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
Email: monther (at) stanford.edu
Nouf Laqtom, Ph.D.
Email: nlaqtom (at) stanford.edu
Email: clin5 (at) stanford.edu
Julia Heiby, Ph.D.
Joint postdoctoral fellow with Dr. Alessandro Ori/FLI
Email: Julia.Heiby (at) leibniz-fli.de
Email: gwmarrah (at) stanford.edu
Wentao Dong, Ph.D.
Email: wdong5 (at) stanford.edu
Email: austinmu (at) stanford.edu
Email: xiongj (at) stanford.edu
Email: miguchi (at) stanford.edu
Ali Ghoochani, Ph.D.
Email: aligh (at) stanford.edu
Email: uchemed (at) stanford.edu
Email: sscharen (at) stanford.edu
Email: kwaminanyame (at) stanford.edu
Laqtom NN, Dong W, Medoh UN, Cangelosi AL, Dharamdasani V, Chan SH, Kunchok T, Lewis CA, Heinze I, Tang R, Grimm C, Dang Do AN, Porter FD, Ori A, Sabatini DM, Abu-Remaileh M . CLN3 is required for the clearance of glycerophosphodiesters from lysosomes. Nature. 2022 Sep 21;. doi: 10.1038/s41586-022-05221-y. [Epub ahead of print] PubMed PMID: 36131016.
Pedram K, Laqtom NN, Shon DJ, Di Spiezio A, Riley NM, Saftig P, Abu-Remaileh M, Bertozzi CR. Lysosomal cathepsin D mediates endogenous mucin glycodomain catabolism in mammals. Proc Natl Acad Sci U S A. 2022 Sep 27;119(39):e2117105119. doi: 10.1073/pnas.2117105119. PubMed PMID: 36122205.
Dong W, Rawat ES, Stephanopoulos G, Abu-Remaileh M. Isotope tracing in health and disease. Curr Opin Biotechnol. 2022 Aug;76:102739. doi: 10.1016/j.copbio.2022.102739. Review. PubMed PMID: 35738210.
Medoh, U. N., Chen, J. Y. & Abu-Remaileh M. Lessons from metabolic perturbations in lysosomal storage disorders for neurodegeneration. Curr Opin in Sys Bio.2022 Nov; doi.org/10.1016/j.coisb.2021.100408. Review.
Forcina GC, Pope L, Murray M, Dong W, Abu-Remaileh M, Bertozzi CR, Dixon SJ. Ferroptosis regulation by the NGLY1/NFE2L1 pathway. Proc Natl Acad Sci U S A. 2022 Mar 15;119(11):e2118646119. doi: 10.1073/pnas.2118646119. PubMed PMID: 35271393; PubMed Central PMCID: PMC8931371.
Abu-Remaileh M#, Wyant GA#, Kim C, Laqtom NN, Abbasi M, Chan SH, Freinkman E, Sabatini DM. Lysosomal metabolomics reveals V-ATPase- and mTOR-dependent regulation of amino acid efflux from lysosomes. Science. 2017 Nov 10;358(6364):807-813. doi: 10.1126/science.aan6298. PubMed PMID: 29074583; PubMed Central PMCID: PMC5704967.
Wyant GA#, Abu-Remaileh M#, Wolfson RL, Chen WW, Freinkman E, Danai LV, Vander Heiden MG, Sabatini DM. mTORC1 Activator SLC38A9 Is Required to Efflux Essential Amino Acids from Lysosomes and Use Protein as a Nutrient. Cell. 2017 Oct 19;171(3):642-654.e12. doi: 10.1016/j.cell.2017.09.046. PubMed PMID: 29053970; PubMed Central PMCID: PMC5704964.
Cantor JR, Abu-Remaileh M, Kanarek N, Freinkman E, Gao X, Louissaint A Jr, Lewis CA, Sabatini DM. Physiologic Medium Rewires Cellular Metabolism and Reveals Uric Acid as an Endogenous Inhibitor of UMP Synthase. Cell. 2017 Apr 6;169(2):258-272.e17. doi: 10.1016/j.cell.2017.03.023. PubMed PMID: 28388410; PubMed Central PMCID: PMC5421364.
For full list visti Google Scholar.
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.
ChEM-H Building, Room: N227
290 Jane Stanford Way
Stanford, CA 94305
Our Lab is located at the new building that hosts both ChEM-H and Wu Tsai Neuroscience Research Center.