Project Objective: Research Insights
Promoting survival and countering hypertrophy of pluripotent stem cell (PSC)-derived chondrocytes
Degenerative joint disease, also known as osteoarthritis, currently affects more than 20 million people in the USA alone, making articular cartilage restoration one of the major priorities in medicine. Articular chondrocyte progenitors are likely to be present only early in development, which explains why previous attempts to engineer articular cartilage using adult stem cells have […]
New Regulators of Spermatogonial Stem Cells: RHOX Homeobox Transcription Factors
Infertility afflicts a remarkably high percentage (~15%) of couples, with male factor defects being responsible for more than ½ of these cases. One-third of these male infertility cases have no known cause. For most infertile men, the only “treatment” is in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), both of which are costly, invasive […]
Differentiation of Human Hematopoietic Stem Cells into iNKT Cells
Blood stem cells living in the bone marrow of adult humans give rise to all of the cells in our blood, including the red blood cells that carry oxygen to supply our body, and the white blood cells such as T and B lymphocytes that fight infections and keep us healthy. Among the T lymphocytes […]
Epigenetic mechanisms that enforce pluripotency in embryonic stem cells
Embryonic stem (ES) cells have the unique ability to self-renew while maintaining a pluripotent state. They can readily be differentiated into all cell types upon exposure to the appropriate stimuli. The differentiation of ES cells into specialist cell types involves the activation of lineage-specific programs of gene expression and the silencing of genes that promote […]
Systems-level discovery of the regulatory mechanisms directing differentiation of hESC
Human embryonic stem cells (hESCs) are capable of unlimited reproduction and retain the ability to differentiate into all cell types in the human body. Therefore, hESCs hold great promise for human cell and tissue replacement therapy. However, our knowledge on how to differentiate them into desired cell types for therapy remains limited. The overall goal […]
Elucidating pathways from hereditary Alzheimer mutations to pathological tau phenotypes
We propose to elucidate pathways of genes that lead from early causes to later defects in Alzheimer’s Disease (AD), which is common, fatal, and for which no effective disease-modifying drugs are available. Because no effective AD treatment is available or imminent, we propose to discover novel genetic pathways by screening purified human brain cells made […]
CD61-driven stemness program in epithelial cancer
Tumors contain a heterogeneous mix of cancer cells with distinct features, including subsets of particularly aggressive stem-like cells. Since a single cancer stem cell can self-renew, divide, and differentiate to reconstitute the heterogeneity of an entire tumor, the ability of one cell to evade therapy or surgical resection could lead to tumor re-growth and disease […]
A Requirement for Protein Homeostasis in the Mediation of Stem Cell Health
Experiments with human embryonic stem cells (hESCs) have clearly demonstrated their capacity to replicate continuously and maintain pluripotency. We hypothesize that the health of hESCs depends in part upon an increased ability to carefully control the health of their proteome. We have found that hESCs have an incredibly high level of proteasomal activity in comparison […]
Misregulated Mitophagy in Parkinsonian Neurodegeneration
Parkinson’s disease (PD), is one of the leading causes of disabilities and death and afflicting millions of people worldwide. Effective treatments are desperately needed but the underlying molecular and cellular mechanisms of Parkinson’s destructive path are poorly understood. Mitochondria are cell’s power plants that provide almost all the energy a cell needs. When these cellular […]
Induced pluripotent stem cells from children with autism spectrum disorders
Autism spectrum disorders (ASD) are a family of disabling disorders of the developing brain that affect about 1% of the population. Studying the biology of these conditions has been difficult as they have been challenging to represent in animal models. The core symptoms of ASD, including deficits in social communication, imagination and curiosity are intrinsically […]