CIRM Stem Cell Biology Training Program
Grant Award Details
Grant Type:
Grant Number:
TG2-01161
Investigator(s):
Award Value:
$5,827,817
Status:
Closed
Progress Reports
Reporting Period:
Year 3
Reporting Period:
Year 4
Reporting Period:
Year 5
Reporting Period:
Year 6+NCE
Grant Application Details
Application Title:
CIRM Stem Cell Biology Training Program
Public Abstract:
This is a proposal to renew funding for the host institution’s Type I Comprehensive Training Program in Stem Cell Biology. Since funding was first applied for in the summer of 2005, stem cell research at the host institution has undergone a major transformation: a center for regenerative medicine and stem cell research was established, and a world class stem cell biologist was recruited to be its director. Seven new faculty, representing a wide spectrum of stem cell-related disciplines, have been recruited as members of the Center. Groundbreaking for construction of a CIRM Stem Cell Facility took place in early [REDACTED] 2008. This initiative was launched with a multi-million dollar gift from a private foundation, and was recently matched with a Major Facilities Award from CIRM. Also with CIRM funding, the host institution has developed a Training Program in Stem Cell Biology which has thus far supported 24 individuals. Key features of this program are a flagship course in stem cell biology, co-taught with two neighboring institutions, as well as courses in stem cell ethics, developmental biology and a practical course in the culture of human ES cells. A yearly retreat was instituted and created a website created, which will soon be the principal mode of recruitment. A major benefit of our stem cell training program has been the promotion of interactions among stem cell biologists, developmental biologists and clinical scientists. The breadth of the program, in terms of the number of faculty and wide range of their expertise in stem cell biology, will provide trainees with many choices of mentor, and it will also make for training that is strongly interdisciplinary. The host institution seeks to continue and improve what is believed to be already an excellent training program in stem cell biology. Funding for 6 predoctoral fellows, 8 postdoctoral fellows, and 2 clinical fellows (a total of 16 slots) is requested. These individuals will be supported for two years, during which they will conduct research with one (or more) of 39 potential mentors. They will take courses in stem cell biology, stem cell ethics, as well as selected optional courses, including developmental biology. They will attend and present their work in the weekly combined stem cell biology/developmental biology research forum and will attend a yearly retreat. Finally, they will benefit from the extensive informal interactions among the students and faculty in stem cell biology. The host institution is also extremely pleased to partner with several nearby institutions for CIRM's "Bridges to Stem Cell Research" program. This program would enable these institutions to place trainees in stem cell labs at the host institution. We note that these collaborative efforts will broaden the influence of our training program substantially and make efficient use of state stem cell resources
Statement of Benefit to California:
This is a proposal to renew funding for the host institution’s Type I Comprehensive Training Program in Stem Cell Biology. Since funding was first applied for in the summer of 2005, stem cell research at the host institution has undergone a major transformation: a center for regenerative medicine and stem cell research was established, and groundbreaking for construction of a CIRM Stem Cell Facility took place in [REDACTED] 2008. The recent establishment of [REDACTED] an innovative agreement among 6 research institutions in [REDACTED] (including the host institution) allows members to share training programs, scientific core facilities and expertise, thus achieving highly efficient use of state funding. In mid-2006, the host institution instituted a Training Program in Stem Cell Biology (which has thus far supported 24 individuals), and seeks to continue and to improve what is believed to be already an excellent training program in stem cell biology. This program will bring great educational, scientific and economic benefit to Californians. Key features of this program are a flagship course in stem cell biology, co-taught with two neighboring institutions, as well as courses in stem cell ethics, developmental biology and a practical course in the culture of human ES cells. A major benefit of our stem cell training program has been the promotion of interactions among stem cell biologists, developmental biologists and clinical scientists. The breadth of the program, in terms of the number of faculty and wide range of their expertise in stem cell biology, will make for training that is strongly interdisciplinary. The structure of the courses, capitalizing on the rich distance learning capabilities of the host institution to produce a highly interactive, yet flexible, course accommodates the diversity of pre- and post-doctoral students as well as clinical fellows. An added benefit is this course structure will allow for enrollment by interested parties statewide and nationally. Further, the agreement between the Institutions to contribute exceptional didactic training to the program regardless of funding by this mechanism truly demonstrates the commitment of each to training in this field. The host institution is also extremely pleased to partner with several nearby institutions for CIRM's "Bridges to Stem Cell Research" program. This program would enable these institutions to place trainees in stem cell labs at the host institution. We note that these collaborative efforts will broaden the influence of our training program substantially and make efficient use of state stem cell resources.
Publications
- Mol Cancer Res (2011): Adaptive basal phosphorylation of eIF2alpha is responsible for resistance to cellular stress-induced cell death in Pten-null hepatocytes. (PubMed: 22009178)
- Proc Natl Acad Sci U S A (2015): Adipogenesis and epicardial adipose tissue: a novel fate of the epicardium induced by mesenchymal transformation and PPARgamma activation. (PubMed: 25646471)
- Diabetologia (2014): Adult-onset deletion of Pten increases islet mass and beta cell proliferation in mice. (PubMed: 24162585)
- Am J Pathol (2016): alphaB-Crystallin Regulates Subretinal Fibrosis by Modulation of Epithelial-Mesenchymal Transition. (PubMed: 26878210)
- Sci Rep (2015): Analysis of a transgenic Oct4 enhancer reveals high fidelity long-range chromosomal interactions. (PubMed: 26435056)
- Biomaterials (2014): Application of stem cells derived from the periodontal ligament or gingival tissue sources for tendon tissue regeneration. (PubMed: 24397989)
- Cell Cycle (2011): Beyond knockout rats: new insights into finer genome manipulation in rats. (PubMed: 21383544)
- Tissue Eng Part A (2014): Bone regeneration potential of stem cells derived from periodontal ligament or gingival tissue sources encapsulated in RGD-modified alginate scaffold. (PubMed: 24070211)
- Int J Cancer (2013): Cancer cells acquire a drug resistant, highly tumorigenic, cancer stem-like phenotype through modulation of the PI3K/Akt/beta-catenin/CBP pathway. (PubMed: 23784558)
- J Gastroenterol Hepatol (2012): Cancer stem cells generated by alcohol, diabetes, and hepatitis C virus. (PubMed: 22320911)
- Nucleic Acids Res (2016): Circular RNA profile in gliomas revealed by identification tool UROBORUS. (PubMed: 26873924)
- Cancer Discov (2019): Circulating tumor cells exhibit metastatic tropism and reveal brain metastasis drivers. (PubMed: 31601552)
- Pharmaceuticals (Basel) (2014): Clinical use of proteasome inhibitors in the treatment of multiple myeloma. (PubMed: 25545164)
- Biomaterials (2013): Co-encapsulation of anti-BMP2 monoclonal antibody and mesenchymal stem cells in alginate microspheres for bone tissue engineering. (PubMed: 23773817)
- PLoS Genet (2016): Competition between Jagged-Notch and Endothelin1 Signaling Selectively Restricts Cartilage Formation in the Zebrafish Upper Face. (PubMed: 27058748)
- Proc Natl Acad Sci U S A (2013): Competitive balance of intrabulge BMP/Wnt signaling reveals a robust gene network ruling stem cell homeostasis and cyclic activation. (PubMed: 23292934)
- Endocr Relat Cancer (2013): Contextual effect of repression of bone morphogenetic protein activity in prostate cancer. (PubMed: 24042462)
- PLoS One (2016): Correction: Identification of Androgen Receptor Splice Variants in the Pten Deficient Murine Prostate Cancer Model. (PubMed: 26998759)
- Pancreas (2015): Crosstalk Between Activated Myofibroblasts and beta Cells in Injured Mouse Pancreas. (PubMed: 26333110)
- Dev Cell (2015): CXCL12 Signaling Is Essential for Maturation of the Ventricular Coronary Endothelial Plexus and Establishment of Functional Coronary Circulation. (PubMed: 26017771)
- Dev Dyn (2015): Deciphering principles of morphogenesis from temporal and spatial patterns on the integument. (PubMed: 25858668)
- Stem Cells (2014): Defining the localization and molecular characteristic of minor salivary gland label retaining cells. (PubMed: 24715701)
- Acta Biomater (2013): Dental mesenchymal stem cells encapsulated in an alginate hydrogel co-delivery microencapsulation system for cartilage regeneration. (PubMed: 23891740)
- J Cell Physiol (2014): Dependence of Castration-Resistant Prostate Cancer (CRPC) Stem Cells on CRPC-Associated Fibroblasts. (PubMed: 24752784)
- BMC Res Notes (2015): Derivation of induced pluripotent stem cells from orangutan skin fibroblasts. (PubMed: 26475477)
- Retrovirology (2015): Determinants in HIV-2 Env and tetherin required for functional interaction. (PubMed: 26248668)
- Annu Rev Anim Biosci (2015): Development, regeneration, and evolution of feathers. (PubMed: 25387232)
- Cancer Res (2014): Differential effects of RUNX2 on the androgen receptor in prostate cancer: synergistic stimulation of a gene set exemplified by SNAI2 and subsequent invasiveness. (PubMed: 24648349)
- Development (2016): Differential regulation of mouse and human nephron progenitors by the Six family of transcriptional regulators. (PubMed: 26884396)
- Curr Opin Genet Dev (2015): Dynamic epithelia of the developing vertebrate face. (PubMed: 25748249)
- Dev Biol (2016): Dysregulated endocardial TGFbeta signaling and mesenchymal transformation result in heart outflow tract septation failure. (PubMed: 26522286)
- EMBO J (2013): Embryonic stem cell self-renewal pathways converge on the transcription factor Tfcp2l1. (PubMed: 23942238)
- J Biomed Mater Res A (2013): Encapsulated dental-derived mesenchymal stem cells in an injectable and biodegradable scaffold for applications in bone tissue engineering. (PubMed: 23983201)
- Development (2015): Eph-Pak2a signaling regulates branching of the pharyngeal endoderm by inhibiting late-stage epithelial dynamics. (PubMed: 25725065)
- J Biol Chem (2014): Evidence that the DNA endonuclease ARTEMIS also has intrinsic 5′-exonuclease activity. (PubMed: 24500713)
- J Evol Biol (2015): Evolution and functional significance of derived sternal ossification patterns in ornithothoracine birds. (PubMed: 26079847)
- Cardiovasc Res (2015): Extracardiac control of embryonic cardiomyocyte proliferation and ventricular wall expansion. (PubMed: 25560321)
- Dev Growth Differ (2013): Feather regeneration as a model for organogenesis. (PubMed: 23294361)
- Development (2018): Fox proteins are modular competency factors for facial cartilage and tooth specification. (PubMed: 29777011)
- Nat Genet (2017): Frequency of mononuclear diploid cardiomyocytes underlies natural variation in heart regeneration. (PubMed: 28783163)
- Proc Natl Acad Sci U S A (2012): G9a functions as a molecular scaffold for assembly of transcriptional coactivators on a subset of glucocorticoid receptor target genes. (PubMed: 23151507)
- Stem Cell Res Ther (2012): The gene expression profiles of induced pluripotent stem cells from individuals with childhood cerebral adrenoleukodystrophy are consistent with proposed mechanisms of pathogenesis. (PubMed: 23036268)
- Nat Protoc (2011): Generating gene knockout rats by homologous recombination in embryonic stem cells. (PubMed: 21637202)
- G3 (Bethesda) (2015): The Genetic Architecture of Hearing Impairment in Mice: Evidence for Frequency-Specific Genetic Determinants. (PubMed: 26342000)
- Stem Cell Reports (2015): The Genetic Landscape of Hematopoietic Stem Cell Frequency in Mice. (PubMed: 26050929)
- Curr Opin Nephrol Hypertens (2011): Genetic manipulations in the rat: progress and prospects. (PubMed: 21546835)
- J Assoc Res Otolaryngol (2016): Genome-Wide Association Analysis Identifies Dcc as an Essential Factor in the Innervation of the Peripheral Vestibular System in Inbred Mice. (PubMed: 27539716)
- Nat Commun (2016): Genome-wide association study and targeted metabolomics identifies sex-specific association of CPS1 with coronary artery disease. (PubMed: 26822151)
- PLoS Genet (2015): Genome-wide association study identifies nox3 as a critical gene for susceptibility to noise-induced hearing loss. (PubMed: 25880434)
- J Dent Res (2013): Gingivae contain neural-crest- and mesoderm-derived mesenchymal stem cells. (PubMed: 23867762)
- PLoS One (2015): Identification of Androgen Receptor Splice Variants in the Pten Deficient Murine Prostate Cancer Model. (PubMed: 26196517)
- Stem Cell Res Ther (2015): Induced pluripotent stem cell models of Zellweger spectrum disorder show impaired peroxisome assembly and cell type-specific lipid abnormalities. (PubMed: 26319495)
- Sci Rep (2016): Induction of site-specific chromosomal translocations in embryonic stem cells by CRISPR/Cas9. (PubMed: 26898344)
- J Cell Physiol (2014): Initial Characterization of Osteoblast Differentiation and Loss of RUNX2 Stability in the Newly Established SK11 Human Embryonic Stem Cell-Derived Cell Line. (PubMed: 25160731)
- PLoS One (2013): Label Retaining Cells (LRCs) with Myoepithelial Characteristic from the Proximal Acinar Region Define Stem Cells in the Sweat Gland. (PubMed: 24058524)
- Dev Cell (2012): The LIM protein Ajuba restricts the second heart field progenitor pool by regulating Isl1 activity. (PubMed: 22771034)
- PLoS One (2013): Loss of survivin in the prostate epithelium impedes carcinogenesis in a mouse model of prostate adenocarcinoma. (PubMed: 23936028)
- Stem Cell Res Ther (2013): Mesenchymal stem cells inhibit multiple myeloma cells via the Fas/Fas ligand pathway. (PubMed: 24025590)
- Nat Commun (2013): Modulation of beta-catenin function maintains mouse epiblast stem cell and human embryonic stem cell self-renewal. (PubMed: 23985566)
- Cell Mol Life Sci (2015): Molecular basis of embryonic stem cell self-renewal: from signaling pathways to pluripotency network. (PubMed: 25595304)
- Cell Metab (2016): NANOG Metabolically Reprograms Tumor-Initiating Stem-like Cells through Tumorigenic Changes in Oxidative Phosphorylation and Fatty Acid Metabolism. (PubMed: 26724859)
- J Bone Miner Res (2015): Natural large-scale regeneration of rib cartilage in a mouse model. (PubMed: 25142306)
- Development (2014): Nkx2-5 regulates cardiac growth through modulation of Wnt signaling by R-spondin3. (PubMed: 25053429)
- PLoS One (2013): Novel biomarkers of arterial and venous ischemia in microvascular flaps. (PubMed: 23977093)
- Hepatology (2015): NUMB phosphorylation destabilizes p53 and promotes self-renewal of tumor-initiating cells by a NANOG-dependent mechanism in liver cancer. (PubMed: 26174965)
- Cell Stem Cell (2013): Ossifying Fibroma Tumor Stem Cells Are Maintained by Epigenetic Regulation of a TSP1/TGF-beta/SMAD3 Autocrine Loop. (PubMed: 24209761)
- Hepatology (2015): Osteopontin deficiency does not prevent but promotes alcoholic neutrophilic hepatitis in mice. (PubMed: 25132354)
- PLoS One (2013): Placental growth factor expression is required for bone marrow endothelial cell support of primitive murine hematopoietic cells. (PubMed: 23936296)
- Proc Natl Acad Sci U S A (2012): Pluripotency factor-mediated expression of the leptin receptor (OB-R) links obesity to oncogenesis through tumor-initiating stem cells. (PubMed: 22207628)
- EMBO Rep (2017): A post-translational modification switch controls coactivator function of histone methyltransferases G9a and GLP. (PubMed: 28615290)
- J Infect Dis (2013): Pre-clinical modeling of CCR5 knockout in human hematopoietic stem cells by zinc finger nucleases using humanized mice. (PubMed: 24151324)
- Cell Stem Cell (2014): Prolonged fasting reduces IGF-1/PKA to promote hematopoietic-stem-cell-based regeneration and reverse immunosuppression. (PubMed: 24905167)
- Aging Cell (2013): PTEN controls beta-cell regeneration in aged mice by regulating cell cycle inhibitor p16ink4a. (PubMed: 23826727)
- J Genet Genomics (2012): Rapid and cost-effective gene targeting in rat embryonic stem cells by TALENs. (PubMed: 22749015)
- JAMA Ophthalmol (2014): Replication of Mycobacterium tuberculosis in retinal pigment epithelium. (PubMed: 24723139)
- Sci Rep (2017): Requirement for Jagged1-Notch2 signaling in patterning the bones of the mouse and human middle ear. (PubMed: 28566723)
- Sci Rep (2015): Resveratrol inhibits epithelial-mesenchymal transition of retinal pigment epithelium and development of proliferative vitreoretinopathy. (PubMed: 26552368)
- Nat Commun (2016): RUNX1 prevents oestrogen-mediated AXIN1 suppression and beta-catenin activation in ER-positive breast cancer. (PubMed: 26916619)
- Stem Cells (2013): Smad1&5 but not Smad8 establish stem cell quiescence which is critical to transform the premature hair follicle during morphogenesis towards the Postnatal State. (PubMed: 24023003)
- PLoS One (2016): Spatial Variations in Vitreous Oxygen Consumption. (PubMed: 26930281)
- Stem Cells (2014): STAT3 Phosphorylation at Tyrosine 705 and Serine 727 Differentially Regulates Mouse ESC Fates. (PubMed: 24302476)
- Prog Retin Eye Res (2015): Stem cell based therapies for age-related macular degeneration: The promises and the challenges. (PubMed: 26113213)
- Invest Ophthalmol Vis Sci (2016): Survival and Functionality of hESC-Derived Retinal Pigment Epithelium Cells Cultured as a Monolayer on Polymer Substrates Transplanted in RCS Rats. (PubMed: 27233037)
- PLoS One (2013): The TBC1D15 Oncoprotein Controls Stem Cell Self-Renewal through Destabilization of the Numb-p53 Complex. (PubMed: 23468968)
- Development (2014): Tbx1 controls the morphogenesis of pharyngeal pouch epithelia through mesodermal Wnt11r and Fgf8a. (PubMed: 25142463)
- EMBO Mol Med (2014): Telomerase governs immunomodulatory properties of mesenchymal stem cells by regulating FAS ligand expression. (PubMed: 24401839)
- Cytokine (2015): TGF-beta2 secretion from RPE decreases with polarization and becomes apically oriented. (PubMed: 25496702)
- Gastroenterology (2016): TLR4 Signaling via NANOG Cooperates With STAT3 to Activate Twist1 and Promote Formation of Tumor-Initiating Stem-Like Cells in Livers of Mice. (PubMed: 26582088)
- Science (2013): Topology of feather melanocyte progenitor niche allows complex pigment patterns to emerge. (PubMed: 23618762)
- J Biol Chem (2015): Unifying the DNA end-processing roles of the artemis nuclease: Ku-dependent artemis resection at blunt DNA ends. (PubMed: 26276388)
- J Vis Exp (2012): Use of LysoTracker to detect programmed cell death in embryos and differentiating embryonic stem cells. (PubMed: 23092960)
- Cancer Discov (2012): VEGF/neuropilin-2 regulation of Bmi-1 and consequent repression of IGF-IR define a novel mechanism of aggressive prostate cancer. (PubMed: 22777769)
- Oncogene (2017): Wnt/beta-catenin activation and macrophage induction during liver cancer development following steatosis. (PubMed: 28671671)
- Stem Cell Rev (2014): Wnt/Catenin Signaling in Adult Stem Cell Physiology and Disease. (PubMed: 24825509)
- Dev Cell (2013): Wnt-Dependent Epithelial Transitions Drive Pharyngeal Pouch Formation. (PubMed: 23375584)
- Stem Cells (2013): Wnt7b is an important intrinsic regulator of hair follicle stem cell homeostasis and hair follicle cycling. (PubMed: 24222445)