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INFORMATION FOR

    Shawn Ferguson, PhD

    Associate Professor of Cell Biology and of Neuroscience
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    About

    Titles

    Associate Professor of Cell Biology and of Neuroscience

    Biography

    Dr. Ferguson earned BSc (Biochemistry-Nutrition) and MSc (Physiology) degrees from the University of Ottawa followed by a PhD in Neuroscience from Vanderbilt University in 2004. From 2004-2010, he was a postdoctoral fellow with Pietro De Camilli in the Department of Cell Biology at Yale. As a postdoc, he studied the membrane trafficking mechanisms that allow neurons to make and recycle the synaptic vesicles that store and release neurotransmitters that support communication between neurons. Although centered on the topic of neuronal cell biology, this research resulted in many additional collaborative studies that focused on how similar membrane trafficking mechanisms are adapted to the needs of other cell types. In 2010, Dr. Ferguson founded his own lab as an assistant professor in the Department of Cell Biology at Yale where he currently holds the rank of Associate Professor (tenured). His research focuses on the intersection between lysosome cell biology and neurodegenerative diseases. The long-term goal of research in the Ferguson lab is to advance understanding of cell biological mechanisms that allow specialized cell types such as neurons, microglia and macrophages to meet the challenges imposed by their unique physiological demands in order to help diagnose, treat and prevent diseases arising from lysosome dysfunction. Motivated by clues coming from human genetics and disease pathology, major ongoing projects in the lab address the role of lysosomes in Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and Parkinson’s disease.

    Appointments

    Education & Training

    PhD
    Vanderbilt University (2004)
    MS
    University of Ottawa (1999)
    BS
    University of Ottawa (1997)

    Research

    Overview

    Dr. Ferguson's research program defines fundamental mechanisms through which lysosome functions adapt to changes in cellular demand. Building on insights from human genetics and disease pathology, his lab has furthermore identified how dysfunctions in the endolysosomal pathway contribute to neurodegenerative diseases. This intersection between lysosomal biology and neurodegeneration forms a common theme across multiple projects. The Ferguson lab investigates these topics using cutting edge cell biological tools across a range of model systems that spans from mammalian cell lines, human induced pluripotent stem cells that are genome edited and differentiated into macrophages, microglia and neurons, and genetically modified mouse models.

    The Ferguson lab identified an mTORC1-dependent regulatory mechanism that coordinates TFEB and related transcription factors, enabling lysosomes to communicate with the nucleus and adjust their function according to cellular needs. The Ferguson team also pioneered findings on the nutrient-regulated recruitment of FLCN-FNIP and C9orf72 (mutated in ALS-FTD) complexes to lysosomes, uncovering new aspects of lysosome biology and critical components linking nutrient sensing to mTORC1 signaling from lysosomes.

    Ferguson lab research into lysosomal transport in neuronal axons revealed how disruptions in this process lead to lysosome accumulation within swollen axons around Alzheimer’s disease amyloid plaques. This opened new lines of research into roles played by the JIP3 and JIP4 proteins as scaffold that link lysosomes to motors and signaling proteins. The recent identification of human JIP3 (MAPK8IP3 gene) and JIP4 (SPAG9 gene) mutations as a cause of human neurodevelopmental diseases raised new questions that they are now exploring concerning the role for these proteins and their functions at lysosomes in brain development.

    Most recently, the Ferguson lab identified a role for LRRK2 in regulating the lysosomal degradative activity of macrophages and microglia. They also uncovered a novel mechanism that connects the STING pathway signaling, lysosomal damage, LRRK2 signaling, and Parkinson’s disease pathogenesis. In parallel, they identified TBK1, a kinase associated with neurodegenerative diseases (ALS-FTD), as being recruited to lysosomes in response to signals related to innate immunity, nutrient availability, and lysosomal stress. Their research furthermore defined Rab7 as a major substrate that mediates the effects of TBK1 at lysosomes. Most prominently, they found that TBK1-mediated phosphorylation of Rab7 suppresses the inhibitory effect of Rab7 on mTORC1 signaling from lysosomes. Additional important discoveries include identification of roles for prosaposin and Surf4 in the lysosomal delivery of newly synthesized progranulin, whose deficiency causes frontotemporal dementia (FTD) characterized by TDP-43 inclusions. With respect to TDP-43, they have characterized broad effects of TDP-43 depletion on organelle homeostasis that parallel its ability to regulation mRNA splicing via the suppression of cryptic exon inclusion.

    These research achievements represent broad contributions to the fields of lysosome cell biology and neurodegenerative disease mechanisms.

    Medical Research Interests

    Alzheimer Disease; Axonal Transport; Frontotemporal Dementia; Lysosomes; Parkinson Disease; Tauopathies; TDP-43 Proteinopathies

    Research at a Glance

    Yale Co-Authors

    Frequent collaborators of Shawn Ferguson's published research.

    Publications

    2025

    2024

    2023

    2022

    2021

    Get In Touch

    Contacts

    Lab Number
    Mailing Address

    Cell Biology

    PO Box 208002, 333 Cedar Street

    New Haven, CT 06520-8002

    United States

    Locations

    • 100 College Street

      Academic Office

      Fl 3rd , Rm Room 344

      New Haven, CT 06510