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166,118 grants matching “stem cells”
Placental models to support embryogenesis in vitro
$1,165,500Magdalena Zernicka-Goetz · California Institute Of Technology · DP1 · FY2021 · HD
Placental models to support embryogenesis in vitro
$1,165,500Magdalena Zernicka-Goetz · California Institute Of Technology · DP1 · FY2023 · HD
Selective interactome vulnerability across the Alzheimerâs disease spectrum
$1,165,481Gabriela Chiosis · Sloan-Kettering Inst Can Research · R01 · FY2023 · AG
Development and Validation of a Marmoset Model of Late-Onset Alzheimer Disease Based on Tau Seeding
$1,165,318Afonso C Silva · University Of Pittsburgh At Pittsburgh · R24 · FY2021 · AG
USING THE PROSTAGLANDIN E2 SIGNALING CASCADE TO MITIGATE THE EFFECTS OF ACUTE AND DELAYED RADIATION EXPOSURE TO HEMATOPOIESIS AND BLOOD STEM CELL FUN
$1,165,121Trustees Of Indiana University · · FY2015 · Department of the Army
Chaperome networks in Alzheimer's disease
$1,165,073Gabriela Chiosis · Sloan-Kettering Inst Can Research · R01 · FY2024 · AG
A CENTER OF MOLECULAR DEVELOPMENTAL HEMATOPOIESIS
$1,164,619Stuart H Orkin · Boston Children'S Hospital · P30 · FY2012 · DK
Transgenic animal production for neuroscience research
$1,164,601James Pickel · National Institute Of Mental Health · Z01 · FY2008 · MH
Integrated Cellular and Tissue Engineering for Ischemic Heart Disease
$1,164,534Jianyi Zhang · University Of Alabama At Birmingham · U01 · FY2022 · HL
PROSTATE CANCER: TRANSITION TO ANDROGEN-INDEPENDENCE
$1,164,524University Of North Carolina Chapel Hill · P01 · FY2001 · CA
Connecting Rare Mutations to Common Pathways
$1,164,521Jeffrey D Milbrandt · Washington University · P50 · FY2025 · HD
Neural Immunity in HIV Dementia
$1,164,241Howard Eliot Gendelman · University Of Nebraska Medical Center · P01 · FY2010 · NS
Mechanistic Analysis of Genetic Modifiers in Parkinson's Disease
$1,164,000Dimitri Krainc · Northwestern University At Chicago · R35 · FY2024 · NS
A Lung-chip microphysiological system to model SARS-CoV-2 infection and test novel therapeutics
$1,163,750Clive Niels Svendsen · Cedars-Sinai Medical Center · UG3 · FY2020 · NS
The 3D genome in transcriptional regulation across the postnatal life span, with implications for schizophrenia and bipolar disorder
$1,163,690Panagiotis Roussos · Icahn School Of Medicine At Mount Sinai · U01 · FY2021 · MH
HEMATOPOIETIC STEM CELLS (HSC) COMPRISE LESS THAN 0.1% OF THE BONE MARROW (BM) OF ADULTS YET THEY PRODUCE ALL BLOOD CELLS THAT ARERESPONSIBLE FOR CONSTANT MAINTENANCE AND IMMUNE PROTECTION OF THE BODY. IN ADDITION TO THE REQUIREMENT FOR HIGH CELL OUTPUT THECONCENTRATION OF THE DIFFERENT BLOOD CELL LINEAGES PRODUCED ARE PRECISELY CONTROLLED TO ALLOW NOT ONLY PRESERVATION OF NORMALHOMEOSTASIS BUT ALSO THE PROMPT RESPONSE TO SPECIFIC STIMULI AND DEMANDS. PREVIOUS STUDIES HAVE SUGGESTED THAT EXPOSURE TO GALACTICCOSMIC RAY (GCR) AND SOLAR PARTICLE EVENT (SPE) RADIATION THAT OCCURS DURING SPACE FLIGHT MAY INCREASE THE LIKELIHOOD OFCARCINOGENESIS WITH LEUKEMIAS BEING ONE OF THE MOST FREQUENT RADIOGENIC CANCERS AND THE ONES WITH THE SMALLEST LATENCY PERIOD. WEHYPOTHESIZE THAT GCR AND SPE RADIATION CAN HAVE A DELETERIOUS IMPACT NOT ONLY AT THE LEVEL OF THE MATURE IMMUNE CELLS AND THEIRCOMMITTED PROGENITORS AS IS CURRENTLY THOUGHT BUT AT THE EARLIER DEVELOPMENTAL STAGE OF THE HSC. GENETIC LESIONS INDUCED BY THISEXPOSURE CAN LEAD DIRECTLY TO LEUKEMIC TRANSFORMATION AND MAY ALSO CAUSE THESE CELLS TO GENERATE A FUNCTIONALLY COMPROMISED IMMUNESYSTEM LACKING THE ABILITY TO EFFECTIVELY FIGHT CHALLENGES SUCH AS PRE-LEUKEMIC TRANSFORMATIONS. AS SUCH ASTRONAUTS WOULD BE DOUBLY ATRISK DUE TO BOTH THE POTENTIAL FOR INDUCTION OF LEUKEMIA BY GCR/SPE RADIATION AND THE REDUCED ABILITY OF THE ASTRONAUTS IMMUNESYSTEMS TO IDENTIFY AND ELIMINATE MALIGNANT CELLS IN THE BODY. SINCE IT HAS ALSO BEEN SHOWN THAT BOTH GENDER AND GENETIC FACTORS LIKELYIMPACT UPON SUSCEPTIBILITY TO LEUKEMOGENESIS IT IS ESSENTIAL TO PRECISELY DEFINE THESE RISKS TO THE HUMAN HEMATOPOIETIC SYSTEM AS A RESULTOF EXPOSURE TO GCR/SPE AND TO ACCURATELY MODEL THE IMPACT OF GENDER AND GENETIC/EPIGENETIC BACKGROUND. UNFORTUNATELY EXISTINGANIMAL MODEL SYSTEMS HAVE NOT ALLOWED THE PRECISE ASSESSMENT OF THE RISKS ASSOCIATED WITH ACUTE OR CHRONIC EXPOSURE OF HUMANHEMATOPOIETIC CELLS TO GCR OR SPE NOR THE ELUCIDATION OF THE MECHANISM INVOLVED.IN THE PRESENT PROPOSAL WE HAVE FORMED A HIGHLY SYNERGISTIC TEAM TO DIRECTLY ADDRESS THIS ISSUE. THIS TEAM COMBINES THECOMPLEMENTARY EXPERTISE OF 6 DIFFERENT LABORATORIES: HUMAN HSC AND CELLS OF THE SUPPORTING BM MICROENVIRONMENT (PORADA ANDALMEIDA-PORADA GROUPS) TISSUE ENGINEERING/SCAFFOLDS (SOKER GROUP) BIOINFORMATICS/GENOMICS (WALKER GROUP) AND RADIATION BIOLOGY(WILSON AND ANDERSON GROUPS). WE WILL USE A VARIETY OF BOTH IN VITRO CELL CULTURE AND IN VIVO TRANSPLANTATION SYSTEMS TO RIGOROUSLY TESTTHE NOVEL HYPOTHESIS THAT GCR AND SPE RADIATION CAN DIRECTLY INDUCE DNA DAMAGE AND MUTATIONS WITHIN PRIMITIVE HSC AND CAN ALSOCONTRIBUTE TO DEFECTIVE HEMATOPOIESIS/IMMUNITY THROUGH SO-CALLED BYSTANDER EFFECTS BY DAMAGING THE BM MICROENVIRONMENTAL CELLSTHAT REGULATE HEMATOPOIESIS.WE ASSERT THAT A MODEL SYSTEM WITH SPECIFIC GENDER-RELATED FACTORS AND GENETIC BACKGROUND WILL ENABLE US TO TEST WHETHER THESE DIRECTAND INDIRECT INSULTS CAN CAUSE THE NORMAL HEMATOPOIETIC SYSTEM TO BE POPULATED BY UNSTABLE CLONES THAT ARE FUNCTIONALLY DEFICIENT ANDMAY BE MORE PRONE TO LEUKEMIA. ACCORDINGLY THE OVERALL GOAL OF THIS PROPOSAL IS TO UTILIZE UNIQUE MODEL SYSTEMS DEVELOPED IN OURLABORATORY TO PRECISELY AND REPRODUCIBLY DEFINE THE EFFECTS OF GCR AND SPE RADIATION ON THE HUMAN HEMATOPOIETIC AND IMMUNESYSTEMS AT BOTH THE MOLECULAR AND FUNCTIONAL LEVELS THEREBY DEFINING THE POSSIBLE RISK OF LEUKEMOGENESIS AS A RESULT OF EXPOSURE.
$1,163,642Wake Forest University Health Sciences · · FY2014 · National Aeronautics and Space Administration
Molecular Mechanisms of Pathogenesis in Huntingtonâs disease
$1,163,530Leslie Michels Thompson · University Of California-Irvine · R35 · FY2021 · NS
Molecular mechanism of thyroid hormone receptor function during metamorphosis
$1,163,470Yun-Bo Shi · Eunice Kennedy Shriver National Institute Of Child Health & Human Development · ZIA · FY2023 · HD
Regulation of stem cell development during tissue remodeling
$1,163,470Yun-Bo Shi · Eunice Kennedy Shriver National Institute Of Child Health & Human Development · ZIA · FY2023 · HD
Hypoxia signaling in cancer development
$1,162,850Zhengping Zhuang · Division Of Basic Sciences - Nci · ZIA · FY2025 · CA
Embryonic Stem Cell-Derived Platelets as Cellular Therapeutics
$1,162,785Mortimer Poncz · Children'S Hosp Of Philadelphia · U01 · FY2013 · HL
Functional Genomics of Platelet Aggregation Using iPS and Derived Megakaryocytes
$1,162,775Lewis C Becker · Johns Hopkins University · U01 · FY2012 · HL
Integrated Cellular and Tissue Engineering for Ischemic Heart Disease
$1,162,722Jianyi Zhang · University Of Alabama At Birmingham · U01 · FY2018 · HL
UCLA SPORE in Prostate Cancer
$1,162,609Robert E Reiter · University Of California Los Angeles · P50 · FY2018 · CA
Selective interactome vulnerability across the Alzheimerâs disease spectrum
$1,162,517Gabriela Chiosis · Sloan-Kettering Inst Can Research · R56 · FY2021 · AG