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20,252 grants found
Showing 18,721 – 18,740 of 20,252 grants
Analyzing the Hypersensitivity of MMR-deficient Colorectal Cancers to mTOR Inhibition and the Response of Cancer Stem Cells
Project Summary Mutations in DNA mismatch repair (MMR) genes are causative in Lynch Syndrome (LS) and defective MMR drives tumorigenesis in a significant proportion (15 - 20%) of s...
Dissecting new mechanisms of lysosome quality control in health and disease
PROJECT SUMMARY Lysosomes function as critical nodes for macromolecular recycling, metabolic rewiring, and pro-growth signaling in cells. Accordingly, defects in lysosome function...
Geranylgeranyl diphosphate synthase inhibitor therapy for multiple myeloma
Project Summary Multiple myeloma (MM) is an incurable bone marrow (BM) cancer characterized by the production of monoclonal protein (MP). Development of drug resistance and off-tar...
SMARCB1 regulated SWI/SNF complex function in Malignant Rhabdoid Tumors
PROJECT SUMMARY A research program will be undertaken to study SMARCB1-regulated SWI/SNF complex function in malignant rhabdoid tumors. Over the past few years, major cancer genome...
Dynamic 3D chromatin remodeling in acute leukemia - Resubmission - 1
ABSTRACT Recent advances in chromatin conformation capture techniques have revolutionized our understanding of chro- matin organization and have provided novel insights at an unpre...
Addressing Chemoresistance in Pancreatic and Ovarian Cancers: Photodynamic Priming and Repurposing of Tetracyclines using Targeted Photo-Activable Multi-Inhibitor Liposome
ABSTRACT The prognosis for patients with advanced stage ovarian or pancreatic cancer has remained dismal for decades. The poor response rates result, in part, from resistance to sa...
Multiplexed time domain fluorescence tomography of tumor biomarkers during immunotherapy
Abstract: Immunotherapy using programmed death 1 receptor (PD-1) blockade, either alone or in combination with existing therapies, has been proven to significantly improve survival...
Molecular mechanisms of T cell responses to a clonal neoantigen resulting from a mutated driver oncogene.
PROJECT SUMMARY/ABSTRACT Immunotherapy induces durable remissions in a subset of patients with highly mutated cancers. However, most cancers are modestly mutated and fail to respon...
Defining the Critical Function and Regulation of NNMT in Breast Cancer Progression and Metastasis
N-methyltransferase (NNMT), a key enzyme in the NAD+ salvage pathway with unclear functions, is expressed highly and specifically in basal-like breast cancer (BLBC). We found that...
Targeting Epigenomic Regulators at the Replication Fork in PDAC
Pancreatic adenocarcinoma (PDAC) remains a therapeutic challenge, making the identification of new targets and development of novel treatment strategies for this disease of paramou...
Targeting Lymph Node Dependent Immune Tolerance in Cancer
Project Summary Background: Malignant melanoma and pancreatic ductal adenocarcinoma (PDAC) typically spread to lymph nodes (LNs) prior to outgrowth in distant tissues. While metast...
Mechanisms of metabolic stress-induced transcriptional regulation in prostate cancer
Metastatic prostate cancer (PCa) remains a major clinical challenge. Although androgen deprivation therapy (ADT) is effective in treating PCa, majority of the patients quickly deve...
Two photon fluorescence microscopy for dermatologic surgery and biopsy
Medicare reimburses over 5 million biopsies resulting in 1.5 million surgical procedures annually for nonmelanoma skin cancer (NMSC). Despite its burden on the health care system,...
DNA Methylation Markers, Genes and Breast Cancer Risk
PROJECT SUMMARY Genome-wide association studies (GWAS) have identified common variants in ~200 genetic loci associated with breast cancer risk. However, it is difficult to translat...
Genetic Predisposition to Chronic Lymphocytic Leukemia (CLL)
Project Summary CLL is the most common leukemia of adults in North America, with about 20,000 new cases per year, and remains incurable. Although a small subset of patients has ind...
Regulation of DGAT - dependent lipogenesis in colonic epithelial growth
Abstract Obesity is characterized by systemic lipid accumulation, inflammation, and enhanced tumorigenesis in different tissues, including colon. With obesity, intracellular lipid...
A novel determinant of prostate cancer growth
Project Summary/Abstract Prostate cancer (CaP) will cause the deaths of more than 33,000 American men in 2020 because systemic treatments for metastatic CaP fail. Actionable target...
Novel TYRO3 inhibitors for treatment of cancer
TYRO3 is a member of the TAM (TYRO3, AXL, MERTK) family of receptor tyrosine kinases. All three family members are aberrantly expressed in cancer cells, where they function to prom...
Development of an NTSR1-Targeted Radiotherapeutic for Colorectal Cancer
Objective: More effective treatment options are needed across all clinical stages of colorectal cancer (CRC), from eliminating residual disease after surgery, improving surgical ca...
Molecular mechanism of EGFRs protein-protein interaction inhibition by a grafted peptide in NSCLC
Project Summary: The long-term objective of this research project is to understand the role of dimerization in extracellular domains (ECD) of epidermal growth factor receptors (EGF...