John Replogle
Director NIH
I am currently a postdoctoral fellow in Michael Ward’s lab at the NIH. In the Ward lab, my research has spanned lysosomal biology, building new cellular models of FTD and ALS, and developing new CRISPR screening tools for iPSC-derived neurons. Recently, we developed a model of TMEM106B fibril formation in human neurons, demonstrating that genotype of TMEM106B and another lysosomal gene, Granulin (GRN), dictate fibril burden in the brain during neurodegeneration. We established that there is a strong relationship between TMEM106B fibrils, lysosomal health, and neurodegeneration.
Prior to my postdoctoral work, I was a graduate student in Angelika Amon’s lab at MIT, where I earned my Ph.D. in 2021. There, I explored the impacts of aneuploidy on cancer tumorigenesis and treatment. In particular, I demonstrated that one of the primary mechanisms driving the broad chemotherapy resistance associated with chromosomal aberrations in cancer is its impact on the cell cycle, causing slower passage through G1 of the cell cycle and reducing efficacy of DNA damaging or mitosis-targeting agents.
Seminars
- How TMEM106B genetic variants modulate ALS–FTD risk and intersect with progranulin-dependent lysosomal biology
- Developed a model system of TMEM106B aggregation that leads to intra-lysosomal fibril formation in human neurons
- Evidence that TMEM106B aggregation induces elevated levels of phospho-TDP-43
- Direct co-localization of TMEM106B fibrils and TDP-43 aggregates within individual lysosomes
- Implications of TMEM106B-driven lysosomal failure as an upstream, targetable mechanism across neurodegenerative diseases
