Research
Dr. Panday's Genome Maintenance and Chromatin Plasticity in Cancer Laboratory at Mayo Clinic develops cutting-edge methods to study the precise signaling and molecular mechanisms that drive stalled fork remodeling and repair in mammals. The lab aims to understand how these processes can go wrong in cancer, and how to use them to create cancer treatments.
These are the research projects underway in Dr. Panday's lab.
Synthetic lethality in cancer
One of the most accurate signs of whether cancer will be deadly is if the cancer has spread — that is, has advanced to the metastatic stage — by the time it is diagnosed. A second strong sign is if the cancer has become resistant to drug therapy.
Synthetic lethality is what happens when multiple gene changes at the same time result in cell death. It is a promising approach to target cancer. In recent years, scientists have found that PARP inhibitors have the potential to be effective treatments for homologous recombination-deficient BRCA-linked cancer by causing synthetic lethality. However, many people who have cancer that's linked to the BRCA gene don't respond to PARP inhibitors. Therefore, there is a pressing need to find new treatments for BRCA-linked cancer.
Dr. Panday's lab is exploring synthetic lethality. The team is studying the detailed mechanism of synthetic lethality and its potential in cancer therapy. The team uses comprehensive genetics and proteomics approaches in this work.
Chromatin plasticity in response to replication stress and tumor formation
Replication stress is a major cause of genome instability and cancer progression. DNA replication occurs in the context of chromatin. Dr. Panday's lab is working to understand the processes of cancer progression in the context of chromatin and find possible targets for treatment. To do this, the lab aims to explain the underlying ways that chromatin is reorganized in response to replication stress and how this goes wrong in cancer development. The Panday lab also explores how changes in the chromatin dynamics impact repair pathway choices at the double-strand breaks and at the stalled forks.
Stalled fork repair pathway choices and cancer progression
During genome replication, replication forks frequently encounter obstacles. These obstacles can cause fork stalling, which can damage the genetic material and cause genetic aberrations. Usually, stalled forks are repaired correctly. But if stalled forks aren't repaired correctly, they can lead to genomic instability — a hallmark of cancer formation and progression.
Dr. Panday's lab uses CRISPR-Cas9 to delete different genes that are associated with DNA repair. This allows the team to identify how the loss of function of one or more of these genes can impact repair quality — that is error-free versus error-prone repair — and quantity at the double-strand breaks and at the stalled forks. The lab also is exploring how different genes interact with BRCA1, including how they suppress error-prone repairs and cancer progression.