Program Type: Discovery
Molecular Characterization of hESC and hIPSC-Derived Spinal Motor Neurons
One of the main objectives of stem cell biology is to create physiologically relevant cell types that can be used to either facilitate the study of or directly treat human disease. Tremendous progress towards these goals has been made in the area of motor neuron disease and spinal cord injury through the findings that motor […]
Human Cardiovascular Progenitors, their Niches and Control of Self-renewal and Cell Fate
For the millions of Americans who are born with or develop heart disease, stem cell research offers the first hope of reversing or repairing heart muscle damage. Thus, early reports suggesting heart regeneration after transplantation of adult bone marrow-derived stem cells were met with great excitement in both the scientific and lay community. However, although […]
Defining the molecular mechanisms of somatic cell reprogramming
The development of methods to “reprogram” adult cells such as skin cells by simultaneously expressing four specific factors — Oct3/4, Sox2, c-Myc and Klf4 — in order to create cells resembling embryonic stem (ES) cells is a major breakthrough in stem cell biology. Our ability to generate these cells, which are known as induced pluripotent […]
Molecular Mechanisms of Reprogramming towards Pluripotency
Stem cell biology and its applications to cell-based therapies, since its inception 30 years ago, has been hindered by the immunological considerations of rejection of non-autologous cells in patients, as well as by ethical concerns. The generation of pluripotent cells from a patient’s own somatic cells has therefore been the holy grail of regenerative medicine. […]
Molecular Characterization and Functional Exploration of Hemogenic Endothelium
Hematopoietic cells are responsible for generating all cell types present in the blood and therefore critical for the provision of oxygen and nutrients to all the tissues in the body. Blood cells are also required for defense against microorganisms and even for the recognition and elimination of tumor cells. Because blood cells have a relatively […]
Modeling the genetic basis of psychopathology in schizophrenia and autism
Research Objective We propose to apply scalable platforms for the characterization of CNVs and genes coupled with detailed characterizations of neurodevelopment of the 4 major CNV loci in model systems and patients. Impact A unified understanding of how genes influence neurodevelopmental processes, circuitry & how these processes influence specific psychiatric disorders will achieve new advances […]
CIRM Center for Neuropsychiatric Stem Cell Proteomics
Research Objective This project will interrogate interactions, distribution, and function of high-confidence neuropsychiatric disorder risk proteins, and identify convergent pathobiology of patient genetic variants. Impact Datasets and stem cell resources in this project will establish a molecularly-informed genotype to phenotype discovery platform for defining druggable pathways in neuropsychiatric disorders. Californians have voted to support stem […]
Translational epigenomics: dissecting cell type-specific function of neuropsychiatric risk genes in vivo
Research Objective Our objective is to enable scalable genetic screening to study how different cell types and epigenetic networks are impacted by risk genes implicated in human psychiatric disorders. Impact We will develop and apply state-of-the-art genomic analysis to seek mechanisms and to design and test therapeutic agents for disorder modifying solutions. Mental health disorders […]
Multiomic Studies of Idiopathic Intellectual Disability and Autism Spectrum Disorder (ID/ASD)
Research Objective We provide mechanistic insight into idiopathic Intellectual Disability (ID) and Autism Spectrum Disorder (ASD) based on aberrant redox-mediated posttranslational modifications related to air pollution Impact How air pollution contributes to ASD/ID should provide impetus for environmental control of such pollution. With our insights into idiopathic ID and ASD, new treatment approaches will become […]
Deep phenotyping of human brain organoid models of autism spectrum disorder to unravel disease heterogeneity and develop biomarkers and treatments
Research Objective We will uncover pathways through which ASD mutations cause disease and close the gap from disease research to therapeutic testing using organoids, primary human neurons, machine learning and AAVs. Impact Our studies are impactful because outcomes will lead to therapeutic avenues to pursue for ASD treatment. 1 in 22 children in California is […]