Explore our Research

1) Inter-organelle contact sites: Mechanisms and functions regulating mitochondria-lysosome contact sites

What we know: Mitochondria and lysosomes are important cellular organelles, which can directly tether together at inter-organelle contact sites known as mitochondria-lysosome contacts, allowing for their bidirectional crosstalk (Nature 2018). Rab7 GTP hydrolysis mediates mitochondria-lysosome contact untethering, and contacts regulate both mitochondrial fission and inter-mitochondrial contact untethering events (Nature 2018; Dev Cell 2019), resulting in lysosomal regulation of mitochondrial network dynamics. Conversely, mitochondria also regulate lysosomal tethering dynamics via a Mid51/Fis1 oligomerization complex which couples together Rab7 and Drp1 GTP hydrolysis machinery (J Cell Biol 2022). 

Mitochondria-lysosome contact sites further mediate calcium transfer between lysosomes and mitochondria via TRPML1 (PNAS 2020) and regulate amino acid homeostasis (Science Advances 2023). Thus, while mitochondria-lysosome contact sites play key roles in both health and disease (reviewed in: Trends in Neurosci 2022; J Cell Biol 2023), whether there are additional roles and regulators of mitochondria-lysosome contact sites is still not known.

Ongoing studies: We are interested in exploring new mechanisms and functions of inter-organelle contact sites including mitochondria-lysosome contacts, to better understand basic cellular homeostasis. 

We are currently using human cell lines to:

• i) identify new regulators of contact sites

• ii) explore additional functions which occur at these contact sites

• iii) study novel interactions between other organelles and mitochondria-lysosome contacts

2) Neurodegenerative diseases: Defective inter-organelle contact dynamics in Parkinson’s disease, Alzheimer’s disease and ALS

What we know: Mitochondrial and/or lysosomal dysfunction are functionally and genetically linked to many neurodegenerative disorders including Parkinson’s and Charcot-Marie Tooth (CMT). Mitochondria-lysosome contact sites are misregulated in different genetic models of Parkinson’s disease (Nature Comm 2021; Science Advances 2023)  and mitochondria-lysosome contact site dynamics are also disrupted in the peripheral neuropathy Charcot-Marie Tooth disease (CMT2B) linked to mutations in Rab7 (Dev Cell 2019; PNAS 2023). 

However, how inter-organelle contact dynamics are mechanistically disrupted in other human disorders remain to be explored. Moreover, properly regulated organelle dynamics and function are highly important for other neurodegenerative diseases including Alzheimer’s disease, ALS and Frontotemporal Dementia, but the mechanisms underlying their disease pathogenesis are still not completely understood.

Ongoing studies: We study new roles for inter-organelle contact site misregulation in neurodegenerative diseases, to ultimately identify pathways and potential therapeutic targets in disease pathogenesis. 

We are currently investigating multiple novel mechanisms which regulate inter-organelle contact site dynamics in disease models of:

• i) Parkinson’s disease and Charcot-Marie Tooth disease

• ii) Neurodegenerative diseases such as Alzheimer’s disease, Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal dementia (FTD) 

• iii) Lysosomal storage diseases and mitochondrial-related disorders

3) Super-Resolution Microscopy: Identifying new cellular pathways and dynamics using live cell imaging

What we know: Using live cell imaging, we previously identified multiple new organelle events, including the dynamics of autophagy receptor recruitment during parkin-mediated mitophagy (PNAS 2014), actin cycling around mitochondrial sub-populations (Nature Comm 2016; Current Opinion in Cell Biology 2024)  

We have also used Structured Illumination Microscopy (SIM) Super-Resolution imaging to identify mitochondria-lysosome contact sites as important hubs for organelle crosstalk  (Nature 2018), as well as the dynamic formation of inter-mitochondrial contact sites (Dev Cell 2019) and inter-lysosomal contact sites (J Cell Biol 2022). However, our understanding of the full complexity of organelle interactions and dynamics at nanoscale resolutions is still incomplete.

Ongoing studies: We leverage advanced Super-Resolution live microscopy techniques to identify new cellular dynamics/pathways, to help advance our understanding of cellular/neuronal function and their misregulation in human diseases. 

We are excited to 

• i) identify new events occurring at the organelle level and within organelles

• ii) explore the regulation of these pathways

• iii) study how these dynamics are disrupted in neurodegenerative and other diseases.