Research in the Douglas lab seeks to understand how stress response pathways alter cell physiology, and ultimately influence the aging process and human disease. Cells possess dormant pathways which are activated under times of stress in order to buffer deleterious effects and help restore the cell to resting homeostasis. We have the ability to harness these latent stress response pathways and apply their protective properties to a multitude of disease models.
Stress Response Signaling in Neurodegeneration and Cancer
The master regulator of the heat shock response, HSF1, has long been linked with cellular protection. As the first eukaryotic transcription factor discovered, HSF1 regulates the expression of several classes of molecular chaperones. These highly inducible genes have well-defined, cytoprotective roles under times of stress and protect against cell death in several models of neurodegeneration.
However, more recent studies have uncovered striking correlations between HSF1 and cancer. To ensure long-term health, animals must maintain HSF1 activity in a delicate balance; too much activity can drive malignancy where as too little HSF1 activity can result in cellular degeneration. The Douglas lab looks to better understand this dichotomy using cell culture, the nematode C. elegans, and murine models.
Mechanisms Behind Traumatic Brain Injury
Traumatic brain injury (TBI) is major health problem which costs the US more than 50 billion dollars annually. Originally thought to be a stochastic process, research has begun to demonstrate that TBI initiates highly regulated responses with the potential to intervene and attenuate both the immediate and long-term consequences of the disease.
Research in the Douglas lab utilizes high-throughput screening methods in the nematode C. elegans to uncover new components within the nervous system which are essential to mediate protection against blunt trauma. In combination, mammalian homologs of these cytoprotective components are further tested in mouse models of brain trauma.