Many chronic disabling diseases such as rheumatoid arthritis, psoriasis, multiple sclerosis and systemic lupus erythematosus are increasingly linked to inappropriate and chronic activation of inflammatory cells. A central event in the pathogenesis of these diseases appears to be an aberrant activation of innate immune sensors, most prominently the Pattern Recognition Receptors (PRRs), by nucleic acids that are released from dead and dying cells. We design nucleic acid-binding polymers in the configuration of either soluble or immobilized polycation to scavenge these PRRs as a molecular strategy to combat inflammation.
Inadequate animal models and poor access to living human brain lead to significant challenges to model psychiatric diseases and to develop neuropsychiatric drugs. Recent advances in human induced pluripotent stem cells (hiPSC) have made it possible to create a patient-specific brain-like neural tissue (referred to as ‘cerebral organoid’) that displays an architecture and neural network activity resembling that of human brain. We generate cerebral organoids from patients with genetic lesions to investigate disease mechanisms responsible for the development of neuropsychiatric disorders in humans. We also generate tissue-engineered blood vessels from induced smooth muscle cells to model Marfan Syndrome and atherosclerosis
Genome editing offers promising solutions to genetic disorders by editing DNA sequences or modulating gene expression. Efficient in vivo delivery remains a significant challenge to the realization of the clinical potential of gene editing. We design nanocarriers with targeting characteristics to achieve efficient gene editing in various tissues. We are evaluating the in vivo efficacy of such a gene editing system that targets three separate genes correlated with cardio-protective point mutations