Welcome to the
Abu-Remaileh Lab at Stanford University
We study the molecular and cellular bases of metabolic adaptation in health and disease
We are interested in identifying novel pathways that enable cellular and organismal adaptation to metabolic stress and changes in environmental conditions. We also study how these pathways go awry in human diseases such as cancer, neurodegeneration and metabolic syndrome, in order to engineer new therapeutic modalities.
To address these questions, our lab uses a multidisciplinary approach to study the biochemical functions of the lysosome in vitro and in vivo. Lysosomes are membrane-bound compartments that degrade macromolecules and clear damaged organelles to enable cellular adaptation to various metabolic states. Lysosomal function is critical for organismal homeostasis—mutations in genes encoding lysosomal proteins cause severe human disorders known as lysosomal storage diseases, and lysosome dysfunction is implicated in age-associated diseases including cancer, neurodegeneration and metabolic syndrome.
By developing novel tools and harnessing the power of metabolomics, proteomics and functional genomics, our lab will define 1) how the lysosome communicates with other cellular compartments to fulfill the metabolic demands of the cell under various metabolic states, 2) and how its dysfunction leads to rare and common human diseases. Using insights from our research, we will engineer novel therapies to modulate the pathways that govern human disease.
Functional characterization of the lysosomal molecular content
Our previous work has revealed surprising dynamics in lysosomal content (proteome and metabolome) as part of the response to changes in environmental conditions. These molecular events are necessary for the cellular adaptation to changes in nutrient availability and metabolic state, which is consistent with the role of the lysosomes in these processes. Our lab will further dissect the physiological roles of the lysosome by mapping and
functionally characterizing its molecular components under various metabolic states in tissue culture cells and in animal models. Using genetic and molecular tools we will then perform followup studies to establish the role of the lysosome in tissue homeostasis.
Monther Abu-Remaileh, Ph.D.
ChEM-H Institute Scholar
Assistant Professor of Chemical Engineering
Assistant Professor of Genetics (by courtesy)
Email: monther (at) stanford.edu
Nouf Laqtom, Ph.D.
Abu-Remaileh M#, Wyant GA#, Kim C, Laqtom N, Abbasi M, Chan SH, Freinkman E, Sabatini DM. (2017) Lysosomal metabolomics reveals V-ATPase- and mTOR-dependent mechanisms for the efflux of amino acids from lysosomes. Science. 358 (6364): 807-813 doi: 10.1126/science.aan6298
Wyant GA#, Abu-Remaileh M#, Wolfson RL, Chen WW, Freinkman E, Danai LV, Vander Heiden M, Sabatini DM. (2017) mTORC1 activator SLC38A9 is required to efflux essential amino acids from lysosomes and use protein as a nutrient. Cell. 171 (3): 642-654 doi: 10.1016/j.cell.2017.09.046
Bayraktar EC, Baudrier L, Özerdem C, Lewis CA, Chan SH, Kunchok T, Abu-Remaileh M, Cangelosi AL, Sabatini DM, Birsoy K, Chen WW. (2019) MITO-Tag Mice enable rapid isolation and multimodal profiling of mitochondria from specific cell types in vivo. Proc Natl Acad Sci U S A. 116 (1): 303-312 doi: 10.1073/pnas.1816656115
Kanarek N, Keys HR, Cantor JR, Lewis CA, Chan SH, Kunchok T, Abu-Remaileh M, Freinkman E, Schweitzer LD, Sabatini DM. (2018) Histidine catabolism is a major determinant of methotrexate sensitivity. Nature. 559 (7715): 632-636 doi: 10.1038/s41586-018-0316-7
Wyant GA#, Abu-Remaileh M#, Frenkel EM, Laqtom N, Dharamdasani V, Lewis CA, Chan SH, Heinze I, Ori A, Sabatini DM. (2018) NUFIP1 is a ribosome receptor for starvation-induced ribophagy. Science. 360 (6390): 751-758 doi: 10.1126/science.aar2663
Mihaylova MM, Cheng CW, Cao AQ, Tripathi S, Mana MD, Bauer-Rowe KE, Abu-Remaileh M, Clavain L, Erdemir A, Lewis CA, Freinkman E, Dickey AS, La Spada AR, Huang Y, Bell GW, Deshpande V, Carmeliet P, Katajisto P, Sabatini DM, Yilmaz ÖH. (2018) Fasting Activates Fatty Acid Oxidation to Enhance Intestinal Stem Cell Function during Homeostasis and Aging. Cell Stem Cell. 22 (5): 769-778 doi: 10.1016/j.stem.2018.04.001
Yu Z, Surface LE, Park CY, Horlbeck MA, Wyant GA, Abu-Remaileh M, Peterson TR, Sabatini DM, Weissman JS, O'Shea EK. (2018) Identification of a transporter complex responsible for the cytosolic entry of nitrogen-containing bisphosphonates. Elife. 7 (pii: e36620) doi: 10.7554/eLife.36620
Cantor JR, Abu-Remaileh M, Kanarek N, Freinkman E, Gao X, Louissaint A Jr, Lewis CA, Sabatini DM. (2017) Physiologic Medium Rewires Cellular Metabolism and Reveals Uric Acid as an Endogenous Inhibitor of UMP Synthase. Cell. 169 (2): 258-272 doi: 10.1016/j.cell.2017.03.023
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. (2017) KICSTOR recruits GATOR1 to the lysosome and is necessary for nutrients to regulate mTORC1. Nature. 543 (7645): 438-442 doi: 10.1038/nature21423
Pacold ME, Brimacombe KR, Chan SH, Rohde JM, Lewis CA, Swier LJ, Possemato R, Chen WW, Sullivan LB, Fiske BP, Cho S, Freinkman E, Birsoy K, Abu-Remaileh M, Shaul YD, Liu CM, Zhou M, Koh MJ, Chung H, Davidson SM, Luengo A, Wang AQ, Xu X, Yasgar A, Liu L, Rai G, Westover KD, Vander Heiden MG, Shen M, Gray NS, Boxer MB, Sabatini DM. (2016) A PHGDH inhibitor reveals coordination of serine synthesis and one-carbon unit fate. Nature Chemical Biology. 12 (6): 452-458 doi: 10.1038/nchembio.2070
Beyaz S, Mana MD, Roper J, Kedrin D, Saadatpour A, Hong SJ, Bauer-Rowe KE, Xifaras ME, Akkad A, Arias E, Pinello L, Katz Y, Shinagare S, Abu-Remaileh M, Mihaylova MM, Lamming DW, Dogum R, Guo G, Bell GW, Selig M, Nielsen GP, Gupta N, Ferrone CR, Deshpande V, Yuan GC, Orkin SH, Sabatini DM, Yilmaz ÖH. (2016) High-fat diet enhances stemness and tumorigenicity of intestinal progenitors. Nature. 531 (7592): 53-58 doi: 10.1038/nature17173
Aran D#, Abu-Remaileh M#, Levy R, Meron N, Toperoff G, Edrei Y, Bergman Y, Hellman A. (2016) Embryonic Stem Cell (ES)-Specific Enhancers Specify the Expression Potential of ES Genes in Cancer. PLoS Genetics. 12 (2): e1005840 doi: 10.1371/journal.pgen.1005840
Birsoy K, Wang T, Chen WW, Freinkman E, Abu-Remaileh M, Sabatini DM. (2015) An Essential Role of the Mitochondrial Electron Transport Chain in Cell Proliferation Is to Enable Aspartate Synthesis. Cell. 162 (3): 540-551 doi: 10.1016/j.cell.2015.07.016
Abu-Remaileh M#, Bender S#, Raddatz G, Ansari I, Cohen D, Gutekunst J, Musch T, Linhart H, Breiling A, Pikarsky E, Bergman Y, Lyko F. (2015) Chronic inflammation induces a novel epigenetic program that is conserved in intestinal adenomas and in colorectal cancer. Cancer Research. 75 (10): 2120-2130 doi: 10.1158/0008-5472.CAN-14-3295
Ludwig G, Nejman D, Hecht M, Orlanski S, Abu-Remaileh M, Yanuka O, Sandler O, Marx A, Roberts D, Benvenisty N, Bergman Y, Mendelsohn M, Cedar H. (2014) Aberrant DNA methylation in ES cells. PLoS One. 9 (5): e96090 doi: 10.1371/journal.pone.0096090
Abu-Remaileh M#, Gerson A#, Farago M, Nathan G, Alkalay I, Zins Rousso S, Gur M, Fainsod A, and Bergman Y. (2010) Oct-3/4 regulates stem cell identity and cell fate decisions by modulating Wnt/β-catenin signaling. EMBO Journal. 29 (19): 3236-3248 doi: 10.1038/emboj.2010.200
Epsztejn-Litman S#, Feldman N#, Abu-Remaileh M#, Shufaro Y, Gerson A, Ueda J, Deplus R, Fuks F, Shinkai Y, Cedar H and Bergman Y. (2008) G9a-mediated de novo methylation is necessary and sufficient to prevent reprogramming of embryonically silenced genes. Nature Structural and Molecular Biology. 15 (11): 1176-1183 doi: 10.1038/nsmb.1476
Current Stanford graduate students from all programs (PhD, MD, PhD/MD) who are interested in joining our lab are welcome to contact Monther directly. Please send a current CV in pdf format.
Postdocs and Clinical Fellows:
Motivated postdocs and clinical fellows with expertise in biochemistry, molecular biology, metabolism, mouse physiology or neurobiology are encouraged to apply. Please email a cover letter, your CV, and contact information for three references to Monther.
Students who are interested in conducting biomedical research and being part of our multidisciplinary team are welcome to email Monther for opportunities.
Current masters students who are enrolled in national or international programs and hoping to join our lab as visiting students (6-12 month duration) to complete their thesis are welcome. Research experience in biology, biochemistry or chemistry is an advantage. Please email a cover letter, your CV, and contacts of two references to Monther.
Shriram Center, 443 Via Ortega, Room 383
Stanford, CA 94305
Our Lab is currently open in Shriram building.
Starting from December 2019, our lab will move to the new research building that hosts ChEM-H/Wu Tsai Neuroscience Research Center.