Stage of Program: Basic or Applied Basic Research (DISC1 and many 1.0 Projects)
WNT signaling and the control of cell fate decisions in human pluripotent stem cells.
With their ability to develop into virtually all mature cell types, human pluripotent stem cells (hPSC) represent a unique and powerful research tool to study the fundamental mechanisms regulating human development. In addition, hPSC provide the “raw material” for the development of cell-based therapies of presently incurable diseases, such as cancer, cardiovascular disease, and neurodegenerative […]
Directing migration of human stem cells with electric fields
Great progress has been made in the last decades to derive many types of human stem cells for potential therapeutic uses. However, practical clinical use is severely limited by several challenges. One of which is the poor homing and integration of transplanted cells with the targeted host tissues – only very few transplanted stem cells […]
Mitochondrial Metabolism in hESC and hiPSC Differentiation, Reprogramming, and Cancer
Stem cell quality and safety in developing regenerative medicine therapies is of utmost importance. Poor outcomes include inadequate functionality, exhaustion, immune rejection, cancer development, and others. Recent studies strongly support our core hypothesis that mitochondrial function determines stem cell quality and safety. Dysfunctional mitochondria foster cancer, diabetes, obesity, neurodegeneration, immunodeficiency, and cardiomyopathy. Unlike whole genome […]
The stem cell microenvironment in the maintenance of pluripotency and reprogramming
Pluripotent stem cell research is just on the verge of beginning to fulfill its promise to revolutionize medicine. Whether they are derived from embryos, or from adult cells that have been reprogrammed, human pluripotent stem cells can be propagated indefinitely in the laboratory and can turn into a wide range of mature cell types, providing […]
The retinoblastoma (RB) gene family in cellular reprogramming
One important aspect of regenerative medicine is the ability to introduce functional stem cells into patients to restore tissue function. This type of therapeutic approach will not be commonly used until several major potential problems have been addressed, including immune rejection and the risk of developing cancer. Induced pluripotent stem cells (iPSCs) hold great promise […]
Identification and characterization of human ES-derived DA neuronal subtypes
Parkinson’s disease (PD) is a neurodegenerative movement disorder that affects 1 in 100 people over the age of 60, one million people in the US and six million worldwide. Patients show a resting tremor, slowness of movement (bradykinesia), postural instability and rigidity. Parkinson’s disease results primarily from the loss of neurons deep in the middle […]
Molecular Characterization of hESC and hIPSC-Derived Spinal Motor Neurons
One of the main objectives of stem cell biology is to create physiologically relevant cell types that can be used to either facilitate the study of or directly treat human disease. Tremendous progress towards these goals has been made in the area of motor neuron disease and spinal cord injury through the findings that motor […]
Human Cardiovascular Progenitors, their Niches and Control of Self-renewal and Cell Fate
For the millions of Americans who are born with or develop heart disease, stem cell research offers the first hope of reversing or repairing heart muscle damage. Thus, early reports suggesting heart regeneration after transplantation of adult bone marrow-derived stem cells were met with great excitement in both the scientific and lay community. However, although […]
Defining the molecular mechanisms of somatic cell reprogramming
The development of methods to “reprogram” adult cells such as skin cells by simultaneously expressing four specific factors — Oct3/4, Sox2, c-Myc and Klf4 — in order to create cells resembling embryonic stem (ES) cells is a major breakthrough in stem cell biology. Our ability to generate these cells, which are known as induced pluripotent […]
Molecular Mechanisms of Reprogramming towards Pluripotency
Stem cell biology and its applications to cell-based therapies, since its inception 30 years ago, has been hindered by the immunological considerations of rejection of non-autologous cells in patients, as well as by ethical concerns. The generation of pluripotent cells from a patient’s own somatic cells has therefore been the holy grail of regenerative medicine. […]