Amanda G. Paulovich

Appointments and Affiliations

Fred Hutchinson Cancer Research Center
Clinical Research Division
Early Detection Initiative
Associate Member, Appointed: 2003
Translational Genomics Research Institute
Adjunct Faculty, Appointed: 2008
University of Washington
Graduate School
Molecular and Cellular Biology Program
Associate Professor, Appointed: 2007
University of Washington
School of Medicine
Medicine
Oncology
Associate Professor, Appointed: 2005
Professional Headshot of Amanda G. Paulovich

Mailing Address

1100 Fairview Avenue North
LE-360
P.O. Box 19024
Seattle, Washington 98109-1024
United States

Contact

Phone: (206) 667-1912
Fax: (206) 667-2277
apaulovi@fhcrc.org
http://labs.fhcrc.org/paulovich/index.html

Degrees

Fellowship, Dana Farber Cancer Institute, Medical Oncology, 2004.
Postdoctoral Fellowship, MIT-Whitehead Center for Genomic Research, Computational Biology (Dr. Eric Lander), 2003.
Residency, Massachusetts General Hospital, Internal Medicine, 2000.
M.D., University of Washington, 1998.
Ph.D., University of Washington, Genetics (Dr. Leland Hartwell), 1996.
B.S., Carnegie Mellon University, Biological Sciences, 1988.

Research Interests

The focus of my laboratory is the study of human phenotypic variation. Sample projects include:

1. Development of high throughput, multiplexed technologies for targeted protein quantification in blood plasma and solid tissues. We use targeted multiple reaction monitoring mass spectrometry coupled to stable isotope dilution and anti-peptide antibody-based enrichment to measure the abundance of proteotypic peptides as surrogates for quantification of proteins of diagnostic interest. Initially, this work is being done in a highly controlled experimental system: inbred mouse strains genetically engineered to develop cancers. The use of mouse models allows us to minimize biological variation ("noise") and to generate as much sample as needed for technology development. Ultimately, we apply working technologies developed using the mouse model to measurement of candidate diagnostic markers in human patients.

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. For example, familial cancer syndromes mostly result from germline mutations that compromise the cellular DNA damage response. Second, somatic inactivation of the DNA damage response is ubiquitous in solid tumors and is associated with chromosomal instability. Third radiation and many chemotherapeutics used to treat cancers are DNA damaging agents. 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) to measure the kinetics of activation of the DNA damage response pathway following gamma-irradiation. 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.

Memberships

American Association for Cancer Research
American Association for Clinical Chemistry
American Chemical Society
American Society for Mass Spectrometry
FHCRC/UW Cancer Consortium
Molecular Signatures Database (MSigDB) Scientific Advisory Board
Radiation Research Society
Scientific Advisory Board, Bio-Rad Life Sciences
Steering Committee, International Biomarker Research Consortium
Steering Committee, NCI Affinity Reagents Project
Technology Advisory Board, Canary Foundation

Honors and Awards

2005, Roger Moe Award for Translational Research, Fred Hutchinson Cancer Research Center
2002-2003, Damon Runyon Research Fellowship, Abbott Fellow, Whitehead Institute Center for Genomics Research, DNA damage response, microarrays, computational biology
1992, Merck Distinguished Fellow Award, University of Washington, S phase regulation in yeast responding to DNA damage
1989, HHMI Research Fellowship, University of Washington, Characterization of transgenic mouse model of pancreatic cancer
1988, Carnegie Mellon Award for Outstanding Research, Carnegie Mellon University, Coordinate Regulation of a ribosomal protein gene family in yeast
1987, Genetics Society of America Undergraduate Research Fellowship, Carnegie Mellon University, Coordinate Regulation of a ribosomal protein gene family in yeast
1986, Beta Beta Beta National Biological Honor Society, Beta Beta Beta National Biological Honor Society

Previous Positions

2005-2010, Assistant Professor, University of Washington, School of Medicine, Medicine, Oncology
2003-2009, Assistant Member, Fred Hutchinson Cancer Research Center, Clinical Research Division, Early Detection Initiative

Recent Publications

2014
2013
2012
2011
2010
2009