Therapeutic/Technology: Exploring stem cell mechanisms
Transcriptional regulation of pluripotency in human embryonic stem cells
All of the diverse cells in the human body contain the same genetic information, and originally arose from a single cell, a fertilized egg. Embryogenesis is a result of cell division followed by differential gene expression, to selectively activate only the genes needed for development of each specialized cell type. By understanding the multiple gene […]
Understanding the status of the X chromosomes in human ESCs and preimplantation embryos
Human embryonic stem cells (hESCs) are able to divide indefinitely and under the proper conditions, can essentially become any cell in the human body. They are derived from the developing human embryo and carry great promise for regenerative medicine. However, these cells demonstrate an instability surrounding the state of the X chromosome. Male (XY) cells […]
Common molecular mechanisms in neurodegenerative diseases using patient based iPSC neurons
A major medical problem in CA is the growing population of individuals with neurodegenerative diseases, including Parkinson’s (PD) and Huntington’s (HD) disease. These diseases affect millions of people, sometimes during the prime of their lives, and lead to total incapacitation and ultimately death. No treatment blocks the progression of neurodegeneration. We propose to conduct fundamental […]
Role of mechanical signaling in stem cell self-renewal and differentiation
Cells feel subtle but constant pushes and tugs from their neighbors inside living organisms. Surprisingly, these tiny mechanical cues have a profound effect on how stem cells grow, divide, and turn into the many different cells that make up the human body. Based on recent findings in developmental, cancer, and stem cell biology, we hypothesize […]
Energy metabolism and aging pathways in human stem cell reprogramming and differentiation
The discovery that human skin cells can be reprogrammed into stem cells holds great promise for therapies for degenerative diseases. As many patients in need of regenerative medicine therapies are middle-aged or older, identifying strategies to improve the reprogramming efficiency and quality of cells from aging donors will be crucial in harnessing the full potential […]
Genetic dissection of human cellular reprogramming to pluripotency
It is now possible to turn adult differentiated cells from a patient into human induced Pluripotent Stem (iPS) cells. These iPS cells hold enormous promise for new therapies in Regenerative Medicine, because they can be coaxed in the laboratory to become any cell type in the human body. While this is a spectacular property, we […]
A new paradigm of lineage-specific reprogramming
Recently, we devised and reported a new regenerative medicine paradigm that entails temporal/transient overexpression of induced pluripotent stem cell based reprogramming factors in skin cells, leading to the rapid generation of “activated” cells, which can then be directed by specific growth factors and small molecules to “relax” back into various defined and homogenous tissue-specific precursor […]
Prostaglandin pathway regulation of self-renwal in hematopoietic and leukemia stem cells
Leukemias are cancers of the blood cells that result from corruption of the normal controls that regulate blood-forming stem cells. They are serious causes of illness and death, and are particularly devastating in children and the elderly. Despite substantial advances in treatment of leukemia, a significant proportion of cases are unresponsive to current therapy. Since […]
Stem Cell Mechanisms Governing Discrete Waves of Gliogenesis in the Childhood Brain
White matter is the infrastructure of the brain, providing conduits for communication between neural regions. White matter continues to mature from birth until early adulthood, particularly in regions of brain critical for higher cognitive functions. However, the precise timing of white matter maturation in the various neural circuits is not well described, and the mechanisms […]
Stem cell models to analyze the role of mutated C9ORF72 in neurodegeneration
Amyotrophic lateral sclerosis (ALS) is an idiopathic adult-onset degenerative disease characterized by progressive weakness from loss of upper and lower motor neurons. Onset is insidious, progression is essentially linear, and death occurs within 3-5 years in 90% of patients. In the US, 5,000 deaths occur per year and in the world, 100,000. In October, 2011, […]