- Biomedical Sciences Graduate Program | John R. Lukens

John R. Lukens

Education

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

Contact

Research Interest(s)

Neuroinflammatory disease

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

  • Gadani S, Walsh J, Lukens J, Kipnis J. Dealing with Danger in the CNS: The Response of the Immune System to Injury. Neuron. 2015;87(1): 47-62. PMID: 26139369 | PMCID: PMC4491143
  • Lukens J, Gurung P, Shaw P, Barr M, Zaki M, Brown S, Vogel P, Chi H, Kanneganti T. The NLRP12 Sensor Negatively Regulates Autoinflammatory Disease by Modulating Interleukin-4 Production in T Cells. Immunity. 2015;42(4): 654-64. PMID: 25888258 | PMCID: PMC4412374
  • Walsh J, Hendrix S, Boato F, Smirnov I, Zheng J, Lukens J, Gadani S, Hechler D, Gölz G, Rosenberger K, Kammertöns T, Vogt J, Vogelaar C, Siffrin V, Radjavi A, Fernandez-Castaneda A, Gaultier A, Gold R, Kanneganti T, Nitsch R, Zipp F, Kipnis J. MHCII-independent CD4+ T cells protect injured CNS neurons via IL-4. The Journal of clinical investigation. 2015;125(2): 699-714. PMID: 25607842 | PMCID: PMC4319416
  • Gurung P, Lukens J, Kanneganti T. Mitochondria: diversity in the regulation of the NLRP3 inflammasome. Trends in molecular medicine. 2014. PMID: 25500014
  • Lukens J, Gross J, Calabrese C, Iwakura Y, Lamkanfi M, Vogel P, Kanneganti T. Critical role for inflammasome-independent IL-1β production in osteomyelitis. Proceedings of the National Academy of Sciences of the United States of America. 2014;111(3): 1066-71. PMID: 24395792 | PMCID: PMC3903206
  • Lukens J, Gurung P, Vogel P, Johnson G, Carter R, McGoldrick D, Bandi S, Calabrese C, Vande Walle L, Lamkanfi M, Kanneganti T. Dietary modulation of the microbiome affects autoinflammatory disease. Nature. 2014;516(7530): 246-9. PMID: 25274309 | PMCID: PMC4268032
  • Lukens J, Kanneganti T. Beyond canonical inflammasomes: emerging pathways in IL-1-mediated autoinflammatory disease. Seminars in immunopathology. 2014;36(5): 595-609. PMID: 24838628 | PMCID: PMC4189983
  • Lukens J, Kanneganti T. SHP-1 and IL-1α conspire to provoke neutrophilic dermatoses. Rare diseases (Austin, Tex.). 2014;2 e27742. PMID: 25054090 | PMCID: PMC4091500
  • Lukens J, Vogel P, Johnson G, Kelliher M, Iwakura Y, Lamkanfi M, Kanneganti T. RIP1-driven autoinflammation targets IL-1α independently of inflammasomes and RIP3. Nature. 2013;498(7453): 224-7. PMID: 23708968 | PMCID: PMC3683390
  • Weinlich R, Oberst A, Dillon C, Janke L, Milasta S, Lukens J, Rodriguez D, Gurung P, Savage C, Kanneganti T, Green D. Protective roles for caspase-8 and cFLIP in adult homeostasis. Cell reports. 2013;5(2): 340-8. PMID: 24095739 | PMCID: PMC3843376
  • Anand P, Malireddi R, Lukens J, Vogel P, Bertin J, Lamkanfi M, Kanneganti T. NLRP6 negatively regulates innate immunity and host defence against bacterial pathogens. Nature. 2012;488(7411): 389-93. PMID: 22763455 | PMCID: PMC3422416
  • Lukens J, Barr M, Chaplin D, Chi H, Kanneganti T. Inflammasome-derived IL-1β regulates the production of GM-CSF by CD4(+) T cells and γδ T cells. Journal of immunology (Baltimore, Md. : 1950). 2012;188(7): 3107-15. PMID: 22345669 | PMCID: PMC3758236
  • Lukens J, Gross J, Kanneganti T. IL-1 family cytokines trigger sterile inflammatory disease. Frontiers in immunology. 2012;3 315. PMID: 23087690 | PMCID: PMC3466588
  • Lukens J, Kanneganti T. Fat chance: not much against NKT cells. Immunity. 2012;37(3): 447-9. PMID: 22999952
  • Lukens J, Dixit V, Kanneganti T. Inflammasome activation in obesity-related inflammatory diseases and autoimmunity. Discovery medicine. 2011;12(62): 65-74. PMID: 21794210 | PMCID: PMC4266394
  • Shaw P, Barr M, Lukens J, McGargill M, Chi H, Mak T, Kanneganti T. Signaling via the RIP2 adaptor protein in central nervous system-infiltrating dendritic cells promotes inflammation and autoimmunity. Immunity. 2011;34(1): 75-84. PMID: 21236705 | PMCID: PMC3057380
  • Lassen M, Lukens J, Dolina J, Brown M, Hahn Y. Intrahepatic IL-10 maintains NKG2A+Ly49- liver NK cells in a functionally hyporesponsive state. Journal of immunology (Baltimore, Md. : 1950). 2010;184(5): 2693-701. PMID: 20124099 | PMCID: PMC2885840
  • Shaw P, Lukens J, Burns S, Chi H, McGargill M, Kanneganti T. Cutting edge: critical role for PYCARD/ASC in the development of experimental autoimmune encephalomyelitis. Journal of immunology (Baltimore, Md. : 1950). 2010;184(9): 4610-4. PMID: 20368281 | PMCID: PMC3001131
  • Lukens J, Dolina J, Kim T, Tacke R, Hahn Y. Liver is able to activate naïve CD8+ T cells with dysfunctional anti-viral activity in the murine system. PloS one. 2009;4(10): e7619. PMID: 19876399 | PMCID: PMC2764869
  • Lukens J, Cruise M, Lassen M, Hahn Y. Blockade of PD-1/B7-H1 interaction restores effector CD8+ T cell responses in a hepatitis C virus core murine model. Journal of immunology (Baltimore, Md. : 1950). 2008;180(7): 4875-84. PMID: 18354211 | PMCID: PMC2904552
  • Holub J, O'Toole-Colin K, Getzel A, Argenti A, Evans M, Smith D, Dalglish G, Rifat S, Wilson D, Taylor B, Miott U, Glersaye J, Lam K, McCranor B, Berkowitz J, Miller R, Lukens J, Krumpe K, Gupton J, Burnham B. Lipid-lowering effects of ethyl 2-phenacyl-3-aryl-1H-pyrrole- 4-carboxylates in rodents. Molecules (Basel, Switzerland). 2007;9(3): 134-57. PMID: 18007418
  • Hwang M, Lukens J, Bullock T. Cognate memory CD4+ T cells generated with dendritic cell priming influence the expansion, trafficking, and differentiation of secondary CD8+ T cells and enhance tumor control. Journal of immunology (Baltimore, Md. : 1950). 2007;179(9): 5829-38. PMID: 17947656
  • Cruise M, Lukens J, Nguyen A, Lassen M, Waggoner S, Hahn Y. Fas ligand is responsible for CXCR3 chemokine induction in CD4+ T cell-dependent liver damage. Journal of immunology (Baltimore, Md. : 1950). 2006;176(10): 6235-44. PMID: 16670334
  • Cruise M, Melief H, Lukens J, Soguero C, Hahn Y. Increased Fas ligand expression of CD4+ T cells by HCV core induces T cell-dependent hepatic inflammation. Journal of leukocyte biology. 2005;78(2): 412-25. PMID: 15894587