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A Visit with Marcel van den Brink

Meet Marcel van den Brink, MD, PhD, whose research includes optimizing gut microbiota — the bacteria, or flora, that live in the gut — to improve outcomes following BMT. He also develops cell therapies to strengthen the immune system after transplant. While primarily focused on BMT, Dr. van den Brink’s work holds potential against many diseases.

Why is the microbiota significant in BMT?

The human microbiota consists of microorganisms, or bacteria, that live in or on our body. Our microbiota is called the “forgotten organ” because it impacts so many aspects of our physiology. It can make the immune system weaker or stronger. Our lab has studied the intestinal microbiota of mice and people undergoing allogeneic BMTs, and we’ve found that gut flora rapidly changes during a transplant.

Do patients’ gut bacteria impact their outcomes?

We are gathering a large collection of stool samples from allogeneic BMT patients around the world and using next generation sequencing to determine their flora composition. In early studies, we found that patients with more diverse gut flora after the procedure generally have better outcomes, and are less likely to develop graft-versus-host disease (GVHD). We have confirmed this result using samples from transplant centers from other countries.

How can you help patients maintain diverse flora after BMT

Antibiotics fight infection following BMT, but they can also disrupt the intestinal microbiota. With the help of DNA sequencing technologies, we’ve learned that patients with even a small amount of a bacteria called Blautia in the gastrointestinal track have a lower chance of developing GVHD. So we’ve begun to choose antibiotics less likely to kill Blautia. We are investigating the possibility of patients storing their own microbiota before they begin treatment, so they can get the healthy flora back when they need it.

What are your next steps?

My collaborator, Dr. Eric Pamer, Director of MSK’s Lucille Castori Center for Microbes, Inflammation, and Cancer, and I are composing an optimal flora ecology to fight or even prevent many adverse reactions to BMT. Once we build this, we can figure out how to help patients through fecal transplant, medication, and diet.

What other types of research are you conducting to improve patient outcomes after BMT?

My lab is investigating ways to stimulate the thymus gland to generate more effective infection and cancer-fighting T cells. We’ve identified growth factors that can achieve this. For instance, we ran a clinical trial in which patients received a weekly injection of recombinant interleukin-7 (IL7) after BMT — and found increased immune cell recovery (see patient story). I also work with Dr. Michel Sadelain, Director of MSK’s Center for Cell Engineering. He developed an immunotherapy called CAR T, which engineers a person’s own immune cells to kill cancer. Together, we are creating a bank of “off-the-shelf” CAR T cells to strengthen the immune systems of people with BMT and many different diseases.

What are you most proud of in your work?

I now measure my success by how well the people do who come out of my lab. It is one of my greatest joys, and my young colleagues are amazing. I might not cure cancer, but maybe they will.