The CTBR awarded 3 seed funding projects to full and associate faculty members for our 2014-2015 grant year. The seed funding projects received $20,000 for one year.
Multifunctional Molecules and Nanoparticles for Head and Neck Cancer Applications
PI: Charles M. Drain, Chemistry Department
The goal of this work is to improve the prognosis for HNSCC for all patients including in underserved populations. There are three core hypotheses. (1) Porphyrin dyes are ideal multifunctional molecular systems for diagnosis, imaging, and treatment of HNSCC because they are biocompatible and have unique photonic and chemical properties that can be readily tuned, bind most metal ions with very high affinity, and can be appended with multiple cancer targeting entities. (2) Multifunctional dyes adsorbed to non-coated silica nanoparticles under normal physiological pH will be released in a lower pH environment around cancer tissues for selective therapy. (3) Biomedical effects of multifunctional porphyrin dyes and dye-coated silica nanoparticles can be evaluated using cultured HNSCC cells, a HNSCC mouse xenograft model, and primary human HNSCC tumorgraft model.Photodynamic therapy (PDT) is being studied as an alternative to surgery, particularly in the treatments of early stage cancers. This proposal is a collaborative effort between Drs. Charles M. Drain (Hunter College of the City University of New York), Ruomei Gao (State University of New York at Old Westbury) and Xinbin Gu (Howard University) that aims to develop multifunctional compounds and nanosystems for efficient earlier diagnosis, targeted delivery, sensitive imaging, and better treatments using PDT for HNSCC. The outcomes of this project will improve all patient outcomes and earlier interventions will diminish the health disparities.
Cancer and Alzheimer, p53 and Tau; is Pin1 the Moderator?
PI: Frida Kleiman, Chemistry Department
mRNA 3’ end processing, regulates the steady-state levels of different mRNAs and contributes to the cells rapid response to stress. We propose to study the basic molecular mechanism of p53, a factor mutated in most cancers, and nuclear tau, the neuronal microtubule associated protein involved in Alzheimer’s disease, regulation of mRNA 3’ processing. Importantly, both p53 and tau functionally interact with PARN deadenylase, an enzyme that regulates mRNA stability, and Pin1, an enzyme that catalyzes the structure of phosphoproteins. The specific hypothesis is that p53 and Tau functionally interact with PARN deadenylase and this regulation is controlled by Pin1 resulting in the regulation of mRNA stability of different genes in stress or disease situation. We will study the role of Tau on the regulation of mRNA 3’ end processing and characterization of the functional interaction between Pin1 and factors involved in mRNA 3’ processing during DDR. The knowledge gained from this proposal will give very novel targets for the disease situation, how the normal balance works. Knowledge gained may also help to manipulate, for therapeutic purposes, the way in which cells respond to DNA damage, affecting cell death or survival, mutation rates or the development of disease.
PVT1 and Racial Disparity in Aggressive Prostate Cancer
PI: Olorunseun Ogunwobi, Biology Department
The objective of this project is to investigate the role of PVT1 and its associated miRNAs in the incidence of aggressive PC in Black men. The specific aims are (1) to determine expression pattern of PVT1 and the miRNAs it encodes in a panel of human prostate cancer cell lines established from Black and White patients with varying degrees of disease aggressiveness, and (2) to determine the functional role and molecular targets of PVT1 and the six miRNAs it encodes in PC using cellular and murine models of PC. We anticipate that our data will provide an indication as to the potential usefulness of either PVT1 or any of its associated miRNAs as biomarkers of a predisposition to the development of aggressive PC in Black men. Our data will serve as the basis for further studies to evaluate the usefulness of any of these novel biomarkers for molecularly targeted therapy specifically in Black men.