Planting a seed; Watching it grow

A conversation with HSCI Seed Grant recipient Benjamin Humphreys, MD, PhD

In the spring of 2007, Benjamin Humphreys, MD, PhD, a young postdoctoral fellow at Brigham and Women’s Hospital (BWH), received the good news that he was the recipient of a highly competitive Harvard Stem Cell Institute Seed Grant. HSCI’s Seed Grants provide two years of funding totaling $180,000 to researchers—often junior faculty—tackling promising early-stage projects that, because they are considered high risk, are often difficult to get funding for.

Today, Humphreys runs his own laboratory at BWH, is a principal faculty member of HSCI, and as of early 2010, is co-leading the HSCI Kidney Program with his frequent collaborator, Andrew McMahon, PhD. As a clinician-scientist, Humphreys also cares for cancer patients with kidney disease at Dana-Farber Cancer Institute.

In this conversation, Humphreys talks about the significant, positive impact that the Seed Grant funding and his involvement in HSCI has had on his research and his career.

SCL: How did you first become involved in HSCI, and what prompted you to apply for a Seed Grant?

BH: My mentor, Joe Bonventre [MD, PhD, chief of the Renal Division at BWH], was head of the HSCI Kidney Program, so I was introduced to HSCI through him. I also used to go to HSCI’s inter-lab meetings, where postdocs and junior faculty would present their work, and from those I began to appreciate the collaborative nature of HSCI. My impression was that HSCI was a group of top-flight scientists who were asking big questions, and believed that the best way to find answers to them is through collaboration. That’s the kind of science I like to do.

I applied for the Seed Grant not only for the funding, important though that is, especially when you’re just starting to become independent. I also wanted to be part of the HSCI community—scientists with expertise in other diseases and disciplines and great ideas that I could collaborate with.

SCL:What were the questions your Seed Grant-funded project was asking, and what did you learn?

BH: Kidneys have a powerful ability to repair themselves. A patient can have his kidneys entirely shut down to the point where he needs to be on dialysis, and within a few weeks, his kidneys can improve and function just fine.

The main question my project [“Epithelial Cell Lineage Analysis During Renal Repair”] asked was, how do kidneys repair themselves following acute injury? If you can understand at the molecular and cellular level how kidneys self-repair, then you can design therapies to expedite the repair if it’s happening too slowly or, if it’s maladaptive as in the case of a condition called kidney fibrosis, to block it.

Four years ago, when I applied for the grant, there were a number of different theories about the mechanisms of kidney repair. Several hypothesized that local or migrating stem cells were responsible for repairing the damaged epithelial cells of the nephrons, the functional units of the kidney that filter the blood.

Through our HSCI-funded project, we found that it was not stem cells but rather the epithelial cells themselves that repair injured kidneys. Further, we found that all kidney epithelial cells can do this. As long as the epithelial cells survive the initial insult, they can re-enter the cell cycle and divide to create daughter cells that replace the cells that were destroyed.

SCL:What is your lab focusing on now?

BH: A large part of my lab’s work now is a direct outgrowth out the Seed Grant project. We’re seeking to discover the signals that tell epithelial cells that damage has occurred and to start dividing so we could manipulate that pathway for therapeutic purposes. We’re taking several complementary approaches to this work, believing this will get us to our goal of new therapies faster.

SCL: If you hadn’t received the HSCI Seed Grant, what would have been your other options?

BH: My project was very ambitious and I had a limited track record so, frankly, I don’t think I would have been able to get funding from traditional sources like the National Institutes of Health. Most likely, I wouldn’t have been able to establish and grow my lab, develop important skills that have since enabled me to obtain additional funding, or to carry on this research. The Seed Grant has made a tremendous difference in my career trajectory not only by funding important science, but also by fostering collaborations that have sped up the pace of discovery.

SCL: HSCI’s emphasis on collaboration among scientists was a real draw for you.What are some examples of how collaboration with other HSCI faculty has enhanced your work?

BH: There are so many! One that stands out is my collaboration with David Breault, [MD, PhD], of Children’s Hospital Boston. I’d heard David give a talk four years ago, and thought, ‘Wow, I need to talk to this guy,’ but I never found the time. I saw him present again at an HSCI Retreat, and this time I introduced myself.

We started a collaboration and ended up writing a grant together that resulted in two shared grants—one from the National Kidney Foundation and another from Genzyme. Along with four other HSCI investigators from various institutions, we recently received an HSCI Junior Faculty Program grant, called Tissue Regeneration and Repair, which David and I will co-lead. None of this would have been possible if HSCI hadn’t brought us in the room together.

My collaboration with Andy McMahon [PhD, program leader of HSCI’s Genome Modification Facility] is another great example. His background and expertise were extremely helpful to me for the techniques I used to understand kidney repair, as was the expertise of his colleague, Akio Kobayashi [PhD], who is now in the BWH Renal Division. Our collaborations continue. For example, Andy and I are coleading the HSCI Kidney Program and are the co-investigators of a federal RO1 grant, which we received in May.

By my calculations, every dollar I received in HSCI Seed Grant funding has generated 2.6 dollars in additional grant funding, all for collaborative projects.

SCL: You’ve participated in the HSCI Internship Program for three consecutive years, and even recently hired your 2009 intern to work in your lab following his graduation in May.Why do you participate in this program?

BH: After graduation from college, where I majored in English, I got a job as a lab tech in a clinician-scientist’s lab in Boston. This sparked a flame of curiosity in me that led to my decision to pursue an MD/PhD, so I know how an experience like this can transform lives.

I find it very rewarding to see my interns’ progress through the summer of their internship and beyond. My first two interns, Wendy Ying and Teresa Wang, just told me they got accepted to medical school, which is very exciting. And my 2009 intern, Rado [Penchev], is so talented, hardworking, and enthusiastic that I was thrilled when he accepted my offer to join our lab full-time as a technician.

SCL:What other HSCI resources have you taken advantage of?

BH: Just about all of them, from the informal ‘Chalk Talks’ where PIs present their work using just a marker and white board, to the annual HSCI Retreat, to the think tanks. The Core Facilities, specifically the Genome Modification Facility and the Flow Cytometry Core at Joslin Diabetes Center, have been critically important to my research. Having this highly specialized technology and expertise readily available—and affordable—absolutely expedites the pace of my research.

SCL: As new co-leader of the Kidney Program, what are your goals?

BH: Andy [McMahon, PhD, Kidney Program co-leader] and I recently held a think tank attended by PIs from throughout HSCI-affiliated institutions, during which we discussed bottlenecks to therapy and developed a list of innovative ways to approach the problem. In the near future, we plan to identify the priorities that will guide our work in the months and years to come, with the ultimate goal of finding new treatments for patients suffering from kidney disease.