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Shmookler Reis Laboratory & Research
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Current research focuses primarily on the molecular genetics of longevity, and mechanisms underlying age-associated diseases including neurodegenerative diseases (Alzheimer's, Parkinson's, and Huntington's) as well as cardiovascular disease, muscle wasting, kidney disease and adult cancers.  We isolate total proteins and immuno-purified aggregates from aged or disease-affected human tissues (or in some cases, tissues from mouse models) and control tissues for proteomic analyses.  Candidate proteins (those that are markedly more or less abundant with age or in disease aggregates) are assessed for functional roles by RNAi knockdown in C. elegans models and by shRNA knockdown in human cell-culture models.
Other areas of investigation: (1.) Mechanisms leading to extreme "hyperlongevity" and stress resistance in class-I PI3K null-mutant worms, unable to make the membrane-tethering molecule PIP3. Two independent C. elegans mutants in the catalytic subunit of PI3KI hold the world record for life-extension by a single mutation―nearly 10-fold. We immunopurified and identified proteins that prefer to bind PIP3 over its precursor, PIP2, and tested many of these for roles in protein aggregation, stress resistance and lifespan. (2.) We created a longevity-mutant panel in a constant genetic background, and sought molecular properties that predict lifespan; lipid saturation and RNA profiles provided the best biomarkers. (3.) We developed novel methods to map genes affecting Darwinian fitness and lifespan in C. elegans, and bone density and post-menopausal bone loss in mice and humans.