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Abreu Lab

Micky & Madeleine Arison Family Foundation Crohn's & Colitis Discovery Lab

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Investigator / Contact Person Maria Abreu

Research

Dr. Abreu research laboratory has shown that toll-like receptor 4 (TLR4) is upregulated in human colitis-associated cancer and some sporadic colon cancers. They demonstrated that TLR4 acts as an oncogene in the intestine and is required for colitis-associated cancer. We have subsequently described that TLR4 signaling activates β-catenin. These seminal observations highlight the intersection between innate immune signaling and tumorigenesis and offer opportunities for clinical intervention. On the translational research side, she first described that Crohn’s disease patients with Nod2 mutations have stricturing disease. This observation is the basis of prognostic testing in Crohn's disease. They have recently described that patients who are on anti-TNF therapy continue to have active disease because levels of anti-TNF in the tissue are insufficient to neutralize local TNF production. This finding offers a mechanistic explanation for anti-TNF failures in IBD.

They have also built a biorepository of specimens from our IBD patients. A great deal of thought has gone into the design of that biorepository. It starts with a very detailed questionnaire that patients and their physicians complete with respect to historical information about the patient. They then collect blood for DNA, RNA, and serum for studies in the future. In addition, patients who have provided their consent and if they are going to undergo any type of endoscopy procedure, we collect biopsies from those patients which are also stored in our biorepository facility. In its totality, Dr. Abreu’s team have approximately 2000 patients in our biobank and have well over 10,000 actual specimen samples in the biorepository. Already this biorepository has lead us to make very significant advances. As an example, they have used it to measure levels of some of the medications that we use resulting in a very important publication for the literature as it relates to optimizing medical therapy for inflammatory bowel disease patients.

Dr. Abreu Crohn’s and Colitis Center is committed to making discoveries into the causes of IBD. To that end, they have placed emphasis on genetics and the genetic-environmental interactions that occur in patients with IBD. One of the striking things that are occurring is the rising rate of inflammatory bowel disease in foreign-born and American-born Hispanic patients. They are witnessing a very rapid increase in the development of inflammatory bowel disease in these patients. They received an NIH Grant to continue the research and identifying whether there are unique genes that underpin inflammatory bowel disease in Hispanic patients. They have also done very careful diet-based studies to try and understand what changes in diet, especially in the immigrant population can most directly correlate with the development of inflammatory bowel disease.

In the basic sciences of IBD, Dr. Abreu’s laboratory collaborates very actively with other departments including Genetics, Biochemistry, and Immunology and Microbiology to make advances in the field. Team science is absolutely essential for us to move the field forward. They have become very interested in the microbial causes of inflammatory bowel disease and are digging deeply to see if we can identify bacteria that is uniquely associated with inflammatory bowel disease. Our hope is to identify populations of bacteria associated with IBD that can be used to direct therapy. They have an NIH grant to look at the development of colon cancer in patients that have ulcerative colitis. To that end, we are very interested in understanding what drives colonic stem cells and leads to the development of cancer. They believe that bacterial signaling may be essential in that process.