Brett, Christopher L - Concordia University

研究领域

Whether they know it or not, everyone recycles. This is because every one of the 3 billion or so cells that make up you recycles biomaterials. To do so, they use specialized tiny organs or organelles called lysosomes. Lysosomes are an essential source of nutrients for cells and they breakdown toxic biomaterials that accumulate in cells as they age. As such, progressive loss of lysosome function is thought to contribute to aging and ultimately death. Lysosomes require 3 processes to function: (1) membrane fusion to receive incoming biomaterials, (2) biomaterial catabolism by lumenal hydrolyses, and (3) nutrient transport by transporter proteins that return products of catabolism (amino acids, sugars, lipids) to the cell. My lab studies the molecular underpinnings of lysosome membrane fusion and nutrient transport. We discovered that during membrane fusion, a portion of the lysosome membrane is internalized and catabolized. Lysosomal transporter proteins are selectively sorted into this area and degraded offering lysosomes a mechanism to to clear damaged transporter proteins or remodel themselves when necessary. This process, which we named the "ILF pathway" seems to be critical for lysosome function when cells are starved or as they age. As my lab continues to study the contributions of ILF pathway to lysosome biology, I aim to translate state-of-the-art knowledge into new strategies to promote longevity and treat age-related diseases.

近期论文

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McNally EK, Karim MA, & Brett CL. (2016) Selective lysosomal transporter degradation by organelle membrane fusion. Developmental Cell. In press. Mattie S, McNally EK, Karim MA, Vali H, & Brett CL. (2016) How and why intralumenal fragments form during vacuolar lysosome fusion. Molecular Biology of the Cell. In press. Khorsand B, Lapointe G, Brett CL, & Oh JK. (2013) Intracellular drug delivery nanocarriers of glutathione-responsive degradable block copolymers having pendant disulfide linkages. Biomacromolecules. 14: 2103-2111. Bögershausen N, Shahrzad N, Chang JX et al. (2013) Recessive TRAPPC11 mutations cause a disease spectrum of limb girdle muscular dystrophy and myopathy with movement disordered intellectual disability. American Journal of Human Genetics. 93: 181-190.