Dr. Luigi Puglielli's research program focuses broadly on molecular mechanisms of neurodevelopment and neurodegeneration. His laboratory employs a combination of biochemical, cellular, molecular, and genetic approaches in in vitro, ex vivo and in vivo models. In 2007, his group reported that nascent proteins could undergo Nε-lysine acetylation in the lumen of the endoplasmic reticulum (ER). This discovery resulted in the identification of a previously unknown biochemical machinery that impacts on the biology of the ER.
Endoplasmic reticulum function is a primary area of focus. The ER acetylation machinery regulates two essential functions of the ER: (i) efficiency of the secretory pathway (as part of quality control) and (ii) disposal of toxic protein aggregates that form within the secretory pathway (through autophagy). Dr. Puglielli's laboratory has generated mouse models that mimic the above diseases and dissected relevant pathogenic pathways. These results support findings obtained from human-based studies and indicate that the ER acetylation machinery plays a crucial role in both neurodevelopmental and neurodegenerative diseases.
Active Research Projects:
- Dissection of biochemical and molecular pathways that link the ER acetylation machinery to neurodevelopmental and neurodegenerative diseases.
- Identification of the biochemical and molecular mechanisms that maintain cross-talk between different intracellular compartments.
- Molecular mechanisms of cognitive loss during aging and Alzheimer’s disease neuropathology.
- Drug discovery for the prevention and cure of neurodevelopmental and neurodegenerative disorders associated with dysfunctional ER acetylation.