1100 Eastlake Avenue. Mailing address: 1100 Fairview Avenue N., E2-112, PO Box 19024, Seattle, WA 98109-1024
The focus of the Paulovich laboratory is the study of human phenotypic variation. Sample projects include:
1. We have developed a novel Multiple Reaction Monitoring (MRM)-based technology for multiplex, sensitive, specific, and precise quantification of large numbers of human proteins (and their modified forms) from typical biospecimens (cell lysates, tissue lysates, body fluids). We are developing thematic assay panels to profile dynamic cell signaling network responses to genetic and environmental perturbations relevant to human disease or drug compound characterization.
2. Development of high throughput functional assays to determine human phenotypic variation in the cellular DNA damage response. The cellular response to DNA damage is clinically relevant in human cancer. Little is known about naturally existing phenotypic variation in the DNA damage response amongst humans, aside from rare familial syndromes. To characterize phenotypic variation in the human population, we are developing high throughput, quantitative assays (e.g. ELISAs, MRMs) to measure the kinetics of activation of the DNA damage response network following DNA damage response network following gamma-irradiation. Understanding human variation in this response may be clinically important for predicting risk for developing. Understanding human variation in this response may be clinically important for predicting risk for developing cancer as well as for predicting toxicity to cancer therapies. Also, because the cellular response to radiation is rapid, dose- dependent, time-dependent, and occurs at clinically relevant doses, these assays may also have utility for biodosimetry in the event of a nuclear disaster.
3. Elucidate the network of genes and pathways that buffer defects in the DNA damage response. The cellular DNA damage response shows robustness in that networks of multiple genes (from multiple cellular pathways) buffer the effects of defects in any one gene in the pathway. We use genetic studies in the model yeast Saccharomyces cerevisiae to discover interacting genes and pathways determining sensitivity to DNA damage, and we subsequently test for conservation of these interactions in human cells using RNA interference. The ultimate goals of these studies are to identify novel therapeutic targets, to discover novel tumor suppressor genes, and to understand the underlying molecular mechanisms of the cellular DNA damage response.
Copyright © 2003-2014 Molecular & Cellular Biology Program, University of Washington
Fred Hutchison Cancer Research Center | University of Washington
Institute for Systems Biology | Seattle Biomed