A researcher working on mutation rates that vary based on the timing of DNA replication and another who compares how normal cells and cancer cells develop have both won a National Institutes of Health (NIH) Director’s New Innovator Award.

The two Cornell researchers, as well as two alumni, were among 48 scientists nationwide who received $1.5 million awards, which support early-career investigators pursuing bold, new approaches to some of the greatest biomedical challenges.

The researchers are Amnon Koren, assistant professor of molecular biology and genetics, and Eftychia Apostolou, assistant professor of molecular biology in medicine at Weill Cornell Medicine. The alumni are Parijat Bhatnagar, Ph.D. ‘07, program director for cell-based medicine in the Biosciences Division at SRI International, and Nikhil U. Nair ’03, assistant professor of chemical and biological engineering at Tufts University.

Koren’s research explores how mutation rates vary from one individual to another. The timing of DNA replication is one of the main factors that affects mutation rates, and his work has shown the replication timing program varies from one person to another at hundreds of loci along the chromosomes.

Koren’s grant project will demonstrate that due to genetic variation in DNA replication timing, every person carries mutation patterns that are unique and encoded in their genomes. Koren and his colleagues will use innovative experimental and computational techniques to create a database of DNA replication timing in thousands of people and in several cell types. They will use the database to describe a new form of human genetic variation and identify the genetic underpinnings of DNA replication timing.

“These discoveries have the potential to influence the understanding, diagnosis and personalized treatment of mutation-driven diseases, namely genetic diseases and cancer,” Koren said.

Apostolou’s work focuses on how the genome is organized, a concept known as chromatin topology, which has only recently been explored. Although scientists have known that genomic architecture is dramatically rearranged when cells divide and faithfully reset in daughter cells, the underlying mechanisms behind the reorganization, how they influence gene expression and how cell identity is re-established once division is completed, have not been explored.

Apostolou will investigate how chromatin topology shapes normal cell development and the factors that enable cancerous tumors to form. Her research will study how transcription factors determine a cell’s outcome and which factors ensure normal, noncancerous cell division. The findings could help investigators understand how cancer cells arise and ultimately prevent this transformation, and could open new avenues for directing stem cell differentiation toward therapeutic cell types.

“As a young researcher, you need your first award, a lot of preliminary data and a high-risk, high-reward project funded,” Apostolou said. “This award will help me generate the data for future NIH applications and high-profile publications.”

Bhatnagar, who received his doctorate in biomedical engineering, is working to develop cellular therapeutics that can seek out disease microenvironments, assess the disease burden and synthesize proportionate amounts of therapeutic agents on disease cells.

Nair, whose bachelor’s degree is in chemical and biomolecular engineering, is focused on altering various aspects of microbial physiology (such as gene regulation and metabolism) to engineer them for biomedical, biochemical and bioenergy applications, and to understand how they interact with each other and their environment.