Program Type: Discovery
Metabolically-driven epigenetic changes in iPSC reprogramming
Generation of induced pluripotent stem cells (iPSCs) from somatic cells through cellular reprogramming offers tremendous potential for therapeutics, the study of disease states, and elucidation of developmental processes. Central to the process of generating a pluripotent cell from a somatic cell is an energy-dependent epigenetic reconfiguration event that must occur to produce iPSCs with characteristics […]
Role of intracytoplasmic pattern recognition receptors in HSC engraftment
The research performed through this project is very important for the fields of solid organ and bone marrow transplantation because it focuses on a potential new target to increase engraftment of stem cells. Currently, patients that receive stem cell transplants from a non-identical donor must take medications to suppress their immune system; otherwise the stem […]
Paracrine and synaptic mechanisms underlying neural stem cell-mediated stroke recovery
Stem cell therapy holds promise for the almost million Americans yearly who suffer a stroke. Preclinical data have shown that human neural stem cells (hNSCs) aid recovery after stroke, resulting in a major effort to advance stem cell therapy to the clinic, and we are currently transitioning our hNSC product to the clinic for stroke […]
Metabolic regulation of cardiac differentiation and maturation
Cells in the body take up nutrients from their environment and metabolize them in a complex set of biochemical reactions to generate energy and replicate. Control of these processes is particularly important for heart cells, which need large amounts of energy to drive blood flow throughout the body. Not surprisingly, the nutritional requirements of heart […]
Assessing the mechanism by which the Bone Morphogenetic Proteins direct stem cell fate
Our goal is to use the mechanisms that generate neuronal networks to create neurons from stem cells, to either replace diseased and damaged tissue or as a source of material to study disease mechanisms. A key focus of such regenerative studies is to restore function to the spinal cord, which is particularly vulnerable to damage. […]
Innate Immune Regulation of Lung Alveolar Stem Cell Renewal in Mouse and Man
The lung, along with the skin and gut are the three organs in perpetual contact with our environment. The lung has evolved mechanisms for repairing injury due to exogenous noxious agents. The timely repair of lung injury is essential and determines the outcome of life or death. The mechanisms that regulate mature alveolar epithelial stem […]
A novel druggable mechanism to safeguard stem cell genome
Safeguarding the genome is essential for cells’ proper functions, and more importantly for safe and efficacious applications involving pluripotent stem cells and adult stem cells. However, how pluripotent or somatic stem cells maintain genome integrity during self-renewal, differentiation, and reprogramming is still largely unknown. We recently identified a small molecule drug that exhibits unprecedented abilities […]
Generation of a functional thymus to induce immune tolerance to stem cell derivatives
Stem cell research offers the promise of replacing missing or damaged tissues in the treatment of disease. Stem-cell-derived transplants still face problems with rejection as in traditional organ transplants. Several drugs can prevent rejection but also suppress the immune system, leaving patients vulnerable to infections and cancer. To avoid rejection without using drugs requires re-educating […]
Molecular basis of plasma membrane characteristics reflecting stem cell fate potential
Stem cells generate mature, functional cells after proteins on the cell surface interact with cues from the environment encountered during development or after transplantation. Thus, these cell surface proteins are critical for directing transplanted stem cells to form appropriate cells to treat injury or disease. A key modification regulating cell surface proteins is glycosylation, which […]
Defining links between chromatin state and developmental competence
This proposal aims to define fundamental mechanisms that underlie the production of human pancreas and liver cells. The proposed research seeks to advance the development of stem cell-based therapies for diabetes and chronic liver disease. Diabetes is characterized by insulin deficiency due to destruction and/or malfunction of insulin-producing beta cells in the pancreas. Diabetic patients […]