Francis Ka-Ming Chan | Scholars@Duke

Francis Ka-Ming Chan
Professor of Immunology

Our lab is interested in how cell death impacts innate inflammation and immune responses. We have a long-standing interest in the biology and signaling mechanism of tumor necrosis factor (TNF), a key cytokine that regulates many inflammatory diseases (e.g. rheumatoid arthritis, inflammatory bowel diseases etc), pathogen infections, and cancer. Several key discoveries made by the PI during his graduate school and postdoctoral training include identification of one of the first cell cycle inhibitors, INK4d-p19 (Mol Cell Biol. 1995, cited over 300 times), and the discovery of the "pre-ligand assembly domain (PLAD)" that mediates TNF receptors signal transduction (Science 2000, cited over 800 times).

In recent years, we have focused our effort on elucidating the signaling mechanism of a novel form of inflammatory cell death termed necroptosis. In 2009, our group identified Receptor Interacting Protein kinase 3 (RIPK3) as a central mediator of necroptosis (Cell, 2009, cited over 1000 times). Current projects include (1) deciphering the signaling mechanisms of necroptosis, (2) interrogation of the biology of RIPK3 and related necroptosis signaling molecules in intestinal wound healing and inflammation, (3) elucidation of the role of necroptosis in pathogen infections, and many others.

We aim to take the knowledge we gain from basic pathway discovery to better understand the principles of immune regulation. We believe our endeavor will pave the way for more efficacious therapeutic intervention in auto-inflammatory diseases, cancers and pathogen infections.

Current research projects in the lab include the following broad areas. Interested students and postdoctoral candidates are encouraged to contact Dr. Chan for more information on rotation projects and research opportunities.

1. The role of necroptosis signal adaptors in inflammatory diseases
We are interested in how the kinases RIPK1 and RIPK3, both of which have critical functions in cell death, contribute to injury-induced inflammation and tissue repair. Currently, we are using mouse models of intestinal injury and inflammation to study the function of these signal adaptors in intestinal homeostasis.

2. The role of cell death in anti-viral immune responses
We have discovered that necroptosis is an important innate immune defense mechanism against certain viruses. We are interested in how host cell death during pathogen infections can alter the course of the host immune response. On the other hand, we are also interested in exploring the mechanisms employed by different viral pathogens in combating the host cell death machinery.

3. Signaling mechanism of RIP kinases in cell death and inflammation
We found that the RIP kinases can promote inflammation through cell death-dependent and independent mechanisms. What are the molecular events that regulate the diverse functions of the RIP kinases? We are using biochemical, cell biological, and genetic tools to dissect the molecular regulation of these important immune signaling molecules.

Current Research Interests

Current research projects in the lab include the following broad areas. Interested students and postdoctoral candidates are encouraged to contact Dr. Chan for more information on rotation projects and research opportunities.

1. The role of necroptosis signal adaptors in inflammatory diseases
We are interested in how the kinases RIPK1 and RIPK3, both of which have critical functions in cell death, contribute to injury-induced inflammation and tissue repair. Currently, we are using mouse models of intestinal injury and inflammation to study the function of these signal adaptors in intestinal homeostasis.

2. The role of cell death in anti-viral immune responses
We have discovered that necroptosis is an important innate immune defense mechanism against certain viruses. We are interested in how host cell death during pathogen infections can alter the course of the host immune response. On the other hand, we are also interested in exploring the mechanisms employed by different viral pathogens in combating the host cell death machinery.

3. Signaling mechanism of RIP kinases in cell death and inflammation
We found that the RIP kinases can promote inflammation through cell death-dependent and independent mechanisms. What are the molecular events that regulate the diverse functions of the RIP kinases? We are using biochemical, cell biological, and genetic tools to dissect the molecular regulation of these important immune signaling molecules.

Current Appointments & Affiliations

Professor of Immunology, Immunology, Basic Science Departments 2019
Member of the Duke Cancer Institute, Duke Cancer Institute, Institutes and Centers 2018

Contact Information

312 Jones Building, DUMC 3010, Durham, NC 27710
Jones 312, DUMC 3010, Durham, NC 27710
franciskaming.chan@duke.edu (919) 613-3892

Background
Education, Training, & Certifications
- Ph.D., University of California - Berkeley 1996
Duke Appointment History
- Instructor in the Department of Immunology, Immunology, Basic Science Departments 2018 - 2019
Leadership & Clinical Positions at Duke
- Vice Chair of Immunology
  Research Quality Officer
Academic Positions Outside Duke
- Professor of Pathology, University of Massachusetts Medical School. 2016 - 2018
- Associate Professor, University of Massachusetts Medical School. 2011 - 2016
- Assistant Professor, University of Massachusetts Medical School. 2002 - 2011
Recognition
Awards & Honors
Research
Selected Grants
- Role of the tumor NLRP3 inflammasome in the generation of anti-PD-1 antibody immunotherapy-associated toxicities awarded by National Institutes of Health 2021 - 2026
- Cell and Molecular Biology Training Program awarded by National Institutes of Health 2021 - 2026
- Exploration of Tumor-Intrinsic NLRP3 Signaling Regulators awarded by National Institutes of Health 2020 - 2025
- Genetic and Genomics Training Grant awarded by National Institutes of Health 2020 - 2025
- Viral inhibition of cell death in host immune responses awarded by National Institutes of Health 2020 - 2025
- Basic Immunology Training Program awarded by National Institutes of Health 2002 - 2025
- Advanced Immunobiology Traning Program for Surgeons awarded by National Institutes of Health 2019 - 2024
- Medical Scientist Training Program awarded by National Institutes of Health 1997 - 2022
- Necroptosis signaling adaptors in inflammatory diseases awarded by National Institutes of Health 2018 - 2021
- Viral mechanisms of necroptosis evasion awarded by National Institutes of Health 2018 - 2019
Publications & Artistic Works
Selected Publications
- Books
  - Galluzzi, Lorenzo, Oliver Kepp, Francis Ka-Ming Chan, and Guido Kroemer. Necroptosis: Mechanisms and Relevance to Disease. Vol. 12, 2017. https://doi.org/10.1146/annurev-pathol-052016-100247.
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- Academic Articles
  - Moriwaki, Kenta, Christa Park, Kazuha Koyama, Sakthi Balaji, Kohei Kita, Ryoko Yagi, Sachiko Komazawa-Sakon, et al. “The scaffold-dependent function of RIPK1 in dendritic cells promotes injury-induced colitis.” Mucosal Immunology, August 30, 2021. https://doi.org/10.1038/s41385-021-00446-y.
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  - Moriwaki, Kenta, Francis K. M. Chan, and Eiji Miyoshi. “Sweet modification and regulation of death receptor signaling pathway.” J Biochem, March 22, 2021. https://doi.org/10.1093/jb/mvab034.
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  - Liu, Zhijun, Himani Nailwal, Jonah Rector, Masmudur M. Rahman, Richard Sam, Grant McFadden, and Francis Ka-Ming Chan. “A class of viral inducer of degradation of the necroptosis adaptor RIPK3 regulates virus-induced inflammation.” Immunity 54, no. 2 (February 9, 2021): 247-258.e7. https://doi.org/10.1016/j.immuni.2020.11.020.
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  - Liu, Zhijun, and Francis Ka-Ming Chan. “Regulatory mechanisms of RIPK1 in cell death and inflammation.” Semin Cell Dev Biol 109 (January 2021): 70–75. https://doi.org/10.1016/j.semcdb.2020.06.013.
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  - Moriwaki, Kenta, Sakthi Balaji, and Francis Ka-Ming Chan. “The death-inducing activity of RIPK1 is regulated by the pH environment.” Sci Signal 13, no. 631 (May 12, 2020). https://doi.org/10.1126/scisignal.aay7066.
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  - Nailwal, Himani, and Francis Ka-Ming Chan. “Necroptosis in anti-viral inflammation.” Cell Death Differ 26, no. 1 (January 2019): 4–13. https://doi.org/10.1038/s41418-018-0172-x.
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  - Galluzzi, Lorenzo, Ilio Vitale, Stuart A. Aaronson, John M. Abrams, Dieter Adam, Patrizia Agostinis, Emad S. Alnemri, et al. “Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.” Cell Death Differ 25, no. 3 (March 2018): 486–541. https://doi.org/10.1038/s41418-017-0012-4.
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  - Rathinam, Vijay A. K., and Francis Ka-Ming Chan. “Inflammasome, Inflammation, and Tissue Homeostasis.” Trends Mol Med 24, no. 3 (March 2018): 304–18. https://doi.org/10.1016/j.molmed.2018.01.004.
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  - Barbosa, Laiana A., Paloma P. Fiuza, Letícia J. Borges, Fellipe A. Rolim, Mayara B. Andrade, Nivea F. Luz, Graziele Quintela-Carvalho, et al. “RIPK1-RIPK3-MLKL-Associated Necroptosis Drives Leishmania infantum Killing in Neutrophils.” Front Immunol 9 (2018): 1818. https://doi.org/10.3389/fimmu.2018.01818.
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  - Luz, Nivea F., Ricardo Khouri, Johan Van Weyenbergh, Dalila L. Zanette, Paloma P. Fiuza, Almerio Noronha, Aldina Barral, et al. “Leishmania braziliensis Subverts Necroptosis by Modulating RIPK3 Expression.” Front Microbiol 9 (2018): 2283. https://doi.org/10.3389/fmicb.2018.02283.
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  - Moquin, David Mark, and Francis Ka-Ming Chan. “Loss-of-Function RNAi Screen to Identify Necrosis-Signaling Molecules.” Methods Mol Biol 1857 (2018): 11–18. https://doi.org/10.1007/978-1-4939-8754-2_2.
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  - Kleino, Anni, Nancy F. Ramia, Gunes Bozkurt, Yanfang Shen, Himani Nailwal, Jing Huang, Johanna Napetschnig, et al. “Peptidoglycan-Sensing Receptors Trigger the Formation of Functional Amyloids of the Adaptor Protein Imd to Initiate Drosophila NF-κB Signaling.” Immunity 47, no. 4 (October 17, 2017): 635-647.e6. https://doi.org/10.1016/j.immuni.2017.09.011.
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  - Orlowski, Gregory M., Shruti Sharma, Jeff D. Colbert, Matthew Bogyo, Stephanie A. Robertson, Hiroshi Kataoka, Francis K. Chan, and Kenneth L. Rock. “Frontline Science: Multiple cathepsins promote inflammasome-independent, particle-induced cell death during NLRP3-dependent IL-1β activation.” J Leukoc Biol 102, no. 1 (July 2017): 7–17. https://doi.org/10.1189/jlb.3HI0316-152R.
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  - DeSouza-Vieira, Thiago, and Francis Ka-Ming Chan. “Bacterial pathogenesis: Pathogenic bacteria attack RHIM.” Nat Microbiol 2 (March 28, 2017): 17042. https://doi.org/10.1038/nmicrobiol.2017.42.
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  - Moriwaki, Kenta, Sakthi Balaji, John Bertin, Peter J. Gough, and Francis Ka-Ming Chan. “Distinct Kinase-Independent Role of RIPK3 in CD11c+ Mononuclear Phagocytes in Cytokine-Induced Tissue Repair.” Cell Rep 18, no. 10 (March 7, 2017): 2441–51. https://doi.org/10.1016/j.celrep.2017.02.015.
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  - Chan, Francis Ka-Ming. “RIPK3 Slams the Brake on Leukemogenesis.” Cancer Cell 30, no. 1 (July 11, 2016): 7–9. https://doi.org/10.1016/j.ccell.2016.06.017.
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  - Farias Luz, Nivea, Sakthi Balaji, Kendi Okuda, Aline Silva Barreto, John Bertin, Peter J. Gough, Ricardo Gazzinelli, et al. “RIPK1 and PGAM5 Control Leishmania Replication through Distinct Mechanisms.” J Immunol 196, no. 12 (June 15, 2016): 5056–63. https://doi.org/10.4049/jimmunol.1502492.
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  - Moriwaki, Kenta, and Francis Ka-Ming Chan. “Necroptosis-independent signaling by the RIP kinases in inflammation.” Cell Mol Life Sci 73, no. 11–12 (June 2016): 2325–34. https://doi.org/10.1007/s00018-016-2203-4.
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  - Moriwaki, Kenta, and Francis Ka-Ming Chan. “Regulation of RIPK3- and RHIM-dependent Necroptosis by the Proteasome.” J Biol Chem 291, no. 11 (March 11, 2016): 5948–59. https://doi.org/10.1074/jbc.M115.700997.
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  - Moriwaki, Kenta, Nivea Farias Luz, Sakthi Balaji, Maria Jose De Rosa, Carey L. O’Donnell, Peter J. Gough, John Bertin, Raymond M. Welsh, and Francis Ka-Ming Chan. “The Mitochondrial Phosphatase PGAM5 Is Dispensable for Necroptosis but Promotes Inflammasome Activation in Macrophages.” J Immunol 196, no. 1 (January 1, 2016): 407–15. https://doi.org/10.4049/jimmunol.1501662.
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  - Moriwaki, Kenta, Sakthi Balaji, and Francis Ka-Ming Chan. “Border Security: The Role of RIPK3 in Epithelium Homeostasis.” Front Cell Dev Biol 4 (2016): 70. https://doi.org/10.3389/fcell.2016.00070.
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  - Moriwaki, Kenta, John Bertin, Peter J. Gough, and Francis Ka-Ming Chan. “A RIPK3-caspase 8 complex mediates atypical pro-IL-1β processing.” Journal of Immunology (Baltimore, Md. : 1950) 194, no. 4 (February 2015): 1938–44. https://doi.org/10.4049/jimmunol.1402167.
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  - Mandal, Pratyusha, Scott B. Berger, Sirika Pillay, Kenta Moriwaki, Chunzi Huang, Hongyan Guo, John D. Lich, et al. “RIP3 induces apoptosis independent of pronecrotic kinase activity.” Molecular Cell 56, no. 4 (November 20, 2014): 481–95. https://doi.org/10.1016/j.molcel.2014.10.021.
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  - Moriwaki, Kenta, Sakthi Balaji, Thomas McQuade, Nidhi Malhotra, Joonsoo Kang, and Francis Ka-Ming Chan. “The necroptosis adaptor RIPK3 promotes injury-induced cytokine expression and tissue repair.” Immunity 41, no. 4 (October 2014): 567–78. https://doi.org/10.1016/j.immuni.2014.09.016.
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  - Chan, Francis Ka-Ming. “Cell biology: A guardian angel of cell integrity.” Nature 513, no. 7516 (September 4, 2014): 38–40. https://doi.org/10.1038/513038a.
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  - Weng, Dan, Robyn Marty-Roix, Sandhya Ganesan, Megan K. Proulx, Gregory I. Vladimer, William J. Kaiser, Edward S. Mocarski, et al. “Caspase-8 and RIP kinases regulate bacteria-induced innate immune responses and cell death.” Proceedings of the National Academy of Sciences of the United States of America 111, no. 20 (May 5, 2014): 7391–96. https://doi.org/10.1073/pnas.1403477111.
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  - Upton, Jason W., and Francis Ka-Ming Chan. “Staying alive: cell death in antiviral immunity.” Mol Cell 54, no. 2 (April 24, 2014): 273–80. https://doi.org/10.1016/j.molcel.2014.01.027.
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  - Zhang, Jianke, and Francis Ka-Ming Chan. “Cell biology. RIPK3 takes another deadly turn.” Science 343, no. 6177 (March 21, 2014): 1322–23. https://doi.org/10.1126/science.1252526.
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  - Sosna, Justyna, Susann Voigt, Sabine Mathieu, Arne Lange, Lutz Thon, Parvin Davarnia, Thomas Herdegen, et al. “TNF-induced necroptosis and PARP-1-mediated necrosis represent distinct routes to programmed necrotic cell death.” Cellular and Molecular Life Sciences : Cmls 71, no. 2 (January 2014): 331–48. https://doi.org/10.1007/s00018-013-1381-6.
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  - McQuade, Thomas, Youngsik Cho, and Francis Ka-Ming Chan. “Positive and negative phosphorylation regulates RIP1- and RIP3-induced programmed necrosis.” Biochem J 456, no. 3 (December 15, 2013): 409–15. https://doi.org/10.1042/BJ20130860.
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  - Moriwaki, Kenta, and Francis Ka-Ming Chan. “RIP3: a molecular switch for necrosis and inflammation.” Genes Dev 27, no. 15 (August 1, 2013): 1640–49. https://doi.org/10.1101/gad.223321.113.
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  - Moquin, David M., Thomas McQuade, and Francis Ka-Ming Chan. “CYLD deubiquitinates RIP1 in the TNFα-induced necrosome to facilitate kinase activation and programmed necrosis.” Plos One 8, no. 10 (January 2013): e76841. https://doi.org/10.1371/journal.pone.0076841.
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  - Chan, Francis Ka-Ming. “Fueling the flames: Mammalian programmed necrosis in inflammatory diseases.” Cold Spring Harb Perspect Biol 4, no. 11 (November 1, 2012). https://doi.org/10.1101/cshperspect.a008805.
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  - Li, Jixi, Thomas McQuade, Ansgar B. Siemer, Johanna Napetschnig, Kenta Moriwaki, Yu-Shan Hsiao, Ermelinda Damko, et al. “The RIP1/RIP3 necrosome forms a functional amyloid signaling complex required for programmed necrosis.” Cell 150, no. 2 (July 2012): 339–50. https://doi.org/10.1016/j.cell.2012.06.019.
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  - Zhang, Haibing, Xiaohui Zhou, Thomas McQuade, Jinghe Li, Francis Ka-Ming Chan, and Jianke Zhang. “Erratum: Corrigendum: Functional complementation between FADD and RIP1 in embryos and lymphocytes.” Nature 483, no. 7390 (March 2012): 498–498. https://doi.org/10.1038/nature10976.
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  - Chan, Francis Ka-Ming, and Eric H. Baehrecke. “RIP3 finds partners in crime.” Cell 148, no. 1–2 (January 20, 2012): 17–18. https://doi.org/10.1016/j.cell.2011.12.020.
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  - Zhang, Haibing, Xiaohui Zhou, Thomas McQuade, Jinghe Li, Francis Ka-Ming Chan, and Jianke Zhang. “Functional complementation between FADD and RIP1 in embryos and lymphocytes.” Nature 471, no. 7338 (March 2, 2011): 373–76. https://doi.org/10.1038/nature09878.
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  - Cho, YoungSik, Thomas McQuade, Haibing Zhang, Jianke Zhang, and Francis Ka-Ming Chan. “RIP1-dependent and independent effects of necrostatin-1 in necrosis and T cell activation.” Plos One 6, no. 8 (2011): e23209. https://doi.org/10.1371/journal.pone.0023209.
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  - Challa, Sreerupa, Melissa Woelfel, Melissa Guildford, David Moquin, and Francis Ka-Ming Chan. “Viral cell death inhibitor MC159 enhances innate immunity against vaccinia virus infection.” J Virol 84, no. 20 (October 2010): 10467–76. https://doi.org/10.1128/JVI.00983-10.
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  - Challa, Sreerupa, and Francis Ka-Ming Chan. “Going up in flames: necrotic cell injury and inflammatory diseases.” Cell Mol Life Sci 67, no. 19 (October 2010): 3241–53. https://doi.org/10.1007/s00018-010-0413-8.
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  - Cho, Young S., Sreerupa Challa, Lauren Clancy, and Francis K-M Chan. “Lipopolysaccharide-induced expression of TRAIL promotes dendritic cell differentiation.” Immunology 130, no. 4 (August 2010): 504–15. https://doi.org/10.1111/j.1365-2567.2010.03266.x.
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  - Moquin, David, and Francis Ka-Ming Chan. “The molecular regulation of programmed necrotic cell injury.” Trends Biochem Sci 35, no. 8 (August 2010): 434–41. https://doi.org/10.1016/j.tibs.2010.03.001.
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  - Cho, Young Sik, Seung Yeon Park, Hee Suk Shin, and Francis Ka-Ming Chan. “Physiological consequences of programmed necrosis, an alternative form of cell demise.” Mol Cells 29, no. 4 (April 2010): 327–32. https://doi.org/10.1007/s10059-010-0066-3.
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  - Cho, Young Sik, Sreerupa Challa, David Moquin, Ryan Genga, Tathagat Dutta Ray, Melissa Guildford, and Francis Ka-Ming Chan. “Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation.” Cell 137, no. 6 (June 2009): 1112–23. https://doi.org/10.1016/j.cell.2009.05.037.
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  - Chan, Francis Ka-Ming. “Three is better than one: pre-ligand receptor assembly in the regulation of TNF receptor signaling.” Cytokine 37, no. 2 (February 2007): 101–7. https://doi.org/10.1016/j.cyto.2007.03.005.
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  - Woelfel, Melissa, Jacqueline Bixby, Michael A. Brehm, and Francis Ka-Ming Chan. “Transgenic expression of the viral FLIP MC159 causes lpr/gld-like lymphoproliferation and autoimmunity.” J Immunol 177, no. 6 (September 15, 2006): 3814–20. https://doi.org/10.4049/jimmunol.177.6.3814.
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  - Sedger, Lisa M., Sarah R. Osvath, Xiao-Ming Xu, Grace Li, Francis K-M Chan, John W. Barrett, and Grant McFadden. “Poxvirus tumor necrosis factor receptor (TNFR)-like T2 proteins contain a conserved preligand assembly domain that inhibits cellular TNFR1-induced cell death.” Journal of Virology 80, no. 18 (September 2006): 9300–9309. https://doi.org/10.1128/jvi.02449-05.
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- Book Sections
  - Moriwaki, K., and F. K. -. M. Chan. “The Inflammatory Signal Adaptor RIPK3: Functions Beyond Necroptosis.,” 328:253–75, 2017. https://doi.org/10.1016/bs.ircmb.2016.08.007.
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  - Chan, Francis Ka-Ming, Nivea Farias Luz, and Kenta Moriwaki. “Programmed necrosis in the cross talk of cell death and inflammation.,” 33:79–106, 2015. https://doi.org/10.1146/annurev-immunol-032414-112248.
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  - Moriwaki, K., and F. K. M. Chan. “Programmed necrosis in immunity and inflammatory diseases.” In Necrotic Cell Death, 177–94, 2014. https://doi.org/10.1007/978-1-4614-8220-8_10.
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- Conference Papers
  - Yi, Fei, Claudia Ouyang, Tori Yamamoto, Anthony Cruz, Francis K. Chan, Nick Frazzette, Stacy Thomas, Nicholas P. Restifo, and Richard M. Siegel. “Non-apoptotic signaling through Fas activates Akt and promotes T cell differentiation through Caspase-8.” In Journal of Immunology, Vol. 198, 2017.
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  - Thomas, Stacy K., Claudia Ouyang, Anthony C. Cruz, Christopher A. Klebanoff, Tori N. Yamamoto, Francis K. Chan, Edward S. Mocarski, Linda Roback, Nicholas P. Restifo, and Richard M. Siegei. “Identifying Fas/CD95 non-apoptotic signaling pathways associated with T cell differentiation.” In Journal of Immunology, Vol. 196, 2016.
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  - Cho, Youngsik, Sreerupa Challa, and Francis Ka-Ming Chan. “A RNA interference screen identifies RIP3 as an essential inducer of TNF-induced programmed necrosis.” In Adv Exp Med Biol, 691:589–93, 2011. https://doi.org/10.1007/978-1-4419-6612-4_62.
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Teaching & Mentoring
Recent Courses

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Education, Training, & Certifications

Duke Appointment History

Leadership & Clinical Positions at Duke

Academic Positions Outside Duke

Awards & Honors

Selected Grants

Selected Publications

Books

Academic Articles

Book Sections

Conference Papers

Recent Courses