Healthy Aging at Tufts Pilot Grants 2019-2020

Project Title: Development of a system for determining the neurotoxicity of air pollutants in human brain tissue models of Alzheimer’s disease

Principal Investigator: Dr. Neelakshi Hudda

An inter-disciplinary collaboration between a neuroscientist and biomedical and environmental engineers at Tufts will take on the ambitious task of investigating the relationship between onset and progression of Alzheimer’s pathology upon exposure to real-world airborne particulate matter. Dr. Hudda and Dr. Durant have studied urban air quality for decades. They believe that the scientific understanding of the mechanisms by which air pollution leads to neurodegenerative disorders is lacking despite the accumulating observational evidence that suggests that traffic-generated particulate air pollution exposure is a risk-factor, in particular for cognitive decline in elderly who reside near highways. The research further builds on the pioneering work from their collaborators, Drs. Nieland and Kaplan, who have developed brain-like tissue models based on stem-cell derived neurons and supporting glial cells. They have shown that their bioengineered, living human like tissues functions in many ways similar to the healthy and diseased human brain. The team is excited to undertake this pilot study as a step towards addressing the critical knowledge gap of how air pollution may cause neurological disease.”

Project Title: Polymorphonuclear leukocyte senescence in age-associated susceptibility to Streptococcus pneumoniae lung infection

Principal Investigator: Dr. Joan Mecsas

Elderly persons are at increased risk for invasive pneumococcal disease. Our results suggest that dysregulation in PMN recruitment, along with defects of PMNs in opsonophagocytic killing, are critical to the susceptibility of aged animals to serious S. pneumoniae infection. However, the study of PMNs at a mechanistic level is challenging, due mostly to the short life-span of the terminally-differentiated PMNs, which precludes genetic methods, such as CRISPR-Cas9-mediated gene disruption. Here we will assess the role of PMN dysfunction in age-associated susceptibility to S. pneumoniae infection and establish an experimental system with immortalized stem cells from young and aged mice that can be induced to differentiation into PMNs in order to systematically assess the contribution of defects in the migratory or microbicidal functions of PMNs in S. pneumoniae infection.

Project Title: Study of Alzheimer’s disease using a novel bioengineered model of iPSC-derived neural tissue

Principal Investigator: Dr. Giuseppina Tesco

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by memory impairments and cognitive deterioration. Current systems to study AD include cell cultures and animal models. Human diseases, however, are often poorly reproduced in animal models. A possible solution for this problem comes from the recent advances in stem cell technology that have allowed the reprogramming of primary cells from human subjects into induced pluripotent stem cells (iPSCs) and their differentiation in neurons (hNeurons), astrocytes (hAstrocytes) and microglia (hMicroglia). We have developed a novel bioengineered 3D model of iPSC-derived neural tissue. Thus, we propose to model Alzheimer’s disease in vitro using patient-derived iPSCs. Given that prevention of AD is expected to be more successful than AD treatment, our 3D brain-like cultures could eventually be used to predict whether an asymptomatic subject will develop AD and to potentially design personalized treatments.

For questions and submission of a proposal, please contact healthyaging@tufts.edu