Project Objective: Research Insights

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 […]

Using human induced pluripotent stem cells to improve our understanding of Idiopathic Pulmonary Fibrosis

Idiopathic Pulmonary Fibrosis (IPF) is a progressive and generally fatal disease that causes scarring of the lungs and therefore an inability to breathe. Its true prevalence is unknown, as it may go unrecognized for many years, but it is generally thought to affect more than 200,000 people in the USA and is five times more […]

iPSC-derived Hepatocytes as Platforms for Research in Viral Hepatitis and Non-alcoholic Steatohepatitis

Hepatitis C and fatty liver disease are the two most common liver diseases in California. Individuals from different backgrounds are susceptible to these liver diseases, but they have unique genetic profiles that may influence the severity of disease and the response to specific therapies. Technology now makes it possible to generate stem cells from a […]

In Utero Embryonic Stem Cell Transplantation to Treat Congenital Anomalies

Many fetuses with congenital blood stem cell disorders such as sickle cell disease or thalassemia are prenatally diagnosed early enough in pregnancy to be treated with stem cell transplantation. The main benefit to treating these diseases before birth is that the immature fetal immune system may accept transplanted cells without needing to use immunosuppressant drugs […]

Human iPSC modeling and therapeutics for degenerative peripheral nerve disease

The applicant is an MD/PhD trained physician scientist, whose clinical expertise is neuromuscular disorders including peripheral nerve disease. The proposal is aimed at providing a research proposal and career development plan that will allow the applicant to develop an independent research program, which attempts to bring stem cell based therapies to patients with peripheral nerve […]

Enhancing hair cell regeneration in mouse and human inner ear

Hearing loss (HL) is a permanent sensory disorder affecting over 278 million people worldwide. In the US and California, 20% of individuals suffer from this sensory deficit. Those affected range from newborns (2 per 1000), to children aged 3-17 (5 per 1000), to adults including the elderly (~33% in aged 65-74 and ~50% >85 years […]