Overview
My research is aimed towards understanding the molecular basis of diseases such as repeat expansion disorders and cancer. The goal of my research is to dissect the DNA replication in human cells at the endogenous locus in vivo to identify defects, which could lead to genomic instability.
Several inherited human neurological and muscular disorders like Friedreich’s ataxia (FRDA), fragile X syndrome (FXS), myotonic dystrophy (DM1), Huntington’s disease and spinocerebellar ataxia type 7 (SCA7) are caused by a trinucleotide repeat expansion. The mechanism leading to repeat instability is still not known and there is currently no cure for these repeat expansion diseases. One goal of my research is to dissect the DNA replication program at the endogenous disease locus and find molecular components driving repeat expansion in human cells. Therefore we are using a unique technique, called single-molecule analysis of replicated DNA (SMARD), which allows us to visualize the DNA replication at the endogenous genomic locus in human cells at single DNA molecule level. Using SMARD we revealed an altered replication program in FXS human embryonic stem cells (hESCs) and in FRDA induced pluripotent stem cells (iPSCs). In addition we found that stalled replication forks are driving GAA repeat expansion in FRDA cells. It is important to understand how repeat expansion occurs in the native chromosomal context for the development of effective therapeutic treatments to prevent repeat expansions in patients with diseases like FRDA and FXS.
Errors in the DNA replication process are also linked to genomic alterations and cancer. The replication could be hindered through difficult to replicate DNA sequences, which would lead to incomplete and incorrect DNA synthesis and induce DNA breaks as well as mutations. My current research is aimed to analyze DNA replication defects causing genomic instability in cancer-prone and reprogrammed cells to prevent genomic instability leading to tumorigenesis.
Highlights
- 1Molecular cell · 2022
- 2The Journal of cell biology · 2020
- 3
Publications
Funding
Active
2 grants- PIR35GM152228-01Repetitive sequences causing genomic instability and cell dysfunctionNational Institute of General Medical Sciences · 2024–2028· 3 renewals
- PIR01ES034733-02Environmental factors and compounds affecting the genomic stability in haploinsufficient BRCA1 cells.National Institute of Environmental Health Sciences · 2023–2028
Completed grants (1)
- PIR03NS106216-02Identification of compounds stabilizing the GAA repeats in Friedreich’s ataxia cellsNational Institute of Neurological Disorders and Stroke · 2018–2020
Clinical research
Active
3 studies- PIBiorepository of Discarded Reproductive Samples from IVF patientsWeill Medical College of Cornell University · OPEN TO ACCRUAL (as of 2026)
- PIProspective study IVF patients with specific germline mutations and advanced maternal age to understand the cause of diminished ovarian reserveWeill Medical College of Cornell University · OPEN TO ACCRUAL (as of 2025)
- PIUsage of patients-derived explants for analysis of the mechanism and factors causing genomic instability and mutagenesis in BRCA1 and 2 carriersWeill Medical College of Cornell University · OPEN TO ACCRUAL (as of 2024)
News mentions
- Prestigious NIH Grant Explores Repetitive DNA Sequences and Cell DysfunctionJanuary 29, 2024
Dr. 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.
- Faulty DNA Repair May Lead to BRCA-Linked CancersNovember 15, 2022
Error-prone DNA replication and repair may lead to mutations and cancer in individuals who inherit a mutant copy of the BRCA1 gene, according to a new study by Weill Cornell Medicine investigators.