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A Sit-Down With Leading Immunologist Stephan Targan, MD

Pioneering IBD Researcher and Clinician Shares Brief History of His Career and Evolution of the Field

Throughout a dedicated career, Stephan Targan, MD, has chiseled away at a condition once considered monolithic: inflammatory bowel disease (IBD). He and his colleagues have uncovered biomarkers that are used to better classify and treat patients, developed biologic drugs that have revolutionized patient care, and pioneered a multisystem approach to IBD.

Targan, who holds the Feintech Family Chair in Inflammatory Bowel Disease and is director of the F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, was recently named by Research.com as one of the best immunology scientists, in recognition of his authorship of over 500 publications in the immunology field alone.

Cedars-Science spoke with Targan about how his work has advanced the field of immunology and the next frontiers in IBD research.

How did you become interested in the field of immunology?

I published my first paper as a high school student working in a gastroenterology lab at UCLA in the 1960s. After medical school, I was particularly interested in IBD because, throughout my internship and residency, nothing was known about the disease. I pursued a combination GI and immunology fellowship when not many people were doing that.

Early on, while I was still in my fellowship, I got my own lab looking into the intestinal mucosa and elucidating molecular mechanisms of natural-killer T-cells, which control inflammation and regulate the microbiome in the gut. As I got more and more into this work, I was also working as an attending physician. You always hear about “bench to bedside,” but it works the other way around, too. IBD is very complex, and through observing patients, I knew we had to crack a very complex disease that was not yet understood.

What is the history of the Cedars-Sinai approach to IBD?

I got lucky at a young age, and in 1989 I was the first clinician-scientist to be selected as chair of the Crohn’s and Colitis Foundation of America National Scientific Advisory Committee. A group of us met for a summit in Palm Springs to put together a roadmap for a new multidisciplinary approach that changed everything and was embraced by the National Institutes of Health (NIH) and pharmaceutical companies. We documented the genetic heterogeneity of IBD: the many different expressions, the importance of the microbiome and genetics, and how we needed to develop precision medicine. We recognized we needed to study patient populations that shared similarities, including the molecular mechanism causing their disease.

In 1992, I came to Cedars-Sinai with NIH grants to build a multidisciplinary IBD center. We started a biobank of patient information and concentrated on genetic biomarker and biological function discovery, so we could categorize patients based on how we know they would respond to certain drugs. I love that our integrated science is being tried and taken up everywhere.

What is your role in the discovery of biologic drugs for IBD?

We were studying TNF, a protein involved in Crohn’s disease, and discovered an antibody that blocked TNF induction of proinflammatory modes. We put all the complex science together, using the biobank as the glue, and in 1996, we led the first trial of a biologic therapy to target TNF. This was the beginning of the biologic era in IBD.

Why is it so critical to develop partnerships in the pharmaceutical industry?

Most academics don’t know how to move their science toward the ultimate target: a drug to go into a patient. That has always been my goal, but it takes a different talent to run a startup. I started a drug discovery and development unit to bring scientists from industry into academic research; that bridge was necessary. When I gathered the right really smart, talented people, led by Janine Bilsborough and including leading geneticist Dermot McGovern, everything fell together. We were able to develop a molecule that directly affected scarring in ulcerative colitis and Crohn’s and is highly concentrated in the gut mucus. Because we had the biobank, we had a drug that was shown to be successful, and we had a pipeline to discover more drug targets. It was just a vision, and now it’s a reality, and it’s only going to expand the field for all autoimmune conditions.

What remains to be known about IBD?

Today, our biggest work focuses on treatment durability and understanding why some people stop responding to a drug they’ve been successfully treated with for years. It’s not just their genetics or because their body developed antibodies, but rather because of another mechanism we don’t yet recognize. We’re now focused on developing IBD scores and treatment “menus” to deal with dominant disease pathways.

Additionally, we need to understand why some people develop IBD after certain environment exposures, including stressful events. We’re just starting, and I’m not young anymore, but I very much want to see this lane open up.

What is your most important contribution to the field of immunology?

So many brilliant, high-quality clinical scientists who have trained at Cedars-Sinai have moved on to do amazing things in industry or to lead major programs and organizations around the world. The number one thing I’ll look back on in my career is the pleasure I’ve had in mentoring physicians and scientists.