CHLA Stem Cell Training Grant
Grant Award Details
Grant Type:
Grant Number:
TG2-01168
Investigator(s):
Award Value:
$5,020,920
Status:
Closed
Progress Reports
Reporting Period:
Year 4
Reporting Period:
Year 5
Reporting Period:
Year 6
Reporting Period:
NCE
Grant Application Details
Application Title:
Stem Cell Training Grant
Public Abstract:
This Level II Training Grant will support seven PhD Post-Doctoral and three MD Clinical Fellows for training in stem cell biology, and the clinical and ethical implications of stem cell research. The program is based in one of the top six of the nation’s pediatric stand alone Institutions. Over the past 25 years, we have built an internationally renowned research program in stem cell biology and its clinical applications. The program was founded on the fields of human hematopoietic stem cell biology, transplantation and gene therapy. In the past two decades, integration of research in developmental biology and tissue regeneration have expanded the reach of the program into other types of somatic stem cells including lung, pancreas, liver, gut, bladder and mesenchymal tissue. In the past 6 years, we have developed expertise in human embryonic stem cell (hESC) culture and differentiation and have established an hESC tissue culture core. A unique focus of Stem Cell Training will be on applications to pediatric disorders such as diabetes, monogenic inherited disorders (cystic fibrosis, muscular dystrophy, sickle cell disease, etc), and congenital birth defects. It is our central hypothesis that childhood disorders will be especially responsive to therapies produced by the use of stem cells; advances in the use of stem cells to treat childhood illnesses will then lead the way to treatments for the many disorders that occur later in life. The training program includes: a didactic course on "Stem Cell Biology, Research Methods and Stem Cell Therapies", a course titled "The Ethics of Stem Cell Research and Therapies" that will review the ethical, legal and social implications of research with human stem cells, participation in multiple existing training activities, an introductory training in laboratory methods in hESC and a didactic training course taught in concert with the [REDACTED]. A Steering Committee with stem cell researchers, clinical physician/scientists and medical educators will oversee selection and supervision of trainees, the mentoring process, and other activities of the training program. The complex biomedical environment and the strength of stem cell research combine to provide a rich milieu for training the next generation of physicians and scientists who will use stem cells as the basis for research and therapy.
Statement of Benefit to California:
This Level II Training Grant will continue to support seven PhD Post-Doctoral and three MD Clinical Fellows for training in stem cell biology, and the clinical and ethical implications of stem cell research. The program is based in one of the top six of the nation's pediatric stand alone Institutions, located in California. Over the past 25 years, we have built an internationally renowned research program in stem cell biology and its clinical applications. The program was founded on the fields of human hematopoietic stem cell biology, transplantation and gene therapy. In the past two decades, integration of research in developmental biology and tissue regeneration have expanded the reach of the program into other types of somatic stem cells including lung, pancreas, liver, gut, bladder and mesenchymal tissue. In the past 6 years, we have developed expertise in human embryonic stem cell (hESC) culture and differentiation and have established an hESC tissue culture core. A unique focus of Stem Cell Training will be on applications to pediatric disorders such as diabetes, monogenic inherited disorders (cystic fibrosis, muscular dystrophy, sickle cell disease, etc), and congenital birth defects. It is our central hypothesis that childhood disorders will be especially responsive to therapies produced by the use of stem cells; advances in the use of stem cells to treat childhood illnesses will then lead the way to treatments for the many disorders that occur later in life. The training program includes: a didactic course on "Stem Cell Biology, Research Methods and Stem Cell Therapies", a course titled "The Ethics of Stem Cell Research and Therapies" that will review the ethical, legal and social implications of research with human stem cells, participation in multiple existing training activities, an introductory training in laboratory methods in hESC and a didactic training course taught in concert with [REDACTED]. A Steering Committee with stem cell researchers, clinical physician/scientists and medical educators will oversee selection and supervision of trainees, the mentoring process, and other activities of the training program. The complex biomedical environment and the strength of stem cell research combine to provide a rich milieu for training the next generation of physicians and scientists who will use stem cells as the basis for research and therapy. This will provide unique benefits to the State of California and its citizens by providing a superbly trained group of stem cell experts whose work is focused on relieving childhood diseases in California. The trainees in this program will also strengthen and accelerate our research efforts in this field.
Publications
- PLoS One (2012): Adoptive transfer of induced-treg cells effectively attenuates murine airway allergic inflammation. (PubMed: 22792275)
- Curr Treat Options Cardiovasc Med (2014): Cardiac regeneration in model organisms. (PubMed: 24496965)
- Dev Dyn (2011): Cell polarity and spindle orientation in the distal epithelium of embryonic lung. (PubMed: 21246661)
- Dev Biol (2015): Differential regenerative capacity of neonatal mouse hearts after cryoinjury. (PubMed: 25555840)
- Endocr Relat Cancer (2011): Embryonic epithelial Pten deletion through Nkx2.1-cre leads to thyroid tumorigenesis in a strain dependent manner. (PubMed: 22167068)
- Development (2011): Eya1 controls cell polarity, spindle orientation, cell fate and Notch signaling in distal embryonic lung epithelium. (PubMed: 21385765)
- J Cell Sci (2012): Eya1 protein phosphatase regulates tight junction formation in lung distal epithelium. (PubMed: 22685326)
- Dev Biol (2011): Eyes absent 1 (Eya1) is a critical coordinator of epithelial, mesenchymal and vascular morphogenesis in the mammalian lung. (PubMed: 21129374)
- Development (2011): FGF10 controls the patterning of the tracheal cartilage rings via Shh. (PubMed: 21148187)
- J Am Soc Nephrol (2012): Injection of Amniotic Fluid Stem Cells Delays Progression of Renal Fibrosis. (PubMed: 22302195)
- Methods Mol Biol (2013): A “living bioreactor” for the production of tissue-engineered small intestine. (PubMed: 23494439)
- BMC Biol (2015): Mesenchymal adenomatous polyposis coli plays critical and diverse roles in regulating lung development. (PubMed: 26092405)
- J Surg Res (2011): Mesenchymal-Specific Inhibition of Vascular Endothelial Growth Factor (VEGF) Attenuates Growth in Neonatal Mice. (PubMed: 21696760)
- J Clin Invest (2012): Mesodermal Pten inactivation leads to alveolar capillary dysplasia-like phenotype. (PubMed: 23023706)
- Am J Respir Cell Mol Biol (2011): The Milieu of Damaged AEC2 Stimulates Alveolar Wound Repair by Endogenous and Exogenous Progenitors. (PubMed: 21700959)
- PLoS One (2011): Modeling initiation of ewing sarcoma in human neural crest cells. (PubMed: 21559395)
- Am J Physiol Lung Cell Mol Physiol (2012): Molecular mechanisms of MMP9 overexpression and its role in emphysema pathogenesis of Smad3-deficient mice. (PubMed: 22610349)
- Tissue Eng Part A (2011): A multicellular approach forms a significant amount of tissue-engineered small intestine in the mouse. (PubMed: 21395443)
- J Surg Res (2011): Murine Tissue-Engineered Stomach Demonstrates Epithelial Differentiation. (PubMed: 21571313)
- J Pathol (2015): A novel profibrotic mechanism mediated by TGFbeta-stimulated collagen prolyl hydroxylase expression in fibrotic lung mesenchymal cells. (PubMed: 25779936)
- J Histochem Cytochem (2012): Numb Expression and Asymmetric Versus Symmetric Cell Division in Distal Embryonic Lung Epithelium. (PubMed: 22713487)
- Nat Cell Biol (2011): Oct4 kinetics predict cell lineage patterning in the early mammalian embryo. (PubMed: 21258368)
- Am J Physiol Lung Cell Mol Physiol (2011): Partial pneumonectomy of telomerase null mice carrying shortened telomeres initiates cell growth arrest resulting in a limited compensatory growth response. (PubMed: 21460122)
- Proc Natl Acad Sci U S A (2010): PDGF signaling is required for epicardial function and blood vessel formation in regenerating zebrafish hearts. (PubMed: 20858732)
- PLoS One (2010): Platelet-derived growth factor receptor beta is critical for zebrafish intersegmental vessel formation. (PubMed: 20593033)
- Development (2010): Signaling via Alk5 controls the ontogeny of lung Clara cells. (PubMed: 20147383)
- Dev Biol (2011): Six1 transcription factor is critical for coordination of epithelial, mesenchymal and vascular morphogenesis in the mammalian lung. (PubMed: 21385574)
- BMC Biol (2013): Spatial-temporal targeting of lung-specific mesenchyme by a Tbx4 enhancer. (PubMed: 24225400)
- Am J Physiol Lung Cell Mol Physiol (2013): TACE in perinatal mouse lung epithelial cells promotes lung saccular formation. (PubMed: 24142516)
- J Vis Exp (2012): Tissue engineering of the intestine in a murine model. (PubMed: 23222891)
- Regen Med (2011): VEGF optimizes the formation of tissue-engineered small intestine. (PubMed: 21916592)
- Nat Protoc (2012): In vitro culture of epicardial cells from adult zebrafish heart on a fibrin matrix. (PubMed: 22262006)