Jane Coffin Childs Research Fellow
I received my bachelor’s degree from Harvard University and my PhD from Stanford University. For my PhD, I worked in Dr. Judith Frydman’s lab and studied how protein misfolding and aggregation lead to toxicity in the neurodegenerative disorder Huntington’s disease. My work elucidated how conformational properties of mutant Huntingtin regulate neurotoxicity and protein homeostasis in Huntington’s disease. I also studied the interaction between mutant Huntingtin and molecular chaperones.
In the Dillin lab, I study how mitochondria recognize and respond to proteotoxic stress and how these mechanisms become compromised in aging or age-related diseases. I am also interested in inter-organelle communication and how this contributes to stress response pathways in aging.
Shen K, Gamerdinger M, Chan R, Gense K, Martin EM, Sachs N, Knight PD, Schlömer R, Calabrese AN, Stewart KL, Leiendecker L, Baghel A, Radford SE, Frydman J, Deuerling E. Mol Cell. 2019 May 16;74(4):729-741.e7. doi: 10.1016/j.molcel.2019.03.012. Epub 2019 Apr 11.
Levy GR, Shen K, Gavrilov Y, Smith PES, Levy Y, Chan R, Frydman J, Frydman L. ACS Chem Neurosci. 2019 Jan 16;10(1):472-481. doi: 10.1021/acschemneuro.8b00353. Epub 2018 Sep 17.
Moehle EA, Shen K, Dillin A. Mitochondrial Proteostasis in the Context of Cellular and Organismal Heath and Aging. J Biol Chem. 2018 Apr 5.
Baias M, Smith PE, Shen K, Joachimiak LA, Żerko S, Koźmiński W, Frydman J, Frydman L. 2017. Structure and Dynamics of the Huntingtin Exon-1 N-terminus: A Solution NMR Perspective. J Am Chem Soc. 139(3):1168-1176.
Shen K, Calamini B, Fauerbach JA, Ma B, Shahmoradian SH, Serrano Lachapel IL, Chiu W, Lo DC, Frydman J. 2016. Control of the structural landscape and neuronal proteotoxicity of mutant Huntingtin by domains flanking the polyQ tract. Elife. 5, e18065.
Duim WC, Jiang Y, Shen K, Frydman J, Moerner WE. 2014. Super-resolution fluorescence of huntingtin reveals growth of globular species into short fibers and coexistence of distinct aggregates. ACS Chem Biol. 9 (12): 2767-2778.
Shen, K., Frydman, J. 2013. The interplay between the chaperonin TRiC and N-terminal region of Huntingtin mediates Huntington’s Disease aggregation and pathogenesis. In: Morimoto, RI, Christen, Y, editors. Protein Quality Control in Neurodegenerative Diseases. Berlin Heidelberg (Germany): Springer-Verlag. p121-132.
Pakotiprapha, D., Samuels, M., Shen, K., Hu, J.H., Jeruzalmi, D. 2012. Structure and mechanisms of the UvrA-UvrB DNA damage sensor. Nat Struct Mol Biol. 19(3)291-8.