Ho-Joon Lee, PhD
Research & Publications
Biography
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Research Summary
My current research is centered around biomedical data science and single cell biology, focusing on machine learning methods. My general interests lie in biomedical artificial intelligence and fundamental biology using tools from diverse fields including deep learning, systems/network biology, and physics.
Extensive Research Description
Three major on-going projects are (1) machine/deep learning of electronic health records and MRI images for ischemic stroke etiology classification with Dr. Richa Sharma of neurology (1 patent pending; https://www.researchsquare.com/article/rs-3367169/v1) (2) single-cell systems immunology of West Nile virus infection with the Montgomery and Kleinstein labs (https://www.biorxiv.org/conten...) (3) single-cell multi-omics data analysis of zebrafish brains and embryos with the Giraldez lab (https://elifesciences.org/arti...).
In response to the COVID-19 pandemic, I have been working on virus-host protein-protein interactions (PPIs) and early drug discovery in silico together with Dr. Prashant Emani (the Gerstein lab) as a COVID HASTE working group of the Yale School of Engineering and Applied Science (see Figure 1 below for an overview; 1 patent pending). The project on virus-host PPIs was partially supported by a seed fund from the Northeast Big Data Innovation Hub and a preprint has been published (https://nebigdatahub.org/a-lan...). A preprint on ligand-protein binding affinity prediction is also available (https://arxiv.org/abs/2310.03946). As an additional effort, with help from two of my former colleagues, Dr. Vinayagam Arunachalam (Pfizer Inc.) and Dr. Yang-Yu Liu (Harvard Medical School, Brigham and Women's Hospital), I carried out controllability analysis of a directed human protein-protein interaction network for SARS-CoV-2 based on our previous paper (https://www.pnas.org/doi/10.10...). A preprint is available here, https://www.biorxiv.org/conten....
My previous research mostly concerned biological questions in systems biology and network medicine by developing algorithms and models through a combination of statistical/machine learning, information theory, and network theory applied to high-throughput multi-dimensional data. It covered genomics, transcriptomics, proteomics, and metabolomics from yeast to mouse to human for integrative analysis of regulatory networks on multiple molecular levels. I previously carried out proteomics and metabolomics along with a computational derivation of dynamic protein complexes for IL-3 activation and cell cycle in murine pro-B cells (https://www.cell.com/cell-repo...; see Figure 2 below), for which I developed integrative analytical tools using diverse approaches from machine learning and network theory. My ongoing interests in methodology include machine/deep learning and topological Kolmogorov-Sinai entropy-based network theory, which are applied to (1) multi-level dynamic regulatory networks in immune response, cell cycle, cancer metabolism, and cell fate decision and (2) single cell-based and mass spectrometry-based omics data analysis. Two specific projects were (1) Dynamic metabolic network modeling of a mammalian cell cycle using multi-omics time-course data in collaboration with the Chandrasekaran lab at the University of Michigan (see Figure 3 below; https://www.biorxiv.org/conten...; https://www.cell.com/iscience/...) and (2) Tri-omics analysis of macrophage polarization in pancreatic cancer in collaboration with the Lyssiotis lab at the University of Michigan Medical School (https://elifesciences.org/arti...).
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Selected Publications
- Metabolic signatures of regulation by phosphorylation and acetylationSmith K, Shen F, Lee H, Chandrasekaran S. Metabolic signatures of regulation by phosphorylation and acetylation. IScience 2022, 25: 103730. PMID: 35072016, PMCID: PMC8762462, DOI: 10.1016/j.isci.2021.103730.
- Multiomic characterization of pancreatic cancer-associated macrophage polarization reveals deregulated metabolic programs driven by the GM-CSF–PI3K pathwayBoyer S, Lee H, Steele N, Zhang L, Sajjakulnukit P, Andren A, Ward M, Singh R, Basrur V, Zhang Y, Nesvizhskii A, di Magliano M, Halbrook C, Lyssiotis C. Multiomic characterization of pancreatic cancer-associated macrophage polarization reveals deregulated metabolic programs driven by the GM-CSF–PI3K pathway. ELife 2022, 11: e73796. PMID: 35156921, PMCID: PMC8843093, DOI: 10.7554/elife.73796.
- Cysteine depletion induces pancreatic tumor ferroptosis in miceBadgley MA, Kremer DM, Maurer HC, DelGiorno KE, Lee HJ, Purohit V, Sagalovskiy IR, Ma A, Kapilian J, Firl CEM, Decker AR, Sastra SA, Palermo CF, Andrade LR, Sajjakulnukit P, Zhang L, Tolstyka ZP, Hirschhorn T, Lamb C, Liu T, Gu W, Seeley ES, Stone E, Georgiou G, Manor U, Iuga A, Wahl GM, Stockwell BR, Lyssiotis CA, Olive KP. Cysteine depletion induces pancreatic tumor ferroptosis in mice. Science 2020, 368: 85-89. PMID: 32241947, PMCID: PMC7681911, DOI: 10.1126/science.aaw9872.
- A large-scale analysis of targeted metabolomics data from heterogeneous biological samples provides insights into metabolite dynamicsLee HJ, Kremer DM, Sajjakulnukit P, Zhang L, Lyssiotis CA. A large-scale analysis of targeted metabolomics data from heterogeneous biological samples provides insights into metabolite dynamics. Metabolomics 2019, 15: 103. PMID: 31289941, PMCID: PMC6616221, DOI: 10.1007/s11306-019-1564-8.
- Auditory metabolomics, an approach to identify acute molecular effects of noise traumaJi L, Lee HJ, Wan G, Wang GP, Zhang L, Sajjakulnukit P, Schacht J, Lyssiotis CA, Corfas G. Auditory metabolomics, an approach to identify acute molecular effects of noise trauma. Scientific Reports 2019, 9: 9273. PMID: 31239523, PMCID: PMC6592947, DOI: 10.1038/s41598-019-45385-8.
- Abnormal oxidative metabolism in a quiet genomic background underlies clear cell papillary renal cell carcinomaXu J, Reznik E, Lee HJ, Gundem G, Jonsson P, Sarungbam J, Bialik A, Sanchez-Vega F, Creighton CJ, Hoekstra J, Zhang L, Sajjakulnukit P, Kremer D, Tolstyka Z, Casuscelli J, Stirdivant S, Tang J, Schultz N, Jeng P, Dong Y, Su W, Cheng EH, Russo P, Coleman JA, Papaemmanuil E, Chen YB, Reuter VE, Sander C, Kennedy SR, Hsieh JJ, Lyssiotis CA, Tickoo SK, Hakimi AA. Abnormal oxidative metabolism in a quiet genomic background underlies clear cell papillary renal cell carcinoma. ELife 2019, 8: e38986. PMID: 30924768, PMCID: PMC6459676, DOI: 10.7554/elife.38986.
- Proteomic and Metabolomic Characterization of a Mammalian Cellular Transition from Quiescence to ProliferationLee HJ, Jedrychowski MP, Vinayagam A, Wu N, Shyh-Chang N, Hu Y, Min-Wen C, Moore JK, Asara JM, Lyssiotis CA, Perrimon N, Gygi SP, Cantley LC, Kirschner MW. Proteomic and Metabolomic Characterization of a Mammalian Cellular Transition from Quiescence to Proliferation. Cell Reports 2017, 20: 721-736. PMID: 28723573, PMCID: PMC5626450, DOI: 10.1016/j.celrep.2017.06.074.
- Controllability analysis of the directed human protein interaction network identifies disease genes and drug targetsVinayagam A, Gibson TE, Lee HJ, Yilmazel B, Roesel C, Hu Y, Kwon Y, Sharma A, Liu YY, Perrimon N, Barabási AL. Controllability analysis of the directed human protein interaction network identifies disease genes and drug targets. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: 4976-4981. PMID: 27091990, PMCID: PMC4983807, DOI: 10.1073/pnas.1603992113.
- Systems-level evidence of transcriptional co-regulation of yeast protein complexes.Lee JW, Zemojtel T, Shakhnovich E. Systems-level evidence of transcriptional co-regulation of yeast protein complexes. Journal Of Computational Biology : A Journal Of Computational Molecular Cell Biology 2009, 16: 331-9. PMID: 19193150, DOI: 10.1089/cmb.2008.17TT.
- Prioritization of gene regulatory interactions from large-scale modules in yeastLee HJ, Manke T, Bringas R, Vingron M. Prioritization of gene regulatory interactions from large-scale modules in yeast. BMC Bioinformatics 2008, 9: 32. PMID: 18211684, PMCID: PMC2244593, DOI: 10.1186/1471-2105-9-32.
- linc-mipep and linc-wrb encode micropeptides that regulate chromatin accessibility in vertebrate-specific neural cellsTornini V, Miao L, Lee H, Gerson T, Dube S, Schmidt V, Kroll F, Tang Y, Du K, Kuchroo M, Vejnar C, Bazzini A, Krishnaswamy S, Rihel J, Giraldez A. linc-mipep and linc-wrb encode micropeptides that regulate chromatin accessibility in vertebrate-specific neural cells. ELife 2023, 12: e82249. PMID: 37191016, PMCID: PMC10188112, DOI: 10.7554/elife.82249.
- Early cellular and molecular signatures correlate with severity of West Nile virus infectionLee H, Zhao Y, Fleming I, Mehta S, Wang X, Wyk B, Ronca S, Kang H, Chou C, Fatou B, Smolen K, Levy O, Clish C, Xavier R, Steen H, Hafler D, Love J, Shalek A, Guan L, Murray K, Kleinstein S, Montgomery R. Early cellular and molecular signatures correlate with severity of West Nile virus infection. IScience 2023, 26: 108387. PMID: 38047068, PMCID: PMC10692672, DOI: 10.1016/j.isci.2023.108387.
- Iron promotes glycolysis to drive colon tumorigenesisLiu Z, Villareal L, Goodla L, Kim H, Falcon D, Haneef M, Martin D, Zhang L, Lee H, Kremer D, Lyssiotis C, Shah Y, Lin H, Lin H, Xue X. Iron promotes glycolysis to drive colon tumorigenesis. Biochimica Et Biophysica Acta (BBA) - Molecular Basis Of Disease 2023, 1869: 166846. PMID: 37579983, PMCID: PMC10530594, DOI: 10.1016/j.bbadis.2023.166846.
- IDDF2023-ABS-0059 Iron promotes glycolysis to drive colon tumorigenesisXue X, Liu Z, Villareal L, Kim H, Falcon D, Haneef M, Martin D, Zhang L, Lee H, Kremer D, Lyssiotis C, Shah Y, Lin H. IDDF2023-ABS-0059 Iron promotes glycolysis to drive colon tumorigenesis. 2023, a72-a73. DOI: 10.1136/gutjnl-2023-iddf.61.
- Dysregulated stem cell niches and altered lymphocyte recirculation cause B and T cell lymphopenia in WHIM syndromeZehentmeier S, Lim VY, Ma Y, Fossati J, Ito T, Jiang Y, Tumanov AV, Lee HJ, Dillinger L, Kim J, Csomos K, Walter JE, Choi J, Pereira JP. Dysregulated stem cell niches and altered lymphocyte recirculation cause B and T cell lymphopenia in WHIM syndrome. Science Immunology 2022, 7: eabo3170. PMID: 36149943, PMCID: PMC9614684, DOI: 10.1126/sciimmunol.abo3170.
- A redox cycle with complex II prioritizes sulfide quinone oxidoreductase-dependent H2S oxidationKumar R, Landry A, Guha A, Vitvitsky V, Lee H, Seike K, Reddy P, Lyssiotis C, Banerjee R. A redox cycle with complex II prioritizes sulfide quinone oxidoreductase-dependent H2S oxidation. Journal Of Biological Chemistry 2021, 298: 101435. PMID: 34808207, PMCID: PMC8683732, DOI: 10.1016/j.jbc.2021.101435.
- 1-deoxysphingolipids bind to COUP-TF to modulate lymphatic and cardiac cell developmentWang T, Wang Z, de Fabritus L, Tao J, Saied EM, Lee HJ, Ramazanov BR, Jackson B, Burkhardt D, Parker M, Gleinich AS, Wang Z, Seo DE, Zhou T, Xu S, Alecu I, Azadi P, Arenz C, Hornemann T, Krishnaswamy S, van de Pavert SA, Kaech SM, Ivanova NB, Santori FR. 1-deoxysphingolipids bind to COUP-TF to modulate lymphatic and cardiac cell development. Developmental Cell 2021, 56: 3128-3145.e15. PMID: 34762852, PMCID: PMC8628544, DOI: 10.1016/j.devcel.2021.10.018.
- Mitochondrial complex II in intestinal epithelial cells regulates T cell-mediated immunopathologyFujiwara H, Seike K, Brooks MD, Mathew AV, Kovalenko I, Pal A, Lee HJ, Peltier D, Kim S, Liu C, Oravecz-Wilson K, Li L, Sun Y, Byun J, Maeda Y, Wicha MS, Saunders TL, Rehemtulla A, Lyssiotis CA, Pennathur S, Reddy P. Mitochondrial complex II in intestinal epithelial cells regulates T cell-mediated immunopathology. Nature Immunology 2021, 22: 1440-1451. PMID: 34686860, PMCID: PMC9351914, DOI: 10.1038/s41590-021-01048-3.
- Differential contributions of sarcomere and mitochondria-related multigene variants to the endophenotype of hypertrophic cardiomyopathyChung H, Kim Y, Cho SM, Lee HJ, Park CH, Kim JY, Lee SH, Min PK, Yoon YW, Lee BK, Kim WS, Hong BK, Kim TH, Rim SJ, Kwon HM, Choi EY, Lee KA. Differential contributions of sarcomere and mitochondria-related multigene variants to the endophenotype of hypertrophic cardiomyopathy. Mitochondrion 2020, 53: 48-56. PMID: 32380161, DOI: 10.1016/j.mito.2020.04.010.
- Regulatory T-cell Depletion Alters the Tumor Microenvironment and Accelerates Pancreatic CarcinogenesisZhang Y, Lazarus J, Steele NG, Yan W, Lee HJ, Nwosu ZC, Halbrook CJ, Menjivar RE, Kemp SB, Sirihorachai VR, Velez-Delgado A, Donahue K, Carpenter ES, Brown KL, Irizarry-Negron V, Nevison AC, Vinta A, Anderson MA, Crawford HC, Lyssiotis CA, Frankel TL, Bednar F, di Magliano M. Regulatory T-cell Depletion Alters the Tumor Microenvironment and Accelerates Pancreatic Carcinogenesis. Cancer Discovery 2020, 10: 422-439. PMID: 31911451, PMCID: PMC7224338, DOI: 10.1158/2159-8290.cd-19-0958.
- NAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndromeFang EF, Hou Y, Lautrup S, Jensen MB, Yang B, SenGupta T, Caponio D, Khezri R, Demarest TG, Aman Y, Figueroa D, Morevati M, Lee HJ, Kato H, Kassahun H, Lee JH, Filippelli D, Okur MN, Mangerich A, Croteau DL, Maezawa Y, Lyssiotis CA, Tao J, Yokote K, Rusten TE, Mattson MP, Jasper H, Nilsen H, Bohr VA. NAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndrome. Nature Communications 2019, 10: 5284. PMID: 31754102, PMCID: PMC6872719, DOI: 10.1038/s41467-019-13172-8.
- Hydrogen sulfide perturbs mitochondrial bioenergetics and triggers metabolic reprogramming in colon cellsLibiad M, Vitvitsky V, Bostelaar T, Bak DW, Lee HJ, Sakamoto N, Fearon E, Lyssiotis CA, Weerapana E, Banerjee R. Hydrogen sulfide perturbs mitochondrial bioenergetics and triggers metabolic reprogramming in colon cells. Journal Of Biological Chemistry 2019, 294: 12077-12090. PMID: 31213529, PMCID: PMC6690701, DOI: 10.1074/jbc.ra119.009442.
- Reprogramming of Colonic Cell Metabolism by H2SVitvitsky V, Libiad M, Bostelaar T, Maebius A, Lee H, Lyssiotis C, Banerjee R. Reprogramming of Colonic Cell Metabolism by H2S. The FASEB Journal 2019, 33: 485.11-485.11. DOI: 10.1096/fasebj.2019.33.1_supplement.485.11.
- Macrophage-Released Pyrimidines Inhibit Gemcitabine Therapy in Pancreatic CancerHalbrook CJ, Pontious C, Kovalenko I, Lapienyte L, Dreyer S, Lee HJ, Thurston G, Zhang Y, Lazarus J, Sajjakulnukit P, Hong HS, Kremer DM, Nelson BS, Kemp S, Zhang L, Chang D, Biankin A, Shi J, Frankel TL, Crawford HC, Morton JP, Pasca di Magliano M, Lyssiotis CA. Macrophage-Released Pyrimidines Inhibit Gemcitabine Therapy in Pancreatic Cancer. Cell Metabolism 2019, 29: 1390-1399.e6. PMID: 30827862, PMCID: PMC6602533, DOI: 10.1016/j.cmet.2019.02.001.
- A Topical Report on the Design Principles of MetabolismHalbrook C, Lee H, Cantley L, Lyssiotis C. A Topical Report on the Design Principles of Metabolism. 2017, 29-44. DOI: 10.1007/978-3-319-61401-4_2.