Hongying Shen, PhD
Assistant Professor of Cellular and Molecular Physiology
Research & Publications
Biography
News
Research Summary
Metabolic pathways are vital for life. Lesions in these pathways are the direct cause of rare diseases known as inborn errors of metabolism, and the rewiring of metabolism is implicated in common diseases, including cancers, diabetes, immune disorders and neurological disorders. In the past, extensive biochemical and genetic studies have reconstructed pathways in the primary energy metabolism. They span major carbohydrate, amino acid, nucleotide and lipid metabolism. However, hundreds of metabolic enzymes and transporters remain orphans, yet might be implicated in human health and disease states. In addition, as the metabolic reactions are compartmentalized within a cell, we have limited understanding of how even some of the most essential metabolites are transported within a cell across the different membrane-bound organelles.
The Shen laboratory will take an integrated approach including biochemistry, cell biology, genetics, genomics and metabolomics to address key questions in cellular metabolism. The two main research directions of the laboratory lie at the interface between metabolic biochemistry and cell biology, including
- orphan metabolic enzymes and transporters
- cell biology of micronutrients and cofactors
We will guide these projects in the laboratory by their broader implications in physiology and human diseases.
Coauthors
Research Interests
Cell Biology; Metabolism; Mass Spectrometry
Selected Publications
- Systems biochemistry to “deorphanize” human mitochondrial proteomeMiros F, Liu R, Shen H. Systems biochemistry to “deorphanize” human mitochondrial proteome. Molecular Cell 2022, 82: 2735-2737. PMID: 35931038, DOI: 10.1016/j.molcel.2022.07.005.
- Combinatorial GxGxE CRISPR screen identifies SLC25A39 in mitochondrial glutathione transport linking iron homeostasis to OXPHOSShi X, Reinstadler B, Shah H, To TL, Byrne K, Summer L, Calvo SE, Goldberger O, Doench JG, Mootha VK, Shen H. Combinatorial GxGxE CRISPR screen identifies SLC25A39 in mitochondrial glutathione transport linking iron homeostasis to OXPHOS. Nature Communications 2022, 13: 2483. PMID: 35513392, PMCID: PMC9072411, DOI: 10.1038/s41467-022-30126-9.
- The Human Knockout Gene CLYBL Connects Itaconate to Vitamin B12Shen H, Campanello GC, Flicker D, Grabarek Z, Hu J, Luo C, Banerjee R, Mootha VK. The Human Knockout Gene CLYBL Connects Itaconate to Vitamin B12. Cell 2017, 171: 771-782.e11. PMID: 29056341, PMCID: PMC5827971, DOI: 10.1016/j.cell.2017.09.051.
- Phylogenetic Analysis Guides Transporter Protein Deorphanization: A Case Study of the SLC25 Family of Mitochondrial Metabolite Transporters.Byrne, K.L.; Szeligowski, R.V.; Shen, H. Phylogenetic Analysis Guides Transporter Protein Deorphanization: A Case Study of the SLC25 Family of Mitochondrial Metabolite Transporters. Biomolecules 2023, 13, 1314.
- Salvage of ribose from uridine or RNA supports glycolysis in nutrient-limited conditionsSkinner O, Blanco-Fernández J, Goodman R, Kawakami A, Shen H, Kemény L, Joesch-Cohen L, Rees M, Roth J, Fisher D, Mootha V, Jourdain A. Salvage of ribose from uridine or RNA supports glycolysis in nutrient-limited conditions. Nature Metabolism 2023, 5: 765-776. PMID: 37198474, PMCID: PMC10229423, DOI: 10.1038/s42255-023-00774-2.
- The C-terminal tail of polycystin-1 suppresses cystic disease in a mitochondrial enzyme-dependent fashionOnuchic L, Padovano V, Schena G, Rajendran V, Dong K, Shi X, Pandya R, Rai V, Gresko N, Ahmed O, Lam T, Wang W, Shen H, Somlo S, Caplan M. The C-terminal tail of polycystin-1 suppresses cystic disease in a mitochondrial enzyme-dependent fashion. Nature Communications 2023, 14: 1790. PMID: 36997516, PMCID: PMC10063565, DOI: 10.1038/s41467-023-37449-1.
- Enhanced access to the human phosphoproteome with genetically encoded phosphothreonineMoen J, Mohler K, Rogulina S, Shi X, Shen H, Rinehart J. Enhanced access to the human phosphoproteome with genetically encoded phosphothreonine. Nature Communications 2022, 13: 7226. PMID: 36433969, PMCID: PMC9700786, DOI: 10.1038/s41467-022-34980-5.
- VPS13D bridges the ER to mitochondria and peroxisomes via MiroGuillén-Samander A, Leonzino M, Hanna MG, Tang N, Shen H, De Camilli P. VPS13D bridges the ER to mitochondria and peroxisomes via Miro. Journal Of Cell Biology 2021, 220: e202010004. PMID: 33891013, PMCID: PMC8077184, DOI: 10.1083/jcb.202010004.
- An IRON-clad Connection between Aging OrganellesShen H. An IRON-clad Connection between Aging Organelles. Cell 2020, 180: 214-216. PMID: 31978339, DOI: 10.1016/j.cell.2019.12.037.
- Itaconyl-CoA forms a stable biradical in methylmalonyl-CoA mutase and derails its activity and repairRuetz M, Campanello GC, Purchal M, Shen H, McDevitt L, Gouda H, Wakabayashi S, Zhu J, Rubin EJ, Warncke K, Mootha VK, Koutmos M, Banerjee R. Itaconyl-CoA forms a stable biradical in methylmalonyl-CoA mutase and derails its activity and repair. Science 2019, 366: 589-593. PMID: 31672889, PMCID: PMC7070230, DOI: 10.1126/science.aay0934.
- Epstein-Barr-Virus-Induced One-Carbon Metabolism Drives B Cell TransformationWang LW, Shen H, Nobre L, Ersing I, Paulo JA, Trudeau S, Wang Z, Smith NA, Ma Y, Reinstadler B, Nomburg J, Sommermann T, Cahir-McFarland E, Gygi SP, Mootha VK, Weekes MP, Gewurz BE. Epstein-Barr-Virus-Induced One-Carbon Metabolism Drives B Cell Transformation. Cell Metabolism 2019, 30: 539-555.e11. PMID: 31257153, PMCID: PMC6720460, DOI: 10.1016/j.cmet.2019.06.003.
- A genetically encoded tool for manipulation of NADP+/NADPH in living cellsCracan V, Titov DV, Shen H, Grabarek Z, Mootha VK. A genetically encoded tool for manipulation of NADP+/NADPH in living cells. Nature Chemical Biology 2017, 13: 1088-1095. PMID: 28805804, PMCID: PMC5605434, DOI: 10.1038/nchembio.2454.
- Comparative Analysis of Mitochondrial N-Termini from Mouse, Human, and Yeast*Calvo SE, Julien O, Clauser KR, Shen H, Kamer KJ, Wells JA, Mootha VK. Comparative Analysis of Mitochondrial N-Termini from Mouse, Human, and Yeast*. Molecular & Cellular Proteomics 2017, 16: 512-523. PMID: 28122942, PMCID: PMC5383775, DOI: 10.1074/mcp.m116.063818.
- Coupling between endocytosis and sphingosine kinase 1 recruitmentShen H, Giordano F, Wu Y, Chan J, Zhu C, Milosevic I, Wu X, Yao K, Chen B, Baumgart T, Sieburth D, De Camilli P. Coupling between endocytosis and sphingosine kinase 1 recruitment. Nature Cell Biology 2014, 16: 652-662. PMID: 24929359, PMCID: PMC4230894, DOI: 10.1038/ncb2987.
- A Novel Multiple Hypothesis Based Particle Tracking Method for Clathrin Mediated Endocytosis Analysis Using Fluorescence MicroscopyLiang L, Shen H, De Camilli P, Duncan JS. A Novel Multiple Hypothesis Based Particle Tracking Method for Clathrin Mediated Endocytosis Analysis Using Fluorescence Microscopy. IEEE Transactions On Image Processing 2014, 23: 1844-1857. PMID: 24808351, PMCID: PMC4373089, DOI: 10.1109/tip.2014.2303633.
- Dynamin triple knockout cells reveal off target effects of commonly used dynamin inhibitorsPark RJ, Shen H, Liu L, Liu X, Ferguson SM, De Camilli P. Dynamin triple knockout cells reveal off target effects of commonly used dynamin inhibitors. Journal Of Cell Science 2013, 126: 5305-5312. PMID: 24046449, PMCID: PMC3828596, DOI: 10.1242/jcs.138578.
- A Multiple Hypothesis Based Method for Particle Tracking and Its Extension for Cell SegmentationLiang L, Shen H, Rompolas P, Greco V, De Camilli P, Duncan JS. A Multiple Hypothesis Based Method for Particle Tracking and Its Extension for Cell Segmentation. 2013, 23: 98-109. PMID: 24683961, PMCID: PMC4122512, DOI: 10.1007/978-3-642-38868-2_9.
- SnapShot: Membrane Curvature Sensors and GeneratorsShen H, Pirruccello M, De Camilli P. SnapShot: Membrane Curvature Sensors and Generators. Cell 2012, 150: 1300-1300.e2. PMID: 22980986, PMCID: PMC3819217, DOI: 10.1016/j.cell.2012.08.017.
- A BAYESIAN METHOD FOR 3D ESTIMATION OF SUBCELLULAR PARTICLE FEATURES IN MULTI-ANGLE TIRF MICROSCOPYLiang L, Shen H, Xu Y, De Camilli P, Toomre D, Duncan J. A BAYESIAN METHOD FOR 3D ESTIMATION OF SUBCELLULAR PARTICLE FEATURES IN MULTI-ANGLE TIRF MICROSCOPY. 2012, 1: 984-987. DOI: 10.1109/isbi.2012.6235722.
- Suppression of EGFR endocytosis by dynamin depletion reveals that EGFR signaling occurs primarily at the plasma membraneSousa LP, Lax I, Shen H, Ferguson SM, De Camilli P, Schlessinger J. Suppression of EGFR endocytosis by dynamin depletion reveals that EGFR signaling occurs primarily at the plasma membrane. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 4419-4424. PMID: 22371560, PMCID: PMC3311323, DOI: 10.1073/pnas.1200164109.
- Recruitment of Endophilin to Clathrin-Coated Pit Necks Is Required for Efficient Vesicle Uncoating after FissionMilosevic I, Giovedi S, Lou X, Raimondi A, Collesi C, Shen H, Paradise S, O'Toole E, Ferguson S, Cremona O, De Camilli P. Recruitment of Endophilin to Clathrin-Coated Pit Necks Is Required for Efficient Vesicle Uncoating after Fission. Neuron 2011, 72: 587-601. PMID: 22099461, PMCID: PMC3258500, DOI: 10.1016/j.neuron.2011.08.029.
- Constitutive activated Cdc42-associated kinase (Ack) phosphorylation at arrested endocytic clathrin-coated pits of cells that lack dynaminShen H, Ferguson SM, Dephoure N, Park R, Yang Y, Volpicelli-Daley L, Gygi S, Schlessinger J, De Camilli P. Constitutive activated Cdc42-associated kinase (Ack) phosphorylation at arrested endocytic clathrin-coated pits of cells that lack dynamin. Molecular Biology Of The Cell 2010, 22: 493-502. PMID: 21169560, PMCID: PMC3038647, DOI: 10.1091/mbc.e10-07-0637.
- Coordinated Actions of Actin and BAR Proteins Upstream of Dynamin at Endocytic Clathrin-Coated PitsFerguson S, Raimondi A, Paradise S, Shen H, Mesaki K, Ferguson A, Destaing O, Ko G, Takasaki J, Cremona O, Toole E, De Camilli P. Coordinated Actions of Actin and BAR Proteins Upstream of Dynamin at Endocytic Clathrin-Coated Pits. Developmental Cell 2010, 18: 332. DOI: 10.1016/j.devcel.2010.02.003.
- Coordinated Actions of Actin and BAR Proteins Upstream of Dynamin at Endocytic Clathrin-Coated PitsFerguson S, Raimondi A, Paradise S, Shen H, Mesaki K, Ferguson A, Destaing O, Ko G, Takasaki J, Cremona O, Toole E, De Camilli P. Coordinated Actions of Actin and BAR Proteins Upstream of Dynamin at Endocytic Clathrin-Coated Pits. Developmental Cell 2009, 17: 811-822. PMID: 20059951, PMCID: PMC2861561, DOI: 10.1016/j.devcel.2009.11.005.