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Functional characterization of lysosome membrane and its protein quality control system
PROJECT SUMMARY The lysosome is an important organelle responsible for digesting and recycling materials, nutrient sensing, and controlling cell proliferation. It is also linked to...
Chemical synthesis to access rare heterocycles and tool compounds to probe bacterial polysaccharide metabolism
Abstract Two emphasis areas are proposed which are underpinned by synthetic organic chemistry. First, new synthetic methodology to access exceptionally rare nitrogen-rich compounds...
Cytokinesis and the Septin Cytoskeleton
Project Summary/Abstract: Cytokinesis is fundamental to life, and the septins form cytoskeletal scaffolds or diffusion barriers of distinct architectures to impact diverse cellular...
Calcium encoding mechanisms in a model plant
All eukaryotes relies on calcium ion (Ca2+) as a second messenger to respond to internal and external signals. Defects in Ca2+-based signaling cause numerous human diseases. Despit...
Development of Computational Tools and Their Applications to Various Biological Systems
PROJECT SUMMARY Biological macromolecules work together in a complex network to carry out essential cellular functions in living organisms. Understanding this complex network of in...
Understanding Hox epigenetic memory formation during motor neuron differentiation
Project Summary Hox genes are crucial for patterning the early embryo along the anterior-posterior axis in all bilateral animal species. Hox dysregulation leads to severe developme...
The Consequences of Aneuploidy
PROJECT SUMMARY/ABSTRACT We are requesting grant support for the Federation of American Societies for Experimental Biology (FASEB) conference “The Consequences of Aneuploidy.” In p...
Aging Neural Systems and Communication Difficulties
PROJECT SUMMARY/ABSTRACT Age-related speech recognition difficulty and its association with poorer memory, increased fatigue, social isolation, and cognitive decline are major publ...
Charting Positive Valence Systems Trajectories in Offspring of Depressed Mothers to Predict Internalizing Symptoms in Early Childhood
PROJECT SUMMARY Offspring of mothers with depression are 2 to 3 times more likely than offspring of never-depressed mothers to develop anxiety and depressive disorders. Meta-analyt...
Ceramide and Cell Metabolism: Defining the Role of Sphingolipids in Modulating Mitochondrial Bioenergetics of Chronic Lymphocytic Leukemia
Project Summary/Abstract Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia and accounts for 20% of leukemia-related deaths annually. In CLL, hyperactivat...
Resolving epigenetic determinants of cellular plasticity programs in non-small cell lung cancer
SUMMARY Pioneering research in cancer biology over the past four decades has uncovered a repertoire of oncogenes and tumor suppressors that initiate and maintain tumorigenesis acro...
Evaluating and Optimizing Novel nSMase2 Inhibitors in the Treatment of Cancers
PROJECT ABSTRACT / SUMMARY: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, but many patients fail to respond. Expanding the response to ICIs is a major g...
Disparities in cardiovascular health in young adults with type 1 diabetes
PROJECT SUMMARY Cardiovascular disease (CVD) is the leading cause of death for people with type 1 diabetes (T1D), and abnormalities preceding overt CVD (left ventricular hypertroph...
Informing optimal dosing of the future antimalarial, artemether-lumefantrine plus amodiaquine, in key neglected target populations of children with severe acute malnutrition and adults living with HIV
PROJECT SUMMARY/ABSTRACT This award will allow Dr Clifford George Banda to characterise the pharmacokinetic and safety profiles of two long-acting artemisinin partner drugs, lumefa...
Leveraging human intracranial recordings to quantitatively characterize basal ganglia output during speech
PROJECT SUMMARY The basal ganglia (BG), a set of highly interconnected nuclei deep in the brain, are critical to normal motor and cognitive functioning in humans; diseases of the B...
Novel inner ear organoid models for studying hair cells in normal development and in the deaf-blindness disease Usher Syndrome Type 1F
Abstract: Novel inner ear organoid models for studying hair cells in normal development and in the deaf- blindness disease Usher Syndrome Type 1F The fundamental human sense of bal...
Understanding the Impact of Dengue Virus Lineage Persistence on Outbreak Potential
Project Summary New solutions are desperately needed to reduce the annual global burden of dengue. As we have witnessed for SARS-CoV-2, virus genomics can be harnessed to directly...
Determinants of susceptibility to pediatric acute myeloid leukemia
PROJECT SUMMARY/ABSTRACT The role of germline genetic variation and viral infection in development and progression has been studied extensively in adult tumors and autoimmune disea...
Molecular and cellular underpinnings of placental malaria
PROJECT SUMMARY/ABSTRACT Malaria in pregnancy poses significant threat to the wellbeing of the mother, fetus, and neonate and in sub- Saharan Africa, it kills 100,000 infants annua...
Metabolic Mechanisms of Recovery in Mild TBI
Project Summary The occurrence of concussion, or mild TBI, has been steadily increasing in incidence over the past decade. One possible consequence of concussion - post-concussion...