Stage of Program: Basic Research and Discovery Stage Programs
Discovery of adhesion ligands for pluripotent human stem cells
We have assembled a team of investigators with complementary expertise in applying the state-of-the-art “one-bead-one-compound” (OBOC) combinatorial library methods to identify synthetic chemical molecules that bind to unique receptors (protein molecules) on the surface of human embryonic stem cells and induced pluripotent stem cells. In this technology, stem cells will be mixed with huge number […]
Regulation of Stem Cell Fate in Bioengineered Arrays of Hydrogel Microwells
Stem cell biology, since its inception 30 years ago, has been hindered by our limited ability to observe and direct the decisions of individual stem cells. In the case of adult tissue-specific stem cells, such as those from blood, muscle or pancreas, the numbers available for clinical use are extremely limited, as in tissue culture […]
Optimization in the Identification, Selection and Induction of Maturation of Subtypes of Cardiomyocytes derived from Human Embryonic Stem Cells
Cardiovascular diseases remain the major cause of death in the western world. Stem and progenitor cell-derived cardiomyocytes (SPC-CMs) hold great promise for the myocardial repair. However, most of SPC-CMs displayed heterogeneous and immature electrophysiological phenotypes with substantial automaticity. Implanting these electrically immature and inhomogeneous CMs to the hearts would be arrhythmogenic and deleterious. Further optimization […]
The Stem Cell Matrix: a map of the molecular pathways that define pluripotent cells
Human embryonic stem cells (hESC) are being considered for a wide range of research and therapeutic uses. Cell therapy is the most challenging of the potential clinical applications and its success will depend on the ability to guide differentiation of hESC into clinically useful cell types. The ideal cell types would possess three features: the […]
Development of an hES Cell-Based Assay System for Hepatocyte Differentiation Studies and Predictive Toxicology Drug Screening
Drug-induced liver toxicity, including that from FDA-approved drugs, is the leading cause of liver failure in the US. One of the biggest road blocks to testing drug-induced liver toxicity prior to clinical studies or release of the drug into the market is the absence of a good model of human drug metabolism in the liver. […]
Directed Evolution of Novel AAV Variants for Enhanced Gene Targeting in Pluripotent Human Stem Cells and Investigation of Dopaminergic Neuron Differentiation
Human embryonic stem cells (hESCs) and induced pluripotent stem (iPS) cells have considerable potential as sources of differentiated cells for numerous biomedical applications. The ability to introduce targeted changes into the DNA of these cells – a process known as gene targeting – would have very broad implications. For example, mutations could readily be introduced […]
Defining the Isoform-Specific Effects of Apolipoprotein E on the Development of iPS Cells into Functional Neurons in Vitro and in Vivo
GOALS We propose to determine the effects of different forms of apoE on the development of induced pluripotent stem (iPS) cells into functional neurons. In Aim 1, iPS cells will be generated from skin cells of adult knock-in (KI) mice expressing different forms of human apoE and in humans with different apoE genotypes. In Aim […]
Mechanisms Underlying the Responses of Normal and Cancer Stem Cells to Environmental and Therapeutic Insults
Adult stem cells play an essential role in the maintenance of tissue homeostasis. Environmental and therapeutic insults leading to DNA damage dramatically impact stem cell functions and can lead to organ failure or cancer development. Yet little is known about the mechanisms by which adult stem cells respond to such insults by repairing their damaged […]
Laying the groundwork for building a tooth: analysis of dental epithelial stem cells
To fix a broken car, the mechanic either repairs or replaces the defective part. Similarly, one of the most promising approaches physicians foresee for treating human disease and ameliorating the aging process is regenerative medicine. A major aim of this field is to restore function by repairing or replacing damaged organs. Scientists envision a day […]
Building Cardiac Tissue from Stem Cells and Natural Matrices
Congestive heart failure afflicts 4.8 million people, with 400,000 new cases each year. Myocardial infarction (MI), also known as a “heart attack”, leads to a loss of cardiac tissue and impairment of left ventricular function. Because the heart does not contain a significant number of multiplying stem, precursor, or reserve cells, it is unable to […]