Dr. Jill Williams' Research Focus

Major Research Interests:
Molecular mechanisms of prostate and bladder cancer progression and metastasis.

Our laboratory is broadly interested in tumor-specific genetic alterations and their role in prostate and bladder tumor progression and metastasis. Overall, our laboratory is engaged in “translational research”—characterization of a clinical problem using molecular biology and cell biology, as well as animal models. We presently have three major research projects funded through federal, local, or pharmaceutical company funding. The first major project examines the role of the eIF4E translation initiation factor in prostate tumor progression, especially its role in tumor angiogenesis, apoptosis, and its regulation of other downstream genes. Our initial studies have shown that eIF4E is elevated in a majority of prostate tumors and has direct and indirect influences on tumor angiogenesis. Blocking the elevation of eIF4E reduces the tumor size, the formation of new blood vessels, and also induces apoptosis. We are continuing to study the molecular mechanisms behind these cellular changes and are developing a virus delivery system for an eIF4E antisense RNA to use as a gene therapy for prostate and bladder cancers, that also have high levels of 4E. Identification of other genes relevant to tumor progression or metastasis that are regulated by eIF4E is also a major focus in the laboratory. The second major project is based on our observation of an increase in tumor angiogenesis in prostate tumors from African-American men and an abnormal pattern of expression of genes with effects on tumor growth, the actin cytoskeleton, cell motility, and invasion. The result is clinically relevant as it may possibly explain, at least in part, the increase in tumor aggressiveness and mortality associated with prostate cancer in the African-American population. Our preliminary studies suggest that some of these gene products may be regulated by dietary fat intake—a known risk factor for cancer as well as coronary heart disease. Our newest direction is in the use of copper chelators to affect prostate tumor progression and metastasis, especially metastasis to bone. Since many of the effects of copper chelation are also anti-inflammatory, copper chelators may also be effective for use in other urological diseases such as prostatitis and interstitial cystitis. We have recently been funded by the DOD to make prostate tissue arrays for correlative studies and will be testing the expression of our newly identified tumor markers for their correlation with clinical disease parameters.

2002 Highlights:

• Rebecca McGaha, was awarded a number of honors this year for a project from our laboratory, “Regulation of Tumor Angiogenesis and Apoptosis Via Suppression of the Translation Initiation Factor eIF4E in Prostate Cancer”, including 1 st place in the Medicine and Health Category at the International ISEF Science Fair.

• Shannon Wallssuccessfully defended her Master’s of Science thesis, “Effect of NS-398 Treatment on Prostate Tumor Growth and Survival”, and presented this work at a Poster Discussion Session at the American Association for Cancer Research annual meeting in San Francisco.

2003 Highlights:

• Rebecca Philips, was named as a Semi-Finalist in both the Intel and Siemens-Westinghouse Science competitions for her project, “Copper Depletion Inhibits Prostate Tumor Angiogenesis and Metastasis”