Boley, Patricia - Date Last Updated: 10/27/2008

Boley, Patricia

Patricia Boley - Email
PhD Candidate - Started 2006
Hails From Ontonagon, MI
Lab of Eric Sandgren, PhD

Undergraduate and Graduate Work
Wayne State University, Detroit, MI
Master of Science, Industrial Toxicology (2005)
University of California San Diego, LaJolla, CA
Bachelor of Science, Animal Physiology & neurosciences (1995)

Memberships
Society of Toxicology

Interests/Hobbies
Has interest in mummies and dragonflies. Hobbies include sports, home improvement, and zymurgy.

Research July 2007
My research project includes use of the comparative hepatocyte growth assay to quantify growth alterations and transformation frequency associated with defined hepatocyte gene changes in vivo, using engineered alterations of oncogenes. Certain genetic defects have strong carcinogenic effects. I am evaluating the roles of several of these gene defects, which were selected based on their proposed central involvement in human and/or mouse liver cancer. This system uses the urokinase-type plasminogen activator (uPA) model of hepatic repopulation, in which transgene-mediated liver damage in uPA transgenic mice allows transplanted hepatocytes to expand as colonies. Hepatocytes are isolated from donor mouse livers by two-stage EDTA/collagenase perfusion and then injected as a suspension into the spleen of uPA transgenic mice, from where they seed the liver via the portal circulation. A mixture of cells from two populations of donor hepatocytes is transplanted and donor hepatocyte growth is compared between the two populations using different marker transgenes. The size of the two donor cell populations at several time points post-transplant are compared using enzyme histochemistry to distinguish between focus types. The recipient liver provides a growth-stimulatory environment for transplanted donor hepatocytes and donor cells proliferate and expand as foci for 4 to 6 weeks. We have found that oncogenes have variable effects on focus growth and combinations of two oncogenic transgenes often display more than additive effects on hepatocyte growth.

One of my goals is to determine whether various combinations of oncogenes are able to cause hepatocytes to continue to grow in quiescent liver (8 to 12 weeks post-transplant). In particular, we want to determine whether genetically altered hepatocytes can initiate growth when present as foci of about 2000 cells surrounded by normal cells in a quiescent adult liver, and whether genetically altered hepatocytes can initiate growth when present as single cells in a quiescent adult liver. These conditions mimic more closely the genesis of cancer in spontaneous disease. To accomplish these goals, we have developed mice in which we can turn on and off transgene expression at a time of our choice.

We also will be collaborating with Dr. Bradfield’s lab to evaluate the pattern of gene expression that accompanies extreme hepatocyte growth potential using microarray. Array data will be compared among sample sets to identify systematic differences in gene expression patterns that correlate with different patterns of abnormal hepatocyte growth.

Date Last Updated: 10/27/2008 webteam@med.wisc.edu