Research Interests

Work in my lab focuses on the molecular machines supporting genetic integrity, DNA replication, recombination and repair. Understanding the molecular bases and regulation of these processes is fundamentally important because accumulation or incomplete repair of DNA lesions, erroneous attempts to reestablish damaged replication forks can lead to genetic instability and chromosomal rearrangements contributing to cancer, aging, chemotherapy resistance, or numerous diseases associated with expansion of repetitive sequences.

We study genome stability at the most fundamental level aiming to determine how a conformational protein dynamics and dynamic protein-protein and protein nucleic acids interactions drive “cellular decision making”. We utilize a broad spectrum of techniques from biochemical reconstitutions of DNA recombination, repair and replication reactions, to structural, biophysical and single-molecule analyses of the proteins and enzymes coordinating these reactions. In our work, we combine several single-molecule approaches. These include single-molecule total internal reflection fluorescence microscopy (smTIRFM), confocal single-molecule Forster Resonance Energy Transfer (smFRET), mass-photometry and correlated optical tweezers and fluorescent microscopy (CTFM). To complement our understanding of architectural plasticity and conformational dynamics of macromolecular complexes with structural information, we use experimental structural approaches, such as cryogenic electron microscopy (Cryo-EM) and X-ray Crystallography.  Our goal is to understand the coordinated and dynamic nucleoprotein transactions critical for high fidelity DNA repair and replication, to dissect the mechanisms that funnel “normal” DNA repair intermediates into “rogue” processes that destabilize the genome and lead to neuromuscular diseases, cancer, and/or emergence of chemotherapeutic resistance, and to be able to manipulate these processes in development of new therapeutics.

Current directions in our research are supported by grants from the National Institutes of Health (NIGMS R35GM131704 MIRA and NCI NIH R01CA232425, R21CA270300) and pilot grants from the University of Iowa HCCC. Several projects in the lab are focused on understanding of (1) how non-canonical DNA structures and repetitive, difficult to replicate DNA sequences affect genome stability; (2) how stalled DNA replication forks are protected and/or channeled into various repair and restart events; (3) how we can target the key protein in the above processes to develop novel therapeutics targeting cancer and repeat expansion diseases.