Pilot Project: Chemopreventive and Therapeutic Activity of Withania Somnifera and Its

Projects

Pilot Project: Chemopreventive and Therapeutic Activity of Withania somnifera and its Mechanism of Action inHuman Breast Cancer
TU: Dr. Karmal Kazal
UAB: Dr. Clinton Grubbs
This pilot project will test the chemopreventive and chemotherapeutic activity of an extract of Withaniasomnifera 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 mechanismof action will be evaluated.Based on the preliminary findings, the primary hypothesis is that the root extract of WS will beeffective in preventing and treating breast cancer and will enhance the anti-tumor efficacy of conventionalchemotherapy drugs such as tamoxifen. Successfully completed, the findings of this project will provideimportant 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 theinteraction between BRCA1 and Ubc9 molecules in relation to their sub-cellular localization in ovariancancer 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 withWilliam Grizzle, MD, PhD (a collaborator from UAB), these efforts will assess the clinical significance ofexpression of these proteins in human ovarian tissues and determine their value in early detection, drugscreening, 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 prognosticand predictive value of a panel of promising molecular markers in colorectal cancer (CRC) tissues (morethan 1,000) collected from AA and non-Hispanic Caucasian (white) patients who underwent treatment atMSM and UAB hospitals. This investigation is also intended to develop the career of Dr. TemesgenSamuel, a junior faculty/Co-Leader at Tuskegee University (TU), who is seeking more experience inunderstanding the basis for cancer health disparities. Further, this project will continue the existingsuccessful 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 establishedinvestigator. The preliminary results of these collaborative studies show a disparity in gene expressionprofiles 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 ofCCRs 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, throughtranscriptional 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 apilot project funded during the current U54 cycle. These collaborative efforts have identified that, in theprocess of breast cancer metastasis, there is a loss of hormone sensitivity and an EMT that increasescellular capacity for migration and invasion in relation to sub-cellular localization of Kaiso. By exploring themolecular mechanisms and effects on Kaiso-associated transcriptional repression, novel therapeuticapproaches can be developed to target lethal metastasis.