Therapeutic/Technology: Exploring disease mechanisms


Ex vivo fate mapping of human lung stem cell plasticity in fibrotic disease

Research Objective This proposal will design new models to study behavior that is specific to human lung stem cells, and screen for drugs that can target abnormal stem cells in fibrotic disease. Impact This study will generate potential new therapeutic approaches to fibrotic lung diseases such as idiopathic pulmonary fibrosis. Major Proposed Activities Development of […]

Modeling Retinitis Pigmentosa using patient-derived human iPSC organoids

Research Objective The objective of this proposal is to develop a human retinal organoid model of adRP to gain insights in pathogenesis and assess clinically relevant approaches to restore RHO protein function. Impact Upon successful completion of this study, we will have established a disease-in-a-dish model and a novel therapeutic approach towards management of the […]

Functional genomics to study cellular convergence across ASD risk genes in neurodevelopment

Research Objective Our objective is to enable scalable genetic screening to study how neurogenesis is impacted by risk genes implicated in human psychiatric disorders. Impact We will develop and apply state-of-the-art genomic analysis to seek mechanisms and disease modifying solutions. Major Proposed Activities Identifying and validating efficient gRNA for gene editing Identify risk gene effects […]

Determining how age-specific heterogeneity of human hematopoietic stem cells and megakaryocyte progenitors contribute to thrombotic disease upon aging

Research Objective Our research will determine how aging of human blood stem cells leads to dramatic increases in disorders of platelets, cells that normally prevent bleeding but form harmful clots when dysregulated. Impact Our findings have the potential to inform prevention and mitigation strategies of bleeding and clotting disorders that contribute to significant morbidity and […]

Understanding Chemotherapy-Induced Peripheral Neuropathy Mechanisms using CRISPRi and Chemical Screens in Human iPSC-Derived Sensory Neurons

Research Objective The research objectives are to identify causal genes for chemotherapy-induced mitochondrial toxicity and neurodegeneration in sensory neurons and drugs that target this toxicity. Impact These studies will open the possibility for genetic or drug targeting to prevent and treat drug-induced peripheral neuropathies and possibly neuropathies caused by disease or inherited. Major Proposed Activities […]

Control of OCT4 abundance and function in human stem cells

Research Objective Our work will reveal an essential pathway that establishes precise levels of the OCT4 transcription factor and protects stem cell identity despite genetic or environmental stress. Impact Our work will enhance our ability to generate and expand high-quality induced pluripotent stem cells from older patients or patients of neurodegenerative disease for use in […]

Modulation of human alveolar stem cells to promote lung regeneration and avoid pulmonary fibrosis

Research Objective Understanding regulators of human alveolar lung stem cell function will promote more normal lung regeneration after injury and avoid the nearly untreatable problem of advanced pulmonary fibrosis. Impact Idiopathic Pulmonary Fibrosis (IPF), Adult Respiratory Distress Syndrome (ARDS), and other chronic fibrotic lung disorders. Major Proposed Activities Modify human fibroblasts to create a supporting […]

A new precision medicine based iPSC-derived model to study personalized intestinal fibrosis treatments in pediatric patients with Crohn’s disease

Research Objective We propose to discover a tool that will utilize patient specific iPSC-derived human mini-guts to identify personalized antifibrotic treatments in pediatric Crohn’s disease patients Impact The major bottleneck in intestinal fibrosis research is the difficulty in obtaining patient-specific biologically relevant cells for in vitro modeling. This iPSC-derived tool would overcome it. Major Proposed […]

An IPSC cell based model of macular degeneration for drug discovery.

Research Objective Towards a cure for age related blindness, we propose to create a human stem cell based model to screen for drugs that are protective against Age related macular degeneration (AMD). Impact With up to 11 million people in the United States affected by AMD, effective treatments against macular degeneration could address vision loss […]

In vitro modeling of human motor neuron disease

Motor neuron (MN) diseases such as spinal muscular atrophy and amyotrophic lateral sclerosis lead to progressive degeneration of MNs, presenting first with muscle weakness, followed by locomotor defects and frequently death due to respiratory failure. While progress has been made in identifying genes associated with MN degeneration, the molecular and cellular processes underlying disease onset […]