Jeannine Gerhardt, an assistant professor of stem cell biology in obstetrics and gynecology and in reproductive medicine at Weill Cornell Medicine, has received a five-year, $2.1 million grant from the National Institute of General Medical Sciences (NIGMS), part of the National Institutes of Health, for the study of repetitive DNA and RNA sequences and the mechanisms by which they cause cell dysfunction and diseases.

The NIGMS Maximizing Investigators’ Research Award is intended to support recipients’ research more broadly and flexibly than standard project grants, which must specify proposed research thoroughly in advance.

“This award is particularly nice because it gives us the flexibility to follow up on any surprising findings as we pursue our research interests,” Gerhardt said.

Repetitive DNA sequences, or DNA repeats, are patterns of nucleotides, the building blocks of DNA, that occur in multiple copies (such as CAGCAGCAGCAG). Some are found only in a specific gene, whereas others occur at multiple sites across the genome. While DNA repeats are common, and most are not harmful, others clearly cause diseases.

How DNA repeats cause cell dysfunction and disease is far from being fully understood. But the broad mechanisms are known to include the disruption of genome replication during cell division due to the formation of abnormal DNA structures, and the transcription of repeat-containing DNA into abnormal RNA structures that can also harm cells in various ways. Huntington’s disease, myotonic dystrophy 1 and 2, Friedreich’s ataxia, Fragile X syndrome, and a form of amyotrophic lateral sclerosis are among the dozens of disorders caused by DNA repeats.

An important disease-related phenomenon connected to some DNA repeats is their tendency to lengthen from one generation to the next. Gerhardt hopes to illuminate how this “repeat-expansion” occurs, in part with experiments in human egg cells, which traditionally have been difficult to maintain and study in the lab.

Gerhardt and her team also will examine more broadly how DNA replication and repair systems cope, or fail to cope, with abnormal repeat-containing DNA structures. In this line of investigation, they will study how the genome-repair process is affected by mutations in repair proteins – such as BRCA1, which has been implicated in many familial breast and ovarian cancers.

“All this falls into the category of basic research,” Gerhardt said, “but the knowledge we gain about the basic mechanisms leading to genomic instability in cells with insufficient BRCA1, for example, will enhance our understanding of how cancer-causing mutations arise in women carrying inherited BRCA1 mutations.”

Jim Schnabel is a freelance writer for Weill Cornell Medicine.