Therapeutic/Technology: Exploring stem cell mechanisms
Investigation of synaptic defects in autism using patient-derived induced pluripotent stem cells
Autism spectrum disorders (ASD) are a group of neurodevelopmental diseases that occur in as many as 1 in 150 children in the United States. Three hallmarks of autism are dysfunctional communication, impaired social interaction, and restricted and repetitive interests and activities. Even though no single genetic defect has been ascribed to having a causative role […]
Functional characterization of mutational load in nuclear reprogramming and differentiation
One of the most potentially powerful aspects of regenerative medicine is stem cell therapy. In this therapy, healthy tissues derived from stem cells will be implanted into patients with damaged tissue in order to restore function. However, there is currently a risk of immune rejection. Human induced pluripotent stem (hiPS) cells have the potential to […]
Phenotypic Analysis of Human ES Cell-Derived Muscle Stem Cells
We study human muscle development, and are actively investigating potential cell-based therapies for the treatment of degenerative muscle diseases, such as muscle dystrophy. This project will define the pathway that muscle stem cells follow as they form new muscle, and identify which muscle stem cells are most useful for therapy. Our approach will be to […]
Triplet Repeat Instability in Human iPSCs
Over twenty human genetic diseases are caused by expansion of simple DNA sequences composed of repeats of three nucleotides (such as CAG, CTG, CGG and GAA) within essential genes. These repeats can occur within the region of a gene that encodes the protein, generally resulting in proteins with large stretches of repeats of just one […]
Neural and general splicing factors control self-renewal, neural survival and differentiation
Human embryonic and patient-specific induced pluripotent stem cells have the remarkable capacity to differentiate into many cell-types, including neurons, thus enabling the modeling of human neurological diseases in vitro, and permit the screening of molecules to correct diseases. Maintaining the pluripotent state of the stem cell, directing the stem cell towards a neuronal lineage, keeping […]
Mechanisms of Direct Cardiac Reprogramming
Heart disease is a leading cause of adult and childhood mortality. The underlying pathology is typically loss of heart muscle cells that leads to heart failure, or improper development of specialized cardiac muscle cells called cardiomyocytes during embryonic development that leads to congenital heart malformations. Because cardiomyocytes have little or no regenerative capacity after birth, […]
Elucidating Molecular Basis of Hypertrophic Cardiomyopathy with Human Induced Pluripotent Stem Cells
Familial hypertrophic cardiomyopathy (HCM) is the leading cause of sudden cardiac death in young people, including trained athletes, and is the most common inherited heart defect. Until now, studies in humans with HCM have been limited by a variety of factors, including variable environmental stimuli which may differ between individuals (e.g., diet, exercise, and lifestyle), […]
Characterization and Engineering of the Cardiac Stem Cell Niche
Despite therapeutic advances, cardiovascular disease remains a leading cause of mortality and morbidity in both California and Europe. New insights into disease pathology, models to expedite in vitro testing and regenerative therapies would have an enormous societal and financial impact. Although very promising, practical application of pluripotent stem cells or their derivatives face a number […]
USP16 controls stem cell number: implications for Down Syndrome
Stem cells are endowed with the ability to self-renew, that means to give rise to other cells with the same potential to regenerate a tissue. Recently, we found a gene that also regulates this mechanism. In addition, expression of high levels of this gene can reduce the number of stem cells in the bone marrow […]
Genomic instability during culturing of human embryonic stem cells
Human embryonic stem cells (hESCs) have important potential in the treatment of human disease. Because they can change into a large number of different cell types, they may be useful in restoring a variety of damaged tissues. One potentially harmful side effect of hESC therapy is cancer due to unregulated growth of the hESCs introduced […]