TU: Dr. Karmal Kazal
UAB: Dr. Clinton Grubbs
This pilot project will test the chemopreventive and chemotherapeutic activity of an extract of Withania somnifera in experimentally induced mammary tumors and in mice bearing xenografted tumors. In addition, its cytotoxicity to breast cancer cells in relation to their expression of estrogen receptors and its mechanism of action will be evaluated. Based on the preliminary findings, the primary hypothesis is that the root extract of WS will be effective in preventing and treating breast cancer and will enhance the anti-tumor efficacy of conventional chemotherapy drugs such as tamoxifen. Successfully completed, the findings of this project will provide important evidence of its safety for future clinical use.
Pilot Project: BRCA1 Deficiency and Epithelial Ovarian Cancers
MSM: Dr. Veena Rao
UAB: Dr. Charles Landen
This pilot project will determine the mechanistic and physiological significance of the interaction between BRCA1 and Ubc9 molecules in relation to their sub-cellular localization in ovarian cancer cells. Based on their preliminary results, they hypothesize that BRCA1, by binding to Ubc9, functions as a tumor suppressor and thereby inhibits growth of ovarian tumors. Also, in collaboration with William Grizzle, MD, PhD (a collaborator from UAB), these efforts will assess the clinical significance of expression of these proteins in human ovarian tissues and determine their value in early detection, drug screening, and predicting clinical outcomes.
Full Project: Molecular Characterization of Aggressive Colon Cancers of African-American Patients
MSM: Dr. Harvey Bumpers
TU: Dr. Temesgen Samuel
UAB: Dr. Upender Manne
The primary goal of this preclinical translational proposal is to determine the prognostic and predictive value of a panel of promising molecular markers in colorectal cancer (CRC) tissues (more than 1,000) collected from AA and non-Hispanic Caucasian (white) patients who underwent treatment at MSM and UAB hospitals. This investigation is also intended to develop the career of Dr. Temesgen Samuel, a junior faculty/Co-Leader at Tuskegee University (TU), who is seeking more experience in understanding the basis for cancer health disparities. Further, this project will continue the existing successful collaboration, established during the currently funded U54 Partnership award, between Dr. Harvey Bumpers of MSM and Dr. Upender Manne of UAB, to assist Dr. Bumpers to become an established investigator. The preliminary results of these collaborative studies show a disparity in gene expression profiles of microsatellite stable (MSS) phenotypes, known for aggressive behavior of colorectal cancers (CRCs) of AAs and whites. Based on these findings, the current hypothesis is that the MSS phenotypes of CCRs from AAs and whites are different, and their capacity to assess patient survival varies with tumor
stage and location.
Full Project: Kaiso as a Prognostic Factor and Potential Therapeutic Target in Breast Cancer
TU: Dr. Clayton Yates
UAB: Dr. William Grizzle
This full project will study if the Kaiso gene is an essential inducer of the progression of breast cancer, through transcriptional regulation of hormone sensitivity and regulation of endothelial-mesenchymal transition (EMT)-related genes. This collaboration between Dr. Yates and Dr. Grizzle was established to conduct a pilot project funded during the current U54 cycle. These collaborative efforts have identified that, in the process of breast cancer metastasis, there is a loss of hormone sensitivity and an EMT that increases cellular capacity for migration and invasion in relation to sub-cellular localization of Kaiso. By exploring the molecular mechanisms and effects on Kaiso-associated transcriptional repression, novel therapeutic approaches can be developed to target lethal metastasis.