Researchers Find Link Between Inflammation, Tissue Regeneration and Wound Repair Response

Discovery has implications for potential new treatments of some cancers and inflammatory bowel disease —

Almost all injuries, even minor skin scratches, trigger an inflammatory response, which provides protection against invading microbes but also turns on regenerative signals needed for healing and injury repair – a process that is generally understood but remains mysterious in its particulars.

Writing in the February 25 online issue of Nature, an international team of scientists, headed by researchers at the University of California, San Diego School of Medicine, report finding new links between inflammation and regeneration: signaling pathways that are activated by a receptor protein called gp130.. … Read the full story from the UC San Diego Newsroom


Dr. William SandbornStudy coinvestigators included Division of Gastroenterology division chief William Sandborn, MD, and Inflammatory Disease Center researchers Brigid S. Boland and John T. Chang.

Other Department of Medicine coauthors included Petrus R. de Jong; and Samuel B. Ho, professor of medicine in the Division of Gastroenterology and Section Chief, Gastroenterology, at the VA San Diego Healthcare System.

Full text of the article (UC San Diego only)

The Role of “Master Regulators” in Gene Mutations and Disease

Researchers identify key proteins that help establish cell function

Researchers at the University of California, San Diego School of Medicine have developed a new way to parse and understand how special proteins called “master regulators” read the genome, and consequently turn genes on and off. … Read the full story from the UC San Diego News Center


Christopher K. Glass, MD, PhDThe principal investigator of the reported study is Christopher K. Glass, MD, PhD, professor of medicine in the Division of Endocrinology & Metabolism and professor of cellular and molecular medicine at UC San Diego.

He is on the faculty of the UC San Diego Institute for Genomic Medicine.

Visit the Glass Laboratory website.

Related UC San Diego news stories:

Fate of the Heart: Researchers Track Cellular Events Leading to Cardiac Regeneration

Studies in zebrafish reveal abundant potential source for repair of injured heart muscle

In a study published in the June 19 online edition of the journal Nature, a scientific team led by researchers from the University of California, San Diego School of Medicine visually monitored the dynamic cellular events that take place when cardiac regeneration occurs in zebrafish after cardiac ventricular injury. Their findings provide evidence that various cell lines in the heart are more plastic, or capable of transformation into new cell types, than previously thought. … Read the full story from the UCSD Newsroom


Dr. Neil Chi

Dr. Neil Chi

Principal investigator of the study is Neil Chi, MD, PhD, assistant professor of medicine in the Division of Cardiology and member of the Institute for Genomic Medicine.

Chi directs the UC San Diego Cardiovascular Genetics Clinic and Cardiac Tissue Harvest and Biorepository Core.

In 2010, he received an NIH Director’s New Innovator Award for his study of cardiac regeneration in zebrafish. He is currently the principal investigator on that project and two R01 grant projects for research in cardiac morphogenesis and cardiac conduction development and disease.

Citation for the report: Zhang R, Han P, Yang H, Ouyang K, Lee D et al. In vivo cardiac reprogramming contributes to zebrafish heart regeneration. Nature (2013) doi:10.1038/nature12322.  |  Read the full text (UCSD only)

More Information About Dr. Chi:

Enhancer RNAs Alter Gene Expression

New class of molecules may be key emerging “enhancer therapy”

In a pair of distinct but complementary papers, researchers at the University of California, San Diego School of Medicine and colleagues illuminate the functional importance of a relatively new class of RNA molecules. The work, published online this week in the journal Nature, suggests modulation of “enhancer-directed RNAs” or “eRNAs” could provide a new way to alter gene expression in living cells, perhaps affecting the development or pathology of many diseases. … Read the full story from the UCSD Newsroom


Christopher K. Glass

Christopher K. Glass, MD, PhD

Drs. Christopher Glass (left) and M. Geoffrey Rosenfeld (at right below) are the principal investigators of the two studies reported in Nature.

M. Geoffrey Rosenfeld, MD

M. Geoffrey Rosenfeld, MD

Christopher Glass, MD, PhD, is professor of medicine and cellular and molecular medicine. M. Geoffrey Rosenfeld is professor of medicine and biology and is a Howard Hughes Medical Institute professor.

Both are members of the Division of Endocrinology & Metabolism in the Department of Medicine.

Citations for the study reports:

Glass report:

Michael T. Y. Lam, Han Cho, Hanna P. Lesch, David Gosselin, Sven Heinz, Yumiko Tanaka-Oishi, Christopher Benner, Minna U. Kaikkonen, Aneeza S. Kim, Mika Kosaka, Cindy Y. Lee, Andy Watt, Tamar R. Grossman, Michael G. Rosenfeld, Ronald M. Evans & Christopher K. Glass.  Rev-Erbs repress macrophage gene expression by inhibiting enhancer-directed transcription.  Nature (2013) doi:10.1038/nature12209. Published online 02 June 2013.  |   Full Text  (UCSD only)

Rosenfeld report:

Wenbo Li, Dimple Notani, Qi Ma, Bogdan Tanasa, Esperanza Nunez, Aaron Yun Chen, Daria Merkurjev, Jie Zhang, Kenneth Ohgi, Xiaoyuan Song, Soohwan Oh, Hong-Sook Kim, Christopher K. Glass & Michael G. Rosenfeld. Functional roles of enhancer RNAs for oestrogen-dependent transcriptional activation. Nature (2013) doi:10.1038/nature12210. Published online 02 June 2013.  |  Full text  (UCSD only)

More Information:

Cholesterol Sets Off Chaotic Blood Vessel Growth

A study at the University of California, San Diego School of Medicine identified a protein that is responsible for regulating blood vessel growth by mediating the efficient removal of cholesterol from the cells. Unregulated development of blood vessels can feed the growth of tumors.  … Read the full story from the UCSD Newsroom


Dr. Yury MillerYury Miller, MD, PhD, left, is senior author of the study report. He is associate professor of medicine in the Division of Endocrinology & Metabolism and faculty member in the Biomedical Sciences Graduate Program.

He first joined UC San Diego as a postdoctoral fellow in Dr. Joseph Witztum’s laboratory in 1998.

Miller is principal investigator of a National Institutes of Health R01 research grant, “Zebrafish Models of Vascular Inflammation and Atherosclerosis,” and a subproject of a P01 research program project with the La Jolla Institute of Allergy & Immunology, “Oxidized lipids and endotoxemia in vascular inflammation.”

Longhou Fang, PhDFirst author Longhou Fang, PhD, left, is a postdoctoral fellow in the Miller laboratory. He is the recipient of a National Institutes of Health K99 postdoctoral award for the project, “AIBP-mediated cholesterol efflux and angiogenesis.”

The other coauthors excepting Drs. Ulrich and Torres-Vásquez are affiliated with the Department of Medicine.

Dr. Philipp Wiesner.

Second-year internal medicine resident Philipp Wiesner, MD, right, who chose Miller as one of his mentors for the investigations he performed during his residency program research rotation, presented data from the vascular inflammation project at Medicine Grand Rounds on May 15.

Wiesner is also a coauthor of the study reported in Nature.

Citation for the study report:  Longhou Fang, Soo-Ho Choi, Ji Sun Baek, Chao Liu, Felicidad Almazan, Florian Ulrich, Philipp Wiesner, Adam Taleb, Elena Deer, Jennifer Pattison, Jesús Torres-Vázquez, Andrew C. Li & Yury I. Miller. Control of angiogenesis by AIBP-mediated cholesterol efflux. Nature (2013) doi:10.1038/nature12166. Published online 29 May 2013.  |  Read the full text (UCSD only)

More Information

Other UC San Diego news stories about Miller’s work:

Philipp Wiesner’s May 15 Medicine Grand Rounds presentation “Oxidized Phospholipids in Inflammation and Atherosclerosis”  |  Watch video (UCSD only)

Blocking Tumor-Induced Inflammation Impacts Cancer Development

How tumors exploit microflora and immune cells to fuel growth

Researchers at the University of California, San Diego School of Medicine report the discovery of microbial–dependent mechanisms through which some cancers mount an inflammatory response that fuels their development and growth. … Read the full story from the UCSD Newsroom


Division of Gastroenterology physician-scientists Bernd Schnabl, MD, and Lars Eckmann, MD, along with former postdoctoral fellow Christoph H. Österreicher are coauthors of the study report.

Dr. Eckmann, professor of medicine, directs the UCSD Center for Tissue Repair, Epithelial Biology and Inflammation, and Transformation (C-TREAT), a National Institutes of Health Digestive Disease Research Development Center. In his research laboratory, he addresses the mechanisms governing infection-related intestinal disease and the host defenses against them; and the pathophysiology of intestinal inflammation.

Dr. Schnabl, assistant professor of medicine, leads a research laboratory whose primary purpose is to investigate cellular and molecular mechanisms involved in the progression of chronic liver diseases with a special emphasis on the gut-liver axis. In 2011, he was awarded a five-year R01 research grant from the National Institute on Alcohol Abuse and Alcoholism for his project, “Microbiome and Intestinal Innate Immune Response in Alcoholic Liver Disease.”

Read the published report in Nature [full text UCSD only]

Citation: Grivennikov SI, Wang K, Mucida D, Stewart CA, Schnabl, B, Jauch D, Taniguchi K, Yu G-Y, Osterreicher CH, Hung KE, Datz C, Feng Y, Fearon ER, Oukka M, Tessarollo L, Coppola V, Yarovinsky F, Cheroutre H, Eckmann L, Trinchieri G, Karin M. Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth. Nature 2012/10/03, advance online publication. http://dx.doi.org/10.1038/nature11465.

Plasticity of Hormonal Response Permits Rapid Gene Expression Reprogramming

Gene expression reprogramming may allow cancer cell growth as well as normal differentiation

Gene expression is the process of converting the genetic information encoded in DNA into a final gene product such as a protein or any of several types of RNA. Scientists have long thought that the gene programs regulated by different physiological processes throughout the body are robustly pre-determined and relatively fixed for every specialized cell. But a new study by researchers from the University of California, San Diego School of Medicine reveals the unsuspected plasticity of some of these gene expression programs. … Read the full story from the UCSD Newsroom

M. Geoffrey Rosenfeld, MD

Co-principal investigator of the study is Dr. M. Geoffrey Rosenfeld (pictured at left). M. Geoffrey Rosenfeld, MD, is Professor of Medicine in the Division of Endocrinology and Metabolism and Howard Hughes Medical Institute investigator.

Department of Medicine coauthor Christopher K. Glass, MD, PhD, is Professor of Medicine in the Division of Endocrinology and Metabolism and Professor of Cellular and Molecular Medicine.

Read the published study in Nature (free full text).

In the Media: Dr. Ajit Varki

Dr. Ajit Varki is one of a team of researchers whose recent study is described in the Wired article, “Rare Gene Glitch a Clue to Genomics Mystery.”

Ajit Varki, M.D., is Professor of Medicine in the Division of Hematology-Oncology and Professor in the Department of Cellular and Molecular Medicine. He co-directs the UC San Diego Glycobiology Research and Training Center and the UC San Diego/Salk Center for Academic Research and Training in Anthropogeny (CARTA). He is Associate Dean of the Physician-Scientist Training Program.