The Archived Projects section provides access to completed research initiatives conducted through the MSM–TU–UAB Partnership. These projects have concluded but remain available for reference and documentation of research accomplishments.
Full Projects – Ended
Access the archive of completed full research projects funded through the partnership.
View Projects →Pilot Projects – Ended
Browse completed pilot research studies supported by the MSM–TU–UAB Partnership.
View Projects →Pre-Pilot Projects – Ended
Explore archived pre-pilot projects that supported early-stage research and development.
View Projects →Full Projects – Ended
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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.
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.
Pilot Projects – Ended
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Pilot Project: ImPact 2.0
MSM Co-Lead Brian Rivers, PhD
UAB Co-Lead: Reagan Durant, MD, MPH
Cancer Clinical Trials (CCT) are the cornerstone of clinical oncology research and provide the foundation for development and implementation of effective cancer therapies. Yet, the most recently published analysis of national enrollment data from breast, lung, prostate, and colon cancer trials, sponsored by the National Cancer Institute (NCI) between 2000 and 2002, show that only 1.3% of eligible African Americans (AAs) were enrolled in CCTs. Although many interventions have focused on approaches to increase the willingness of AAs to participate in CCTs perhaps efforts should be focused on increasing the opportunities among AAs to participate in CCTs. One such promising intervention, the IMPaCT program of the O' Neal Cancer Center, increased AA participation in clinical trials from 11% to 21% over a four-year span. We propose to augment and adapt the IMPaCT patient navigation model, IMPaCT 2.0, for implementation at Morehouse Healthcare (MH) and Grady Hospital (Grady), one of the largest safety-net hospitals in the nation to increase AA participation in clinical trials (currently less than 10%). The proposed research is novel because of the 1) enhancement of the patient navigation (PN) model for clinical trials with a dual focus on AA recruitment and retention, and 2) integration of CTNs with a mobile tablet CTTS intervention for matching of AAs with clinical trials at a safety-net hospital and a less research-intense environment.
CD24-Dependent Inactivation of Mutant p53 in Metastatic Castration-Resistant Prostate Cancer
MSM Co-Lead James W. Lillard, Jr., PhD, MBA
UAB Co-Lead: Lizhong Wang, PhD
African American (AA) men have the highest rate of prostate cancer (PC) among any racial or ethnic group [1]. They also have a higher rate of death due to development of metastatic and castration-resistant PCs (CRPCs). In a U54 CA118948 Pre-Pilot project, we found that, in AA PC cases, CD24 expression in PC tumors was associated with an aggressive tumor stage, especially with distant metastasis. We also identified distributions of the CD24 genetic variant among AAs, European Americans (EAs), and Asians. In particular, highly expressed alleles of CD24 were more frequent in AAs than in EAs and Asians, which should result in higher levels of CD24 expression in AA PC cases (see our preliminary data). Furthermore, our bioinformatic analysis of public datasets found that a higher level of CD24 mRNA expression correlated with later stage and metastatic PC. We therefore hypothesize that CD24 promotes mutant p53 inactivation, which contributes to tumor metastasis in AA CRPC patients. Our results will provide a better understanding of CRPC metastasis, especially in AA PC patients. Since silencing of CD24 functionally restores (mutant) p53 CD24 may be a therapeutic target. Validating our hypothesis will create a new target for the treatment of metastatic CRPCs, benefitting those at a higher risk for developing this type of cancer, especially AA men.
Molecular Regulation of KAISO in Prostate Cancer
TU Co-Lead: Clayton C. Yates, PhD
UAB Co-Lead: William E. Grizzle, MD, PhD
Although prostatic adenocarcinoma is the most commonly diagnosed cancer in U.S. males, the death rate from this cancer is lower than would be expected. African Americans (AAs) who have prostate cancer (PCa) typically have more aggressive disease and make up a disproportionate number of the deaths from this disease; however, many patients with PCa do not die of PCa even if untreated (i.e., indolent PCa). We have recently studied expression of the molecule, Kaiso, in PCa and found that Kaiso is increased in aggressive PCas, especially in PCas of AAs. Also, we have found that Kaiso is involved in facilitating the epigenetic suppression of genes (e.g., E-cadherin) and, via this silencing of specific genes, causes the epithelial-to-mesenchymal transition (EMT) in PCas. Therefore, the objectives of our proposal are to demonstrate the molecular mechanisms regulating the nuclear expression of Kaiso and to show that Kaiso can be targeted therapeutically to reduce EMT and associated metastases of PCa. Based on the above, and preliminary findings pointing towards a role for Kaiso in the phenotypic plasticity that underlies tumor dissemination, we hypothesize that subcellular localization of Kaiso can be targeted to limit dissemination and prevent metastatic tumor growth.
Role of leptin-Notch axis in pancreatic cancer
MSM Lead: Ruben Gonzalez-Perez
UAB Lead: Chris Klug, PhD
This project will investigate: (1) whether obesity and leptin-Notch signaling are critical for pancreatic cancer (PC) development, PC stem cells (PCSC) and drug resistance; (2) whether PC from patients of different ethnicities respond differently to leptin signaling; and (3) whether the potent, non-toxic and novel antagonist of leptin signaling we developed, IONP-LPrA2, could be an effective adjuvant for chemotherapeutics used in PC treatment. Preliminary data show that leptin stimulates PC proliferation, PCSC self-renewal and impairs PC chemotherapeutic efficacy. These investigations will help to understand whether obesity and leptin-Notch signaling could cause PC health disparity, and will help the development of novel targeted therapies and improve PC chemotherapeutic efficacies, and advance our limited understanding of the roles of obesity, and leptin signaling in PC progression and chemoresistance.
Altered Metabolic Switch and BRCA1-Associated Cancers
MSM Lead: Veena Rao, PhD
UAB Lead: Yuchang Fu, PhD
MSM Lead:Veena Rao, PhD
UAB Lead:Yuchang Fu, PhD
This project will explore the hypothesis that BRCA1 functions as a tumor suppressor through its sequestration of UBE21, a pivotal regulator of glucose transporter, resulting in regulated glucose uptake. Our recent results show that BRCA1 proteins bind to UBC9 and that the lack of binding by disease-associated mutant BRCA1 proteins resulted in deregulated Ubc9 levels and loss of growth suppression by BRCA1 proteins in TNBC. Based on these preliminary results we hypothesize that BRCA1 (by binding to Ubc9) regulates GLUT-4 facilitated glucose uptake and glycolysis resulting in tumor suppression of TNBC.
Racial differences in exosome signaling promote tumor aggressiveness in African American breast cancer patients
TU Lead: Clayton C. Yates, PhD
UAB Co-Lead: William E. Grizzle, MD, PhD
This project will delineate the role of the transcriptional repressor Kaiso, as the regulator of epithelial-to-mesenchymal transition (EMT) and chemoresistance through the transfer of genetic and epigenetic material contained in exosomes. Others and we have found that AA patients have increased expression of markers related to EMT and that this is associated with a relapse of breast tumors from front-line therapy. We will determine Kaiso’s role in regulating a novel form of cellular communication.
Racial Differences in Molecular Characteristics of Cervical Cancer and Response to Treatment
MSM Lead: Roland Matthews, MD
UAB Co-Lead: Chandrika Piyathilake, MPH, PhD
The 5-year survival rates for cervical cancer (CC) are significantly lower for African American (AA) compared to Caucasian American (CA) women. Since the underlying differences in molecular characteristics of CCs as an explanation for disparities in mortality have received little or no attention, we propose to investigate whether such differences in CCs contribute to racial differences in survival.
Dual Targeting Nanoscale Drug Delivery Systems for Treatment of Metastatic Prostate Cancer
TU Lead: Mohamed Abdalla, PhD
UAB Lead: Keshav Singh, PhD
Prostate cancer (PCa) is currently the most commonly diagnosed cancer and the second-leading cause of cancer death in men in the United States. Therapeutic options for patients with metastatic hormone-refractory PCa are very limited. This project will focus on developing dual targeting nanoscale drug delivery systems (DT-NDDSs), which will utilize a combination of a panel of novel designed peptides with enhanced binding affinities to receptors on prostate cancer (PC) cells.
Chemopreventive and Therapeutic Activity of Withania somnifera and its Mechanism of Action in Human Breast Cancer
TU Lead: Dr. Karmal Kazal
UAB Lead: 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.
BRCA1 Deficiency and Epithelial Ovarian Cancers
MSM Lead: Dr. Veena Rao
UAB Lead: 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.
Pre Pilot-Projects – Ended
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Role of TTP-Lin28-let-7-axis in Colorectal Cancer Treatment Responses
TU Lead Amit Tiwari, PhD
UAB Lead Esther Suswam, PhD
The proposed study will assess the importance of the TTP-Lin28-let-7 signaling pathway in the regulation of chemotherapy responses in colorectal cancers (CRCs). The proposal will evaluate the TTP/Lin28/let-7 pathway (which may be inactivated in CRCs – allowing deregulation of oncogenes such as Lin28B) in CRC primary tumors based on p53 status and assess the importance of this pathway in modulating tumor progression and responses to chemotherapy.
Association of CD24 and Progression of Prostate Cancer in African-Americans
MSM Lead James Lillard, PhD
UAB Lead Lizhong Wang, PhD
This proposal focuses on exploring the role CD24 expression (gene and subsequent protein expression) have in prostate cancer (PCa) among African American, Caucasian, and Asian men. The application is based on hypothesis that CD 24 is linked to risk and progression of PCa (as CD24 is over-expressed in many cancer types) and preliminary applicant data indicates growth, progression, and metastasis is reduced via CD24 mutation in murine models).