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.
Pilot Project: Altered Metabolic Switch and BRCA1-Associated Cancers
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.
Pilot Project: Racial differences in exosome signaling promote tumor aggressiveness in African American breast cancer patients
TU Lead: Clayton Yates, PhD
UAB Lead: William 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.
Pilot Project: Racial Differences in Molecular Characteristics of Cervical Cancer and Response to Treatment
MSM Lead: Roland Matthews, MD
UAB 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.
Pilot Project: 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.