Discovering the Causes of IBD
At the IBD Institute, our scientists focus on elucidating diseases causes and courses, identifying patients most likely to benefit from a specific treatment option, and illuminating avenues for the future development of promising drugs. This research component is directed by David Underhill, PhD, the Janis and William Wetsman Family Chair in Inflammatory Bowel Disease, and consists of senior investigators with programs representing each of the major scientific disciplines.
Our research is supported by funding from the National Institutes of Health, pharmaceutical companies and private foundations.
Research Snapshots
Gislaine Martins, PhD, studies molecular regulation of immune responses, particularly the mechanisms regulating immune cell function in nonlymphoid tissues and its implications for inflammatory diseases. The Martins Lab aims to identify pathways that can be harnessed to manipulate immune cell function and potentially interfere with ongoing immune responses associated with chronic inflammatory conditions.
Teams working under the leadership of Kathrin Michelsen, PhD, have developed in vivo and in vitro modeling systems to define the biologic consequences of IBD-associated genetic variations. With these techniques, the Michelsen Lab is furthering the discovery that the gene TNFSF15 and the protein it encodes, TL1A, are not only master regulators of intestinal inflammation. At present, the team is investigating the role of TNFSF15/TL1A in Paneth cell and epithelial cell function, and the development of severe disease phenotypes and forms of IBD characterized by complications such as fibrostenosis.
Dr. Stephan Targan, the Feintech Family Chair in Inflammatory Bowel Disease, and the Targan Lab team have shown that TL1A levels can influence regulatory cells, leading to either a proregulatory or a protective mucosal environment. Work in the IBDI labs on TL1A has led to human testing of blocking this protein as a treatment for IBD. In addition, the Targan Lab is investigating T-cell subsets, such as T follicular helper (Tfh)-like cells, which are particularly aggressive in patients with certain gene variations. Understanding the essential regulatory mechanisms of highly aggressive T-cell populations' highly aggressive T- cells may suggest novel approaches for managing the subsets of IBD patients in which inflammation is caused by these T-cells.
David Underhill, PhD, and his laboratory group have discovered that fungi are among the microbes normally found in the gastrointestinal tract and on the skin surface. Fungi play a role in inflammation and IBD. The Underhill Lab has shown people with Crohn's disease have increased amounts of several fungi in their intestinal mucosa. Dr. Underhill works to determine how the interaction between these fungi and the immune system contributes to the inflammatory response.
Andrea J. Wolf, PhD, is an immunologist studying the cellular responses of phagocytic cells to microbes. The Wolf Lab focuses on how recognition of microbes by phagocytic cells impacts the metabolism of phagocytic cells and how metabolic changes alter the innate inflammatory responses to microbes. These interactions are not only vital to how the body fights infection but are also important during inflammation in general. The Wolf Lab applies the understanding of immunometabolism of phagocytic cells to diseases like IBD and cancer.
Maria T. Abreu, MD, and her laboratory team focus on ways to prevent and treat IBD and inflammatory colon cancer. The Abreu Lab seeks to understand how the relationship between a patient’s immune system and their gut microbes may lead to gut inflammation or even the development of tumors. Dr. Abreu’s research also explores how the host-gut microbe relationship is influenced by environmental and genetic factors, including the impact of diet. Topics investigated by the lab include discovering the bacterial causes of IBD, leveraging the microbiome to prevent the development of colon cancer in IBD patients, understanding the genetic architecture of IBD in the Hispanic/Latinx community, and the use of diet as an intervention in the long-term management of IBD.
Suzanne Devkota, PhD, and her laboratory group are working to understand the role of the microbiome in IBD. The microbiome refers to the microbial inhabitants of the gastrointestinal tract and their interactions with genes and the immune system. Dr. Devkota's group has discovered that creeping fat provides a mechanism for transporting bacteria into the intestine. The Devkota Lab is also studying the effect of diet on the microbiome.
Ivan Vujkovic-Cvijin, PhD, and his team seek to identify gut microbes that spur harmful inflammation in inflammatory bowel diseases (IBD) as well as other human inflammatory diseases. Vujkovic-Cvijin has identified gut microbial signatures that may contribute to HIV-associated inflammatory diseases, immunotherapy responses in the setting of cancer and various monogenic immune diseases. Vujkovic-Cvijin's Lab is actively seeking to uncover methods by which to modulate the human gut microbiota for therapeutic benefit.
All IBDI investigators seek to discover and define the relationships between a set of IBD-associated autoantibodies in serum with other biological markers (e.g., genes) and disease severity or behavior. Such information contributes to the ability to identify distinct clinical subgroups from within patients with ulcerative colitis and Crohn's disease, which is essential for tailoring existing treatments for the needs of individual patients. We have already discovered that combinations of markers in serum and elsewhere, along with genetic profiles, can predict prognosis and treatment outcomes, disease natural history, response to treatments and the need for surgery. Understanding the implications of these markers for IBD will enable identification of disease subtypes most likely to benefit from new drugs, and prevent patients from receiving strong medications from which they are unlikely to benefit.
Robert Barrett, PhD, and his laboratory team are using human intestinal organoid technology to learn more about the mechanisms underpinning inflammatory bowel disease (IBD). The current research focus of the Barrett Lab is developing a personalized model of intestinal fibrosis, which is a common and potentially serious complication of IBD. This fibrosis model involves directing induced pluripotent stem cells (iPSCs), generated from affected IBD patients, to form human intestinal organoids and subsequently determine their responses to cytokines associated with this complication. Small, microengineered chip technology will be used to examine how microbes and cell-cell interactions play a role in this process.
David Casero, PhD, develops and applies computational methods for the analyses of high-throughput, multi-omics data. His laboratory aims to bridge the gap between traditional approaches where one type of omics data provides a snapshot into potential disease biomarkers, and current multi-omics efforts that can provide information into the actual drivers of disease. The Casero Lab is particularly interested in the establishment and maintenance of normal tissue homeostasis, supported by molecular interactions between members of the tissue microenvironment (e.g., epithelial, mesenchymal and immune cells) and additional factors (e.g., signals from microbial cells). A proper understanding of these interactions is instrumental to gain insights into the etiology of some complex diseases like IBD and cancer.
Rivkah Gonsky, PhD, and her team are involved in research to move upward advancement from laboratory studies toward integration to clinical applications in prognostics and therapeutics. Their projects are two-pronged based on first identifying the biology and unique molecular pathways mediating severe disease and then applying this knowledge to develop biomarkers for diagnostics, therapeutic drug repurposing and new drug development. These studies have led to the identification of genetic and molecular properties of RNASET2, which holds promise for the development of a unique and durable IBD therapeutic.
Under the leadership of Janine Bilsborough, PhD, this unit is dedicated to advancing the development of new therapeutic treatments identified by researchers within the IBD Institute. By employing both in vivo and in vitro models for target validation, along with clinical metadata including genetic information, this group facilitates the development of personalized medicine approaches for IBD treatment. The goal of the unit is to help accelerate the application of fundamental scientific discoveries to create new, precisely targeted treatments for individuals suffering from IBD.
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Inflammatory Bowel & Immunobiology Research Institute
110 George Burns Road.
Davis Building, Suite D4063
Los Angeles CA 90048