Upcoming Events

PACHE
July 23-24, 2018
NCI Shady Grove Campus in Rockville, Maryland

Internal Advisory Committee Meeting
July 25, 2018
University of Alabama at Birmingham

Annual Cancer Research Symposium
July 25-26, 2018 
University of Alabama at Birmingham


Partnering Institutions

Morehouse School of Medicine (MSM)
Tuskegee University (TU)
University of Alabama at Birmingham (UAB)


Contact - PI

 MSM: James Lillard, PhD
   TU: Roberta Troy, PhD
 
UAB: Upender Manne, PhD


Program Managers

 MSM: Jennifer Creighton
 TU: Chiquita Lee
UAB: Suzanne Byan-Parker

 

 

 

 

 

 

 

 

 

 

 


Overall Partnership Summary


This type-2 application is to strengthen and build upon the established U54 Partnership between Morehouse School of Medicine (MSM), Tuskegee University (TU), and the UAB Comprehensive Cancer Center (UABCCC). The Partnership, located in the heart of the Southeast, a region with a large, historically underserved, African American population, has the overall goal of attaining excellence in research focused on elimination of cancer health disparities and on reducing the cancer burden among underserved populations in the region. The partnering institutions possess unique strengths that complement each other in achieving the proposed goal through integrated research, education, and outreach. The primary objectives are to enhance productive cancer research programs, to develop a pipeline of racial/ethnic minority investigators in cancer research at MSM and TU, and to increase the level of involvement of investigators conducting research on cancer disparities at the UAB CCC. The Partnership has four Cores (Administrative, Outreach, Research Education, and Planning & Evaluation); two Full Research Projects; a Pilot Research Project; and two Shared Resources (Bioethics and Biostatistics/Bioinformatics). With these assets and activities, the Partnership will: 1) through the full projects, identify molecular mechanisms and new therapeutic targets for metastatic prostate cancer, which is present at a higher rate in African American men, and, through the pilot project, adapt the current, successful patient navigation program for racial/ethnic minority recruitment at the UAB CCC for implementation at the MSM and Grady Hospital; 2) through the Outreach Core, apply an innovative cancer survivor care plan at MSM, TU, and the UAB CCC by linking community- and health system-based patient navigators and advisors to improve satisfaction with care, and implement culturally appropriate community health education for cancer survivors and caregivers; 3) through the Research Education Core, employ an integrated cancer research education program that involves capacity building and linkages to undergraduate and graduate students and junior faculty, allowing them to pursue careers in cancer research; and 4) provide funding for additional Pilot Research projects. The Planning & Evaluation Core will continually assess/evaluate the outcomes of the cores, research projects, and shared resources. The Bioethics Shared Resource will promote and ensure adherence to bioethical principles and address ethical considerations in relationships between the institutions and between the institutions and communities. The Biostatistics/Bioinformatics Shared Resource will deliver statistical and bioinformatics support for all activities. Together, we will contribute to elimination of cancer health disparities.


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 University of Alabama at Birmingham Comprehensive Cancer Center (UAB CCC), 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.



Full Project 1: 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.

Full Project 2: 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.