Lab Website: http://www.medicine.uiowa.edu/biochem/labs/mariaspies/

DNA recombination, replication and repair

Work in my lab focuses on the molecular machines supporting genetic integrity, DNA recombination and repair. We strive to build a coherent mechanistic description of the composite cellular pathways that orchestrate the central steps in homology directed DNA repair. Specifically, we aim to define how RAD51 recombinase, RAD52 and BRCA2 recombination mediators, mismatch repair proteins and recombinational DNA helicases are integrated into the DNA repair and maintenance machines through a network of molecular associations and posttranslational modifications. The ultimate goal of our research is to go beyond deciphering the fundamental molecular mechanisms of the enzymes, proteins, and macromolecular ensembles orchestrating DNA repair to find an Achilles’ heel in their mechanism of action or malfunction. This will enable us to contribute to an emerging generation of targeted therapies aimed at attacking specific aspects of cancer and aging-related diseases.

A salient feature of my research program is a strong multi- and interdisciplinary approach, which is firmly rooted in nearly two decades of my experience in analyzing the proteins involved in DNA recombination and repair. I have an extensive training in using biochemical, biophysical and single-molecule approaches to solve the molecular mechanism of recombinational proteins. My lab combines biochemical reconstitutions of DNA recombination, repair and replication reactions with biophysical, structural and single-molecule analyses of the proteins and enzymes coordinating these reactions. The projects carried out in my lab range from a biochemical and single-molecule reconstitutions to combined HTS/CADD campaigns to identify scaffolds that can be developed into potent inhibitors of human DNA repair proteins.

PubMed link

Department/Program Affiliations:
Biochemistry
Molecular Medicine