Janice D. Pata
BS: California Institute of Technology (1986)
PhD: University of Colorado at Boulder (1994)
Postdoctoral Fellow: Yale University (2003)
Janice Pata, PhD, has served as the Chair of Biomedical Sciences since 2016. Her current research is focused on understanding the structures and molecular mechanisms of the enzymes that replicate the genome of Staphylococcus aureus DNA replication errors contribute to the evolution of antibiotic resistance.
Genome replication is a fundamentally important process in all cells and viruses. Mistakes made during replication cause mutations as well as large scale genome rearrangements, which can ultimately cause antibiotic resistance in bacteria as well as aging, cancer and resistance to chemotherapy in humans. Cells contain multiple polymerases, yet our understanding of how all these enzymes contribute to genome stability is far from complete.
Of particular interest is how the DNA polymerases that are responsible for the majority of genome duplication are replaced by the more specialized polymerases that are responsible for translesion synthesis across from damaged DNA bases. While the translesion polymerases help cells tolerate DNA damage, they have a 10- to 1000-fold higher error rate than replicative polymerases and can substantially increase the frequency of mutations. The situation is made even more complex since most cells have multiple translesion polymerases, each with their own lesion-bypass and mutational specificities. Genome stability is thus critically dependent on which polymerase carries out DNA synthesis.
The main research focus in the Pata Laboratory is on the replicative and translesion polymerases of Staphylococcus aureus, which is responsible for approximately 300,000 antibiotic-resistant infections and 10,000 deaths every year in the United States. We characterize the relationships between the structure and biochemical activity of these polymerases using X-ray crystallography, pre-steady-state enzyme kinetics and site-directed mutagenesis and follow the evolution of antibiotic resistance in a model bioreactor system that recapitulates clinically relevant mutations identified in patients. Our goal is to identify new strategies for combating these infections.
We also have active collaborations with Dr. Alex Ciota to study the error-prone RNA genome replication of flaviviruses and with Drs. Kathleen McDonough and Haixin Sui to study transcriptional regulation in Mycobacterium tuberculosis.
- Cellular and viral genome replication
- Mutagenesis and the evolution of antimicrobial drug resistance
- Structural biology & enzymology of protein-nucleic acid interactions
- Drug target discovery and therapeutics
- Genes and genomes
- Structural biology
Current major activities
- Chair, Department of Biomedical Sciences
- Steering Committee Member, Women in Science and Health (WISH)
- Mentoring Faculty Member, RNA Training Program