Dennis Ko
Associate Professor in Molecular Genetics and Microbiology
Using Pathogens to Decipher Genetic Variation Connecting Cell Biology and Disease Susceptibility
Despite improvements in public health, advancements in vaccines, and the development of many classes of antibiotics, infectious disease is still responsible for over a quarter of all deaths worldwide. However, even for the most devastating of pandemics, individuals demonstrate a large variability in the severity of infection. The long-term goal of the lab is to understand the genetic basis for differences in susceptibility to infection and related inflammatory disorders. We approach this question through a combination of experimental and computational approaches that combine high-throughput cell biology with quantitative human genetics. The identified genetic differences serve as the starting point for exploring new cell biology and human disease susceptibility genes.
Despite improvements in public health, advancements in vaccines, and the development of many classes of antibiotics, infectious disease is still responsible for over a quarter of all deaths worldwide. However, even for the most devastating of pandemics, individuals demonstrate a large variability in the severity of infection. The long-term goal of the lab is to understand the genetic basis for differences in susceptibility to infection and related inflammatory disorders. We approach this question through a combination of experimental and computational approaches that combine high-throughput cell biology with quantitative human genetics. The identified genetic differences serve as the starting point for exploring new cell biology and human disease susceptibility genes.
Current Appointments & Affiliations
- Associate Professor in Molecular Genetics and Microbiology, Molecular Genetics and Microbiology, Basic Science Departments 2020
- Assistant Professor in the Department of Medicine, Medicine, Clinical Science Departments 2012
- Associate of the Duke Initiative for Science & Society, Duke Science & Society, Initiatives 2017
Contact Information
- 0049 CARL Building, Box 3053, 213 Research Drive, Durham, NC 27710
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dennis.ko@duke.edu
(919) 684-5834
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Duke Molecular Genetics and Microbiology Profile
- Background
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Education, Training, & Certifications
- M.D., Stanford University 2005
- Ph.D., Stanford University 2003
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Duke Appointment History
- Assistant Professor in Molecular Genetics and Microbiology, Molecular Genetics and Microbiology, Basic Science Departments 2012 - 2020
- Recognition
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In the News
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Awards & Honors
- Research
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Selected Grants
- Genetic and Genomics Training Grant awarded by National Institutes of Health 2020 - 2025
- HUMAN GENETIC VARIATION REGULATING SALMONELLA HOST-PATHOGEN INTERACTIONS AND DISEASE SUSCEPTIBILITY awarded by National Institutes of Health 2015 - 2025
- Duke CTSA (TL1) awarded by National Institutes of Health 2018 - 2023
- Mechanisms of methylthioadenosine signaling during Salmonella infection awarded by National Institutes of Health 2019 - 2022
- Medical Scientist Training Program awarded by National Institutes of Health 1997 - 2022
- STAT3-dependent manipulation of host transcription and immune responses by Salmonella awarded by National Institutes of Health 2019 - 2022
- Host-Directed Therapy to Circumvent Immune Evasion by Leishmania major awarded by Burroughs Wellcome Fund 2019 - 2021
- Molecular Mycology and Pathogenesis Training Program awarded by National Institutes of Health 2019 - 2021
- SALMONELLA HIJACKING OF STAT3 AND CONSEQUENCES FOR DISEASE awarded by National Institutes of Health 2019 - 2021
- Regulation of Salmonella virulence by interspecies methylthioadenosine signaling awarded by National Institutes of Health 2019 - 2021
- AN ATLAS OF SHARED GENETIC ARCHITECTURE CONNECTING CELL BIOLOGY AND HUMAN DISEASE awarded by National Institutes of Health 2018 - 2021
- Human Genetic Variance and Cellular Responses to Sexually Transmitted Infections awarded by University of Maryland, Baltimore 2015 - 2020
- Genetics Training Grant awarded by National Institutes of Health 1979 - 2020
- Organization and Function of Cellular Structure awarded by National Institutes of Health 1975 - 2020
- Human Genetic Variance and Cellular Responses to Sexually Transmitted Infections awarded by University of Maryland 2009 - 2019
- Characterization of a novel Salmonella regulator of IL-10 production and its role in pathogenesis awarded by National Institutes of Health 2016 - 2018
- A role for pathogen-induced IL-10 production in susceptibility to MS awarded by National Multiple Sclerosis Society 2014 - 2015
- Functional genomics of human variation to Salmonella invasion awarded by National Institutes of Health 2012 - 2015
- Publications & Artistic Works
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Selected Publications
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Academic Articles
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Schott, Benjamin H., Alejandro L. Antonia, Liuyang Wang, Kelly J. Pittman, Barbara S. Sixt, Alyson B. Barnes, Raphael H. Valdivia, and Dennis C. Ko. “Modeling of variables in cellular infection reveals CXCL10 levels are regulated by human genetic variation and the Chlamydia-encoded CPAF protease.” Sci Rep 10, no. 1 (October 26, 2020): 18269. https://doi.org/10.1038/s41598-020-75129-y.Full Text Link to Item
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Gibbs, Kyle D., Erica J. Washington, Sarah L. Jaslow, Jeffrey S. Bourgeois, Matthew W. Foster, Robyn Guo, Richard G. Brennan, and Dennis C. Ko. “The Salmonella Secreted Effector SarA/SteE Mimics Cytokine Receptor Signaling to Activate STAT3.” Cell Host Microbe 27, no. 1 (January 8, 2020): 129-139.e4. https://doi.org/10.1016/j.chom.2019.11.012.Full Text Link to Item
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Antonia, Alejandro L., and Dennis C. Ko. “Leishmaniasis: A spectrum of diseases shaped by evolutionary pressures across diverse life cycle.” Evolution, Medicine, and Public Health 2020, no. 1 (January 2020): 139–40. https://doi.org/10.1093/emph/eoaa032.Full Text
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Bourgeois, J. S., C. M. Smith, and D. C. Ko. “These Are the Genes You're Looking For: Finding Host Resistance Genes.” Trends in Microbiology, January 1, 2020. https://doi.org/10.1016/j.tim.2020.09.006.Full Text
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Antonia, Alejandro, Monica Alvarez, Esme Trahair, Kyle Gibbs, Kelly Pittman, Alyson Barnes, Jeffrey Smith, et al. “Pathogen-encoded evasion of CXCL10 and T cell responses,” February 22, 2019. https://doi.org/10.1101/557876.Full Text Open Access Copy
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Antonia, Alejandro L., Kyle D. Gibbs, Esme D. Trahair, Kelly J. Pittman, Amelia T. Martin, Benjamin H. Schott, Jeffrey S. Smith, et al. “Pathogen Evasion of Chemokine Response Through Suppression of CXCL10.” Frontiers in Cellular and Infection Microbiology 9 (January 2019): 280. https://doi.org/10.3389/fcimb.2019.00280.Full Text
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Bourgeois, Jeffrey S., Daoguo Zhou, Teresa L. M. Thurston, James J. Gilchrist, and Dennis C. Ko. “Methylthioadenosine Suppresses Salmonella Virulence.” Infect Immun 86, no. 9 (September 2018). https://doi.org/10.1128/IAI.00429-18.Full Text Link to Item
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Wang, Liuyang, Kelly J. Pittman, Jeffrey R. Barker, Raul E. Salinas, Ian B. Stanaway, Graham D. Williams, Robert J. Carroll, et al. “An Atlas of Genetic Variation Linking Pathogen-Induced Cellular Traits to Human Disease.” Cell Host Microbe 24, no. 2 (August 8, 2018): 308-323.e6. https://doi.org/10.1016/j.chom.2018.07.007.Full Text Link to Item
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Jaslow, Sarah L., Kyle D. Gibbs, W Florian Fricke, Liuyang Wang, Kelly J. Pittman, Mark K. Mammel, Joshua T. Thaden, et al. “Salmonella Activation of STAT3 Signaling by SarA Effector Promotes Intracellular Replication and Production of IL-10.” Cell Rep 23, no. 12 (June 19, 2018): 3525–36. https://doi.org/10.1016/j.celrep.2018.05.072.Full Text Link to Item
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Alvarez, Monica I., and Dennis C. Ko. “Reply to Gilchrist et al.: Possible roles for VAC14 in multiple infectious diseases.” Proc Natl Acad Sci U S A 115, no. 16 (April 17, 2018): E3604–5. https://doi.org/10.1073/pnas.1803533115.Full Text Link to Item
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Antonia, Alejandro L., Liuyang Wang, and Dennis C. Ko. “A real-time PCR assay for quantification of parasite burden in murine models of leishmaniasis.” Peerj 6 (2018): e5905. https://doi.org/10.7717/peerj.5905.Full Text Link to Item
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Corona, Erik, Liuyang Wang, Dennis Ko, and Chirag J. Patel. “Systematic detection of positive selection in the human-pathogen interactome and lasting effects on infectious disease susceptibility.” Plos One 13, no. 5 (2018): e0196676. https://doi.org/10.1371/journal.pone.0196676.Full Text Link to Item
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Alvarez, Monica I., Luke C. Glover, Peter Luo, Liuyang Wang, Elizabeth Theusch, Stefan H. Oehlers, Eric M. Walton, et al. “Human genetic variation in VAC14 regulates Salmonella invasion and typhoid fever through modulation of cholesterol.” Proc Natl Acad Sci U S A 114, no. 37 (September 12, 2017): E7746–55. https://doi.org/10.1073/pnas.1706070114.Full Text Open Access Copy Link to Item
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Galarza-Muñoz, Gaddiel, Farren B. S. Briggs, Irina Evsyukova, Geraldine Schott-Lerner, Edward M. Kennedy, Tinashe Nyanhete, Liuyang Wang, et al. “Human Epistatic Interaction Controls IL7R Splicing and Increases Multiple Sclerosis Risk.” Cell 169, no. 1 (March 23, 2017): 72-84.e13. https://doi.org/10.1016/j.cell.2017.03.007.Full Text Link to Item
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Wang, Liuyang, Emily R. Ko, James J. Gilchrist, Kelly J. Pittman, Anna Rautanen, Matti Pirinen, J Will Thompson, et al. “Human genetic and metabolite variation reveals that methylthioadenosine is a prognostic biomarker and an inflammatory regulator in sepsis.” Science Advances 3, no. 3 (March 8, 2017): e1602096. https://doi.org/10.1126/sciadv.1602096.Full Text Open Access Copy
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Oehlers, Stefan H., Maria Vega Flores, Christopher J. Hall, Liuyang Wang, Dennis C. Ko, Kathryn E. Crosier, and Philip S. Crosier. “A whole animal chemical screen approach to identify modifiers of intestinal neutrophilic inflammation.” Febs J 284, no. 3 (February 2017): 402–13. https://doi.org/10.1111/febs.13976.Full Text Link to Item
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Pittman, Kelly J., Luke C. Glover, Liuyang Wang, and Dennis C. Ko. “The Legacy of Past Pandemics: Common Human Mutations That Protect against Infectious Disease.” Plos Pathog 12, no. 7 (July 2016): e1005680. https://doi.org/10.1371/journal.ppat.1005680.Full Text Link to Item
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Jaslow, Sarah, Liuyang Wang, and Dennis Ko. “Contribution to Virulence of a Novel Anti-inflammatory Effector in Salmonella enterica.” Open Forum Infect Dis 2, no. Suppl 1 (December 2015): 693. https://doi.org/10.1093/ofid/ofv131.68.Full Text Link to Item
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McCauliff, Leslie A., Zhi Xu, Ran Li, Sarala Kodukula, Dennis C. Ko, Matthew P. Scott, Peter C. Kahn, and Judith Storch. “Multiple Surface Regions on the Niemann-Pick C2 Protein Facilitate Intracellular Cholesterol Transport.” J Biol Chem 290, no. 45 (November 6, 2015): 27321–31. https://doi.org/10.1074/jbc.M115.667469.Full Text Link to Item
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Wang, Liuyang, Stefan H. Oehlers, Scott T. Espenschied, John F. Rawls, David M. Tobin, and Dennis C. Ko. “CPAG: software for leveraging pleiotropy in GWAS to reveal similarity between human traits links plasma fatty acids and intestinal inflammation.” Genome Biol 16 (September 15, 2015): 190. https://doi.org/10.1186/s13059-015-0722-1.Full Text Open Access Copy Link to Item
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Lee, Soo Chan, Alicia Li, Silvia Calo, Makoto Inoue, Nam K. Tonthat, Judith M. Bain, Johanna Louw, et al. “Calcineurin orchestrates dimorphic transitions, antifungal drug responses and host-pathogen interactions of the pathogenic mucoralean fungus Mucor circinelloides.” Mol Microbiol 97, no. 5 (September 2015): 844–65. https://doi.org/10.1111/mmi.13071.Full Text Link to Item
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Gao, Dahai, Dennis C. Ko, Xinmin Tian, Guang Yang, and Liuyang Wang. “Expression Divergence of Duplicate Genes in the Protein Kinase Superfamily in Pacific Oyster.” Evol Bioinform Online 11, no. Suppl 1 (2015): 57–65. https://doi.org/10.4137/EBO.S30230.Full Text Link to Item
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Lee, Soo Chan, R Blake Billmyre, Alicia Li, Sandra Carson, Sean M. Sykes, Eun Young Huh, Piotr Mieczkowski, Dennis C. Ko, Christina A. Cuomo, and Joseph Heitman. “Analysis of a food-borne fungal pathogen outbreak: virulence and genome of a Mucor circinelloides isolate from yogurt.” Mbio 5, no. 4 (July 8, 2014): e01390–e01314. https://doi.org/10.1128/mBio.01390-14.Full Text Link to Item
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Ko, Dennis C., and Sarah L. Jaslow. “The marriage of quantitative genetics and cell biology: a novel screening approach reveals people have genetically encoded variation in microtubule stability.” Bioarchitecture 4, no. 2 (March 2014): 58–61. https://doi.org/10.4161/bioa.28481.Full Text Link to Item
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Salinas, Raul E., Cassandra Ogohara, Monica I. Thomas, Kajal P. Shukla, Samuel I. Miller, and Dennis C. Ko. “A cellular genome-wide association study reveals human variation in microtubule stability and a role in inflammatory cell death.” Mol Biol Cell 25, no. 1 (January 2014): 76–86. https://doi.org/10.1091/mbc.E13-06-0294.Full Text Open Access Copy Link to Item
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Ko, Dennis C., and Thomas J. Urban. “Understanding human variation in infectious disease susceptibility through clinical and cellular GWAS.” Plos Pathog 9, no. 8 (2013): e1003424. https://doi.org/10.1371/journal.ppat.1003424.Full Text Open Access Copy Link to Item
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Tobin, David M., Francisco J. Roca, John P. Ray, Dennis C. Ko, and Lalita Ramakrishnan. “An enzyme that inactivates the inflammatory mediator leukotriene b4 restricts mycobacterial infection.” Plos One 8, no. 7 (2013): e67828. https://doi.org/10.1371/journal.pone.0067828.Full Text Open Access Copy Link to Item
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Ko, Dennis C., Eric R. Gamazon, Kajal P. Shukla, Richard A. Pfuetzner, Dale Whittington, Tarah D. Holden, Mitchell J. Brittnacher, et al. “Functional genetic screen of human diversity reveals that a methionine salvage enzyme regulates inflammatory cell death.” Proc Natl Acad Sci U S A 109, no. 35 (August 28, 2012): E2343–52. https://doi.org/10.1073/pnas.1206701109.Full Text Link to Item
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Tobin, David M., Francisco J. Roca, Sungwhan F. Oh, Ross McFarland, Thad W. Vickery, John P. Ray, Dennis C. Ko, et al. “Host genotype-specific therapies can optimize the inflammatory response to mycobacterial infections.” Cell 148, no. 3 (February 3, 2012): 434–46. https://doi.org/10.1016/j.cell.2011.12.023.Full Text Link to Item
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McElwain, M. A., D. C. Ko, M. D. Gordon, H. Fyrst, J. D. Saba, and R. Nusse. “A suppressor/enhancer screen in Drosophila reveals a role for Wnt-mediated lipid metabolism in primordial germ cell migration.” Plos One 6, no. 11 (2011). https://doi.org/10.1371/journal.pone.0026993.Full Text
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McElwain, Mark A., Dennis C. Ko, Michael D. Gordon, Henrik Fyrst, Julie D. Saba, and Roel Nusse. “A suppressor/enhancer screen in Drosophila reveals a role for wnt-mediated lipid metabolism in primordial germ cell migration.” Plos One 6, no. 11 (2011): e26993. https://doi.org/10.1371/journal.pone.0026993.Full Text Link to Item
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Vinh, Dani B. N., Dennis C. Ko, Richard A. Rachubinski, John D. Aitchison, and Samuel I. Miller. “Expression of the Salmonella spp. virulence factor SifA in yeast alters Rho1 activity on peroxisomes.” Mol Biol Cell 21, no. 20 (October 15, 2010): 3567–77. https://doi.org/10.1091/mbc.E10-06-0482.Full Text Link to Item
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Fong, Christine, Dennis C. Ko, Michael Wasnick, Matthew Radey, Samuel I. Miller, and Mitchell Brittnacher. “GWAS analyzer: integrating genotype, phenotype and public annotation data for genome-wide association study analysis.” Bioinformatics 26, no. 4 (February 15, 2010): 560–64. https://doi.org/10.1093/bioinformatics/btp714.Full Text Link to Item
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Ko, Dennis C., Kajal P. Shukla, Christine Fong, Michael Wasnick, Mitchell J. Brittnacher, Mark M. Wurfel, Tarah D. Holden, et al. “A genome-wide in vitro bacterial-infection screen reveals human variation in the host response associated with inflammatory disease.” American Journal of Human Genetics 85, no. 2 (August 6, 2009): 214–27. https://doi.org/10.1016/j.ajhg.2009.07.012.Full Text
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Ko, Emily Ray, Dennis Ko, Carolyn Chen, and Joseph S. Lipsick. “A conserved acidic patch in the Myb domain is required for activation of an endogenous target gene and for chromatin binding.” Mol Cancer 7 (October 7, 2008): 77. https://doi.org/10.1186/1476-4598-7-77.Full Text Link to Item
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Ko, D. C., L. Milenkovic, S. M. Beier, H. Manuel, J. A. Buchanan, and M. P. Scott. “Cell-autonomous death of cerebellar purkinje neurons with autophagy in niemann-pick type C disease.” Plos Genetics 1, no. 1 (July 1, 2005): 0081–0095. https://doi.org/10.1371/journal.pgen.0010007.Full Text
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Ko, Dennis C., Jonathan Binkley, Arend Sidow, and Matthew P. Scott. “The integrity of a cholesterol-binding pocket in Niemann-Pick C2 protein is necessary to control lysosome cholesterol levels.” Proceedings of the National Academy of Sciences of the United States of America 100, no. 5 (March 2003): 2518–25. https://doi.org/10.1073/pnas.0530027100.Full Text
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Ko, D. C., M. D. Gordon, J. Y. Jin, and M. P. Scott. “Dynamic movements of organelles containing Niemann-Pick C1 protein: NPC1 involvement in late endocytic events.” Molecular Biology of the Cell 12, no. 3 (March 2001): 601–14. https://doi.org/10.1091/mbc.12.3.601.Full Text
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Ko, D. C., M. T. Marr, J. Guo, and J. W. Roberts. “A surface of Escherichia coli sigma 70 required for promoter function and antitermination by phage lambda Q protein.” Genes Dev 12, no. 20 (October 15, 1998): 3276–85. https://doi.org/10.1101/gad.12.20.3276.Full Text Link to Item
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Roberts, J. W., W. Yarnell, E. Bartlett, J. Guo, M. Marr, D. C. Ko, H. Sun, and C. W. Roberts. “Antitermination by bacteriophage lambda Q protein.” Cold Spring Harb Symp Quant Biol 63 (1998): 319–25. https://doi.org/10.1101/sqb.1998.63.319.Full Text Link to Item
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Conference Papers
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Feng, Liping, Alex Antonia, Amy Murtha, and Dennis Ko. “Racial Disparity in Ureaplasma Parvum Induced Inflammatory Responses.” In Reproductive Sciences, 24:174A-174A. SAGE PUBLICATIONS INC, 2017.Link to Item
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Wang, L., M. I. Alvarez, L. C. Glover, K. J. Pittman, K. D. Gibbs, and D. C. Ko. “The Hi-HOST Phenome Project: Interpreting human genetic diversity through high-throughput cell biology.” In Molecular Biology of the Cell, Vol. 27. AMER SOC CELL BIOLOGY, 2016.Link to Item
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- Teaching & Mentoring
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Recent Courses
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