Seeding innovation, independence, and success

Every spring, approximately 10 investigators at HSCI-affiliated institutions receive the exciting news that they have received an HSCI seed grant, which provides two years of funding, totaling $180,000, for researchers engaged in diverse areas of stem cell research aligned with HSCI’s mission.

The Seed Grant Program, which in the past six years has awarded more than $11 million to 63 recipients, is very competitive. Every year, recipients are selected by a multi-institutional committee of HSCI faculty members from a pool that typically consists of 50-60 highly qualified candidates. While the grants are frequently awarded to early career scientists, any investigator, no matter how experienced, may be considered if he or she is exploring a new avenue of research related to stem cells.

What makes HSCI seed grants so valuable to recipients is that they fund projects that are difficult, if not impossible, to fund from other sources because they are high risk, are early stage, or lack sufficient preliminary data. In fact, sometimes they are all three.

With this funding and access to HSCI’s extensive resources and assistance, many HSCI seed grant recipients have been able to acquire the data and experience necessary to compete subsequently for major grants from the National Institutes of Health, disease foundations, and industry. “According to a recent internal survey we conducted, seed grant recipients received on average three times our initial investment in subsequent funding,” said HSCI Executive Director Brock Reeve. “By any standard, that’s a very high return on investment.”

‘Broad ideas’

One case in point is Paul Yu, MD, PhD, of Massachusetts General Hospital. Yu was awarded a 2009 seed grant for his project aimed at identifying bone-forming progenitor cells in diseases characterized by the formation of pathologic bone, typically within skeletal muscle and connective tissues and often in response to injury. In addition to contributing to a greater understanding of these incurable, life-limiting diseases — the first step toward treatment — Yu’s research seeks to find out how this maladaptive repair response might ultimately be exploited for regenerative purposes to engineer bone for individuals in whom bone is lost due to injury or disease.

Based on the findings from his seed-grant funded work, Yu was recently awarded a highly competitive federal RO1 grant, which typically provides from $100,000 to $250,000 a year for up to four or five years, to continue his research in this area. “What makes the HSCI seed grants so valuable is that they fund broad ideas that may not have all the preliminary data,” said Yu. “I’m very fortunate to have received this support, as my seed grant enabled me to generate the data required to compete successfully for the RO1, which will allow me to continue this research.”

‘Truly invaluable’

Seed grant recipient Caroline Burns, PhD, also of Massachusetts General Hospital, has submitted applications for three federal grants based on the work initiated through her HSCI seed grant. Burns has received positive scores on her submissions and expects to learn in the coming months that some, or perhaps all, have been awarded. Her 2008 seed grant-funded research was focused on understanding the mechanisms by which adult zebrafish regenerate their heart muscle — a process that might conceivably be activated in people whose hearts have been damaged by heart attacks.

“My seed grant was truly invaluable on two levels,” said Burns. “First, it allowed me to switch my research focus and go off in a different, exciting new direction [cardiac regeneration]. It also enabled me to acquire sufficient data to apply for federal funding, which simply would not have been possible otherwise.”

Thanks to her 2008 seed grant, Massachusetts General Hospital neuroscientist Paola Arlotta, PhD, was able to create cells that resemble corticospinal motor neurons (CSMNs) from neural progenitor cells. Creating CSMNs for drug screening is of keen interest to Arlotta and many other scientists because they are one of two neuronal cell types that die in amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease) and are the cells that are permanently damaged in spinal cord injury.

‘A real confidence builder’

“With the seed grant funding, I was able to acquire the data that enabled me to get an RO1 grant plus a continuation of funding from a disease foundation,” said Arlotta. Her findings were also recently published in Nature Neuroscience — exposure that Arlotta said gets her “off and running” in terms of getting additional support. As is the case with most other seed grant recipients, it is not only the money that Arlotta found so valuable. “Receiving an HSCI seed grant is important to junior faculty because it’s a real confidence builder at a time in your career when you need it,” she said.

Children’s Hospital Boston researcher William Pu, MD, used the funds from his 2008 seed grant to pursue research of epicardial cardiac progenitor cells and their potential role in contributing to the repair of heart muscle. “HSCI support came at a pivotal time when my start-up funding was winding down and my research program was picking up,” said Pu. His seed grant enabled him to obtain the data to get an RO1 grant, as well as gain additional support as a member of the Progenitor Cell Biology Consortium.

‘A jewel of the Boston research community’

“A real success story,” is how Stephen Haggarty, PhD, of Massachusetts General Hospital, describes his experience as a 2008 seed grant recipient. “This support was truly the seed that enabled me to get the preliminary data for federal funding consisting of both an R21 and R01 grant and to jump-start my ability to obtain additional private funding,” he said. Haggarty’s HSCI-supported research centered on creating induced pluripotent stem (iPS) cell models of the single-gene disorder Fragile X syndrome, the most common heritable form of intellectual disability, and elucidating a pathway that is implicated in its development as a potential target for treatment.

That work was a springboard for much of Haggarty’s current research, which is aimed at creating stem cell models of complex, multigenic neuropsychiatric disorders, such as bipolar disorder and schizophrenia. Here again, being able to create and study human neurons in a dish and follow their development and ability to form functional synapses opens up new avenues for understanding diseases and discovering treatments.

“HSCI’s Seed Grant Program is just one example of the institute’s inclusive and supportive model, which gives investigators like me access to state-of-the-art technologies and, more importantly, intellectual input from world-class stem cell scientists,” said Haggarty. “It is truly a jewel of the Boston research community.”