John R. Lukens

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Primary Appointment

Assistant Professor, 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 Ć¢independent 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

Lammert CR, Lukens JR, Modeling Autism-Related Disorders in Mice with Maternal Immune Activation (MIA)., 2019; Methods in molecular biology (Clifton, N.J.). 1960() 227-236. PMID: 30798536

Lammert C. R., Frost E. L., Bolte A. C., Paysour M. J., Shaw M. E., Bellinger C. E., Weigel T. K., Zunder E. R., Lukens J. R., Cutting Edge: Critical Roles for Microbiota-Mediated Regulation of the Immune System in a Prenatal Immune Activation Model of Autism, 2018; J Immunol. 201(3) 845-850. PMID:

Bolte A. C., Lukens J. R., Th17 Cells in Parkinson's Disease: The Bane of the Midbrain, 2018; Cell Stem Cell. 23(1) 5-6. PMID:

Walsh J. T., Hendrix S., Boato F., Smirnov I., Zheng J., Lukens J. R., Gadani S., Hechler D., Golz G., Rosenberger K., Kammertons T., Vogt J., Vogelaar C., Siffrin V., Radjavi A., Fernandez-Castaneda A., Gaultier A., Gold R., Kanneganti T. D., Nitsch R., Zipp F., Kipnis J., MHCII-independent CD4+ T cells protect injured CNS neurons via IL-4, 2018; J Clin Invest. 125(2) 699-714. PMID:

Louveau A, Herz J, Alme MN, Salvador AF, Dong MQ, Viar KE, Herod SG, Knopp J, Setliff JC, Lupi AL, Da Mesquita S, Frost EL, Gaultier A, Harris TH, Cao R, Hu S, Lukens JR, Smirnov I, Overall CC, Oliver G, Kipnis J, CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature., 2018; Nature neuroscience. 21(10) 1380-1391. PMID: 30224810 | PMCID: PMC6214619

McKee C. A., Lukens J. R., Emerging Roles for the Immune System in Traumatic Brain Injury, 2016; Front Immunol. 7() 556. PMID:

Frost E. L., Lukens J. R., The brain's reward circuitry regulates immunity, 2016; Nat Med. 22(8) 835-7. PMID:

Gurung P., Lukens J. R., Kanneganti T. D., Mitochondria: diversity in the regulation of the NLRP3 inflammasome, 2015; Trends Mol Med. 21(3) 193-201. PMID:

Gadani S. P., Walsh J. T., Lukens J. R., Kipnis J., Dealing with Danger in the CNS: The Response of the Immune System to Injury, 2015; Neuron. 87(1) 47-62. PMID:

Lukens J. R., Gurung P., Shaw P. J., Barr M. J., Zaki M. H., Brown S. A., Vogel P., Chi H., Kanneganti T. D., The NLRP12 Sensor Negatively Regulates Autoinflammatory Disease by Modulating Interleukin-4 Production in T Cells, 2015; Immunity. () . PMID:

Lukens J. R., Gurung P., Vogel P., Johnson G. R., Carter R. A., McGoldrick D. J., Bandi S. R., Calabrese C. R., Vande Walle L., Lamkanfi M., Kanneganti T. D., Dietary modulation of the microbiome affects autoinflammatory disease, 2014; Nature. 516(7530) 246-9. PMID:

Lukens J. R., Gross J. M., Calabrese C., Iwakura Y., Lamkanfi M., Vogel P., Kanneganti T. D., Critical role for inflammasome-independent IL-1beta production in osteomyelitis, ; Proc Natl Acad Sci U S A. 111(3) 1066-71. PMID:

Shaw P. J., Lukens J. R., Burns S., Chi H., McGargill M. A., Kanneganti T. D., Cutting edge: critical role for PYCARD/ASC in the development of experimental autoimmune encephalomyelitis, ; J Immunol. 184(9) 4610-4. PMID:

Lukens J. R., Dixit V. D., Kanneganti T. D., Inflammasome activation in obesity-related inflammatory diseases and autoimmunity, ; Discov Med. 12(62) 65-74. PMID:

Shaw P. J., Barr M. J., Lukens J. R., McGargill M. A., Chi H., Mak T. W., Kanneganti T. D., Signaling via the RIP2 adaptor protein in central nervous system-infiltrating dendritic cells promotes inflammation and autoimmunity, ; Immunity. 34(1) 75-84. PMID:

Anand P. K., Malireddi R. K., Lukens J. R., Vogel P., Bertin J., Lamkanfi M., Kanneganti T. D., NLRP6 negatively regulates innate immunity and host defence against bacterial pathogens, ; Nature. 488(7411) 389-93. PMID:

Lukens J. R., Barr M. J., Chaplin D. D., Chi H., Kanneganti T. D., Inflammasome-derived IL-1beta regulates the production of GM-CSF by CD4(+) T cells and gammadelta T cells, ; J Immunol. 188(7) 3107-15. PMID:

Lukens J. R., Gross J. M., Kanneganti T. D., IL-1 family cytokines trigger sterile inflammatory disease, ; Front Immunol. 3() 315. PMID:

Lukens J. R., Vogel P., Johnson G. R., Kelliher M. A., Iwakura Y., Lamkanfi M., Kanneganti T. D., RIP1-driven autoinflammation targets IL-1alpha independently of inflammasomes and RIP3, ; Nature. 498(7453) 224-7. PMID:

Weinlich R., Oberst A., Dillon C. P., Janke L. J., Milasta S., Lukens J. R., Rodriguez D. A., Gurung P., Savage C., Kanneganti T. D., Green D. R., Protective roles for caspase-8 and cFLIP in adult homeostasis, ; Cell Rep. 5(2) 340-8. PMID:

Lukens J. R., Kanneganti T. D., Beyond canonical inflammasomes: emerging pathways in IL-1-mediated autoinflammatory disease, ; Semin Immunopathol. 36(5) 595-609. PMID: