Mechanisms of mismatch repair mediated cell death after alkylating agent exposure

NIH RePORTER · NIH · R00 · $243,279 · view on reporter.nih.gov ↗

Abstract

 DESCRIPTION (provided by applicant) Dr. Eva Goellner received her bachelor's degree in Chemical Engineering and Biomedical Engineering from Carnegie Mellon University in 2006. She did her Ph.D. research at the University of Pittsburgh, School of Medicine in the Laboratory of Dr. Robert Sobol. Her work primarily focused on the mechanisms behind the toxicity of repair intermediates that are generated when the DNA base excision repair (BER) pathway cannot complete repair. Her work helped elucidate the interaction of BER repair intermediates with cellular metabolism. Her graduate work resulted in a first author manuscript in Cancer Research, two co-first author manuscripts, a first author review and several co-author works and provided a strong background in cellular and molecular biology, mammalian cell culture, pharmacology and measurements of cellular metabolism. Dr. Goellner joined the laboratory of Dr. Richard Kolodner in October of 2011 working on a separate DNA repair pathway, DNA mismatch repair (MMR), that repairs mispairs formed during normal replication. Mismatch repair requires an excision step to remove the DNA up to and including the mispair, however deletion of the only known exonuclease involved, Exo1, does not have the strong mutator phenotype expected of a required MMR component. This lead to the hypothesis that Exo1-independent and Exo1-dependent subpathways exist. Dr. Goellner received an NIH NRSA Ruth L. Kirschstein F32 postdoctoral fellowship to perform a screen for mutations in the loading clamp, PCNA, that specifically disrupted Exo1-independent MMR. Using Saccharomyces cerevisiae Dr. Goellner identified a number of the desired mutations and through the study of them provided a model of how Exo1-independent MMR is carried out. This work was published in a first author manuscript in Molecular Cell, a first author review and a co-author paper currently under revision. Her postdoctoral work provided her with a new model system and technical expertise in yeast genetic screens and biochemistry. Dr. Goellner's postdoctoral work and the mentored portion of this award will be carried at the Ludwig Institute for Cancer Research at the University of California School of Medicine Campus. The Ludwig Institute is a diverse group of researchers in nine research laboratories spanning topics of genetics, genome integrity, proteomics, structural biology, chromosome biology, cell biology and cell signaling. The San Diego branch is part of a worldwide community of Ludwig Institute Centers and is characterized by its excellence in research. These nine laboratories work together to provide a highly collaborative environment in which almost any biological problem can be answered through an in-house collaboration, and it provides a high quality research environment, with each laboratory regularly publishing in the highest impact journals. The Ludwig Institute has an excellent track record in producing postdoctoral fellows that go on to...

Key facts

NIH application ID
9970503
Project number
5R00ES026653-05
Recipient
UNIVERSITY OF KENTUCKY
Principal Investigator
Eva Marie Goellner
Activity code
R00
Funding institute
NIH
Fiscal year
2020
Award amount
$243,279
Award type
5
Project period
2018-09-01 → 2022-07-31