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166,118 grants matching “stem cells”
MSC Exosome Treatment for BPD: Impact on Immunity and Lung Development
$884,913Stella Kourembanas · Boston Children'S Hospital · R01 · FY2023 · HL
A Modern Confocal Microscope to Maintain and Expand the Continuity of Basic Biology Research
$884,837Benjamin Abrams · University Of California Santa Cruz · S10 · FY2025 · OD
Training Grant in Cardiovascular Research
$884,826Peter Libby · Brigham And Women'S Hospital · T32 · FY2020 · HL
Therapeutic Targeting of Human AML Stem Cells
$884,768Craig T. Jordan · University Of Colorado Denver · R35 · FY2024 · CA
NHGRI Sample Repository for Human Genetic Research
$884,735Laura Scheinfeldt · Coriell Institute For Medical Research · U24 · FY2024 · HG
THE EVOLUTION OF CELL-CELL ADHESION AND THE ASSEMBLY OF EPITHELIAL TISSUES WERE INTIMATELY COUPLED TO THE EVOLUTION OF COMPLEX MULTICELLULARITY. EPITHELIA HAVE ESSENTIAL ROLES FROM ACTING AS AN ENVIRONMENTAL BARRIER AND PARTITIONING ORGANISMS INTO DISCRETE COMPARTMENTS TO COORDINATING MORPHOGENESIS DURING DEVELOPMENT. WE PROPOSE TO EXPLORE THE EARLY EVOLUTION OF EPITHELIA - STRUCTURES THAT WE PREDICT WOULD BE ADVANTAGEOUS IN COMPLEX LIFE FORMS ANYWHERE TO UNDERSTAND INNOVATIONS IN THE ANIMAL STEM-LINEAGE THAT CONTRIBUTED TO THE EVOLUTION OF ANIMAL BODY PLANS. DEFINING FEATURES OF EPITHELIA ARE THE ADHESION MODULES THAT TETHER CELLS TO EACH OTHER ENABLE FOLDING AND BENDING OF SHEETS AND TUBES OF CELLS DEFINE APICAL/BASAL POLARITY AND SPECIFY GENE EXPRESSION. OUR FOCUS IS ON THE CADHERIN/CATENIN MODULE (CCM) WHICH FORMS THE MOLECULAR FOUNDATION OF ADHERENS JUNCTIONS IN ALL STUDIED BILATERIAN TISSUES AND IS HYPOTHESIZED TO HAVE EVOLVED IN CONCERT WITH ANIMAL MULTICELLULARITY. FORMATION OF THESE JUNCTIONS APPEARS TO BE THE EARLIEST EVENT IN EPITHELIAL MORPHOGENESIS AND IT SERVES AS A SPATIAL LANDMARK FOR FORMATION OF OTHER TYPES OF CELL-CELL JUNCTIONS. EXPERIMENTAL DISRUPTION OF THE CCM PERTURBS EPITHELIAL DEVELOPMENT INTEGRITY AND POLARITY. OUR OBJECTIVE IS TO EXAMINE HOW AN ANCIENT ACTINMYOSIN SCAFFOLD COMMON TO ALL EUKARYOTES WAS RECRUITED BY THE MORE RECENTLY EVOLVED CCM TO COORDINATE CELL INTERACTIONS NECESSARY FOR MULTICELLULARITY AND TISSUE DIVERSITY. IMPORTANTLY THIS MULTI-FUNCTIONAL MODULE IS PRESENT IN ALL ANIMAL LINEAGES AND POTENTIALLY SATISFIES ALL REQUIREMENTS FOR MULTICELLULAR ADHESION AND MORPHOGENESIS - CADHERINS ENABLE ADHESION BETWEEN CELLS AND CATENINS BIND TO THE ACTIN SCAFFOLD TO ORGANIZE MULTICELLULAR ARCHITECTURE AND CAN SIGNAL TO THE NUCLEUS TO CHANGE GENE EXPRESSION. WE HAVE A DETAILED MECHANISTIC UNDERSTANDING OF THE COMPONENT PARTS AND FUNCTION OF THIS ADHESION MODULE IN BILATERIAN ANIMALS BUT THE EARLY EVOLUTION OF THIS MODULE IS FAR LESS CLEAR. OUR APPROACH IS TO EXAMINE THE FUNCTION OF CCM PROTEINS IN KEY NON-BILATERIAN ANIMAL LINEAGES INCLUDING CNIDARIANS CTENOPHORES AND SPONGES. LITTLE IS KNOWN ABOUT HOW THEY FUNCTION IN THESE ORGANISMS NOR HOW THEY EVOLVED TO TAKE ON NOVEL ROLES TO ENABLE MULTICELLULAR COMPLEXITY. WHAT IS THE MINIMAL SET OF ADHESION PROTEINS NECESSARY FOR THE COORDINATION OF CELL-CELL ADHESION AND LINKAGE TO THE ACTIN CYTOSKELETON AND ARE BASIC FUNCTIONS OF THIS SET SHARED BY ALL ANIMALS? THE CCM IS A LIKELY CANDIDATE AND WE WILL TEST THIS HYPOTHESIS BY OBSERVING CCM PROTEINS IN CELLS AND TISSUES OF NON-BILATERIAN METAZOANS DURING MORPHOGENESIS BY EXAMINING PHYSICAL INTERACTIONS BETWEEN THESE PUTATIVE EPITHELIAL PROTEINS WITH COMPARATIVE BIOCHEMISTRY AND USING FUNCTIONAL GENETICS TO DELETE AND REPLACE GENES PUTATIVELY INVOLVED IN TISSUE MORPHOGENESIS AND CELL-CELL ADHESION. OTHER POTENTIAL CADHERIN-RELATED PROTEINS SIGNALING AND ACTIN-BINDING PROTEINS WILL BE IDENTIFIED USING BIOINFORMATIC DISSECTION OF GENOMES. RESULTS WILL BE INTEGRATED WITH KNOWN PROPERTIES OF THE CADHERIN-CATENIN ADHESION MODULE IN BILATERIANS. OUR EXPERIMENTAL APPROACH IS UNUSUALLY COMPREHENSIVE AND INTERDISCIPLINARY FOR BROAD COMPARATIVE STUDIES AND INVOLVES A DIVERSE TEAM TO TACKLE THIS PROBLEM THAT COMPRISES EVOLUTIONARY-DEVELOPMENTAL BIOLOGISTS (LOWE/MARTINDALE) AN EVOLUTIONARY-CELL BIOLOGIST (NICHOLS) AND A BIOCHEMIST/STRUCTURAL BIOLOGIST (WEIS). THE CAPACITY TO DEVELOP ROBUST TISSUES THAT PROVIDE A PHYSICAL AND CHEMICAL BARRIER TO THE OUTSIDE ENVIRONMENT AND FACILITATE TISSUE SPECIALIZATION IS A BASIC CHARACTERISTIC OF COMPLEX LIFE. THE WORK OUTLINED IN THIS PROPOSAL ADDRESSES FUNDAMENTAL QUESTIONS ABOUT THE ASSEMBLY OF A KEY CELLULAR INNOVATION EARLY IN ANIMAL EVOLUTION EPITHELIA ARE AT THE CORE OF HYPOTHESES OF THE EVOLUTION OF MULTICELLULARITY AND ANIMAL BODY-PLAN COMPLEXITY AND THEREFORE CENTRAL TO THE NASA EXOBIOLOGY MISSION OF UNDERSTANDING ADVANCED LIFE.
$884,711University Of Denver · · FY2020 · National Aeronautics and Space Administration
The Role of Stem Cells and the Microenvironment in Gastrointestinal Cancers
$884,640Timothy Cragin Wang · Columbia University Health Sciences · R35 · FY2019 · CA
Host-pathogen interactions in filarial worm infections
$884,615Elodie Ghedin · National Institute Of Allergy And Infectious Diseases · ZIA · FY2025 · AI
Deciphering how 3D genome organization orchestrates cardiac cellular identity
$884,375Rajan Jain · University Of Pennsylvania · R35 · FY2023 · HL
Prevention of Graft-Versus-Host-Disease in the Era of Adoptive Immunotherapy
$884,291Marie Bleakley · Fred Hutchinson Cancer Research Center · P01 · FY2020 · CA
Molecular dissecting and targeting YAP1 mediated cancer stemness and immune suppression in advanced gastric adenocarcinoma
$884,176Shumei Song · Coriell Institute For Medical Research · R01 · FY2025 · CA
Enhancing the Development of New Regenerative Medicine Therapies:Proposal to Build a Robust Clinical Research Development and Data Hub
$884,154Joseph E Finkelstein · Icahn School Of Medicine At Mount Sinai · OT2 · FY2019 · HL
Duke-UNC-Wash U Partnership for Early Phase Clinical Trials in Cancer
$884,114James L Abbruzzese · Duke University · UM1 · FY2016 · CA
Clonal hematopoiesis in the Women's Health Initiative
$884,044Alexander P Reiner · Fred Hutchinson Cancer Research Center · R01 · FY2019 · HL
Enhance Prevention in Couples (EPIC)
$884,036Wafaa M. El-Sadr · Columbia University Health Sciences · R01 · FY2012 · AI
Function interactions between mitogen-activated protein kinases (MAPKs) and SARS-CoV-2
$883,797Jeffrey R Johnson · Icahn School Of Medicine At Mount Sinai · R01 · FY2023 · AI
Human Epilepsy Genetics - Mosaic Mutations in Focal Epilepsy
$883,490Christopher A Walsh · Boston Children'S Hospital · R37 · FY2025 · NS
STEM CELLS FOR TOLERANCE INDUCTION
$883,394University Of Miami School Of Medicine · U19 · FY2004 · AI
Epigenetic and Genetic Control of Human and Murine Beta Cell Development and Fate
$883,290Seung K Kim · Stanford University · U01 · FY2013 · DK
Clinical Interventional Studies of HIV Reservoirs
$883,072Frank Maldarelli · Division Of Basic Sciences - Nci · ZIA · FY2025 · CA
Function of human & mouse Beta-globin locus control regions
$883,022Mark T Groudine · Fred Hutchinson Cancer Research Center · R37 · FY2015 · DK
Attacking stress tolerance in cancer
$882,960David A Cheresh · University Of California, San Diego · R35 · FY2023 · CA
Myocardial Repair by Targeted Stem Cells
$882,950James W Larrick · Panorama Research, Inc. · R44 · FY2009 · HL
Human iPSC Model for Elucidating Crosstalk Signaling and Secretomes
$882,881Joseph C Wu · Stanford University · R01 · FY2020 · HL
Advancing continuous biomanufacturing of monoclonal antibodies using an experimentally validated modeling platform
$882,827Marianthi Ierapetritou · University Of Delaware · U01 · FY2024 · FD