Stage of Program: Basic Research and Discovery Stage Programs
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 […]
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 […]