Our research focuses on the characterization of the cellular and molecular mechanisms by which vesicular cargoes and organelles including mitochondria, undergo intracellular cytoskeleton-based transport in neurons, and how defective transport and endolysosomal pathways play a role in neurodegeneration and aging. We use a combination of cell biology, molecular genetics, biochemistry, proteomics, and high-resolution microscopy in mammalian neurons, mice, and in Caenorhabditis elegans. In these systems, we have generated models for prion diseases, Alzheimer’s Disease and related tauopathies, and for the transthyretin (TTR) amyloid diseases, to identify and characterize the molecular mechanisms of neuronal toxicity. Our focus ranges from the dissection of subcellular-level pathways -to scrutinize the spreading of misfolded proteins and the role of liquid-liquid phase separation in disease-, to organismal/behavioral/neuronal brain circuit level questions. We develop quantitative high- and super-resolution imaging platforms to dissect subcellular-level mechanisms of protein movement and trafficking inside neurons. With these newfound mechanistic insights, we are actively screening small molecule compounds that ameliorate neurodegenerative phenotypes and behavioral outputs. We are also actively characterizing the targets of action and pathways of engagement of these small molecules. Our goal is to translate these findings to the development of therapeutics to test in human clinical trials. We are also investigating the role of endogenous retroviruses and of exogenous viruses in neurodegeneration, using in cellulo and in vivo mouse models.
Our Commitment to Diversity, Equity, and Inclusion:
The Encalada Lab takes pride in our inclusive lab culture, committed to promoting, enhancing, and maintaining diversity, equity, and respect of all of our lab members and of the community around us, regardless of ability designation or disability status, gender, sexual orientation, age, race/ethnicity, religion, cultural background, socioeconomic, citizen, or immigration status.
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