Therapeutic/Technology: Exploring disease mechanisms
In vitro modeling of human motor neuron disease
Motor neuron (MN) diseases such as spinal muscular atrophy and amyotrophic lateral sclerosis lead to progressive degeneration of MNs, presenting first with muscle weakness, followed by locomotor defects and frequently death due to respiratory failure. While progress has been made in identifying genes associated with MN degeneration, the molecular and cellular processes underlying disease onset […]
Elucidating pathways from hereditary Alzheimer mutations to pathological tau phenotypes
We propose to elucidate pathways of genes that lead from early causes to later defects in Alzheimer’s Disease (AD), which is common, fatal, and for which no effective disease-modifying drugs are available. Because no effective AD treatment is available or imminent, we propose to discover novel genetic pathways by screening purified human brain cells made […]
Misregulated Mitophagy in Parkinsonian Neurodegeneration
Parkinson’s disease (PD), is one of the leading causes of disabilities and death and afflicting millions of people worldwide. Effective treatments are desperately needed but the underlying molecular and cellular mechanisms of Parkinson’s destructive path are poorly understood. Mitochondria are cell’s power plants that provide almost all the energy a cell needs. When these cellular […]
Human iPSC modeling and therapeutics for degenerative peripheral nerve disease
The applicant is an MD/PhD trained physician scientist, whose clinical expertise is neuromuscular disorders including peripheral nerve disease. The proposal is aimed at providing a research proposal and career development plan that will allow the applicant to develop an independent research program, which attempts to bring stem cell based therapies to patients with peripheral nerve […]
The HD iPSC Consortium: Repeat Length Dependent Phenotypes for Assay Development
Epithelial progenitors and the stromal niche as therapeutic targets in lung disease
Chronic lung disease is an enormous societal and medical problem in California and the nation as a whole, representing the third most likely cause of death. Treatment costs were $389.2 billion in 2011 and are expected to reach $832.9 billion in 2021 according to the Milken Institute. Chronic lung diseases cover a spectrum of disorders […]
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 […]
Mapping and modeling endothelial cell fate decisions for pulmonary arterial hypertension
Research Objective We will build a foundational model and experimental platform to catalog all genes that promote and protect against PAH, with the potential to extend to many other developmental and disease processes. Impact The studies aim to identify genetic targets for PAH therapy and develop a predictive model to accelerate stem cell research and […]
Lewy body dementia, 𝛼-synuclein, and cell-specific mechanisms of neurodegeneration
Research Objective We will generate insights about mechanisms by which 𝛼-synuclein leads to neurodegeneration of the forebrain and substantia nigra, regions affected in Lewy body dementias and Parkinson disease. Impact If the proposed studies are successfully achieved, they will impact our understanding of Lewy body dementias specifically and 𝛼-synucleinopathies and neurodegeneration more broadly. Major Proposed […]
Neuroimmune interactions in the developing human brain
Research Objective This project will identify mechanisms by which immune cells regulate human brain development, and use stem cell derived models to identify pathological changes induced by congenital virus infection. Impact Neurodevelopmental disorders caused by immune cell perturbations will be impacted by the fundamental understanding of how immune system controls normal development of the brain. […]