Our understanding of the origin and functions of microglia has grown to such an extent it is as if a new CNS cell has been discovered. These advances have opened up new avenues to understand the role of microglia in normal CNS function and disease. Most importantly, microglia imaging and targeting for disease treatment have become possible. Dr. Butovsky’s lab is interested in the biology of microglia and the interplay between peripheral innate immunity in brain development, homeostasis, aging and neurodegenerative conditions.
Dr. Butovsky has made seminal discoveries including the identification of the TGFβ-dependent homeostatic M0-microglia and the second major microglia phenotype, neurodegenerative MGnD-microglia which is regulated by TREM2-APOE pathway. These findings led to the establishment of national and international collaborations to develop microglial targets to treat neurodegenerative diseases.
Dr. Butovsky’s lab is internationally recognized for redefining microglia and identifying novel therapy targets. The group specializes in the generation of novel methods including: 1) microglia arrays utilizing novel spatial technologies to determine unique microglia phenotypes associated with pathologies; 2) generation of microglia and monocyte specific mAbs; 3) generation of transgenic mice to target microglia and myeloid brain infiltrates; 4) developing PET-based microglial biomarkers; and 5) developing microglia-specific therapeutic delivery strategies.
Current lab directions include: 1) investigation of environmental cues, early life stress, and the genetic factor APOE4 associated with development of AD; 2) developing a novel transgenic mouse model to target MGnD-microglia; 3) replacing microglia carrying major AD risk factors with functional microglia utilizing iPSCs; 4) reprogramming human blood monocytes into microglia-like cells to restore microglial functions; 5) modulating and restoring functional crosstalk between microglia-monocyte and microglia-adaptive immunity in neuroinflammation; 6) identification of immune cell-based biomarkers predictive of ALS progression