Two Yale researchers have been awarded the National Institutes of Health Director’s New Innovator Award — one of the most competitive grants for young scientists offered by the NIH.

Forrest Crawford, a Yale School of Public Health professor, and Shangqin Guo, a professor of cell biology at the Yale Stem Cell Center, were among 48 researchers nationwide to receive the award, which was announced on Oct. 4. The New Innovator Award is one of four grants under the NIH’s High-Risk, High-Reward Research Program, which provides funding for “exceptionally creative” scientists who produce innovative, high-impact research proposals, according to the NIH’s website.

“The New Innovator Award is designed to support early-career stage investigators who propose unusually bold projects,” said Ravi Basavappa, the leader of the High-Risk, High-Reward Research Program. “The expectations are that these investigators have unusual potential, because they have already established a track record and have been able to overcome substantial technical and conceptual hurdles in the past.”

Of all the NIH grants, the annual New Innovator Award has consistently seen one of the lowest success rates since it was first introduced in 2007. The NIH defines the success rate of a grant as the percentage of grant applications that receive funding.

According to Basavappa, the program typically sees around 500 to 600 applicants each year, while the number of final awardees varies depending on available funding.

Ten Yale faculty members have been awarded the New Innovator Award since it was created in 2007, but this is the first time that a faculty member for either the Yale School of Public Health or Yale Stem Cell Center has received the prestigious award.

Crawford, whose research focuses on solving mathematical and statistical problems in public health, epidemiology and biology, was granted the award for a project titled “Network-based epidemiology for hidden and hard-to-reach populations.”

Crawford said that vulnerable groups such as sex workers, men who have sex with men and people who inject drugs are often socially stigmatized or legally criminalized, so it can be difficult for researchers to collect health-related data through ordinary sampling methods. Researchers instead find study participants by asking subjects to recruit social contacts who also fit the study inclusion criteria, a technique known as respondent-driven sampling. But according to Crawford, while this social network-driven method helps researchers amass a large group of subjects, the interconnected nature of these subjects often prevents researchers using traditional statistical methods to draw accurate conclusions about health status and risk factors.

“Studies of vulnerable, hard-to-reach populations are incredibly important for public-health policymaking in the U.S. and internationally, but the way researchers currently analyze data from these studies may produce seriously mistaken inferences,” Crawford said. “Errors in estimates of disease or risk factor prevalence can hinder efforts to direct public-health resources where they are most needed.”

In his proposal, Crawford outlined a plan to develop new tools for researchers to better characterize and analyze the data obtained from respondent-driven sampling of hidden and hard-to-reach populations.

Yale School of Public Health Dean Paul Cleary praised Crawford’s proposed work for being “methodologically sophisticated and innovative,” as well as for having significant potential implications for public-health research and program development.

At the Yale Stem Cell Center, Guo works on elucidating the differentiation processes of cells. For her New Innovator Award project, Guo plans to tackle the question of why some cells are more prone to becoming malignant, or cancerous, than others, and how to identify and characterize the cancer cell-of-origin.

“The textbook has been saying cancer is caused by mutations,” Guo said. “On the surface level this seems right, but on a deeper level this cannot be the entire answer. If we can find the last clue, in theory we should be able to not only treat cancer that is already there, but also prevent normal cells from becoming cancerous.”

According to Guo, recent developments in cancer research have resulted in evidence that cannot be explained by any of the existing theories on cancer formation. This implies there must be an unidentified mechanism or property that causes cells to express mutations, she said. For her project, Guo introduced a new hypothesis: Accelerated cell cycles could be responsible for making certain cells particularly susceptible to becoming cancerous cells.

Yale Stem Cell Center Director Haifan Lin called Guo’s work “transformative,” commending her for proposing a unique approach to testing her hypothesis.

“Dr. Guo, to my knowledge, is the first person to systematically propose and explore this truly paradigm-shifting concept,” Lin said. “I think it could transform the entire field of cancer research — for all types of cancer — and influence other cancer-related fields like developmental biology and research on cell-fate determination, so the significance [of Guo’s research] truly is tremendous.”

According to Basavappa, the New Innovator Award recipients are invited to present their research ideas at an annual symposium for all awardees of the High-Risk, High-Reward Research Program.

This year, the symposium will be held Dec. 5–7 on the NIH Main Campus in Bethesda, Maryland.

Zainab Hamid contributed sourcing.