4339 CNSI 570 Westwood Plaza, Building 114 Los Angeles CA 90095-1770 Phone: (310) 206-5585Lab Phone: (310) 983-3212Website: Li Lab

My interest in the microbiome research began from The Sorcerer II Global Ocean Sampling Expedition led by the J Craig Venter Institute several years ago, where I applied bioinformatics to study microbial protein families in the ocean microbiome. The current research in my lab focuses on understanding the human microbiome, the collective genome of trillions of microorganisms residing in the human body, and its interactions with the host in relation to human health and diseases. Using multi-disciplinary approaches, including genomics, metagenomics, bioinformatics, high-throughput sequencing, microbiology, and biochemistry, we aim to identify the molecular mechanism of the human microbiome in health and disease pathogenesis and to develop diagnostic markers and therapeutics for microorganism-related human diseases. By combining computational and experimental approaches, the ultimate goal of my research is to understand the human-microbiota symbiotic system at both molecular level and systems level.

My research group is highly experienced in high-throughput sequencing and data analysis with expertise in bioinformatics, 16S rDNA sequence analysis, metagenomic shotgun sequence analysis, RNA-Seq data analysis, and genome assembly, annotation and comparison. I was funded by the Human Microbiome Project (HMP) among the 15 Demonstration Projects to study the role of the human skin microbiome in acne. I am currently funded by the NIGMS and NIDCR to study the human skin microbiome and oral microbiome and their associations with diseases.

Relevant Recent Publications

  1. Kang D, Shi B, Erfe MC, Craft N, Li H. Vitamin B12 modulates the transcriptome of the skin microbiota in acne pathogenesis. Science Translational Medicine. 2015; 293(7): 293ra103.
  2. Liu J, Yan R, Zhong Q, Ngo S, Bangayan NJ, Nguyen L, Lui T, Liu M, Erfe MC, Craft N, Tomida S, Li H. The Diversity and Host Interactions of Propionibacterium acnes Bacteriophages on Human Skin. The ISME Journal. 2015; 9: 2078-2093.
  3. Shi B, Chang M, Martin J, Mitreva M, Lux R, Klokkevold P, Sodergren E, Weinstock GM, Haake SK, Li H. Dynamic Changes in the Subgingival Microbiome and Their Potential for Diagnosis and Prognosis of Periodontitis. mBio. 2015; 6(1): e01926-14.
  4. Liu J, Cheng A, Bangayan NJ, Barnard E, Curd E, Craft N, Li H. Draft Genome Sequences of Propionibacterium acnes Type Strain ATCC6919 and Antibiotic-Resistant Strain HL411PA1. Genome Announcements. 2014; 2(4): e00740-14.
  5. Kasimatis G, Fitz-Gibbon S, Tomida S, Wong M, Li H. Analysis of Complete Genomes of Propionibacterium acnes Reveals a Novel Plasmid and Increased Pseudogenes in an Acne Associated Strain. BioMed Research International. 2013; 2013: 918320.
  6. Tomida S, Nguyen L, Chiu BH, Liu J, Sodergren E, Weinstock GM, Li H. Pan-Genome and Comparative Genome Analyses of Propionibacterium acnes Reveal Its Genomic Diversity in the Healthy and Diseased Human Skin Microbiome. mBio. 2013; 4(3): e00003-13.
  7. Fitz-Gibbon S, Tomida S, Chiu BH, Nguyen L, Du C, Liu M, Elashoff D, Erfe MC, Loncaric A, Kim J, Modlin RL, Miller JF, Sodergren E, Craft N, Weinstock GM, Li H. Propionibacterium acnes Strain Populations in the Human Skin Microbiome Associated with Acne. Journal of Investigative Dermatology. 2013; 133: 2152-2160.

Active Funding in Microbiome-Related Research

Funding Agency/Grant Number:NIH R01 GM099530
Title:“Population Dynamics of P. acnes and Their Phages in the Human Skin Microbiome”
Funding Agency/Grant Number:NIH R01 DE021574
Title:“Metagenomic Study of the Periodontal Microbiome in Healthy and Diabetic Subjects”

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Jake Lusis, PhD
Professor, Departments of Medicine, Cardiology, Human Genetics, Microbiology, Immunology & Molecular Genetics, UCLA
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Home UCLA Med-Cardio/Microbio 3730 MRL BOX 951679 Los Angeles CA 90095-1679 Phone: (310) 825-1359Website: Lusis Laboratory

My PhD is in biophysics but somehow I ended up doing mouse genetics for my postdoc. I’m still doing mouse genetics, now with a focus on complex genetic traits, particularly those related to cardiovascular and metabolic disorders. With the development of high throughput technologies, such as expression arrays and sequencing, we have found it useful to marry such data with genetic analysis (‘systems genetics’). I also enjoy teaching.

Relevant Recent Publications

  1. Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, Feldstein AE, Britt EB, Fu X, Chung YM, Wu Y, Schauer P, Smith JD, Allayee H, Tang WH, DiDonato JA, Lusis AJ, Hazen SL. (2011) Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 472:57-63. PMCID:PMC3086762
  2. Bennett BJ, Vallim TQ, Wang Z, Shih DM, Meng Y, Gregory J, Allayee H, Lee R, Graham M, Crooke R, Edwards PA, Hazen S, Lusis AJ. (2013) Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation. Cell Metab. 17:49-60. PMCID:PMC3771112
  3. Elin Org, Brian W. Parks, Jong Wha J Joo, Benjamin Emert, William Schwartzman, Eun Yong Kang, Margarete Mehrabian, Calvin Pan, Rob Knight, Robert Gunsalus, Thomas A. Drake, Eleazar Eskin, and Aldons J. Lusis. (2015) Genetic and environmental control of host-gut microbiota interactions. Genome Res., in press.

Active Funding in Microbiome-Related Research

Funding Agency/Grant Number:NIH PO1 HL28481
Title:“Molecular genetic approaches in atherosclerosis research.”
Goals:This program project is concerned with the identification and characterization of genetic factors contributing to energy homeostasis and metabolic disease. The emphasis is on combined human-mouse approaches.

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Emeran Mayer, MD, PhD
Director, Oppenheimer Center for Neurobiology of Stress; Division of Digestive Diseases, David Geffen School of Medicine at UCLA
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Address 10833 Le Conte Avenue Center for Health Sciences 42-210 MC:737818 Los Angeles CA 90095 Phone: (310) 206-0192Fax: (310) 825-1919Website: UCLA Oppenheimer Center for Neurobiology of Stress

Dr. Emeran Mayer is a Professor in the Departments of Medicine, Physiology and Psychiatry at the David Geffen School of Medicine at UCLA, Executive Director of the Oppenheimer Center for Neurobiology of Stress, and Co-director of the CURE: Digestive Diseases Research Center at UCLA. He is a world renowned gastroenterologist and neuroscientist with 30 years of experience in the study of clinical and neurobiological aspects of how the digestive system and the nervous system interact in health and disease, and his work has been continuously supported by the National Institutes of Health (NIH). He is currently principal investigator on 4 NIH grants including a center grant from ORWH/NIDDK on sex differences in brain gut interactions, a consortium grant by NIDDK on pelvic pain syndromes, a RO1 grant on the effects of cognitive behavioral therapy on brain signatures in IBS and a ROI grant on brain gut microbiome interactions in inflammatory and functional GI disorders (both from NIDDK). He has published over 320 peer-reviewed articles (average H index 90), including 100 chapters and reviews, co-edited four books, and organized several interdisciplinary symposia in the area of visceral pain and mind body interactions. His current research focus is on the role of the gut microbiota in modulating brain gut interactions, and their role in emotion regulation, chronic visceral pain and obesity.

Relevant Recent Publications

  1. Labus JS, Naliboff B, Kilpatrick L, Liu C, Ashe-McNalley C, dos Santos IR, Alaverdyan M, Woodworth D, Gupta A, Ellingson BM, Tillisch K, Mayer EA. Pain and Interoception Imaging Network (PAIN): A multimodal, multisite, brain-imaging repository for chronic somatic and visceral pain disorders. Neuroimage, 2015 Apr 19. pii: S1053-8119(15)00308-0. doi10.1016/j.neuroimage.2015.04.018. [Epub ahead of print] PMID: 25902408
  2. Mayer EA, Knight R, Mazmanian SK, Cryan JF, Tillisch K. Gut Microbes and the Brain: Paradigm Shift in Neuroscience. J Neurosci Nov 12;34(46):15490-6, 2014. PMCID: PMC4228144
  3. Mayer EA, Labus JS, Tillisch K, Cole DE, Baldi P. Towards a Systems View of Irritable Bowel Syndrome, Nat Rev Gastroenterol Hepatol. 2015, in press

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Anna-Barbara Moscicki, MD
Chief, Adolescent Medicine; Professor of Pediatrics, David Geffen School of Medicine at UCLA
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Home 10833 Le Conte Avenue MDCC 22-432 MC:175217 Los Angeles CA 90095 Phone: (310) 206-6345Fax: (310) 206-4855

Dr. Moscicki is Professor of Pediatrics at UCLA, Division Chief of Adolescent Medicine, Dr. Moscicki’s career has focused on adolescent gynecology and STI research with a specific focus in Human Papillomavirus, HIV infection and mucosal immunology. She trained in STI epidemiology and mucosal immunology. Dr. Moscicki has been the PI of a natural history study of HPV in adolescents and young women since 1990, one of the longest running HPV cohorts of which she was awarded an NIH MERIT. She has over 200,000 stored specimens from this cohort including cervical lavages, cervical biopsies, anal swabs, oral gargles, serum and blood clots. She serves on numerous national and international committees, including the W.H.O., N.I.H., American Society for Colposcopy and Cervical Pathology, and the American Cancer Society. Her work was influential in forming the new cervical cancer screening guidelines and triage of abnormal cytology in young women. She is also involved in health outcomes in perinatally HIV infected children including sexual risk behaviors, substance use, oral health, microbiomes, and HPV.

She has been involved in HIV research for over 20 years including member of the Adolescent Medicine HIV/AIDS Research Network, Adolescent Therapeutic Network , IMPAACT and PHACS. In PHACS, she is a member of the scientific Leadership Group, and co-chair of the Adolescent Working Group and co-PI of the Oral Health study in PHACS which focuses on the role of the microbiome in oral health.

Relevant Recent Publications

  1. Daud, II, Scott ME, Ma Y, Shiboski S, Farhat S, Moscicki AB. Association between toll-like receptors expression and human papillomavirus type 16 persistence. Int J Cancer 2011;128(4):879-86.
  2. Hwang LY, Scott M, Ma Y, Moscicki AB. Higher levels of cervicovaginal inflammatory and regulatory cytokines and chemokines in healthy young women with immature cervical epithelium. Journal of Reproductive Immunology 2011; 88:66-71.
  3. Moscicki AB, Kaul R, Ma Y, Scott ME, Daud, II, Bukusi EA, Shiboski S, Rebbapragada A, Huibner S, Cohen CR. Measurement of mucosal biomarkers in a phase 1 trial of intravaginal 3% StarPharma LTD 7013 gel (VivaGel) to assess expanded safety. J Acquir Immune Defic Syndr 2012;59(2):134-140.
  4. Weinberg A, Song LY, Saah A, Brown M, Moscicki AB, Meyer III WA, Bryan J, Levin MJ for the IMPAACT/PACTG P1047 team. Humoral, mucosal and cell-mediated immunity against vaccine and non-vaccine genotypes after administration of quadrivalent human papillomavirus vaccine to HIV-infected children. Journal of Infectious Diseases. 2012; 206(8):1309-1318.
  5. Scott ME, Shvetsov YB, Thompson PJ, Hernandez BY, Zhu X, Wilkens LR, Killeen J, Vo D, Moscicki AB, Goodman MT. Cervical Cytokines and Clearance of Incident Human Papillomavirus Infection: Hawaii HPV Cohort Study. International Journal of Cancer. 2013; 133(5):1187-96.
  6. Moscicki AB, Ma Y, Farhat S, Jay J, Hanson E, Benningfield S, Jonte J, Godwin-Medina C, Wilson R, Shiboski S. Natural history of anal human papillomavirus infection in heterosexual women and risks associated with persistence. Clin Infect Dis 2014;58(6):804-11
  7. Scott ME, Ma Y, Farhat S, Moscicki AB. Expression of nucleic acid-sensing Toll-like receptors predicts HPV16 clearance associated with an E6-directed cell-mediated response. Int J Cancer. Oct 23 2014. [e-pub ahead of print]

Active Funding in Microbiome-Related Research

Funding Agency/Grant Number:NIH NCI R37CA051323-26
Title:“Natural history of HPV”
Funding Agency/Grant Number:NIH NICHD U01 HD052102
Title:“Oral Health in Perinatally HIV infected adolescents”

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Mohamad Navab, PhD
Adjunct Professor of Medicine, Department of Cardiology, David Geffen School of Medicine at UCLA
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Address 52-266 CHS Los Angeles CA 90095 Phone: (310) 206-2678

Dr. Mohamad Navab is a Professor in the Departments of Medicine, Cardiology at the David Geffen School of Medicine at UCLA, with 32 years of research experience in the study of atherosclerosis, lipids and artery wall metabolism. His work has been continuously supported by the National Institutes of Health (NIH). He is CoProject Leader on an NIH PPG/grant that is going into its 31st year. He has published 195 peer-reviewed articles (average H index 90), including 100 chapters and reviews, co-edited two books, and organized three interdisciplinary symposia in the area of lipids and artery wall metabolism. His current research focus is on the role of the role of small intestine, systemic inflammation and cardiovascular function. He has been involved in studies of gut microbiota in dyslipidemia and the effect of HDL mimetic peptides on it.

Relevant Recent Publications

Source and role of intestinally derived lysophosphatidic acid in dyslipidemia and atherosclerosis. Navab M et al. J Lipid Res. 2015;56:871-87

Transgenic 6F tomatoes act on the small intestine to prevent systemic inflammation and dyslipidemia caused by Western diet and intestinally derived lysophosphatidic acid. Navab M, et al. J Lipid Res. 2013;54:3403-18

Intestine may be a major site of action for the ApoA-I mimetic peptide 4F whether administered subcutaneously or orally. Navab M, et al. J Lipid Res. 2011; 52:1200-10.

HDL and cardiovascular disease: atherogenic and atheroprotective mechanisms. Navab M, Nat Rev Cardiol. 2011;8:222-32

Mechanisms of disease: proatherogenic HDL–an evolving field. Navab M, Nat Clin Pract Endocrinol Metab. 2006 ;2:504-11.

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Victoria Niklas, MD, MA
Professor, Department of Pediatrics, David Geffen School of Medicine at UCLA; Director, Neonatal Intensive Care Unit and Newborn Services, Olive View-UCLA Medical Center
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Dr. Victoria Niklas is a Professor in the Department of Pediatrics at the David Geffen School of Medicine at UCLA and the Director of the Neonatal Intensive Care Unit and Newborn Services at Olive View-UCLA Medical Center. Dr. Niklas earned her medical degree from Harvard Medical School and a master’s degree in Biochemistry and Molecular Biology from Harvard University. She completed her residency in pediatrics at Children’s Hospital Los Angeles and a fellowship in perinatal and neonatal medicine at UCLA.

Dr. Niklas has over 25 years of experience as a clinician investigator and neonatologist integrating basic and translational science in diseases afflicting the newborn. Her career has focused on understanding the immune system in the susceptibility of the newborn to infection and inflammation in the body’s largest mucosal surface, the intestine. She is a recognized expert in mouse models of intestinal immune T cell development and the pathogenesis of intestinal inflammation, in diseases such as necrotizing enterocolitis, a life-threatening intestinal disease of primarily premature infants. More recently, she was the site PI for a phase I/II RCT of enteral human recombinant lactoferrin evaluating its role in reducing hospital-acquired infections (HAI) in very low birth weight infants. Lactoferrin was safe and reduced HAI in premature infants. Also, the normally pathogenic flora was reduced in the feces of lactoferrin treated infants when compared to controls, suggesting one possible mechanism whereby lactoferrin reduced HAI in these infants.

Dr. Niklas wishes to extend these studies by exploring metagenomic signatures of maternal disease (such as obesity) in the taxonomic composition of the gut microbiota acquired by the newborn at birth. Well-described microbial signatures of obesity in adults may result in disease-associated microbial signatures in the newborn intestine. Hence, maternal flora may have a long-lasting impact on the infant’s later risk of diseases, such as obesity, in later life. The reduction in childhood obesity among breastfed infants suggests that components in breast milk (lactoferrin, milk’s microbiome, or milk oligosaccharides) may lower this risk. Possibly by influencing heritability or stability of an obesity-associated intestinal microbiome. Advanced genomic tools and sequencing will be used to explore the composition and diversity of this microbiome between mother and baby. It is, however, envisioned, that a “Mother Baby Cohort” will serve as a springboard for extended “life studies” enabling interdisciplinary, interventional and observational studies of health and disease. These endeavors will advance knowledge and ultimately improve care practices in the management in the perinatal interface with a far-reaching impact on our understanding of health and the origins of disease throughout life.

Relevant Recent Publications

  1. Sherman MP, Miller MM, Sherman J, Niklas V. Lactoferrin and necrotizing enterocolitis. Curr Opin Pediatr. 2014 Apr; 26(2): 146-50. PubMed PMID: 24503532.
  2. Sherman MP, Zaghouani H, Niklas V. Gut microbiota, the immune system, and diet influence the neonatal gut-brain axis. Pediatr Res. 2015 Jan; 77(1-2): 127-35. PubMed PMID: 25303278.
  3. Sherman MPS, Adamkin DH, Radmacher PG, Sherman J and Niklas V. Protective Proteins in Human Milk: Lactoferrin Steps Forward. NeoReveiws 13(5): 293-301, 2012.
  4. Sherman MP, Sherman J, Arcinue R and Niklas V. Lactoferrin meets the NICU Habitat: Effects on the fecal microbiome of VLBW infants. Submitted, 2015.
  5. Sherman MP, Adamkin DH, Niklas V, Radmacher P Sherman J, Wertheimer F and Petrak K. Randomized Trial of Human Recombinant Lactoferrin (Talactoferrin) Oral Solution in Preterm Infants, In preparation 2015

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Charalobos Pothoulakis, MD
Director of Research, UCLA Center for Inflammatory Bowel Diseases; Professor, Pathology and Laboratory Medicine Digestive Diseases/Gastroenterology, David Geffen School of Medicine at UCLA
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Address 675 Charles E. Young Dr. South MRL RM# 1240, Box 957019 Los Angeles CA 90095 Phone: (310) 825-9104

Dr. Pothoulakis is the Eli and Edythe Broad Professor of Medicine at the Department of Medicine at UCLA. He is the Director of the IBD Research Center, and the Chair of Research at the Division of Digestive Diseases at UCLA.. He is currently an Associate Editor for the American Journal of Physiology, Gastrointestinal and Liver Physiology and a member of the founding Editorial Board of the new AGA Journal Cellular and Molecular Gastroenterology and Hepatology. He is also the Chair of the Regulatory Peptides, Cell Signaling and Molecular Biology Section of the AGA. He is an author of over 185 original articles and numerous reviews and book chapters. His research program is primarily focused on the role of neuropeptides and hormones in several disease states, including Inflammatory Bowel Disease, Irritable Bowel Syndrome. Dr. Pothoulakis has been contributing to the Clostridium difficile field since its inception and published over 100 manuscripts in mechanisms of action of this pathogen and its toxins. He also works on mechanisms of probiotics in intestinal inflammation and he is one of the pioneers in this field. Dr. Pothoulakis’ research projects have been supported by multiple grants from the National Institutes of Health with no interruption over the past 25 years, as well as by grants from the Broad Foundation, the Crohn’s and Colitis Foundation and several pharmaceutical companies.

Relevant Recent Publications

  1. Kokkotou E, Moss AC, Torres D, Karagiannides I, Cheifetz A, Liu S, O’Brien M, Maratos-Flier E, Pothoulakis C. Melanin-Concentrating Hormone as a mediator of intestinal inflammation. Proc Natl Acad Sci (USA) 2008; 105:10613-8 PMCID: PMC2492477
  2. Savidge TC, Urvil P, Oezguen N, Kausar A, Choudhury A, Acharya V, Pinchuk I, Torres AG, English RD, Wiktorowicz JE, Leoffelholz M, Kumar R, Shi L, Nie W, Feng H, Braun W, Herman B, Stamler JS, Pothoulakis C. Host S-nitrosylation inhibits clostridial small molecule-activated glucosylating toxins. Nature Medicine; 2011; 17(9):1136-41. PMCID: PMC3277400
  3. Koon HW, Ho S, Hing TC, Cheng M, Chen X, Ichikawa Y, Kelly CP, Pothoulakis C. Fidaxomicin inhibits Clostridium difficile toxin A–mediated enteritis in the mouse ileum. Antimicr Agents Chemother 2014; 58(8):4642-50.
  4. Chen X, Fruehauf J, Katchar KK, Mustafa N, Koon HW, Xu H, Zhao D, Kokkotou E, Goldsmith JD, Pothoulakis C, Kelly CP. Saccharomyces boulardii inhibits EGF receptor signaling and intestinal tumor growth in Apc(min) mice. Gastroenterology 2009; 137:914-23
  5. Pothoulakis C. Review Article: anti-inflammatory mechanisms of action of Saccharomyces boulardii. Alim Pharmacol Ther, 2009 ; 30(8):826-33.

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Sang Hoon Rhee, PhD
Adjunct Associate Professor, Division of Digestive Diseases, David Geffen School of Medicine at UCLA
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Dr. Rhee’s research focuses on studying roles of host-microbial interaction in the gastrointestinal tract. Specifically, the lab has been investigating the function of Toll-like receptors (TLRs) which is a family of pattern recognition receptor recognizing microbial products to elicit inflammatory and innate immune responses. Recently, Dr. Rhee demonstrated that TLR5 is associated with the development and progress of inflammatory bowel diseases. Moreover, Dr. Rhee’s studies also showed that TLR5 plays an important role to elicit innate immunity to regulate anti-tumor activity. Studies to be presented will include a role of TLR5 in regulating colon cancer and a potential mechanism to modulate anti-tumor activity against colonic tumor. This research program has a record of continuous support from the NIH/NIDDK, Crohn’s and Colitis Foundation of America, Flight Attendant Medical Research Institute at both UCLA and Harvard Medical School.

Relevant Recent Publications

  1. Choi YJ., Im E., Pothoulakis C., and Rhee SH. TRIF modulates TLR5-dependent responses by inducing proteolytic degradation of TLR5. (2010) The Journal of Biological Chemistry 285: 21382-21390. PMCID: PMC2898416.
  2. Choi YJ., Im E., Chung HK., Pothoulakis C., and Rhee SH. TRIF mediates Toll-like receptor 5-induced signaling in intestinal epithelial cells (2010) The Journal of Biological Chemistry 285:37570-37578. PMCID: PMC2988362.
  3. Im E., Riegler FM., Pothoulakis C., and Rhee SH. Elevated lipopolysaccharide in the colon evokes intestinal inflammation, aggravated in immune modulator-impaired mice. (2012) The American Journal of Physiology – Gastrointestinal and Liver Physiology 303(4):G490-7. PMCID: PMC3423140. (Selected as an “Editor’s Pick” from the journal).
  4. Im E., Jung J., and Rhee SH.., Toll-like receptor 5 engagement induces IL-17C expression in intestinal epithelial cells. (2012) Journal of Interferon & Cytokine Research 32:583-591. PMCID: PMC3514012.
  5. Choi YJ., Jung J., Chung HK., Im E., and Rhee SH., PTEN regulates TLR5-induced intestinal inflammation by controlling Mal/TIRAP recruitment. (2013) The FASEB Journal 27:243-254. PMCID: PMC3528317
  6. Im E., Jung J, Pothoulakis C., and Rhee SH. Disruption of Pten speeds onset and increases severity of spontaneous colitis in Il10–/– mice. (2014) Gastroenterology 147:667-679. PMCID: PMC4143453.

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Claudia Sanmiguel, MD
Director, Ingestive Behavior and Obesity Program, Oppenheimer Center for Neurobiology of Stress; Division of Digestive Diseases, David Geffen School of Medicine at UCLA
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Claudia Sanmiguel is the Ingestive Behaviors and Obesity Program (IBOP) director at the Oppenheimer Center for Neurobiology of Stress (CNS) and she is a clinical instructor at the UCLA Digestive Diseases Division. She was born in Bogota, Colombia where she studied Medicine at the Pontificia Universidad Javeriana and specialized in Internal Medicine and Gastroenterology. Then she moved to Alberta, Canada where she did research on gastrointestinal motility and the use of artificial pacemakers and stimulators for the treatment of gastrointestinal disorders. She continued her research career at the Cleveland Clinic in Ohio and at the Cedars Sinai Medical Center in Los Angeles, where she explored the use of pacemakers and electrical stimulators for the treatment of obesity and obesity related diabetes mellitus, as well as, studied gastric electromechanical signals related to eating behavior and satiety. As part of pursuing a research career in United States, she completed her residency in Internal Medicine at Cedars-Sinai Medical Center and trained in Gastroenterology at the University of California Los Angeles. She has continued her pursue on understanding the mechanisms that regulate eating behavior in health and in obesity, and the role of the brain/gut/microbiome axis in interpreting and regulating those behaviors. She has published several papers in well known GI and bioengineering journals and presented her research results in North American and International meetings. She currently has partial NIH funding for a study on the role of brain activity and changes in eating behavior in weight loss after bariatric surgery and how some peripheral signals coming from visceral fat and gut microbiome may play a role in obesity and weight loss. She is also doing research on neuroplasticity in brain areas related to eating hehaviors in response to neuromodulation.

Recent Relevant Publications

  1. Sanmiguel C, Gupta A, Mayer EA. Gut Microbiome and Obesity: A Plausible Explanation for Obesity. Curr Obes Rep. 2015 Jun;4(2):250-261.
  2. Sanmiguel CP, Gupta A, Labus LS, Coveleskie K, KaragiannidisI , AlaverdyanM, Ashe-McNalley C, Stains J, and others. Adiposity Is Associated With Alterations Within the Brain Reward System in Adult Subjects. Gastroenterology 2015, Vol. 148, Issue 4, S-674
  3. Gupta A, Mayer EA, Sanmiguel CP, Van Horn JD, Woodworth D, Ellingson BM, Fling C, Love A, Tillisch K, Labus JS. Patterns of Brain Structural Connectivity Differentiate Lean from Overweight Subjects. Neuroimage-Clinical, 2015; 7: 506–517.
  4. Sanmiguel CP, Coveleskie K, Gupta A, Kilpatrick L, Labus J, Ashe-McNalley C, Dutson EP, Mayer EA. Association of abdominal fat with resting state low frequency brain activity in human subjects. Neurogastroenterology & Motility. 2013; 25, Suppl 1:14
  5. Sanmiguel CP, Ito Y, Hagiike M, Conklin JL, Lalezari D, Soffer EE. The effect of eating on Lower Esophageal Sphincter electrical activity. American Journal of Physiology Gastrointest Liver Physiology. 2009 Apr; 296(4): G793-797.
  6. Sanmiguel CP, Conklin JF, Cunneen SA, Barnett P, Phillips EH, Kipnes M, Pilcher J, Soffer EE. Gastric Electrical Stimulation with the TANTALUS® System in Obese Type 2 Diabetes Patients: Effect on Weight and Glycemic Control. J Diabetes Science and Technology. 2009; 3: 964-970
  7. Sanmiguel CP, Haddad W, Aviv R, Cunneen SA, Phillips EH, Kapella W, Soffer EE. The TANTALUS TM System for obesity: effect on gastric emptying of solids and ghrelin plasma levels. Obes Surg. 2007; 17: 1503-9.
  8. Aviv R, Policker S, Brody F, Bitton O, Haddad W, Kliger a, Sanmiguel CP, Soffer EE. Circadian patterns of gastric electrical and mechanical activity in dogs. Neurogastroenterol Motil. 2008; 20:63-8
  9. Aviv R, Sanmiguel CP, Kliger A, Policker S, Haddad W, Hagiike M, Soffer EE. The use of gastric electrical signals for algorithm for Automatic Eating Detection in dogs. Neurogastroenterol Motil.; 2008, 20:369-76.

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Robert Schiestl, PhD
Professor, Departments of Pathology and Laboratory Medicine, Environmental Health Sciences, Radiation Oncology, Jonsson Comprehensive Cancer Center, UCLA
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Phone: (310) 267-2087

Robert H. Schiestl has obtained his PhD from the University of Vienna at the age of 23 years. He was postdoctoral fellow at Edmonton, Alberta, Rochester, NY, and Chapel Hill, NC before being professor at Harvard at the age of 31 where he stayed for 10 years. Since 15 years he is professor at UCLA with 187 publications, 10 patents and 2 startup companies.
Intestinal microbiota plays a role in the nutrient metabolism, modulation of the immune system, arthritis, obesity and intestinal inflammation. In the literature there have been huge differences in the same Atm deficient mice in different labs reported. When our lab moved from Harvard to UCLA we found a similar difference in genetic instability and logevity. When we changed the intestinal microbiota back to conventional microbiota we could reproduce the phenotype at Harvard. We tested Atm deficient mice for genotoxicity, genetic instability, DNA damage, inflammation markers, cancer latency and longevity and high throughput sequencing of the intestinal microbiota. Isogenic mice from different housing facilities showed a four fold difference in life expectancy, a 4.5 fold difference in genetic instability and DNA damage. The onset of lymphomas was significantly 2 fold different. We sequenced the microbiota of both facilities and found Lactobacillus johnsonii 456 as dominant bacterial strain in the health beneficial microbiota. Just this bacterium by itself reduced genotoxicity, reduced inflammation and reduced levels of cytotoxic T cells in the liver and blood. We also found similar differences in Trp53 deficient and even in wildtype mice. The underlying mechanisms is probably due to inflammation promotion or suppression mediated by the intestinal microbiota. The understanding of this effect may lead to a breakthrough in the understanding of the causes of carcinogenesis, which might lead to prevention of AT, a currently incurable progressive disease and possibly other cancer-prone DNA repair deficient diseases or even wildtype mice and people.

Relevant Recent Publications

  1. Yamamoto, L. I. Maier , A. T. Dang , D. Berry , J. Liu, P. M. Ruegger , J. Yang, P. A. Soto, L. L. Presley, R. Reliene , A. M. Westbrook , B. Wei , A. Loy , C.r Chang , J. Braun , J. Borneman, R. H. Schiestl (2013) Intestinal bacteria modify lymphoma penetrance in genetically susceptible mice via inflammation-mediated systemic host oxidative stress and leucocyte genotoxicity- Cancer Research 73(14):4222-4232 July 15, 2013 PMCID: PMC3718495
  2. Westbrook, A. and R.H. Schiestl (2010) Atm deficient mice exhibit increased sensitivity to dextran sulfate sodium-induced colitis characterized by elevated DNA damage and persistent immune activation. Cancer Research 70, 1875, March 1, 2010. PMCID: PMC2831166

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Wenyuan Shi, PhD
Professor and Chairman, Oral Biology, UCLA School of Dentistry Professor, Microbiology and Molecular Genetics, UCLA School of Medicine Founding scientist and chief science officer, C3 Jian Inc.
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Home 10833 Le Conte Avenue Los Angeles CA 90095-1668 Phone: (310) 825-8356Fax: (310) 794-7109

Dr. Wenyuan Shi is a chairman and professor of Oral Biology at UCLA Schools of Dentistry. Dr. Shi’s laboratory has been using multidisciplinary approaches to study oral microbial pathogenesis with a specific focus on microbial biofilm, inter-species interaction and signal transduction. In addition, Dr. Shi’s laboratory is actively involved in the development of next generation of diagnostic and therapeutic tools against oral microbial infections, including instant chairside detection of oral pathogens and peptide based targeted antimicrobial therapeutics. These translational research efforts have resulted in novel technologies that are licensed and developed by major pharmaceutical, dental and biotech companies. Dr. Shi is also the founding scientist, chief science officer, and chairman of the scientific advisory board of C3 Jian Inc. (www.c3-jian.com).

Dr. Shi obtained his BS degree from Fudan University (Shanghai) in 1984, acquired his Ph.D degree from University of Wisconsin-Madison in 1991 and fulfilled his postdoctoral training at University of California-Berkeley during 1992-1995. He is co-author and co-inventor of over 200 scientific articles and patents.

Relevant Recent Publications

  1. He, X., T. Yan, L. Guo, R. Lux, D. R. Zusman and W. Shi. 2010. In vitro communities derived from oral and gut microbial floras inhibit the growth of bacteria of foreign origins. Microbial Ecology. 60(3):665-76 PMCID: PMC2954289
  2. He, X., T. Yan, L. Guo, R. Lux, D. R. Zusman and W. Shi. 2010. Oral-derived bacterial flora defends its domain by recognizing and killing intruders—a molecular analysis using Escherichia coli as a model intestinal bacterium. Microbial Ecology. 60(3):655-64 PMCID: PMC2954290
  3. He, X., W. Hu, J. He, H. Guo, R. Lux and W. Shi. 2011 Community-based interference against of human integration of Pseudomonas aeruginosa into human salivary microbial biofilm. Molecular Oral Microbiology. 26: 1-16. PMCID:PMC3327514
  4. He, X., J. McLean, L. Guo, R. Lux and W. Shi 2013. The social structure of microbial community involved in colonization resistance. The ISME Journal 8(3):564-74. PMCID:PMC3930314

Active Funding in Microbiome-Related Research

Funding Agency/Grant Number:NIH NIDCR 1R01DE023810
Title:“Domestication and characterization of TM7-the most elusive oral phylum”
Funding Agency/Grant Number:NIH NIDCR 1-R01-DE020102
Title:“Making a quantum leap in plaque research with modern sciences”
Funding Agency/Grant Number:NIH NIDCR 1-R01-DE021108
Title:“Molecular analysis of F. nucleatum interspecies interactions in biofilms”
Funding Agency/Grant Number:NIH NIGMS 1 R01 GM095373
Title:“Moving beyond diversity by revealing biological functions of uncultured bacteria”

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Kirsten Tillisch, MD
Director, Mind Body Research Program, Oppenheimer Center for Neurobiology of Stress; Associate Professor, Department of Medicine, David Geffen School of Medicine at UCLA
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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.

Relevant Recent Publications

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.

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Elizabeth Volkmann, MD, MS
Clinical Instructor, Division of Rheumatology, Department of Medicine, David Geffen School of Medicine at UCLA
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Dr. Elizabeth Volkmann is a Clinical instructor in the Department of Medicine, Division of Rheumatology at UCLA. She is the Founder and Director of the Connective Tissue Disease-Interstitial Lung Disease (CTD-ILD) Integrative Clinic Program at UCLA. She received her medical degree from UCLA David Geffen School of Medicine, and subsequently completed her residency in Internal Medicine and fellowships in Rheumatology and Medical Education at UCLA. During her fellowship, she participated in the Specialty Training and Advanced Research (STAR) Program and earned her Master of Science degree in Clinical Research.

Her clinical and research expertise is in systemic sclerosis (scleroderma), a rare and disabling autoimmune disease that affects gastrointestinal function in the majority of patients. She is currently the principal investigator of an innovative study to characterize the gastrointestinal tract microbiome in patients with systemic sclerosis. This study aims to investigate the hypothesis that the systemic sclerosis disease state is associated with altered colonic microbial composition at the human mucosal-luminal interface, and to determine whether certain microbial genera contribute to symptoms of gastrointestinal tract dysfunction in patients with systemic sclerosis. If affirmed, such genera could provide specific targets for intervention to avert or treat this important clinical dimension of systemic sclerosis.

Recent Relevant Publications/Presentations:

  1. Volkmann ER, Chang, Y-L, Barroso N, et al. Systemic sclerosis is associated with a unique colonic microbial consortium. Annals Rheumatic Diseases 2015;74:151.
  2. Volkmann ER. Systemic sclerosis is associated with a unique colonic microbial consortium. Oral Presentation at the European League Against Rheumatism Annual Congress, 2015. Rome, Italy.

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David Walker, PhD
Professor, Department of Integrative Biology and Physiology, UCLA
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Address 2018 Terasaki Life Sciences Building Los Angeles CA 90025 Phone: (310) 825-7179

Dr. Walker is a Professor in the department of Integrative Biology and Physiology at the University of California, Los Angeles (UCLA). He is also a faculty member of the Molecular Biology Institute at UCLA. Dr. Walker completed his Ph.D. degree at the University of Manchester, UK. He then went on to carry out postdoctoral work with Seymour Benzer at the California Institute of Technology. He joined the faculty at UCLA as an Assistant Professor in 2007 and was promoted to Associate Professor in 2012 and full Professor in 2015. Dr. Walker has a long-standing interest in the biological mechanisms of aging. In recent years, his research group has made important insights into the relationship between intestinal aging and organismal aging. In this work, Dr. Walker is exploring the relationships between age-related changes in microbiota composition, intestinal physiology and the health and viability of the aging host organism.

Dr. Walker is the recipient of several awards, including an Ellison Medical Foundation New Scholar in Aging award as well as a Career Development Award from the UCLA Older Americans Independence Center. Most recently, Dr. Walker is the recipient of a Julie Martin Mid-Career Award in Aging Research from the American Federation for Aging Research (AFAR).

Relevant Recent Publications:

  1. Clark, R.I., Salazar, A, Yamada, R, Fitz-Gibbon, S, Morselli, M, Alcaraz, J, Rana, A, Rera, M, Pelligrini, M, Ja, WW, Walker. D.W. (2015) Distinct shifts in microbiota composition during Drosophila aging impair intestinal function and drive mortality. Cell Reports (in press)
  2. Ulgerhait, M, Rana, A, Rera, M, Graniel, J, Walker D.W. (2014) AMPK modulates tissue and organismal aging in a non-cell-autonomous manner. Cell Reports 8: (6), p1767–1780.
  3. Rera, M, Clark, R.I., Walker D.W. (2012) Intestinal barrier dysfunction links metabolic and inflammatory markers of aging to death in Drosophila. Proc Natl Acad Sci USA 109(52): 21528-33.
  4. Rera, M, Bahadorani S, Cho J, Koehler, C, Hur, JH, Ulgerhait, M, Jones, DL, Walker DW. (2011). Modulation of longevity and tissue homeostasis by the Drosophila homolog of PGC-1. Cell Metabolism 14(5):623-34

Active Funding in Microbiome-Related Research

Funding Agency/Grant Number:NIH 1R01AG049157
Title:“Role of Intestinal Homeostasis in Organismal Aging”

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