Stage of Program: Basic or Applied Basic Research (DISC1 and many 1.0 Projects)
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 […]
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 […]
Mechanisms in Choroid Plexus Epithelial Development
Buried deep inside the brain are cells known as choroid plexus epithelial (CPe) cells. Although not as famous as other cells in the nervous system, CPe cells perform a large number of important jobs that keep the brain and spinal cord healthy. They produce the fluid (known as cerebrospinal fluid, or CSF) that bathes the […]
The roles of non-coding RNAs in the self-renewal and differentiation of pluripotent stem cells
There are thousands of cell types in the animal body, many of which can be derived from embryonic stem cells (ES cells), a pluripotent cell type that thrive in cell culture condition. ES cells differentiate into various cell type in a tissue culture dish in response to different growth factor/cytokine treatment, which can be transplanted […]
Mechanisms of small RNA regulation in early embryonic development
The promise of embryonic stem cells in regenerative medicine is based on their potential to make every cell in the body, a property coined pluripotency. With rapid recent advances in technology, it is becoming relative straightforward to make embryonic stem cell-like lines from adult tissues. In the near future, the generation of these lines will […]