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Bedside to Bench: New Pathways for Understanding IBD

Dr. Aida Habtezion and Stanford make promising advances through technology and collaboration

Aida Habtezion Kenneth Rainin FoundationAs a clinician and researcher, Dr. Aida Habtezion has dedicated her years of medical expertise and Stanford University’s advanced technology to understanding and combating Inflammatory Bowel Disease (IBD). While the Habtezion Lab is uniquely focused in its scientific pursuit, Dr. Habtezion wants to ensure that the research maintains the perspective of those who struggle with the condition every day. She promotes the “bedside-to-bench” approach through an active registry the lab initiated. This registry connects scientists, clinicians and patients to share human data and foster communication across disciplines.

Dr. Habtezion embraces the opportunity to make a profound difference. Given the challenges of living with IBD, and the elusive search for effective treatment, let alone a cure, the team is passionate about their scientific mission. The Habtezion Lab is grappling with particularly heady questions in the IBD mystery: How do inflammatory cells get into the gut? What are the trafficking patterns? And what exactly are these molecules that create the cells perpetuating inflammation?

Creating More Human Connections

The lab’s most promising advances center on replicating how IBD manifests itself in patients. The lab is exploring why patients develop the disease in only certain areas of the bowel, and why some medications don’t work for particular individuals. They use a range of human samples and collaborate with clinicians and researchers from complementary fields. Enlisting Stanford’s mass cytometry (CyTOF) and recruiting and studying patients who have different types of IBD, the Habtezion Lab is attempting to understand the signals that might lead to various forms of the disease. In the process, they hope to learn whether the clinical manifestations mirror the differential molecular pathways and signals in the immune cells.

The Habtezion Lab received a welcome boost through the Kenneth Rainin Foundation’s collaborative Synergy Award. This award enabled the team to test an encouraging hypothesis that the microbiome has a direct influence on IBD. Patients with ulcerative colitis who have had surgery to remove the large intestine and create a pouch—or new rectum—from the small intestine, display a 46% higher risk of inflammation of the pouch or pouchitis compared to familial adenomatous polyposis (FAP) patients who also have a surgical pouch. Researching the host’s immune response, they have found important differences in the metabolomics between those that do and do not develop pouchitis.

In collaboration with her colleague, associate professor of microbiology and immunology Dr. Justin Sonnenburg, Dr. Habtezion and team, which includes Dr. Sidhartha Sinha, are examining the microbiota from which these metabolites originate. By taking the metabolites that are highly expressed in IBD patients, recreating them in a mouse model, and changing the metabolomics, the researchers can increase inflammation in the gut of the mouse. Similarly, by inhibiting some molecular pathways, inflammation is reduced. This could lead to exploration of disease pathogens and therapeutic targets. In addition, it could provide a better understanding of the communication between the microbial and the host’s immune response.

Leading the Way Through Team Science

In the same way that molecular pathways reveal new insights, Dr. Habtezion believes collaborative pathways are essential for delivering breakthroughs in IBD understanding and treatment. She’s particularly encouraged by new therapies coming through the pipeline, capable of providing significant patient relief during our lifetime. To facilitate the bedside-to-bench and bench-to-bedside approach, her lab together with Stanford clinical IBD director Dr. Sarah Streett has created a registry to connect scientists with clinicians working in this field. The hope is that the registry will provide access to more human samples and human data. And furthermore, that this kind of “team science” will draw expertise from diverse people, advance a more transformative type of research, and forge better communication across the IBD ecosystem.

Dr. Habtezion also encourages younger scientists to meet people in the field, learn from each other and expand their networks. Working in silos enables researchers to develop specializations. However, to understand the whole animal or patient system requires expertise in many areas. Dr. Habtezion is working on being more of an extrovert herself. Afterall, she knows the potential for scientific breakthrough could come through the next person you meet.

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