Three University of Michigan investigators have been acknowledged by the National Institutes of Health’s prestigious High-Risk, High-Reward Research program.

Sundeep Kalantry, professor of human genetics, has received the NIH Director’s Transformative Research Award, which promotes cross-cutting, interdisciplinary approaches and supports individuals and teams of investigators who propose research that could potentially create new, or challenge existing, paradigms.

Changyang Linghu, assistant professor of cell and developmental biology, and Longhua Guo, assistant professor of molecular and integrative physiology, have received the NIH Director’s New Innovator Award, which supports unusually innovative research from early career investigators who are within 10 years of their final degree or clinical residency and have not yet received an NIH R01 or equivalent grant.

“The HRHR program champions exceptionally bold and innovative science that pushes the boundaries of biomedical and behavioral research. The groundbreaking science pursued by these researchers is poised to have a broad impact on human health,” said Tara Schwetz, deputy director for Program Coordination, Planning, and Strategic Initiatives at the National Institutes of Health.

The High-Risk, High-Reward Research program supports investigators at each career stage who propose innovative research that, due to its inherent risk, may struggle in the traditional NIH peer-review process.

Kalantry’s lab works in the broad area of chromosome biology and seeks to understand how females with two X chromosomes express X-linked genes at the same level as in males with a single X chromosome.

“The NIH Director’s Transformative Award lets us chase ideas that controvert accepted wisdom,” Kalantry said. “This award will help us define novel factors and mechanisms that equalize gene expression between the sexes. Understanding how the two sexes reach X chromosome gene expression equality not only reveals how female and male cells manage differences in their sex chromosomes but more generally informs how cells equalize gene expression despite differences in chromosome number, for example in disorders with aneuploidies.”

Linghu’s lab is broadly interested in the fundamental principles governing the activities and interactions in large networks of molecules and cells that drive brain computation, learning and memory, and aging. To tackle this question of “emergence” in neuroscience, his lab is developing and applying novel technologies that enable large-scale, multiplexed monitoring and interrogation of molecular and cellular physiological activities in the living brain.

“Technology and discovery are the yin and yang of science, where new technologies empower novel discoveries and new discoveries inspire innovative technologies,” said Linghu, who is also an affiliate faculty member at the Michigan Neuroscience Institute, Single Cell Spatial Analysis Program and Department of Biomedical Engineering.

“The NIH Director’s New Innovator Award will support our efforts to develop and apply radically innovative technologies to probe and decode cellular activities across the living brain and potentially facilitate new hypotheses, collaborations and discoveries in neuroscience.”

Guo’s lab aims to address the most cutting-edge questions in aging, regeneration and global rejuvenation in two long-lived organisms—the planarians, or Schmidtea mediterranea, and the leopard geckos, or Eublepharis macularius—using expertise from the fields of genetics, genomics, molecular, cellular and developmental biology.

“The whole world is getting older. To mitigate age-associated diseases has never been more important,” Guo said. “The NIH Director’s New Innovator Award will support us to study radically innovative ideas on aging, regeneration and rejuvenation in extremely long-lived models. I feel very fortunate that there is such a mechanism that funds high-risk projects and gives us the freedom to explore and to discover.”

These awards echo a similar commitment by the university to invest in high-risk science, said Steve Kunkel, chief scientific officer for Michigan Medicine and executive vice dean for research at the Medical School.

“NIH recognition for these investigators shines a spotlight on the pursuit of bold science here at U-M,” he said. “These awards, much like our Research Scouts funding program, support investigators who are taking on high-risk projects that have the potential to be transformative.”