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The Journey from Innovator to Pioneer

Dr. Gwendalyn Randolph, a long-time researcher of lymphatics and cellular transport, and more recently Inflammatory Bowel Disease (IBD), was awarded the prestigious National Institutes of Health (NIH) Director’s 2015 Pioneer Award. She credits the Kenneth Rainin Foundation’s early-stage grantmaking with helping her get to this critical milestone.

We recently spoke with Dr. Randolph to congratulate her on this momentous achievement and learn more about her journey into IBD research.  Here is a recap of that conversation.

Early Funding Seeds Collaboration

In 2011, the Rainin Foundation awarded Dr. Randolph a $100,000 Innovator Award to explore the interface between adipose antigen-presenting cells, lymphatics, and the expansion of adipose tissue in IBD.  This funding was an opportunity for Dr. Randolph to take her basic science knowledge of lymphatics and apply it to human disease in collaboration with a highly supportive team of clinical collaborators led by Dr. Jean-Frederic Colombel at Mount Sinai.  “Technically and conceptually everything about the project was new,” reflected Dr. Randolph.  Despite this challenge, the Randolph lab moved the project forward quickly, and received two more years of funding from the Rainin Foundation.

It was during this time, that Dr. Randolph said, the real progress was made.  Her lab overcame the decades-old difficulty of imaging lymphatics in the gut by developing a novel methodology using 3-D confocal microscopy.  The technique has allowed her team to peer more deeply and broadly into human intestinal tissue than ever before, an approach that will undoubtedly aid in understanding the pathophysiology of IBD.

GwenRandolph_3dImaging

Confocal microscopy image of blood vessels (green) and lymphatic vessels (red) in the mesentery of a Crohn’s disease patient (Courtesy of Dr. Randolph).

 

After three years of funding from the Foundation, Dr. Randolph and her team had sufficient data to apply for and be awarded the NIH Director’s Pioneer Award. The NIH’s funding will support the next stage of her research conducting patient-based studies to explore how blood vessel remodeling and lymphatic vasculature changes contribute to IBD pathogenesis.  She hopes this project will stretch minds in the field away from thinking that all the answers lie in examining the microbiome and the immune response. “We hope to get specific in explaining how key, distinctive features of diseases like Crohn’s emerge, and we hypothesize that vascular changes are pivotal,” said Dr. Randolph. With this approach, she hopes to identify links between IBD and fibrosis, which may result in patients requiring surgical intervention.

Creating Space for Researchers to Fail

The way the Rainin Foundation views risk seems to be out of the norm in the field of philanthropy.  We invest in high-risk research knowing there will be failures, but also projects that could potentially lead to big gains.

From the outside, Dr. Randolph may not seem like a person who knows much about failure, but in fact she does, and she believes failures have been vital to her success as a scientist. “It’s so out-of-the-box that the Rainin Foundation would consider our first application because I had done nothing to prove I wouldn’t fail. I didn’t have the credentials and preliminary data related to my proposal that is so often needed for any grant, including those presumably not requiring preliminary data. Even just doing translational science is asking people to face potential failure,” said Dr. Randolph. It is through this lens that she has sought to understand IBD, not simply seeking to prove her hypotheses correct, but to make real progress towards understanding the mechanisms underlying the disease and following the science where it leads.

More broadly, scientific failures in the form of negative data, most often go unpublished and unrewarded.  “I think it is hugely problematic that we often feel that we cannot talk about failure. It can feel like you have to work hard to hide failure, so failed data doesn’t get out. I think that atmosphere leads investigators to do ’safer‘ research that will yield a lot of data, even if the data-yielding approaches are less relevant to disease,’’ said Dr. Randolph.  The more the Rainin Foundation can provide innovative researchers like Dr. Randolph with space to fail, the greater our chances of finding a cure for IBD.

Bridging Scientific Disciplines

Randolph figure

Inflammatory bowel disease bridges scientific disciplines.

As an outsider to the field of IBD research, Dr. Randolph sees great potential for the integration of numerous scientific disciplines into the study of IBD. Her work shows, for instance, that vascular biologists can provide valuable insights into specific mechanisms that lead to IBD pathology.  This raises the question, what can other disciplines contribute to our understanding of IBD?

The Rainin Foundation is honored to have been a part of Dr. Randolph’s journey into IBD research. Her trajectory exemplifies how novel ideas coupled with early funding can lead to real advancement in understanding IBD. We are eager to see the outcomes of her patient studies.

Congratulations, Dr. Randolph!

 

Top Photo: Dr. Randolph at her confocal microscope, which is used by her lab to follow specific changes in vascular and lymphatic integrity that may promote disease.


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