1. Cancer Chemoprevention.
a. As the P.I. on a NIH/NCI grant R01 CA101052 I am studying how lycopene (the red carotenoid in the tomato) might prevent prostate cancer in men. This research is divided into two parts, a laboratory investigation into the effects of lycopene on prostate cancer cells grown in culture, and a clinical trial involving healthy men and men with prostate cancer. We have developed a liquid chromatography-tandem mass spectrometry (LC-MS-MS) assay to measure DNA oxidation products in cellular DNA and another LC-MS-MS assay for the measurement of lipid oxidation. These assays are being used to explore the antioxidant effect of lycopene on the human prostate and on blood markers in vivo. Presently, I am directing a clinical trial involving healthy men who are taking a lycopene dietary supplement. In this placebo-controlled double-blind study, the primary endpoints that are being tested are that lycopene, as an antioxidant, should reduce urinary levels of the DNA oxidation product 8-oxo-deoxyguanosine, and reduce blood levels of the lipid peroxidation product malondialdehyde. PSA levels will also be measured, since some publications indicate that lycopene should lower serum PSA.
b. I am a Project Leader in a NIH/NCI Program Project grant P01 CA48112 with P.I. Dr. John Pezzuto. This program is directed toward the discovery of cancer chemoprevention agents in plants. My role is to use mass spectrometry to screen extracts of terrestrial plants and marine bacteria for potential cancer chemoprevention agents. After lead compounds are identified, I am using mass spectrometry to investigate their metabolism and bioavailability. Up for competitive renewal in 2004, this grant was funded for another five years beginning April 1, 2005.
2. High Throughput Drug Discovery and Development.
a. A second R01-type grant on which I am P.I. was reassigned to our UIC/NIH Center for Botanical Dietary Supplements Research (a P50 grant) as Project 3. In addition to being the Project Leader of Project 3, I am the Core Leader of the mass spectrometry Analytical Core of the center, co-investigator of the Administrative Core, and Co-Director of the Center with P.I. Dr. Norman Farnsworth. The focus of my research within the Center is the identification of the active compounds in botanicals used to treat symptoms of menopause in women, and then the investigation of the bioavailability, pharmacokinetics, and metabolism of these compounds both in vitro and in vivo. A renewal grant application was successful during 2004. As a result, this center is funded for another five years (until 2010).
b. I am co-investigator with P.I. Dr. Judy Bolton on two NIH-funded R01 grants concerning tamoxifen and estrogens. In this collaboration, I am using mass spectrometry to help determine the mechanisms by which estrogen, equine estrogens, and tamoxifen might cause cancer.
c. I am co-investigator with P.I. Dr. Greg Thatcher on an NIH-funded R01 grant concerning oy and isoflavone and their effects on breast cancer. I am using LC-MS-MS in this effort for the quantitative analysis of isoflavone in mammary tissue and for the analysis of DNA oxidation levels in cells treated with these compounds.
d. In on-going collaboration with researchers at Wageningen University in the Netherlands, I have been investigating in humans the bioavailability of beta-carotene and its bioconversion to vitamin A. I have been using LC-MS-MS for the measurement of a stable-isotopically labeled form of beta-carotene in plasma from children and adults who received oral supplements. In my current R01 grant on lycopene, I am extending this methodology to the determination of the bioavailability of lycopene.
a. I am a co-investigator with Dr. John Solaro on his NIH grant P01 HL062426, entitled, "Cardiac maladaptation." My role is to guide the LC-MS/MS proteomics analysis of changes in phosphorylation that occur in troponin molecules during congestive heart failure.
b. I am a co-investigator with PI Larry Tobacman on his NIH grant RO1 HL63774 entitled, "Dynamic interactions of cardiac troponin and tropomyosin." My role to provide expertise in LC-MS/MS proteomics to facilitate the study of troponin and tropomyosin interactions using deuterium exchange methods.
Funding for this laboratory is provided by the National Institutes of Health:
* The National Cancer Institute
* National Center for Research Resources
* Office of Dietary Supplements