BIOGRAPHICAL SKETCH NAME: Chang, Lin
eRA COMMONS USER NAME (credential, e.g., agency login): changl2 POSITION TITLE: Professor of Medicine
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable. Add/delete rows as necessary.)
INSTITUTION AND LOCATION DEGREE
applicable) (if
Completion Date
MM/YYYY FIELD OF STUDY University of California, Los Angeles, CA B.S. 06/1982 Biochemistry
UCLA School of Medicine M.D. 06/1986 Medicine
Harbor-UCLA Medical Center Residency 06/1989 Internal Medicine UCLA Affiliated GI Fellowship Training Program Fellowship 06/1992 Gastroenterology
A. Personal Statement
I am a gastroenterologist and physician scientist. My research has focused on brain-gut bidirectional communications, specifically the role of stress, clinical symptoms, health outcomes, and treatment in IBS. I have been performing clinical and translational research studies, including clinical treatment trials for over 25 years. My 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, Past President of the American Neurogastroenterology and Motility Society (ANMS), and member of the Rome Foundation Board of Directors. As Vice-Chief of the UCLA Division of Digestive Diseases, GI Fellowship Program Director, and GI T32 grant selection committee member, I will also assist with mentorship, recruitment and retention of Center members, including junior faculty. In the current proposal, I will serve as Multi-PI of the new UCLA: Digestive Diseases Research Core Center for the Study of Cellular Signaling and Communication (UCLA: DDRCC-SigCo) and will work closely with Dr. Rozengurt to oversee all activities, including the Research Cores, Enrichment Program and Pilot & Feasibility program, for which I serve on the selection committee.
Ongoing and recently completed projects that I would like to highlight include:
U54 DK123755 (MPI: Mayer, Chang) 05/01/20 – 04/30/25
SCORE title: Sex related differences in Brain Gut Microbiome Interactions in Irritable Bowel Syndrome Role: MPI, SCORE; Co-Lead, Project 1, Leadership Administrative Core, and Career Enhancement Core R44DK116362
Rivier, Larauche, Behan (MPI) Role: Subcontract Co-I, phase 2 (05/01/19-04/30/21) 06/01/18 – 04/30/22
Targeting IBS with Astressin
UCLA Innovation Fund, New Ventures Division, UCLA Technology Development Group 12/11/18 - present Role: Co-PI
IBS Diagnostic Test
SPARC OT2OD024899
(PI: Taché) Role: Co-I, Milestone 5 09/01/20 – 08/31/22
Comprehensive Structural and Functional Mapping of Mammalian Colonic Nervous System
Milestone 5: Quantitation of extrinsic and intrinsic innervation and nerve-mast/glial cell interactions in 3D imaging of the human colonic mucosal biopsies for neuromodulation in patients with irritable bowel syndrome (IBS)
1P50 DK64539
(PI: Mayer) Role: Co-Director of SCOR, PI of Project 1 09/30/02– 08/31/19
Center for Neurovisceral Sciences and Women’s Health R01 DK048351
(PI: Mayer) Role: Co-I
09/30/96 – 07/31/20, NCTE until 07/31/21
Perception and Modulation of Visceral Sensations Patent:
Provisional patent: DNA methylation-based biomarkers for irritable bowel syndrome, U.S. application no.
62/678,618, filed on 5/31/2018 Citations:
1. Videlock EJ, Shih W, Adeyemo M, Mahurkar-Joshi S, Presson AP, Polyartchou P, Alberto M, Iliopoulos D, Mayer EA, Chang L. Effect of IBS and sex on HPA axis response and peripheral GR expression.
Psychoneuroendocrinology 2016; 69:67-76. PMCID: PMC4977028
2. Videlock EJ, Mahurkar-Joshi S, Hoffman J, Iliopoulos D, Pothoulakis C, Mayer EA, Chang L. Sigmoid mucosal gene expression supports alterations of neuronal signaling in irritable bowel syndrome with constipation. American Journal of Physiology – Gastrointestinal and Liver Physiology 2018;315:G140- G157. PMCID: PMC6109711
3. Mahurkar-Joshi S, Chang L. Epigenetic Mechanisms in Irritable Bowel Syndrome. Front Psychiatry.
2020 Aug 14;11:805. PMCID: PMC7456856
4. Mahurkar-Joshi S, Rankin CR, Soroosh A, Videlock EJ, Verma A, Khandadash A, Iliopoulos D,
Pothoulakis C, Mayer EA, Chang L. The colonic mucosal microRNAs miR-219a-5p and miR-338-3p are downregulated in irritable bowel syndrome and are associated with barrier function and MAPK pathway.
Gastroenterology 2021;S0016-5085;00430-3. Online ahead of print, PMC pending B. Positions, Scientific Appointments and Honors
Positions and Scientific Appointments
2017 – Present Vice-Chief, Vatche and Tamar Manoukian Division of Digestive Diseases, UCLA 2016 – 2019 NIH Clinical Integrative and Molecular Gastroenterology Study Section
2015 – 2016 NIDDK Workshop on Functional Gastrointestinal Disorders, Planning Committee 2015 – 2019 Gastrointestinal Drugs Advisory Committee of the FDA
2013 – Present Program Director, UCLA GI Fellowship Program
2008 – Present ANMS; President (2012-2014), Council (2008 - 2016), ANMS Institute (2017-2023) 2007 – 2012 NIDDK Data and Safety Monitoring Board- EPISOD
2006 – Present Professor of Medicine in Residence, Div. of Digestive Diseases, UCLA School of Medicine, Co-Director, G. Oppenheimer Center for Neurobiology of Stress and Resilience
2005 – 2020 Rome Foundation Board of Directors,
2005 – 2010 Gastrointestinal Drugs Advisory Committee of the FDA
2005 – Present American Gastroenterological Association (AGA); Councilor (2005-2012), Clinical Research Councilor, AGA Governing Board (2018-2021)
2004– 2019 NIH ad hoc reviewer: CIGP study section (2004); Digestive Sciences Small Business and Bioengineering scientific review panel (2007, 2008); NIH Center for Scientific Review- CFS study section (2008); Challenge grants (2009); Somatosensory and Chemosensory
Systems (SCS) study section (2010); R21 grants (2012); Diabetic Complications Consortium (DiaComp): Pilot & Feasibility (2019)
2000 – 2006 Associate Professor of Medicine, Div. of Digestive Diseases, UCLA School of Medicine, Co-Director, Center for Neurovisceral Sciences and Women’s Health at UCLA
1997 – 2000 Assistant Professor of Medicine, Div. of Digestive Diseases, UCLA School of Medicine 1994 – Present Member, American College of Gastroenterology (ACG)
1993 – 1997 Assistant Professor of Medicine, GI division, Harbor-UCLA Medical Center, UCLA 1992 – 1993 Associate Consultant, Gastroenterology, Mayo Clinic, Rochester, MN
Honors
2021 AGA Distinguished Educator Award
2019 Women in Neurogastroenterology and Motility Award, ANMS 2018 Innovation Fund MedTech competition recipient award 2017 UCLA/CSMC Mid-Career Women's Leadership Program 2009 AGA Distinguished Clinician Award
2002 Janssen Award in Gastroenterology, Basic or Clinical Research
2002 Women in Gastroenterology and Wyeth Award for Gender Based Research, ACG 1995 Auxiliary Award, American College of Gastroenterology
C. Contributions to Science
1. The role of sex differences in the clinical presentation and pathophysiology of IBS.
My research has focused on the observation that IBS is a female predominant disorder that is associated with stress-induced exacerbations of abdominal pain and other GI symptoms. Our studies demonstrated sex and gender differences in clinical symptoms, visceral perception, autonomic nervous system function, central brain activation patterns, peripheral immune markers, and stress response to a visceral stressor. Specifically, we found that: 1) Women report abdominal pain, constipation and bloating with visible abdominal distension more than men; 2) Postmenopausal women with IBS have more severe overall IBS symptoms than premenopausal women while there is no difference in severity in similar age-matched men with IBS, 3) IBS women showing greater perceptual responses to rectosigmoid distension, which could explain the greater vulnerability to visceral pain in women; 3) Women show greater activation in brain regions concerned with emotional arousal and men showing greater activation in regions concerned with cognitive responses to visceral pain; 4) Men with IBS have a greater cardiosympathetic/vagal balance in response to colonic stimulation compared to women with IBS; 5) Women with IBS had decreased colonic mucosal expression of the IL-10, and NK-1 receptors vs. healthy women and men with IBS suggesting that colonic mucosal inflammation does not have a consistently primary role but an altered colonic immune response may exist in women with IBS; and 6) Men with IBS have an enhanced stress hormone response (i.e., cortisol levels) to hormone stimulation and a visceral stressor. Taken together, sex and gender affect brain-gut interactions involved in pain perception and stress response in IBS and help to explain the female predominance in IBS.
1. Chang L, Mayer EA, Labus J, Schmulson M, Lee OY, Olivas TI, Stains J, Naliboff BD. Effect of sex on perception of rectosigmoid stimuli in irritable bowel syndrome. Am J Physiol-Regulatory,
Integrative and Comparative Physiology 291:R277-R284, 2006.
2. Chang L, Adeyemo M, Karagiannides I, Videlock EJ, Bowe C, Shih W, Presson AA, Yuan PQ, Gong H, Singh S, Cortina G, Licudine A, Tache Y, Pothoulakis C, Mayer EA. Serum and colonic immune markers in irritable bowel syndrome. American Journal of Gastroenterology 2012; 107:262-72.
PMCID: PMC3297737
3. Videlock EJ, Shih W, Adeyemo M, Mahurkar-Joshi S, Presson AP, Polyartchou P, Alberto M, Iliopoulos D, Mayer EA MD, Chang L. Effect of IBS and sex on HPA axis response and peripheral GR expression. Psychoneuroendocrinology 2016; 69:67-76. PMCID: PMC4977028
4. Lenhart A, Naliboff B, Shih W, Gupta A, Tillisch K, Liu C, Mayer EA, Chang L. Postmenopausal Women with Irritable Bowel Syndrome (IBS) Have More Severe Symptoms Than Premenopausal Women with IBS. Neurogastroenterol Motil. 2020;00: e13913. PMCID: PMC7529855
2. The role of chronic stress and early adverse life events in IBS.
We and others have demonstrated evidence that IBS is a stress-sensitive disorder. Current stress is associated with the onset and symptom flares in IBS. Past studies found that chronic stress in the form of
sexual, emotional and physical abuse is more prevalent in IBS patients compared to healthy individuals. In addition to a higher prevalence of abuse in IBS patients, we demonstrated that these patients have higher prevalence of early adverse life events (EALs) during childhood, including a history of mental illness in a household member, and that stressful life events are associated with overall greater IBS symptom and pain severity. Furthermore, we showed that negative stressful life events are increased in IBS and resilience is lower in IBS. My research focusing on the central stress response in IBS, specifically the hypothalamic- pituitary-adrenal (HPA) axis and autonomic nervous system have found that: 1) Individuals with EALs have an enhanced cortisol response to a visceral stressor, 2) IBS patients have a dysregulated HPA axis and diurnal rhythm, 3) In response to pharmacologic stress hormone challenges (CRH and ACTH), there was a significant IBS and sex interaction, where men with IBS had higher cortisol responses vs. healthy men, while women with IBS had lower responses vs. healthy women, 4) HPA axis function correlated with glucocorticoid receptor expression in peripheral blood mononuclear cells (PBMC) suggesting that the latter can be a reflection of HPA axis sensitivity to negative feedback. Taken together, our findings support that alterations in HPA axis function exist in IBS and may be due to experiencing chronic stress in early life and adulthood and decreased negative feedback via glucocorticoid receptors.
a. VidelockE, AdeyemoM, Licudine A, HiranoM, OhningG, MayerM, MayerEA, Chang L. Childhood trauma is associated with increased hypothalamic-pituitary-adrenal (HPA) axis responsiveness in irritable bowel syndrome. Gastroenterology 2009; 137: 1954-1962. PMCID: PMC2789911
b. Park SH, Videlock EJ, Shih W, Presson AP, Mayer EA, Chang L. Adverse Childhood Experiences are Associated with Irritable Bowel Syndrome and Gastrointestinal Symptom Severity.
Neurogastroenterology and Motility 2016; 28:1252-1260. PMCID: PMC4956522
c. Parker CH, Naliboff BD, Shih W, Presson AP, Videlock EJ, Mayer EA, Chang L. Negative Events During Adulthood are Associated with Symptom Severity and Altered Stress Response in Irritable Bowel Syndrome. Clinical Gastroenterology and Hepatology 2019; 17: 2245-2252. PMCID:
PMC6609507
d. Parker CH, Naliboff BD, Shih W, Presson AP, Kilpatrick LA, Gupta A, Liu C, Keefer L, Sauk J, Hirten R, Sands BE, Chang L. Resilience in irritable bowel syndrome is lower compared to the general population and other chronic gastrointestinal conditions. Clinical Gastroenterology and Hepatology.
2019;17: 2245–2252. PMCID: PMC6609507 3. Mechanisms underlying pain perception in IBS
My research focused on studied pathophysiologic mechanisms underlying IBS including those associated with visceral pain. Earlier in my research career, I studied pathophysiologic mechanisms that were shared between IBS and fibromyalgia, a somatic chronic pain disorder that commonly overlaps with IBS. I received the NIH grants, Clinical Associate Physician (CAP) Award and a R01 for this research. We found that IBS and fibromyalgia are stress-related conditions with evidence of a dysregulated basal circadian rhythm of the HPA axis, are characterized by hyperalgesia to visceral and somatic stimuli, respectively, and show alterations in the cortical processing of interoceptive (visceral) and exteroceptive (somatic) stimuli. More recently, I have focused on peripheral mechanisms in IBS, particularly identifying molecular signatures in the colonic mucosa associated with IBS and that can explain symptoms and identify novel drug targets. For example, we found that there is involvement of peripheral mechanisms, particularly pathways mediating neuronal signaling in IBS with constipation. We have recently identified alterations in miRNA expression and DNA methylation profile in colonic mucosa that are associated with relevant pathophysiologic mechanisms and symptoms in IBS.
a. Chang, L, Berman S, Mayer EA, Suyenobu B, Derbyshire SWG, Naliboff BD Vogt B, FitzGerald LZ, Mandelkern MA. Brain responses to acute visceral and somatic stimuli in patients with irritable bowel syndrome and fibromyalgia. American Journal of Gastroenterology 2003; 98:1354-1361.PMID:
12818281
b. Chang L, Adeyemo M, Karagiannides I, Videlock EJ, Bowe C, Shih W, Presson AA, Yuan PQ, Gong H, Singh S, Cortina G, Licudine A, Tache Y, Pothoulakis C, Mayer EA. Serum and colonic immune markers in irritable bowel syndrome. American Journal of Gastroenterology 2012; 107(2):262-72.
PMC3311761
c. Videlock EJ, Mahurkar-Joshi S, Hoffman J, Iliopoulos D, Pothoulakis C, Mayer EA, Chang L.
Sigmoid mucosal gene expression supports alterations of neuronal signaling in irritable bowel
syndrome with constipation. American Journal of Physiology – Gastrointestinal and Liver Physiology 2018;315: G140-G157. PMCID: PMC6109711
4. Health outcomes in IBS.
I have conducted clinical research studies including health services research and clinic treatment trials in IBS for 20 years and this work has resulted in 39 peer-reviewed papers. Our team has compiled a large and comprehensive database of clinical and physiologic data collected in IBS patients, healthy individuals and other patient groups with chronic visceral or somatic pain. This database has resulted in key findings in IBS including: 1) Characterization of GI and extraintestinal symptoms in IBS and bowel habit subtypes; 2) Predictors of symptom severity and health-related quality of life; and 3) sex and gender differences in clinical presentation. I was Co-PI in the development of a multicenter cohort of IBS patients (IBS Proof Cohort) in the U.S. where we measured patient reported outcomes and developed a framework for IBS symptoms for use in clinical trials. I was also Co-I on a U01 NIH Patient Reported Outcomes Measurement Instrument System (PROMIS) grant to develop the first GI symptom scale validated to measure GI symptom severity in patients with a variety of GI diseases as well as in the general population. We obtained a large, investigator-initiated grant to develop an automated internet-based GI symptom assessment using the GI PROMIS symptom scale and educational platform for clinical practice.
a. Spiegel BMR, Strickland A, Naliboff BD, Mayer EA, Chang L. Predictors of patient-assessed illness severity in irritable bowel syndrome. American Journal of Gastroenterology 2008;103: 2536-43.
PMCID: PMC2949074.
b. Spiegel BMR, Bolus RE, Harris LA, Lucak SL, Mayer EA, Naliboff BD, Chey WD, Sayuk G, Esrailian E, Lembo A, Karsan HA, Tillisch K, Talley J, Chang L. Characterizing abdominal pain in IBS:
guidance for study inclusion criteria and outcome measurement. Alimentary Pharmacology and Therapeutics 2010;32 :1192-202. PMCID: PMC4118306
c. Naliboff BD, Kim S, Bolus R, Bernstein CN, Mayer EA, Chang L. Gastrointestinal and Psychological Mediators of Health Related Quality of Life in IBS and IBD: A Structural Equation Modeling Analysis.
American Journal of Gastroenterology 2012;107:451–459. PMCID: PMC3855477 d. Lee AD, Spiegel BM, Hays RD, Melmed GY, Bolus R, Khanna D, Khanna P, Chang L.
Gastrointestinal Symptom Severity in Inflammatory Bowel Disease, Irritable Bowel Syndrome and the General Population. Neurogastroenterology and Motility 2017;29: 10.1111/nmo.13003. PMCID:
PMC5393974 Full list of published work:
https://www.ncbi.nlm.nih.gov/sites/myncbi/lin.chang.1/bibliography/40548865/public/?sort=date&direction=a scending
Web of Science ID AAI-4333-2021
