John R. Lukens

Education

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

Primary Appointment

  • Assistant Professor of Research, Neuroscience

Contact

Research Interest(s)

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

Selected Publications

  • 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.
  • Bolte A. C., Lukens J. R.. Th17 Cells in Parkinson's Disease: The Bane of the Midbrain Cell Stem Cell. 23(1): 5-6.
  • Frost E. L., Lukens J. R.. The brain's reward circuitry regulates immunity Nat Med. 22(8): 835-7.
  • 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 Neuron. 87(1): 47-62.
  • Gharagozloo M., Gris K. V., Mahvelati T., Amrani A., Lukens J. R., Gris D.. NLR-Dependent Regulation of Inflammation in Multiple Sclerosis- Dependent Regulation of Inflammation in Multiple Sclerosis Front Immunol. 8 2012.
  • Gurung P., Fan G., Lukens J. R., Vogel P., Tonks N. K., Kanneganti T. D.. Tyrosine Kinase SYK Licenses MyD88 Adaptor Protein to Instigate IL-1alpha-Mediated Inflammatory Disease Immunity. 46(4): 635-648.
  • Gurung P., Lukens J. R., Kanneganti T. D.. Mitochondria: diversity in the regulation of the NLRP3 inflammasome Trends Mol Med. 21(3): 193-201.
  • 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 J Immunol. 201(3): 845-850.
  • 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.
  • Lukens J. R., Dixit V. D., Kanneganti T. D.. Inflammasome activation in obesity-related inflammatory diseases and autoimmunity Discov Med. 12(62): 65-74.
  • 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.
  • Lukens J. R., Gross J. M., Kanneganti T. D.. IL-1 family cytokines trigger sterile inflammatory disease Front Immunol. 3 315.
  • 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 Immunity. .
  • 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 Nature. 516(7530): 246-9.
  • Lukens J. R., Kanneganti T. D.. Beyond canonical inflammasomes: emerging pathways in IL-1-mediated autoinflammatory disease Semin Immunopathol. 36(5): 595-609.
  • 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.
  • McKee C. A., Lukens J. R.. Emerging Roles for the Immune System in Traumatic Brain Injury Front Immunol. 7 556.
  • Rhoads J. P., Lukens J. R., Wilhelm A. J., Moore J. L., Mendez-Fernandez Y., Kanneganti T. D., Major A. S.. Oxidized Low-Density Lipoprotein Immune Complex Priming of the Nlrp3 Inflammasome Involves TLR and FcgammaR Cooperation and Is Dependent on CARD9 J Immunol. 198(5): 2105-2114.
  • 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.
  • 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.
  • 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 J Clin Invest. 125(2): 699-714.
  • 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.