Dr. Janine Gerhardt, an assistant professor of obstetrics and gynecology and stem cell biology in reproductive medicine at Weill Cornell Medicine, received a five-year, $2.1 million grant from the National Institute of General Medical Sciences (NIGMS), part of the National Institutes of Health, to study repetitive DNA and RNA sequences in health and Mechanisms by which they cause cell dysfunction and disease.
The NIGMS Maximizing Investigators Research Award is intended to support recipients’ research more broadly and flexibly than standard project grants, which must thoroughly specify the proposed research in advance.
This award is particularly nice because it gives us the flexibility to pursue any surprising results while pursuing our research interests.”
Dr. Janine Gerhardt, assistant professor of stem cell biology in obstetrics and gynecology and reproductive medicine at Weill Cornell Medicine
Repetitive DNA sequences, or DNA repeats, are patterns of nucleotides, the building blocks of DNA, that occur in multiple copies (eg CAGCAGCAGCAG…). Some are found only in a specific gene, while others occur at multiple sites throughout the genome. Although DNA repeats are common, and most are harmless, others clearly cause disease.
How DNA replication causes cell dysfunction and disease is not fully understood. But among the broader mechanisms are the disruption of genome replication during cell division due to the formation of abnormal DNA structures and the replication of repeat-containing DNA into abnormal RNA structures that are known to damage the cell in several ways. Huntington’s disease, myotonic dystrophy 1 and 2, Friedreich’s ataxia, Fragile X syndrome and a form of amyotrophic lateral sclerosis are among dozens of disorders caused by DNA repeats.
An important disease-related phenomenon associated with some DNA repeats is their tendency to lengthen from one generation to the next. Dr. Gerhard hopes to understand how this “repeat-expansion” occurs, as part of experiments in human egg cells, which have traditionally been difficult to maintain and study in the laboratory.
Dr. Gerhardt and his team will examine more broadly how DNA replication and repair systems cope with 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 is implicated in many familial breast and ovarian cancers.
“All of this falls into the category of basic research, but the knowledge we gain about the basic mechanisms that lead to genomic instability in cells with insufficient BRCA1, for example, how cancer-causing mutations arise in women who carry inherited BRCA1 mutations will improve our understanding of.”Dr. Gerhard said.