URI Assistant Professor has powerful weapons to track birth of killers
KINGSTON, R.I. -- July 10, 2003 -- University of Rhode Island Assistant Professor Roberta S. King is on the hunt. Her game, however, is so small and insidious that she needs very powerful, expensive equipment to track and monitor it.
The biomedical scientist in URIs College of Pharmacy, who is trying to crack the mysteries of the very first steps of carcinogenesis, the development of cancer, now has the right tools at her disposal thanks to the Rhode Island Biomedical Research Infrastructure Networks (BRIN) Centralized Research Core Facility.
"My focus is how metabolism of xenobiotics can lead to carcinogenesis. In simpler terms, this means how metabolism of compounds foreign to the body can initiate changes which lead to uncontrolled cell growth," said King, a member of the federally funded research network. "We are focusing on a particular metabolism enzyme family, the sulfotransferases."
In her breast cancer research, she is looking at estrogen sulfotransferase and how it regulates the activity of estrogen. Many compounds in peoples diets and a few medications reduce the activity of (inhibit) estrogen sulfotransferase, according to King.
"What we don't know is whether this inhibition is potent enough to cause increased cellular level of estrogen and subsequent increased cell proliferation. The dietary inhibitors of sulfotransferase are not specific, that is they affect many other enzymes so it is difficult to determine which effects are due to the sulfotransferase pathway," King said.
King's research is designed to solve these problems and her work has been made much easier with several of the high-end instruments now available in the Core Facility.
King will be using the SGI molecular modeling workstation and accompanying Accelyrs Insight II software for 3D modeling simulations. "I will be looking at three-dimensional structures of enzymes such as estrogen sulfotransferase to design very specific inhibitors for these enzymes. You need very powerful technology and software because these molecules are quite large. In a water molecule, there are three atoms, but with what we are looking at, we are talking about 2,000 to 3,000 atoms in one molecule."
In her colon cancer research, King has been analyzing the basic building blocks of life and how they are affected by compounds introduced to the body. "I am looking at metabolites that covalently bind with DNA."
Those changed versions of DNA, called DNA adducts, can be examined using the Typhoon 9410 high performance imager in the newly established lab. "These DNA adducts are formed at very low levels. I will be looking at carcinogen metabolism in general and seeing what increases or decreases DNA adduct formation. In chemical carcinogenesis, creation of the DNA adduct is the very beginning of the disease process," King said.
King will also be using the cell culture facility. "This is very important because I dont have this facility in my lab. It would be very expensive to acquire it (the cell culture equipment), and yet I need to be looking at cells as better models of the human situation." Shell be using the cell culture facility to examine cell behavior in colon, liver and breast cancer.