Research Description

Longevity molecules that counteract aging and extend lifespan have long been a dream of humanity. Compared to ad libitum feeding, dietary restriction (DR) consistently extends lifespan and prevents age-related diseases. We discovered that a common metabolite, alpha-ketoglutarate (a-KG), acts as a direct molecular connection between nutrient signals, mitochondrial processes, and a major aging regulator mTOR (Chin et al. Nature 2014). Endogenous molecules such as a-KG that increase longevity suggest that an internal “fountain of youth” may exist that is accessible to interventions. Subsequent studies in the area by many labs, including our own, have shown enormous hopes and possibilities for both the prevention and treatment of aging-related diseases, including cancer, heart disease, diabetes, neurodegenerative diseases, immune dysfunction, and stem cell failure. Another major area of interest in the lab is in technology and method development. Development of effective and safe therapies is the holy grail of medicine. For small-molecule drugs, a key challenge remains the identification of the molecular targets underlying drug therapeutic effects and adverse side effects. We have developed DARTS (drug affinity responsive target stability), a simple, universally applicable target identification approach that analyzes direct drug binding to its target protein without requiring labeling or immobilization of either party (Lomenick et al. 2009). DARTS combined with mass spectrometry (DARTS-MS) can identify unknown binding targets of small molecules using any cell lysate or protein mixture, and DARTS combined with Western blotting can test or screen candidate binding targets.

Current Lab Members

  • Chieh Chen | Graduate Student |
  • BS, Genetics and Genetic Engineering, Fudan University
  • PhD, Biochemistry and Molecular Biology, USC School of Medicine
  • Postdoctoral, Chemistry and Chemical Biology, Harvard University
  • Member, Molecular Biology Institute
  • Member, JCCC