Our research focuses on:

1. DNA re­arrange­ments in tu­mor cells

2. Mis­match re­pair and tan­dem re­peat in­stabil­ity

3. Role of DNA re­pair in chemo-res­ist­ant ovarian can­cers

1. DNA rearrangements in tumor cells

We are developing allele-specific PCR methods to detect de novo DNA rearrangements at breakpoint hotspots and LINE-1 retrotransposon insertion directly in primary tumor cells. Our studies aim to shed light on the frequency and origins of these chromosomal aberrations and the molecular mechanisms generating them.

2. Mismatch repair and tandem repeat instability

Mismatch repair (MMR) is responsible for surveillance and maintenance of DNA integrity. Our objective is to gain mechanistic insight into how levels of MMR proteins contribute to in vivo tandem repeat instability, which reflects MMR defects and leads to tumorigenesis in certain tissues. Our approach is to assay tissue- and age- specific micro- and minisatellite instability in MMR-proficient (Mlh1+/+) and MMR-deficient mouse models with various levels of MMR proteins (Mlh1+/- and Mlh1-/-). 

In vivo localization of MutSα to the chromatin is controlled through interactions with PWWP domain of MSH6 and H3K36me3 histone mark. Our research aims to gain insight in how mutations in PWWP domain may contribute to MMR efficiency and to study how local abundance of H3K36me3 affects the local mutation rate in Mlh1-/- mice using single cell approach.


3. Role of DNA repair in chemo-resistant ovarian cancers

Correct DNA repair is essential for maintaining cellular integrity and preventing DNA damage-induced cellular death and genome instability. In humans, defective DNA repair predisposes carriers to developmental defects, degenerative diseases and cancer.  Remarkably, the DNA repair defects that are known to cause certain tumors, such as breast and ovarian, can also be used to specifically target the cancers themselves.

We have developed an ex vivo protocol that predicts response to chemotherapy in ovarian cancer patients and that can allow us to identify new ways to exploit DNA repair deficiencies in chemo-resistant and recurrent tumors (