CROHN'S RESEARCH SPOTLIGHT
Propel a Cure is pleased to be featuring these international Crohn's disease research teams.
UNIVERSITY OF CALIFORNIA, SAN DIEGO
Dr. Pradipta Ghosh is a clinician scientist and professor in the Department of Medicine and Cellular and Molecular Medicine at the University of California, San Diego. She is also the Director of the Institute for Network Medicine as well as the Executive Director and Co-founder of the HUMANOID Center of Research Excellence.
Dr. Ghosh is inspired by transdisciplinary ideas and seeks to understand the fundamental rules of biological communication and networking with the goal “to design drugs that can fix the broken machines in diverse diseases.” Most systems, such as our bodies or our cells, appear diverse, complex, and heterogeneous. However, there are fundamental unifying principles operating and abiding by the same laws of nature. Combining novel mathematical tools, computational algorithms and multi-omic approaches to view networks inside cells, Dr. Ghosh and colleagues have been able to identify disease patterns, high-value biomarkers and drug targets for diseases that have no cure.
Any tissue with stem cells can be grown as an organoid. HUMANOID™’s approach allows researchers to isolate, expand, and biobank 3D organoids from healthy and diseased human tissues to study organ physiology and human disease; microbes, immune cells, or non-immune support cells can also be incorporated into a model. This technology is also being introduced into clinical trials as part of a “Phase 0”, which can help gauge the efficacy and toxicity of potential drugs before testing them on human patients. HUMANOID™’s organoids can also replicate critical aspects of human disease and facilitate personalized medicine by testing existing drugs or multi-drug cocktails to help individual patients.
UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL
Dr. Ryan Balfour Sartor is a board-certified gastroenterologist with expertise in managing difficult-to-treat patients with inflammatory bowel diseases (IBD) and a mucosal immunologist/microbiologist with a long-term interest in understanding mechanisms by which resident microbiota induce chronic intestinal inflammation vs. mucosal homeostasis. His research develops and studies rodent models of chronic, immune-mediated intestinal inflammation relevant to IBD and performs clinically relevant translational studies involving IBD patients.
He has explored the functional consequences of microbial communities in selectively colonized gnotobiotic mice and following fecal transplants using murine or human donors. In addition, he investigates host genetically-determined immune responses to luminal resident microbial components using gnotobiotic mice and patient-derived samples, and studies the influence of environmental factors on intestinal microbiota composition and function.
The effect of diet on bacterial metabolic function/bacterial interaction are recent areas of interest. Parallel translational studies in IBD patients explore microbial biomarkers that identify risk of recurrence after Crohn’s disease surgery and onset of pouchitis after colectomy for ulcerative colitis.
HARVARD MEDICAL SCHOOL, BOSTON
Dr. Kate Jeffrey is Executive Director of Immunology and Epigenetices at Moderna and has recently taken a leave of absence from several other positions. These include Associate Professor of Medicine at Harvard Medical School, Principal Investigator in Immunology at Massachusetts General Hospital,Faculty of Harvard immunology and Virology, and Associate member of the Broad Institute of MIT and Harvard.
Dr. Jeffrey’s research focuses on the epigenomic regulation of innate immunity in health and disease. Her work established inhibitors of epigenetic enzymes as anti-inflammatory agents and she recently was the first to describe a loss of an epigenetic enzyme called SP 140 in patients with IBD, as well as with MS. More recently, Dr. Jeffrey has turned her focus on the virome, e.g., viruses that live in the gut, seeking to understand how our intestinal virome influences host innate immunity.
This is an area of study that has, up until recently, not garnered the same attention as gut bacteria, but appears to play a central role in Crohn’s disease. With her findings, Dr. Jeffrey hopes to create personalized, virome-focused therapies that may reduce, reverse or prevent Inflammatory Bowel Disease development through targeted elimination or replacement of disease or health-driving intestinal viruses.
Her findings are very exciting and hold enormous promise!
McGILL UNIVERSITY, MONTREAL, CANADA
Dr. Marcel Behr is an elected fellow at the American Academy of Microbiology, a physician/scientist and also a full professor at McGill University in the Department of Medicine, as well as an associate member in the departments of Epidemiology, Biostatistics, Microbiology, and Immunology. He is the founding director of the McGill University’s International TB Centre and was recently named director of McGill’s Interdisciplinary Initiative in Infection and Immunity.
Dr. Behr’s research focuses on both Mycobacterium Tuberculosis (TB) and Mycobacterium Avium, studying the tuberculosis bacterial genome and the genomic composition of Mycobacterium Avium to understand their pathogenesis (how it causes infection and how infection progresses to disease) and epidemiology of disease (how it spreads among people), and developing better diagnostic tools. In addition, he is studying the role of host pattern recognition receptors, especially NOD2 during infection. He believes that Crohn’s disease shares many similarities with other mycobacteria and sees an association with certain genetic mutations, such as NOD2 that are implicated in both Crohn’s disease and mycobacterial infections.
Research Goal: Dr. Marcel Behr’s research focuses primarily on mycobacteria and its etiological role in human disease. He believes that mycobacterium avium paratuberculosis, which causes Johne's disease in many animals, may play a role in the etiology of Crohn’s disease.
UNIVERSITY HOSPITALS, LEUVEN, BELGIUM
Bram Verstockt MD, PhD, is a gastroenterologist, holding positions as a clinician and researcher in both the Department of Gastroenterology and Hepatology and the Department of Chronic Diseases and Metabolism | KU Leuven at the University Hospitals Leuven, Belgium. He is interested in translational research focusing primarily on the development of predictive and prognostic markers for a more personalized medicine in IBD, as well as on unravelling IBD disease heterogeneity and perianal disease through multi-omics approaches. Additionally, Dr. Verstockt does clinical research on monitoring tools (including intestinal ultrasound), real-life IBD data (including therapeutic drug monitoring) and is involved in various international studies. In addition, he serves as a reviewer for multiple reviewers including The Lancet, Nature Reviews Gastroenterology and Hepatology, Gut, Gastroenterology, Lancet Gastroenterology and Hepatology, Annals of Internal Medicine, American Journal of Gastroenterology.
Research Goal: To determine predictive biomarkers in disease evolution, including disease heterogeneity and response to treatments.
FEINSTEIN INSTITUTES, NEW YORK
Dr. Kevin Tracey, a neurosurgeon by training and CEO of the Feinstein Institutes in New York, along with his colleagues, discovered the direct inflammatory activity of tumor necrosis factor-alpha (TNF), which eventually led to the development of medicines such as Remicade and Humira.
More recently, Dr. Tracey and his lab have been pioneers in the development of devices utilizing bioelectronic medicine, with a particular focus on the role of the vagus nerve in sending signals to the immune system. This work has huge potential to offer safe, life-changing solutions for those suffering from Crohn’s disease, ulcerative colitis, and other inflammatory and autoimmune diseases.
Research Goal: The team is seeking to more fully understand and continue to develop bioelectronic medicine for use in treating Crohn's disease and other chronic conditions.
INSERM INSTITUTE, PARIS
Dr. Benoit Chassaing earned his PhD in microbiology at the University of Clermont-Ferrand (France), focusing on the possible role of adherent-invasive E. coli (AIEC) in the etiology of Crohn's disease. He also spent time at Georgia State University prior to his current position leading the Chassaing Lab at INSERM in Paris, which specializes in studying the impact of the environment on our microbiota and has conducted groundbreaking research on the role of food additives in inflammation.
The Chassaing lab has previously reported that emulsifiers, highly used by the food industry, are able to detrimentally alter the intestinal microbiota, characterized by an increased ability to penetrate the normally protective mucus layer and increased pro-inflammatory potential. They demonstrated that consumption of emulsifying agents is sufficient to induce intestinal inflammation that will manifest as chronic colitis in genetically susceptible hosts.
Research Goal: Focusing on the mechanisms beyond such observations and understanding how dietary emulsifiers can directly impact the intestinal microbiota and characterize its members which are driving inflammation.
DARTMOUTH COLLEGE
Dr. Mark Sundrud was recently appointed a Principal Investigator, at Dartmouth-Hitchcock Medical Center as well as Professor, in the Departments of Medicine, Microbiology & Immunology, Geisel School of Medicine at Dartmouth College, in Hanover, New Hampshire.
Previously, Dr. Sundrud was at the University of Florida’s Scripps Institute of Biomedical Research. While there, his team found that certain immune cells in the small intestine have evolved a molecular sensing mechanism to protect themselves from the toxic effects of high bile acid concentrations in the small intestine.
Bile acids are made in the liver and released during a meal to help with digestion and absorption of fats and fat-soluble vitamins. Bile is chemically similar to detergent and too much can lead to inflammation and potentially injure the intestinal lining.
The research team has discovered that a type of circulating immune system cell called a T helper cell 17, or TH17, can play an important role in digestion. When those circulating cells reach the end part of the small intestine, if they encounter too much bile, they adapt by switching on production of a gene called MDR1. They found that if the MDR1 gene is not present in those circulating immune cells or is mutated in a way that makes it ineffective, bile acids can accumulate in the ilium and injure the intestine.
In his latest study, Dr. Sundrud uncovered the mechanism that T-cells use to sense and respond to bile acids in the small intestine to increase MDR1 activity. According to Sundrud, about 10 percent of patients with Crohn’s disease have disease that is driven by bile reabsorption issues, and he is hoping to attract funding to continue this important work.
Research Goal: To continue the work validating the behaviors of MDR1 deficient CD4+T cells in Crohn’s disease patients and the therapeutic potential of bile acid sequestrants.
MICHAEL G. DEGROOTE INSTITUTE
Propel a Cure is pleased and excited to introduce Dr. Brian Coombes, Professor and Chair of Biochemistry & Biomedical Sciences at the esteemed Michael G. DeGroote Institute for Infectious Disease Research (IIDR) at McMaster University. Scientists in Dr. Coombes' lab are conducting basic research to understand the microbes that drive chronic inflammation during Crohn's disease, with a focus on adherent-invasive E. coli.
The innate immune system is a host’s first line of defense against foreign invaders, but pathogens like AIEC use sophisticated strategies to overcome the innate immune system in order to colonize, establish a host niche, and transmit to new hosts. Dr. Coombes' lab has embarked on a line of research to understand the components of the innate immune system involved in protection against enteric pathogens such as Salmonella, pathogenic E. coli, and bacteria associated with Crohn’s disease.
Research Goal: Identifying and understanding microbes driving chronic inflammation leading to Crohn's disease, with a focus on adherent-invasive E. coli and the immune system.
STANFORD UNIVERSITY
Propel a Cure is especially excited to be supporting the eminent immunologist, Dr. Mark Davis and his team in the Davis Lab at Stanford University.
Research Goal: Identification of circulating and tissue-resident CD4+ T cells specific for disease-driving antigens in Crohn’s disease
Propel a Cure has prioritized the funding of a study that would lead to the identification of circulating and tissue-resident CD4+ T cells specific for disease-driving antigens in Crohn’s disease. T cells are a type of white blood cell that appear to have a major role in the body’s overactive inflammatory response that is seen in Crohn’s.
If you would like to contribute or find out more about this study, please contact propelacure@gmail.com.
STANFORD UNIVERSITY
Propel a Cure is especially excited to be supporting the eminent immunologist, Dr. Mark Davis and his team in the Davis Lab at Stanford University.
Research Goal: Identification of circulating and tissue-resident CD4+ T cells specific for disease-driving antigens in Crohn’s disease
Propel a Cure has prioritized the funding of a study that would lead to the identification of circulating and tissue-resident CD4+ T cells specific for disease-driving antigens in Crohn’s disease. T cells are a type of white blood cell that appear to have a major role in the body’s overactive inflammatory response that is seen in Crohn’s.
STANFORD UNIVERSITY
Propel a Cure is especially excited to be supporting the eminent immunologist, Dr. Mark Davis and his team in the Davis Lab at Stanford University.
Research Goal: Identification of circulating and tissue-resident CD4+ T cells specific for disease-driving antigens in Crohn’s disease
Propel a Cure has prioritized the funding of a study that would lead to the identification of circulating and tissue-resident CD4+ T cells specific for disease-driving antigens in Crohn’s disease. T cells are a type of white blood cell that appear to have a major role in the body’s overactive inflammatory response that is seen in Crohn’s.
If you would like to contribute or find out more about this study, please contact propelacure@gmail.com.
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
Dr. Dolinger is an advanced pediatric IBD fellow at the Icahn School of Medicine at Mount Sinai in New York City. Dr. Dolinger’s research focuses primarily on the use of intestinal ultrasound as a novel, non-invasive tool to monitor inflammatory bowel disease activity and treatment response in order to improve outcomes and enhance shared understanding. Dr. Dolinger leads the Henry and Elaine Kaufman intestinal ultrasound program at the Susan and Leonard Feinstein Inflammatory Bowel Disease Center, the first of its kind in the United States.