(Boston)—Julia TCW, PhD, assistant professor of pharmacology, physiology & biophysics at Boston University Chobanian & Avedisian School of Medicine and bioinformatics program at Boston University, has received a $420,000 Carol and Gene Ludwig Award for Neurodegeneration Research. In addition, she has also been awarded $500,000 from the Edward N. & Della L. Thome Memorial Foundation Awards Program in Alzheimer’s Disease Drug Discovery Research. Both awards will fund her Alzheimer’s disease (AD) research.
Alzheimer’s disease is a progressive neurodegenerative disorder and the most common cause of dementia, affecting more than 5.8 million individuals in the U.S. AD research has largely focused on the disease endpoint pathologies, β-amyloid (Aβ) plaques and neurofibrillary tangles (tau). Studies have demonstrated that AD pathology begins to accumulate 10-20 years prior to clinical presentation. Molecular changes driven by disease-associated genetic variants likely occur even earlier.
Among significant variants identified in a genome-wide association study for AD, Apolipoprotein E (APOE) is the most significant genetic risk factor for late-onset AD. First discovered in 1993, it is present in 64% of sporadic, late-onset AD and at least 80% of familial cases. The fundamental basis through which the APOE4 variant confers heightened risk for AD may be initiated as early as fetal brain development.
Astrocytes and microglia play critical roles in neural circuit formation during brain development. TCW’s group recently reported that APOE4 induces robust species-specific dysfunction in lipid metabolism in human astrocytes and microglia, but not astrocytes and microglia isolated from APOE targeted-replacement (APOE-TR) in experimental models.
As a Ludwig investigator, TCW proposes to investigate molecular and cellular mechanisms of protective Christchurch variant (a rare variant that helps protect the brain and dramatically slows the progression of AD) effects on astrocytes derived from human AD patient-induced pluripotent stem cells (hiPSCs). “We expect this study will reveal protective mechanisms that could potentially be targetable for therapeutics,” she adds.
Using funds from the Edward N. and Della L. Thome Memorial Foundation, TCW will study the role of cholesterol in neurodegeneration. The goal of this research is to develop pharmacological interventions targeting cholesterol that are accumulated in AD patient brains.
TCW received her PhD and AM in molecular and cellular biology from Harvard University. She then pursued her postdoctoral research in the department of neuroscience at the Ronald M. Loeb Center for Alzheimer’s Disease at Icahn School of Medicine at Mount Sinai, New York. Subsequently she served there as research faculty in the department of genetics and genomic sciences and neuroscience where her research focus was on the development of iPSC models and AD genetics.
In addition to these grants, TCW has been awarded a National Institutes of Health’s (NIH) National Institute on Aging grant, the Druckenmiller Fellowship award from New York Stem Cell Foundation, a K award from the National Institutes of Health-National Institute of Aging, a BrightFocus Foundation grant, and was named a 2022 Toffler Scholar by the Karen Toffler Charitable Trust.
The Carol and Gene Ludwig Family Foundation supports medical research with a focus on neurodegenerative disorders, especially Alzheimer’s disease, in addition to education and community engagement.
The Edward N. & Della L. Thome Memorial Foundation was created in 2002 to advance the health of older adults through the support of direct service projects and medical research on diseases and disorders affecting older adults.