Headshot of Xin Gu

Xin Gu, Ph.D.

Assistant Professor of Cancer Biology (DFCI)
Assistant Professor of Cell Biology (HMS)

Xin Gu, Ph.D. joined Harvard Medical School and Dana-Farber Cancer Institute as an Assistant Professor of Cell Biology in September 2024. She received her Bachelor of Science degree in Biology at Peking University, then obtained her Ph.D. in Biology at Massachusetts Institute of Technology. She performed postdoctoral work in the Department of Neurobiology at Harvard Medical School.

The Gu Lab focuses on elucidating how cells regulate proteasomal degradation independently of ubiquitination. We discovered a non-canonical proteolysis mechanism, the midnolin-proteasome pathway, that bypasses ubiquitination to selectively degrade numerous stimulus-responsive and cell-type specific transcription factors including EGR1, IRF4, Fos, NeuroD1, STAT3, and NR4A1. The Gu lab will characterize the midnolin-proteasome pathway using biochemical, structural, and cellular experiments. Additionally, genetically engineered animal models will be used to determine the roles of midnolin in organismal physiology and pathology. The long-term goal is to manipulate the midnolin-proteasome pathway either genetically or pharmacologically to control brain functions, modulate the immune system, and destroy cancer cells. The Gu lab is also interested in identifying other ubiquitin-independent mechanisms that degrade different substrate repertoires as well as the crosstalk of protein homeostasis with chromatin biology and metabolism. Overall, we seek to elucidate fundamental mechanisms related to cell biology using a diverse experimental tool kit.

Dana Farber Cancer Institute

Dept. of Cancer Biology, LC-6312

360 Longwood Avenue

Boston MA. 02115

Lab Phone: (617) 632-4594

The midnolin-proteasome pathway catches proteins for ubiquitination-independent degradation.
Authors: Authors: Gu X, Nardone C, Kamitaki N, Mao A, Elledge SJ, Greenberg ME.
Science
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A central role for regulated protein stability in the control of TFE3 and MITF by nutrients.
Authors: Authors: Nardone C, Palanski BA, Scott DC, Timms RT, Barber KW, Gu X, Mao A, Leng Y, Watson EV, Schulman BA, Cole PA, Elledge SJ.
Mol Cell
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Author Correction: Sestrin mediates detection of and adaptation to low-leucine diets in Drosophila.
Authors: Authors: Gu X, Jouandin P, Lalgudi PV, Binari R, Valenstein ML, Reid MA, Allen AE, Kamitaki N, Locasale JW, Perrimon N, Sabatini DM.
Nature
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Sestrin mediates detection of and adaptation to low-leucine diets in Drosophila.
Authors: Authors: Gu X, Jouandin P, Lalgudi PV, Binari R, Valenstein ML, Reid MA, Allen AE, Kamitaki N, Locasale JW, Perrimon N, Sabatini DM.
Nature
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Structure of the nutrient-sensing hub GATOR2.
Authors: Authors: Valenstein ML, Rogala KB, Lalgudi PV, Brignole EJ, Gu X, Saxton RA, Chantranupong L, Kolibius J, Quast JP, Sabatini DM.
Nature
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Structural basis for the docking of mTORC1 on the lysosomal surface.
Authors: Authors: Rogala KB, Gu X, Kedir JF, Abu-Remaileh M, Bianchi LF, Bottino AMS, Dueholm R, Niehaus A, Overwijn D, Fils AP, Zhou SX, Leary D, Laqtom NN, Brignole EJ, Sabatini DM.
Science
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Arg-78 of Nprl2 catalyzes GATOR1-stimulated GTP hydrolysis by the Rag GTPases.
Authors: Authors: Shen K, Valenstein ML, Gu X, Sabatini DM.
J Biol Chem
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SAMTOR is an S-adenosylmethionine sensor for the mTORC1 pathway.
Authors: Authors: Gu X, Orozco JM, Saxton RA, Condon KJ, Liu GY, Krawczyk PA, Scaria SM, Harper JW, Gygi SP, Sabatini DM.
Science
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KICSTOR recruits GATOR1 to the lysosome and is necessary for nutrients to regulate mTORC1.
Authors: Authors: Wolfson RL, Chantranupong L, Wyant GA, Gu X, Orozco JM, Shen K, Condon KJ, Petri S, Kedir J, Scaria SM, Abu-Remaileh M, Frankel WN, Sabatini DM.
Nature
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