Interdisciplinary Training in Stem Cell Biology, Engineering and Medicine
Grant Award Details
Grant Type:
Grant Number:
TG2-01164
Investigator(s):
Award Value:
$6,888,557
Status:
Closed
Progress Reports
Reporting Period:
Year 4
Reporting Period:
Year 4
Reporting Period:
Year 5
Reporting Period:
Year 6
Reporting Period:
NCE Progress Report
Grant Application Details
Application Title:
Interdisciplinary Training in Stem Cell Biology, Engineering and Medicine
Public Abstract:
This proposed Comprehensive Training Program will include 16 CIRM Scholars, three clinical fellows, eight postdoctoral fellows, and five pre-doctoral fellows. Our multidisciplinary program will provide training opportunities in stem cell biology, engineering, and medicine, with a focus on applying stem cell research toward the goal of treating human disease. Coursework offered as a part of this program will cover basic stem cell biology and current and potential uses of stem cells in regenerative medicine, as well as ethical, legal and social issues in stem cell research. CIRM Scholars' research projects may investigate fundamental biomedical problems such as the molecular basis of stem cell pluripotency, stem cell differentiation into mature tissues such as blood, nerve and muscle, or the reduction of stem cell regenerative capacity with ageing. CIRM Scholars whose expertise is in engineering may work to develop controlled environments for expansion and tissue-specific differentiation of human embryonic stem cells, or devices to enable or evaluate the results of stem cell transplantation. Clinical Fellows will integrate basic and translational research, with particular emphasis on cord blood transplantation for genetic or malignant blood diseases. This program will train leading young physicians, scientists and engineers who will contribute to the understanding of stem cell biology and to the development of stem cell-based therapies, as well as advancing the medical, intellectual, technological and economic strength of the State of California.
Statement of Benefit to California:
This proposed training program will develop highly skilled scientists, engineers, and clinical researchers to help ensure California’s continued leadership in biomedical research and engineering. The basic biological research component of this program seeks to identify molecules or biochemical pathways that could function as targets for enhancing or blocking stem cell differentiation. The resulting information could thus serve as a catalyst for drug development. Translational research projects that will be part of the proposed program include development of synthetic materials to support stem cell culture and tissue engineered blood vessel or nerve grafts. The program also includes engineering of novel equipment for imaging and isolation of stem cells. A primary goal of this work is to build new products to be developed and marketed by California biotechnology companies for research and clinical use. The clinical research component of our proposed program will attempt to expand the circumstances under which umbilical cord blood transplantation can be used to cure genetic blood diseases such as sickle cell anemia and thalassemia. These conditions afflict a significant number of individuals in California, particularly in underserved populations, and require expensive and tissue-damaging treatment throughout patients’ lives. Success of this program will benefit the State of California by providing extended and enhanced quality of life for patients with genetic blood diseases, as well as a reduction in the anticipated amount of medical treatment cured patients will require over their lifetime.
Publications
- J Cell Biol (2014): Actin and dynamin2 dynamics and interplay during clathrin-mediated endocytosis. (PubMed: 24891602)
- Elife (Cambridge) (2013): Acute stress enhances adult rat hippocampal neurogenesis and activation of newborn neurons via secreted astrocytic FGF2. (PubMed: 23599891)
- Aging (Albany NY) (2012): Age dependent increase in the levels of osteopontin inhibits skeletal muscle regeneration. (PubMed: 22915705)
- Cell Rep (2014): Age-related dysfunction in mechanotransduction impairs differentiation of human mammary epithelial progenitors. (PubMed: 24910432)
- Nat Neurosci (2012): Astrocytes regulate adult hippocampal neurogenesis through ephrin-B signaling. (PubMed: 22983209)
- Tissue Eng Part C Methods (2014): Automated Video-Based Analysis of Contractility and Calcium Flux in Human-Induced Pluripotent Stem-Derived Cardiomyocytes Cultured over Different Spatial Scales. (PubMed: 25333967)
- Mol Psychiatry (2012): Basolateral amygdala regulation of adult hippocampal neurogenesis and fear-related activation of newborn neurons. (PubMed: 21670733)
- Stem Cells (2014): Biomaterial microenvironments to support the generation of new neurons in the adult brain. (PubMed: 24449485)
- Stem Cell Res Ther (2012): Biophysical regulation of stem cell behavior within the niche. (PubMed: 23241436)
- Gerontology (2015): Breast Cancer beyond the Age of Mutation. (PubMed: 26539838)
- Mol Cell (2013): The Colossus of ubiquitylation: decrypting a cellular code. (PubMed: 23438855)
- PLoS One (2011): Comparative Study of Hematopoietic Differentiation between Human Embryonic Stem Cell Lines. (PubMed: 21603627)
- Methods Mol Biol (2014): Conjugation of proteins to polymer chains to create multivalent molecules. (PubMed: 24014311)
- Cancer Res (2015): Constitutive activation of Myosin-dependent contractility sensitizes glioma tumor-initiating cells to mechanical inputs and reduces tissue invasion. (PubMed: 25634210)
- Cell (2011): Control of Embryonic Stem Cell Lineage Commitment by Core Promoter Factor, TAF3. (PubMed: 21884934)
- PLoS One (2013): Deficiency of MIWI2 (Piwil4) induces mouse erythroleukemia cell differentiation, but has no effect on hematopoiesis in vivo. (PubMed: 24376547)
- Cells Tissues Organs (2011): Derivation of Smooth Muscle Cells with Neural Crest Origin from Human Induced Pluripotent Stem Cells. (PubMed: 22005509)
- Cell Mol Bioeng (2014): Developing Defined and Scalable 3D Culture Systems for Culturing Human Pluripotent Stem Cells at High Densities. (PubMed: 25419247)
- Nat Commun (2012): Differentiation of multipotent vascular stem cells contributes to vascular diseases. (PubMed: 22673902)
- Stem Cell Reports (2013): Dissecting the Roles of miR-302/367 Cluster in Cellular Reprogramming Using TALE-based Repressor and TALEN. (PubMed: 24319658)
- Proc Natl Acad Sci U S A (2014): Distinct phases in the positive selection of CD8+ T cells distinguished by intrathymic migration and T-cell receptor signaling patterns. (PubMed: 24927565)
- Sci Signal (2013): Distinct temporal patterns of T cell receptor signaling during positive versus negative selection in situ. (PubMed: 24129702)
- J Cell Biol (2013): DNA methyltransferase-3-dependent nonrandom template segregation in differentiating embryonic stem cells. (PubMed: 24127215)
- J Control Release (2012): Drug-eluting microfibrous patches for the local delivery of rolipram in spinal cord repair. (PubMed: 22634093)
- Science (2015): Dynamics of CRISPR-Cas9 genome interrogation in living cells. (PubMed: 26564855)
- Elife (2014): The dyskerin ribonucleoprotein complex as an OCT4/SOX2 coactivator in embryonic stem cells. (PubMed: 25407680)
- J Immunol (2013): Ebf1 and c-Myb repress rag transcription downstream of Stat5 during early B cell development. (PubMed: 24068669)
- Biomaterials (2011): The effect of matrix stiffness on the differentiation of mesenchymal stem cells in response to TGF-beta. (PubMed: 21397942)
- Biomaterials (2014): The effect of multivalent Sonic hedgehog on differentiation of human embryonic stem cells into dopaminergic and GABAergic neurons. (PubMed: 24172856)
- Biomaterials (2012): The effect of stromal cell-derived factor-1alpha/heparin coating of biodegradable vascular grafts on the recruitment of both endothelial and smooth muscle progenitor cells for accelerated regeneration. (PubMed: 22884813)
- Neurobiol Dis (2014): Efficient derivation of cortical glutamatergic neurons from human pluripotent stem cells: a model system to study neurotoxicity in Alzheimer’s disease. (PubMed: 24055772)
- Cell Cycle (2012): The emerging functions of the p53-miRNA network in stem cell biology. (PubMed: 22580472)
- Curr Opin Cell Biol (2015): Endocrine aspects of organelle stress-cell non-autonomous signaling of mitochondria and the ER. (PubMed: 25677685)
- Biomaterials (2011): Engineered polymer-media interfaces for the long-term self-renewal of human embryonic stem cells. (PubMed: 21774983)
- Tissue Eng Part C Methods (2011): Engineering Bi-layer Nanofibrous Conduits for Peripheral Nerve Regeneration. (PubMed: 21501089)
- Adv Drug Deliv Rev (2014): Engineering strategies to mimic the glioblastoma microenvironment. (PubMed: 25174308)
- Mol Ther (2011): An Evolved Adeno-associated Viral Variant Enhances Gene Delivery and Gene Targeting in Neural Stem Cells. (PubMed: 21224831)
- Mol Cell Proteomics (2011): Extensive determination of glycan heterogeneity reveals an unusual abundance of high-mannose glycans in enriched plasma membranes of human embryonic stem cells. (PubMed: 22147732)
- Mech Dev (2014): Follistatin interacts with Noggin in the development of the axial skeleton. (PubMed: 24514266)
- Proc Natl Acad Sci U S A (2013): A fully defined and scalable 3D culture system for human pluripotent stem cell expansion and differentiation. (PubMed: 24248365)
- Sci Rep (2015): Human iPSC-based Cardiac Microphysiological System For Drug Screening Applications. (PubMed: 25748532)
- Exp Biol Med (Maywood) (2011): Improved engraftment with minimal graft-versus-host disease after major histocompatibility complex-mismatched cord blood transplantation with photochemically treated donor lymphocytes. (PubMed: 21454375)
- Biomaterials (2011): Induced pluripotent stem cells for neural tissue engineering. (PubMed: 21514663)
- Chem Biol (2011): Inhibitors of tyrosine phosphatases and apoptosis reprogram lineage-marked differentiated muscle to myogenic progenitor cells. (PubMed: 21944754)
- Mol Cell (2013): The intertwined roles of transcription and repair proteins. (PubMed: 24207023)
- IEEE Trans Med Imaging (2013): Linearity and shift invariance for quantitative magnetic particle imaging. (PubMed: 23568496)
- Cell (2014): Looping back to leap forward: transcription enters a new era. (PubMed: 24679523)
- Cell Rep (2015): Machine-Learning-Based Analysis in Genome-Edited Cells Reveals the Efficiency of Clathrin-Mediated Endocytosis. (PubMed: 26387943)
- Prog Mol Biol Transl Sci (2014): Matrix regulation of tumor-initiating cells. (PubMed: 25081621)
- Cell Cycle (2014): microRNAs and cilia: An ancient connection. (PubMed: 25025146)
- Nature (2014): miR-34/449 miRNAs are required for motile ciliogenesis by repressing cp110. (PubMed: 24899310)
- J Exp Med (2013): MK5 activates Rag transcription via Foxo1 in developing B cells. (PubMed: 23878308)
- Nat Nanotechnol (2013): Multivalent ligands control stem cell behaviour in vitro and in vivo. (PubMed: 24141540)
- J Clin Invest (2013): Opposing chemokine gradients control human thymocyte migration in situ. (PubMed: 23585474)
- Nat Commun (2014): Oxytocin is an age-specific circulating hormone that is necessary for muscle maintenance and regeneration. (PubMed: 24915299)
- Neuron (2011): p63 Regulates Olfactory Stem Cell Self-Renewal and Differentiation. (PubMed: 22153372)
- Genes Dev (2014): A positive feedback between p53 and miR-34 miRNAs mediates tumor suppression. (PubMed: 24532687)
- Annu Rev Chem Biomol Eng (2011): Progress and prospects for stem cell engineering. (PubMed: 22432628)
- Development (2014): Ptch2 mediates the Shh response in Ptch1-/- cells. (PubMed: 25085974)
- Immunol Cell Biol (2010): Quantifying subcellular distribution of fluorescent fusion proteins in cells migrating within tissues. (PubMed: 20956985)
- Nat Immunol (2014): Quantitative and temporal requirements revealed for Zap70 catalytic activity during T cell development. (PubMed: 24908390)
- PLoS One (2013): Regenerative Capacity of Old Muscle Stem Cells Declines without Significant Accumulation of DNA Damage. (PubMed: 23704914)
- Sci Transl Med (2016): Selection-free genome editing of the sickle mutation in human adult hematopoietic stem/progenitor cells. (PubMed: 27733558)
- Nat Methods (2014): Single-cell western blotting. (PubMed: 24880876)
- Cell Rep (2013): SIRT3 Reverses Aging-Associated Degeneration. (PubMed: 23375372)
- Circ Res (2013): Smooth muscle cells: to be or not to be? Response to Nguyen et Al. (PubMed: 23093574)
- Stem Cells Dev (2013): Sodium butyrate promotes generation of human induced pluripotent stem cells through induction of the miR302/367 cluster. (PubMed: 23534850)
- Integr Biol (Camb) (2013): Sorting single satellite cells from individual myofibers reveals heterogeneity in cell-surface markers and myogenic capacity. (PubMed: 23407661)
- Anticancer Agents Med Chem (2011): Sphingolipid signaling and hematopoietic malignancies: to the rheostat and beyond. (PubMed: 21707493)
- PLoS One (2012): Sphingosine-1-phosphate enhances satellite cell activation in dystrophic muscles through a S1PR2/STAT3 signaling pathway. (PubMed: 22606352)
- FASEB J (2014): Sphingosine phosphate lyase regulates myogenic differentiation via S1P receptor-mediated effects on myogenic microRNA expression. (PubMed: 24158395)
- J Vis Exp (2012): Stereotaxic surgery for excitotoxic lesion of specific brain areas in the adult rat. (PubMed: 22847556)
- Mol Psychiatry (2014): Stress and glucocorticoids promote oligodendrogenesis in the adult hippocampus. (PubMed: 24514565)
- Acta Biomater (2013): Synovial stem cells and their responses to the porosity of microfibrous scaffold. (PubMed: 23523935)
- Cell Mol Life Sci (2014): Tracking migration during human T cell development. (PubMed: 24682469)
- Trends Cell Biol (2012): Transcriptional regulation by coactivators in embryonic stem cells. (PubMed: 22572610)
- Biomed Tech (Berl) (2013): Twenty-fold acceleration of 3D projection reconstruction MPI. (PubMed: 23940058)
- Nature (2012): Ubiquitin-dependent regulation of COPII coat size and function. (PubMed: 22358839)
- Hematol Oncol Clin North Am (2010): Umbilical cord blood transplantation for thalassemia major. (PubMed: 21075286)
- PLoS One (2011): Uniaxial mechanical strain modulates the differentiation of neural crest stem cells into smooth muscle lineage on micropatterned surfaces. (PubMed: 22016804)
