Award Type: Fundamental Mechanisms (Track 1)
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 […]
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 […]
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 […]
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 […]