In the Kowalczykowski Lab we are primarily interested in the biochemistry of the proteins that are involved in homologous recombination mediated DNA repair. Our lab utilizes a number of approaches to address our scientific questions including biophysical chemistry, molecular biology and single molecule biophysics. The DNA in each of your cells spontaneously suffers approximately 10 double strand breaks (DSB) every day and approximately 50,000 nicks. This damage is a result of a host of factors including, but not limited to, oxidative damage from metabolic side products, UV damage, and failed or improper cellular processes like DNA replication. If left unrepaired or if inefficiently repaired, chromosomes begin to fragment and cells either undergo apoptosis or become cancerous.

In order to repair broken DNA, our cells have evolved two pathways: the first is Non-Homologous End Joining, where the blunt ends of a DSB are ligated together. This often results in a loss of sequence infomation and/or a frameshift. This 'sloppy' repair is usually of little consequence because of the large percentage of non-coding DNA in eukaryotic genomes. The second pathway uses Homologous Recombination (HR) to efficiently repair a DSB without error and is an essential pathway for maintaining genomic stability. In fact, defects in HR are associated with chromosomal instability, which manifest as either cancer or genetic diseases like Fanconi Anemia.

Specifically, a group of proteins called mediators are essential for HR. These proteins facilitate HR by loading a strand exchange protein (RecA, Rad51) onto ssDNA that has been coated with a single strand binding protein (SSB, RPA). I am primarily interested in RecFOR, the bacterial functional homolog of human BRCA2. Both RecFOR and BRCA2 are mediators, and ~ 5% of all breast cancer and ~ 90% of all familial breast cancer has been found to be associated with mutations that map to BRCA2. By advancing our understanding of how RecFOR functions in E. coli, we can make more intelligent inferences about the biochemical function of its functional homologs like BRCA2.

Awards and Honors:
Vincent Cangelosi Scholarship for Outstanding Freshmen: LSU, 2001
Chancellor's Future Leader in Undergraduate Reasearch: LSU, 2000-2004
HHMI Undergraduate Summer Research Fellow: LSU, 2003
Upper Division Honors Distinction in Biochemistry: LSU, 2004
Cum Laude: LSU, 2004
NIH Molecular and Cellular Biology Trainee: UC Davis, 2006-7

Interests:
Protein-DNA interactions;
Biophysical Chemistry;
Single Molecule Biophysics;
DNA Recombination, Replication and Repair;
Mechanistic Biochemistry;
Equilibrium and Pre-steady state kinetics;
Thermodynamics;

Links to Labs I think are really interesting:

Links for Procrastination

Reconstructed model of a RecA filament determined via EM Tomography. Image is from the cover of the March 26, 1993 issue of Science.

Biochemistry Love Haikus, The Science Creative Quarterly, April-May 2006