Therapeutic/Technology: Model system development

Editing of Parkinson’s disease mutation in patient-derived iPSCs by zinc-finger nucleases

The goal of this proposal is to establish a novel research tool to explore the molecular basis of Parkinson’s disease (PD) – a critical step toward the development of new therapy. To date, a small handful of specific genes and associated mutations have been causally linked to the development of PD. However, how these mutations […]

Developing a method for rapid identification of high-quality disease specific hIPSC lines

Elucidating how genetic variation contributes to disease susceptibility and drug response requires human Induced Pluripotent Stem Cell (hIPSC) lines from many human patients. Yet, current methods of hIPSC generation are labor-intensive and expensive. Thus, a cost-effective, non-labor intensive set of methods for hIPSC generation and characterization is essential to bring the translational potential of hIPSC […]

Use of hiPSCs to develop lead compounds for the treatment of genetic diseases

This study will use Ataxia-Telangiectasia (A-T), an early-onset inherited neurodegenerative disease of children, as a model to study the mechanisms leading to cerebellar neurodegeneration and to develop a drug that can slow or halt neurodegeneration. We will start with skin cells that were originally grown from biopsies of patients with A-T who specifically carry “nonsense” […]

Development of small molecule screens for autism using patient-derived iPS cells

Autism Spectrum Disorders (ASDs) are a heritable group of neuro-developmental disorders characterized by language impairments, difficulties in social integrations, and the presence of stereotyped and repetitive behaviors. There are no treatments for ASDs, and very few targets for drug development. Recent evidence suggests that some types of ASDs are caused by defects in calcium signaling […]

Site-specific integration of Lmx1a, FoxA2, & Otx2 to optimize dopaminergic differentiation

The objective of this study is to develop a new, optimized technology to obtain a homogenous population of midbrain dopaminergic (mDA) neurons in a culture dish through neuronal differentiation. Dopaminergic neurons of the midbrain are the main source of dopamine in the mammalian central nervous system. Their loss is associated with one of the most […]

Crosstalk: Inflammation in Parkinson’s disease (PD) in a humanized in vitro model

Parkinson’s Disease (PD) is the most common neurodegenerative movement disorder. It is characterized by motor impairment such as slowness of movements, shaking and gait disturbances. Age is the most consistent risk factor for PD, and as we have an aging population, it is of upmost importance that we find therapies to limit the social, economic […]

Niche-Focused Research: Discovery & Development of Hematopoietic Regenerative Factors

Bone marrow and peripheral blood transplantation utilizing blood stem cells can provide curative treatment for patients with cancers and non-cancerous diseases of the blood and immune systems. Such treatments can be curative because the stem cells contained within the bone marrow or peripheral blood of healthy donors are capable of replacing the entirety of the […]

Generation of functional cells and organs from iPSCs

The development of induced pluripotent stem cell (iPSC) technology may be the most important advance in stem cell biology for the future of medicine. This technology allows one to generate a patient’s own pluripotent stem cells (PSCs) from skin or blood cells. iPSCs can then be reprogrammed to multiply and produce high quality mature cells […]

In Utero Model to Assess the Fate of Transplanted Human Cells for Translational Research and Pediatric Therapies

nfants with inherited blood diseases (such as sickle cell anemia, thalassemia, bleeding disorders) or other inherited metabolic disorders can be identified early in development using sophisticated diagnostic tests. Currently, the treatment for many of these childhood illnesses may include bone marrow transplantation which is complicated by: (1) the toxicity associated with chemotherapy or radiation-based regimens […]

Mouse Models for Stem Cell Therapeutic Development

Stem cells have tremendous potential for treating human diseases, as they have the unique capacity to develop into any cell type in the body and to proliferate indefinitely. The development of new therapies based on the transplantation of human stem cells (HuSC) into patients is a major focus of California researchers. A critical step prior […]