John R. Lukens

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Primary Appointment

Associate Professor of Neuroscience, Neuroscience

Education

  • BS, Biology, University of Richmond
  • PhD, Immunology, University of Virginia
  • Postdoc, Immunology, St. Jude Children's Research Hospital

Research Disciplines

Biochemistry, Experimental Pathology, Immunology, Infectious Diseases/Biodefense, Microbiology, Molecular Biology, Neuroimmunology, Neuroscience, Neuroscience, Translational Science

Research Interests

Understanding How Immunological Pathways Contribute to Neurodegenerative, Neurodevelopmental, Mental and Behavior Disorders

Research Description

Our laboratory is focused on understanding how immunological pathways contribute to neurodegenerative, neurodevelopmental, mental and behavior disorders. We are actively investigating the cellular and molecular pathways that contribute to neuroinflammation and central nervous system (CNS)-related tissue damage. We are particularly interested in elucidating the mechanisms that regulate inflammatory cytokine production in the CNS in response to both tissue injury and CNS infection. To this end, we utilize models of multiple sclerosis, CNS injury, neurodegenerative disease, autism spectrum disorder and CNS infection to identify the cell types and molecular pathways that are responsible for neuroinflammation. Our previous work has identified IL-1-dependent signaling as a critical regulator of inflammatory cytokine production and tissue destruction in a model of multiple sclerosis. Future work in our laboratory will focus on further characterizing the immunological signaling pathways that control neuroinflammation in models of neurodegeneration, CNS injury and CNS infection.
We are also exploring how modulation of the microbial landscape in the intestine influences the development of CNS disorders. Emerging data suggests that crosstalk between the intestinal microbiome (collection of trillions of microbes that peacefully live within us) and the brain is a pivotal regulator of many CNS diseases; however, the mechanisms by which the microbiome can influence CNS disease pathogenesis remain poorly defined. In our lab, we are investigating how microbiota-dependent control of immune responses specifically influences neurological disease pathogenesis, CNS function and mental health.
Effective treatment strategies are desperately needed for most CNS diseases including Alzheimer's disease, amyotrophic lateral sclerosis (ALS), CNS injury, autism and various forms of CNS infectious disease. Perturbations in immune responses are widely believed to centrally contribute to the pathogenesis of many, if not all, neurological disorders. In the Lukens laboratory, we believe that a more complete characterization of the interactions between the immune and nervous systems will lead to improved understanding of complex neurological disorders in humans and will help to identify novel and promising therapeutic targets to treat CNS diseases.
Research Interests:
(1) Roles and regulation of IL-1 family cytokines in neurodegenerative disorders and CNS injury.
(2) Control of demyelinating neuroinflammation by innate immune sensors.
(3) Investigation of how microbiome-dependent regulation of immune responses influences cognition, behavior, mental health and neurodegenerative disease.
(4) Regulation of glia cell function by inflammatory caspases.
(5) Identification of the innate signaling pathways that are required to mount protective immune responses against CNS pathogens

Personal Statement

My laboratory is focused on understanding how immunological pathways contribute to neurodegenerative, neurodevelopmental, mental and behavioral disorders. We are investigating the cellular and molecular pathways that contribute to neuroinflammation and CNS-related tissue damage. We are particularly interested in investigating the mechanisms that regulate IL-1 production in response to both pathogen- and danger-associated stimuli. To this end, we utilize models of multiple sclerosis, traumatic brain injury and central nervous system infection to explore how inflammasome-dependent and âindependent IL-1 production influences inflammatory responses and tissue damage. Our previous work has identified IL-1-dependent signaling as a critical regulator of the immune responses that contribute to neuroinflammation and autoinflammatory tissue destruction. Future work in my laboratory will focus on further characterizing the sensors that orchestrate innate-mediated proinflammatory cytokine production and the molecular pathways that promote IL-1 production in the central nervous system

Training

  • Interdisciplinary Training Program in Immunology
  • Predoctoral Training in Neuroscience

Selected Publications

2024

Zengeler, K. E., & Lukens, J. R. (2024). Microglia pack a toolbox for life.. Trends in immunology, 45(5), 338-345. doi:10.1016/j.it.2024.03.010

Mangalmurti, A., & Lukens, J. R. (2024). Suppressing activity in the lateral habenula improves arthritic and depressive-like symptoms in a model of rheumatoid arthritis. BRAIN BEHAVIOR AND IMMUNITY, 118, 115-116. doi:10.1016/j.bbi.2024.02.026

2023

Samuels, J. D., Lukens, J. R., & Price, R. J. (2023). Emerging roles for ITAM and ITIM receptor signaling in microglial biology and Alzheimer's disease-related amyloidosis. JOURNAL OF NEUROCHEMISTRY. doi:10.1111/jnc.15981

Ennerfelt, H., Holliday, C., Shapiro, D. A., Zengeler, K. E., Bolte, A. C., Ulland, T. K., & Lukens, J. R. (2023). CARD9 attenuates Aβ pathology and modifies microglial responses in an Alzheimer's disease mouse model. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 120(24). doi:10.1073/pnas.2303760120

D'Alessandro, A., Lukens, J. R., & Zimring, J. C. (2023). The role of PIMT in Alzheimer's disease pathogenesis: A novel hypothesis. ALZHEIMERS & DEMENTIA, 19(11), 5296-5302. doi:10.1002/alz.13115

Johnson, A. M. M., & Lukens, J. R. R. (2023). The innate immune response in tauopathies. EUROPEAN JOURNAL OF IMMUNOLOGY, 53(6). doi:10.1002/eji.202250266

Samuels, J. D., Moore, K. A., Ennerfelt, H. E., Johnson, A. M., Walsh, A. E., Price, R. J., & Lukens, J. R. (2023). The Alzheimer's disease risk factor INPP5D restricts neuroprotective microglial responses in amyloid beta-mediated pathology. ALZHEIMERS & DEMENTIA, 19(11), 4908-4921. doi:10.1002/alz.13089

Zengeler, K. E., & Lukens, J. R. (2023). Misguided antibodies change the course of brain development. MOLECULAR PSYCHIATRY, 28(5), 1833-1835. doi:10.1038/s41380-023-02042-x

Kumar, S., Budhathoki, S., Oliveira, C. B., Kahle, A. D., Calhan, O. Y., Lukens, J. R., & Deppmann, C. D. (2023). Role of the caspase-8/RIPK3 axis in Alzheimer's disease pathogenesis and Aβ-induced NLRP3 inflammasome activation. JCI INSIGHT, 8(3). doi:10.1172/jci.insight.157433

Walsh, A. E. E., & Lukens, J. R. R. (2023). Engineering mighty microglia. JOURNAL OF EXPERIMENTAL MEDICINE, 220(3). doi:10.1084/jem.20222070

Bolte, A. C., Shapiro, D. A., Dutta, A. B., Ma, W. F., Bruch, K. R., Kovacs, M. A., . . . Ginhoux, F. (2023). The meningeal transcriptional response to traumatic brain injury and aging. ELIFE, 12. doi:10.7554/eLife.81154

Ennerfelt, H., & Lukens, J. R. (2023). Microglia rely on SYK signalling to mount neuroprotective responses in models of Alzheimer's disease and multiple sclerosis. CLINICAL AND TRANSLATIONAL MEDICINE, 13(1). doi:10.1002/ctm2.1178

2022

Zengeler, K. E., Shapiro, D. A., Bruch, K. R., Lammert, C. R., Ennerfelt, H., & Lukens, J. R. (2023). SSRI treatment modifies the effects of maternal inflammation on in utero physiology and offspring neurobiology. BRAIN BEHAVIOR AND IMMUNITY, 108, 80-97. doi:10.1016/j.bbi.2022.10.024

Ennerfelt, H., Frost, E. L., Shapiro, D. A., Holliday, C., Zengeler, K. E., Voithofer, G., . . . Lukens, J. R. (2022). SYK coordinates neuroprotective microglial responses in neurodegenerative disease. CELL, 185(22), 4135-+. doi:10.1016/j.cell.2022.09.030

Lukens, J. R., & Williams, J. L. (2022). An introduction to neuroimmunology. IMMUNOLOGICAL REVIEWS, 311(1), 5-8. doi:10.1111/imr.13133

Zengeler, K. E., & Lukens, J. R. (2022). Taking the parkin brakes off of neuronal NLRP3 drives inflammasome activation and neurodegeneration in Parkinson's disease. NEURON, 110(15), 2356-2358. doi:10.1016/j.neuron.2022.06.015

Natale, N. R., Lukens, J. R., & Petri, W. A. J. (2022). The nervous system during COVID-19: Caught in the crossfire. IMMUNOLOGICAL REVIEWS, 311(1), 90-111. doi:10.1111/imr.13114

Mangalmurti, A., & Lukens, J. R. (2022). How neurons die in Alzheimer's disease: Implications for neuroinflammation. CURRENT OPINION IN NEUROBIOLOGY, 75. doi:10.1016/j.conb.2022.102575

Lukens, J. R., & Eyo, U. B. (2022). Microglia and Neurodevelopmental Disorders. ANNUAL REVIEW OF NEUROSCIENCE, 45, 425-445. doi:10.1146/annurev-neuro-110920-023056

Zengeler, K. E., & Lukens, J. R. (2022). Maternal inflammation is hard for offspring to stomach. IMMUNITY, 55(1), 6-+. doi:10.1016/j.immuni.2021.12.005

2021

Bolte, A. C., & Lukens, J. R. (2021). Review Neuroimmune cleanup crews in brain injury. TRENDS IN IMMUNOLOGY, 42(6), 480-494. doi:10.1016/j.it.2021.04.003

Zengeler, K. E., & Lukens, J. R. (2021). Innate immunity at the crossroads of healthy brain maturation and neurodevelopmental disorders. NATURE REVIEWS IMMUNOLOGY, 21(7), 454-468. doi:10.1038/s41577-020-00487-7

Belanger, M. C., Ball, A. G., Catterton, M. A., Kinman, A. W. L., Anbaei, P., Groff, B. D., . . . Pompano, R. R. (2021). Acute Lymph Node Slices Are a Functional Model System to Study Immunity Ex Vivo. ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE, 4(1), 128-142. doi:10.1021/acsptsci.0c00143

2020

Zengeler, K. E., & Lukens, J. R. (2021). Inflammation stresses out brain development. NATURE NEUROSCIENCE, 24(2), 155-157. doi:10.1038/s41593-020-00775-4

Satkovich, J., Anderson, C. J., Medina, C. B., Ottolini, M., Lukens, J. R., & Kendall, M. M. (2020). RIPK3-Dependent Recruitment of Low-Inflammatory Myeloid Cells Does Not Protect from Systemic Salmonella Infection. MBIO, 11(5). doi:10.1128/mBio.02588-20

Bolte, A. C., Dutta, A. B., Hurt, M. E., Smirnov, I., Kovacs, M. A., McKee, C. A., . . . Lukens, J. R. (2020). Meningeal lymphatic dysfunction exacerbates traumatic brain injury pathogenesis. NATURE COMMUNICATIONS, 11(1). doi:10.1038/s41467-020-18113-4

Batista, S. J., Still, K. M., Johanson, D., Thompson, J. A., O'Brien, C. A., Lukens, J. R., & Harris, T. H. (2020). Gasdermin-D-dependent IL-1α release from microglia promotes protective immunity during chronic Toxoplasma gondii infection. NATURE COMMUNICATIONS, 11(1). doi:10.1038/s41467-020-17491-z

Ennerfelt, H. E., & Lukens, J. R. (2020). The role of innate immunity in Alzheimer's disease. IMMUNOLOGICAL REVIEWS, 297(1), 225-246. doi:10.1111/imr.12896

Lukens, J. R., & Anand, P. K. (2020). Adapt(ed) to repair - TH2 immune responses in the bladder promote recurrent infections. NATURE IMMUNOLOGY, 21(6), 597-599. doi:10.1038/s41590-020-0689-2

Przanowska, R. K., Sobierajska, E., Su, Z., Jensen, K., Przanowski, P., Nagdas, S., . . . Dutta, A. (2020). miR-206 family is important for mitochondrial and muscle function, but not essential for myogenesis in vitro. FASEB JOURNAL, 34(6), 7687-7702. doi:10.1096/fj.201902855RR

Lammert, C. R., Frost, E. L., Bellinger, C. E., Bolte, A. C., McKee, C. A., Hurt, M. E., . . . Lukens, J. R. (2020). AIM2 inflammasome surveillance of DNA damage shapes neurodevelopment. NATURE, 580(7805), 647-+. doi:10.1038/s41586-020-2174-3

Su, Z., Frost, E. L., Lammert, C. R., Przanowska, R. K., Lukens, J. R., & Dutta, A. (2020). tRNA-derived fragments and microRNAs in the maternal-fetal interface of a mouse maternal-immune-activation autism model. RNA BIOLOGY, 17(8), 1183-1195. doi:10.1080/15476286.2020.1721047

2019

Kumar, S., & Lukens, J. R. (2019). NLRP3 sets the table for a parasitic meal. JOURNAL OF LEUKOCYTE BIOLOGY, 106(3), 505-507. doi:10.1002/JLB.4CE0319-088R

Paysour, M. J., Bolte, A. C., & Lukens, J. R. (2019). Crosstalk Between the Microbiome and Gestational Immunity in Autism-Related Disorders. DNA AND CELL BIOLOGY, 38(5), 405-409. doi:10.1089/dna.2019.4653

Ruhl, D., Du, T. -T., Wagner, E. L., Choi, J. H., Li, S., Reed, R., . . . Shin, J. -B. (2019). Necroptosis and Apoptosis Contribute to Cisplatin and Aminoglycoside Ototoxicity. JOURNAL OF NEUROSCIENCE, 39(15), 2951-2964. doi:10.1523/JNEUROSCI.1384-18.2019

Lammert, C. R., & Lukens, J. R. (2019). Modeling Autism-Related Disorders in Mice with Maternal Immune Activation (MIA). MOUSE MODELS OF INNATE IMMUNITY, 2 EDITION, 1960, 227-236. doi:10.1007/978-1-4939-9167-9_20

2018

Louveau, A., Herz, J., Alme, M. N., Salvador, A. F., Dong, M. Q., Viar, K. E., . . . Kipnis, J. (2018). CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature. NATURE NEUROSCIENCE, 21(10), 1380-+. doi:10.1038/s41593-018-0227-9

Bolte, A. C., & Lukens, J. R. (2018). Th17 Cells in Parkinson's Disease: The Bane of the Midbrain. CELL STEM CELL, 23(1), 5-6. doi:10.1016/j.stem.2018.06.016

Lammert, C. R., Frost, E. L., Bolte, A. C., Paysour, M. J., Shaw, M. E., Bellinger, C. E., . . . Lukens, J. R. (2018). Cutting Edge: Critical Roles for Microbiota-Mediated Regulation of the Immune System in a Prenatal Immune Activation Model of Autism. JOURNAL OF IMMUNOLOGY, 201(3), 845-850. doi:10.4049/jimmunol.1701755

2017

Gurung, P., Fan, G., Lukens, J. R., Vogel, P., Tonks, N. K., & Kanneganti, T. -D. (2017). Tyrosine Kinase SYK Licenses MyD88 Adaptor Protein to Instigate IL-1α-Mediated Inflammatory Disease. IMMUNITY, 46(4), 635-648. doi:10.1016/j.immuni.2017.03.014

Trifiletti, D. M., Smith, A., Mitra, N., Grover, S., Lukens, J. N., Cohen, R. B., . . . Swisher-McClure, S. (2017). Beyond Positive Margins and Extracapsular Extension: Evaluating the Utilization and Clinical Impact of Postoperative Chemoradiotherapy in Resected Locally Advanced Head and Neck Cancer. JOURNAL OF CLINICAL ONCOLOGY, 35(14), 1550-+. doi:10.1200/JCO.2016.68.2336

Rhoads, J. P., Lukens, J. R., Wilhelm, A. J., Moore, J. L., Mendez-Fernandez, Y., Kanneganti, T. -D., & Major, A. S. (2017). Oxidized Low-Density Lipoprotein Immune Complex Priming of the Nlrp3 Inflammasome Involves TLR and FcγR Cooperation and Is Dependent on CARD9. JOURNAL OF IMMUNOLOGY, 198(5), 2105-2114. doi:10.4049/jimmunol.1601563

Gharagozloo, M., Gris, K. V., Mahvelati, T., Amrani, A., Lukens, J. R., & Gris, D. (2018). NLR-Dependent Regulation of inflammation in Multiple Sclerosis-Dependent Regulation of inflammation in Multiple Sclerosis. FRONTIERS IN IMMUNOLOGY, 8. doi:10.3389/fimmu.2017.02012

2016

Frost, E. L., & Lukens, J. R. (2016). The brain's reward circuitry regulates immunity. NATURE MEDICINE, 22(8), 835-837. doi:10.1038/nm.4157

Mckee, C. A., & Lukens, J. R. (2016). Emerging Roles for the Immune System in Traumatic Brain Injury. FRONTIERS IN IMMUNOLOGY, 7. doi:10.3389/fimmu.2016.00556

2015

Gadani, S. P., Walsh, J. T., Lukens, J. R., & Kipnis, J. (2015). Dealing with Danger in the CNS: The Response of the Immune System to Injury. NEURON, 87(1), 47-62. doi:10.1016/j.neuron.2015.05.019

Lukens, J. R., Gurung, P., Shaw, P. J., Barr, M. J., Zaki, M. H., Brown, S. A., . . . Kanneganti, T. -D. (2015). The NLRP12 Sensor Negatively Regulates Autoinflammatory Disease by Modulating Interleukin-4 Production in T Cells. IMMUNITY, 42(4), 654-664. doi:10.1016/j.immuni.2015.03.006

Walsh, J. T., Hendrix, S., Boato, F., Smirnov, I., Zheng, J., Lukens, J. R., . . . Kipnis, J. (2015). MHCII-independent CD4+ T cells protect injured CNS neurons via IL-4. JOURNAL OF CLINICAL INVESTIGATION, 125(2), 699-714. doi:10.1172/JCI176210

Edwards, B. A., Harris, T. L., Floersh, H., Lukens, J. R., Zaki, M. H., Vogel, P., . . . McGargill, M. A. (2015). Drak2 is not required for tumor surveillance and suppression. INTERNATIONAL IMMUNOLOGY, 27(3), 161-166. doi:10.1093/intimm/dxu146

2014

Gurung, P., Lukens, J. R., & Kanneganti, T. -D. (2015). Mitochondria: diversity in the regulation of the NLRP3 inflammasome. TRENDS IN MOLECULAR MEDICINE, 21(3), 193-201. doi:10.1016/j.molmed.2014.11.008

Lukens, J. R., Gurung, P., Vogel, P., Johnson, G. R., Carter, R. A., McGoldrick, D. J., . . . Kanneganti, T. -D. (2014). Dietary modulation of the microbiome affects autoinflammatory disease. NATURE, 516(7530), 246-+. doi:10.1038/nature13788

Lukens, J. R., & Kanneganti, T. -D. (2014). Beyond canonical inflammasomes: emerging pathways in IL-1-mediated autoinflammatory disease. SEMINARS IN IMMUNOPATHOLOGY, 36(5), 595-609. doi:10.1007/s00281-014-0434-8

Lukens, J. R., Gross, J. M., Calabrese, C., Iwakura, Y., Lamkanfi, M., Vogel, P., & Kanneganti, T. -D. (2014). Critical role for inflammasome-independent IL-1β production in osteomyelitis. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 111(3), 1066-1071. doi:10.1073/pnas.1318688111

2013

Weinlich, R., Oberst, A., Dillon, C. P., Janke, L. J., Milasta, S., Lukens, J. R., . . . Green, D. R. (2013). Protective Roles for Caspase-8 and cFLIP in Adult Homeostasis. CELL REPORTS, 5(2), 340-348. doi:10.1016/j.celrep.2013.08.045

Lukens, J. R., Vogel, P., Johnson, G. R., Kelliher, M. A., Iwakura, Y., Lamkanfi, M., & Kanneganti, T. -D. (2013). RIP1-driven autoinflammation targets IL-1α independently of inflammasomes and RIP3. NATURE, 498(7453), 224-+. doi:10.1038/nature12174

2012

Lukens, J. R., & Kanneganti, T. -D. (2012). Fat Chance: Not Much against NKT Cells. IMMUNITY, 37(3), 447-449. doi:10.1016/j.immuni.2012.09.006

Anand, P. K., Malireddi, R. K. S., Lukens, J. R., Vogel, P., Bertin, J., Lamkanfi, M., & Kanneganti, T. -D. (2012). NLRP6 negatively regulates innate immunity and host defence against bacterial pathogens. NATURE, 488(7411), 389-+. doi:10.1038/nature11250

Lukens, J. R., Barr, M. J., Chaplin, D. D., Chi, H., & Kanneganti, T. -D. (2012). Inflammasome-Derived IL-1β Regulates the Production of GM-CSF by CD4+ T Cells and γδ T Cells. JOURNAL OF IMMUNOLOGY, 188(7), 3107-3115. doi:10.4049/jimmunol.1103308

Lukens, J. R., Gross, J. M., & Kanneganti, T. -D. (2012). IL-1 family cytokines trigger sterile inflammatory disease. FRONTIERS IN IMMUNOLOGY, 3. doi:10.3389/fimmu.2012.00315

2011

Lukens, J. R., Dixit, V. D., & Kanneganti, T. -D. (2011). Inflammasome Activation in Obesity-related Inflammatory Diseases and Autoimmunity. DISCOVERY MEDICINE, 11(62), 65-74. Retrieved from https://www.webofscience.com/

Shaw, P. J., Barr, M. J., Lukens, J. R., McGargill, M. A., Chi, H., Mak, T. W., & Kanneganti, T. -D. (2011). Signaling via the RIP2 Adaptor Protein in Central Nervous System-Infiltrating Dendritic Cells Promotes Inflammation and Autoimmunity. IMMUNITY, 34(1), 75-84. doi:10.1016/j.immuni.2010.12.015

2010

Shaw, P. J., Lukens, J. R., Burns, S., Chi, H., McGargill, M. A., & Kanneganti, T. -D. (2010). Cutting Edge: Critical Role for PYCARD/ASC in the Development of Experimental Autoimmune Encephalomyelitis. JOURNAL OF IMMUNOLOGY, 184(9), 4610-4614. doi:10.4049/jimmunol.1000217

Lassen, M. G., Lukens, J. R., Dolina, J. S., Brown, M. G., & Hahn, Y. S. (2010). Intrahepatic IL-10 Maintains NKG2A+Ly49- Liver NK Cells in a Functionally Hyporesponsive State. JOURNAL OF IMMUNOLOGY, 184(5), 2693-2701. doi:10.4049/jimmunol.0901362