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201,169 grants found
Showing 199,181 – 199,200 of 201,169 grants
Linear energy transfer (LET) dependencies for understanding pancreatic tumor control and relevant molecular endpoints in support of RBE-based heavy-ion radiotherapy
This proposal brings together a unique interdisciplinary team with complementary expertise in high-LET radiobiology, pancreatic cancer research, and high-LET physics. It leverages...
Exploiting sex-dependent brain injury response for nanoparticle therapeutics
Abstract Traumatic brain injury (TBI) afflicts over 1.7 million persons per year in the U.S. alone, resulting in substantial economic burden annually. To date, despite promising pr...
Functional Significance of Ferritin Light Chain in Sepsis-associated Kidney Injury
Sepsis accounts for nearly 50% of acute kidney injury (AKI) in the intensive care unit and significantly impacts mortality. However, therapy for sepsis-associated AKI (SA-AKI) has...
SARM1 functional polymorphisms and their contribution to ALS risk
Motor axon loss is a cardinal symptom of amyotrophic lateral sclerosis (ALS). Axon loss can be driven by a genetically encoded program in which the axon survival factors NMNAT2 and...
Structural Biology of Dopamine Signaling
Abstract Human dopamine signaling pathway induces and facilitates dopamine neurotransmission through the mesolimbic dopaminergic pathway, which modifies reward-related behaviors an...
Central Nervous System Plasticity in Airway Disease
PROJECT SUMMARY Exacerbations (asthma attacks) account for nearly one-third of all asthma deaths. Despite psychiatric illness as a risk factor for death from asthma, and many conne...
The role and mechanistic regulation of cPLA2alpha in eicosanoid biosynthesis and wound healing
In recent years, new technological advancements in small molecule analyses (e.g., lipidomics) have identified a biochemical manifestation of impaired wound healing: the development...
Developmental Regulation of Gene Expression by Long Undecoded Transcript Isoforms
PROJECT SUMMARY Dynamic gene expression programs drive essential biological processes including cellular differentiation and stress response pathways. During these processes, cells...
A Leukemia Cell-Specific Coiled-Coil Protein for Treatment of Chronic Myeloid Leukemia
Project Summary/Abstract The long-term goals of this proposal are to explore the protein dimerization interface as an area for therapeutic intervention. Protein dimerization/oligom...
Using Genetic Diversity to Manage Neurological Disease
Project Summary/Abstract Understanding and treating genome abnormalities that lead to rare genetic neurodegenerative diseases such as Niemann-Pick C1 globally managing cholesterol...
Interplay between AMPK and Hippo Signaling Regulates Ocular Antiviral Response to Zika virus infection
PROJECT SUMMARY: Zika virus (ZIKV) is a teratogenic human pathogen that causes congenital eye and brain diseases. Affected babies exhibit vision impairment and associated ocular pa...
Serial immunotherapy combination to modulate the tumor environment in patients with metastatic gastroesophageal cancer
PROJECT SUMMARY/ABSTRACT Development of effective therapies is an urgent unmet medical need for patients with metastatic gastroesophageal adenocarcinoma (mGEA). The advent of immun...
Enabling Mass Spectrometry Analysis of the Sulfoproteome
Project Summary Tyrosine O-sulfation, i.e., transfer of a sulfonate group to tyrosine amino acid residues in proteins, is a widespread posttranslational modification (PTM) in eukar...
Synthesis and Chemical Biology of Bioactive Natural Products
Project Summary/Abstract This proposal describes our program focused on the development of novel chemical reactions for complex molecule synthesis, innovative strategies for molecu...
Molecular functions of human zinc transporter-8 in pancreatic beta cells
The long-term goal of our research is to understand how the molecular and cellular functions of zinc transporter-8 (ZnT8) modulate pathophysiologic responses of human pancreatic be...
Interplay Between Nuclear Organization and Function
PROJECT SUMMARY/ABSTRACT Goals: Peri-Centromeric Heterochromatin (PCH) is required for genome stability/DNA repair, chromosome pairing, nuclear architecture, and transposon and gen...
Assessing the Influence of the Human Lipidome on Risk of Diabetes in a Minority Population
PROJECT SUMMARY Type 2 diabetes is a major public health concern. Diabetes currently affects 25.8 million people in the US alone and 90-95% of all cases are type 2. There are many...
Pericytes differentiate into smooth muscle cells through HIF2a/SDF1 activation
ABSTRACT Pulmonary arterial hypertension (PAH) is a life-threatening disorder characterized by elevated lung pressures, right heart failure, and premature death. Current therapies...
Fluid shear stress mechanotransduction at endothelial cell-cell junctions
Project Summary This project aims to understand in molecular detail how fluid shear stress acting on endothelial cells triggers mechanical activation of signaling pathways at cell-...
Soft drusen in rhesus macaques as a nonhuman primate model of early age-related macular degeneration
PROJECT SUMMARY Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly, but current treatments target advanced stages when interventions may be l...