{"id":269,"date":"2015-09-08T09:34:56","date_gmt":"2015-09-08T13:34:56","guid":{"rendered":"https:\/\/med.virginia.edu\/neuroscience\/?page_id=269"},"modified":"2024-09-18T16:12:19","modified_gmt":"2024-09-18T20:12:19","slug":"john-lukens-ph-d","status":"publish","type":"page","link":"https:\/\/med.virginia.edu\/neuroscience\/faculty\/primary-faculty\/john-lukens-ph-d\/","title":{"rendered":"John Lukens, Ph.D."},"content":{"rendered":"

\"John_Lukens_2016\"<\/p>\n

Assistant Professor<\/p>\n

B.S., 2003 University of Richmond<\/p>\n

Ph.D., 2008 University of Virginia<\/p>\n

Postdoctoral Research, 2008-2014<\/p>\n

St. Jude Children’s Research Hospital
\nJohn.Lukens@virginia.edu<\/a><\/p>\n

Lukens Lab website<\/a><\/p>\n

 <\/p>\n

Research in the Lukens Laboratory<\/p>\n

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.\u00a0To 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.<\/p>\n

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 ,<\/ins> the mechanisms by which the microbiome can influence CNS disease pathogenesis remain\u00a0poorly defined. In our lab ,<\/ins> we are investigating how microbiota-dependent control of immune responses specifically influences neurological disease pathogenesis, CNS function and mental health.<\/p>\n

Effective treatment strategies are desperately needed for most CNS diseases including Alzheimer\u2019s 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.\u00a0 In the Lukens laboratory,<\/ins> 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.<\/p>\n

 <\/p>\n

Research Interests:<\/p>\n

(1)\u00a0\u00a0 Roles and regulation of IL-1 family cytokines in neurodegenerative disorders and CNS injury.<\/p>\n

(2)\u00a0\u00a0 Control of demyelinating neuroinflammation by innate immune sensors.<\/p>\n

(3)\u00a0\u00a0 Investigation of how microbiome-dependent regulation of immune re s<\/ins>ponses influences cognition, behavior, mental health and neurodegenerative disease.<\/p>\n

(4)\u00a0\u00a0 Regulation of glia cell function by inflammatory caspases.<\/p>\n

(5)\u00a0\u00a0 Identification of the innate signaling pathways that are required to mount protective immune responses against CNS pathogens.<\/p>\n

 <\/p>\n

Selected Publications<\/p>\n

Gadani SP, Walsh JT,\u00a0Lukens JR<\/strong>*<\/sup>, Kipnis J*<\/sup>. Dealing with danger in the CNS: The response of the immune system to injury<\/a>.\u00a0Neuron<\/em><\/strong>. 2015 Jul 1;87(1):47-62. * Co-corresponding author<\/p>\n

Lukens JR<\/strong>, Gurung P, Shaw PJ, Barr MJ, Zaki MH, Brown SA, Vogel P, Chi H, Kanneganti TD. The NLRP12 sensor negatively regulates autoinflammatory disease by modulating interleukin-4 production in T cells.<\/a>\u00a0Immunity<\/em><\/strong>. 2015 Apr 21;42(4):654-64.<\/p>\n

Walsh JT, Hendrix S, Boato F, Smirnov I, Zheng J,\u00a0Lukens JR<\/strong>, Gadani S, Hechler D, G\u00f6lz G, Rosenberger K, Kammert\u00f6ns T, Vogt J, Vogelaar C, Siffrin V, Radjavi A, Fernandez-Castaneda A, Gaultier A, Gold R, Kanneganti TD, Nitsch R, Zipp F, Kipnis J. MHCII-independent CD4+ T cells protect injured CNS neurons via IL-4.<\/a>\u00a0\u00a0J Clin Invest<\/strong>. 2015 Feb;125(2):699-714.<\/p>\n

Gurung P,\u00a0Lukens JR<\/strong>, Kanneganti TD. Mitochondria: diversity in the regulation of the NLRP3 inflammasome.<\/a>\u00a0Trends Mol Med<\/strong>. 2015 Mar;21(3):193-201.<\/p>\n

Lukens JR<\/strong>, Gurung P, Vogel P, Johnson RG, Carter RA, McGoldrick DJ, Bandi SR, Calabrese CR, Vande Walle L, Lamkanfi M, Kanneganti TD. Dietary modulation of the microbiome affects autoinflammatory disease<\/a>. Nature<\/i><\/strong>. DOI: 10.1038\/nature13788. PMID:25274309.<\/p>\n

Lukens JR<\/strong>, Kanneganti TD. Beyond canonical inflammasomes: emerging pathways in IL-1-mediated autoinflammatory disease<\/a>. Seminars in Immunopathology<\/i><\/strong>. 2014. Sep;36(5):595-609.<\/p>\n

Lukens JR<\/strong>, Gross JM, Calabrese CR, Iwakura Y, Lamkanfi M, Vogel P, Kanneganti TD.\u00a0 Critical role for inflammasome-independent IL-1b production in osteomyelitis.<\/a> PNAS<\/strong><\/i>.\u00a0 2014 Jan 21;111(3):1066-71.<\/p>\n

Lukens JR<\/strong>, Kanneganti TD. SHP-1 and IL-1a conspire to provoke neutrophilic dermatoses<\/a>.\u00a0 Rare Diseases<\/i><\/strong>. 2014 Jan; 2(1): 1-5 e27742. doi: 10.4161\/rdis.27742.<\/p>\n

Weinlich R, Oberst A, Dillon CP, Janke LJ, Milasta S, Lukens JR<\/strong>, Rodriguez DA, Gurung P, Savage C, Kanneganti TD, Green DR. Protective Roles for Caspase-8 and cFLIP in Adult Homeostasis<\/a>. Cell Reports<\/i><\/strong>. 2013 Oct 2. doi:pii: S2211-1247(13)00505-6.<\/p>\n

Lukens JR<\/strong>, Vogel P, Johnson GR, Kelliher MA, Iwakura Y, Lamkanfi M, Kanneganti TD.\u00a0 RIP1-driven autoinflammation targets IL-1a independently of inflammasomes and RIP3<\/a>.\u00a0 Nature<\/i><\/strong>. 2013 Jun 13;498(7453):224-7.<\/p>\n

Lukens JR<\/strong>, Gross JM, Kanneganti TD. IL-1 family cytokines trigger sterile inflammatory disease.<\/a> Front Immunol<\/i><\/strong>. 2012;3:315.<\/p>\n

Lukens JR<\/strong>, Kanneganti TD. Fat chance: not much against NKT cells.<\/a> Immunity<\/i><\/strong>. 2012 Sep 21;37(3):447-9.<\/p>\n

Anand PK, Malireddi RK, Lukens JR<\/strong>, Vogel P, Bertin J, Lamkanfi M, Kanneganti TD. NLRP6 negatively regulates innate immunity and host defence against bacterial pathogens.<\/a> Nature<\/i><\/strong>. 2012 Aug 16;488(7411):389-93.<\/p>\n

Lukens JR<\/strong>, Barr MJ, Chaplin DD, Chi H, Kanneganti TD.\u00a0 Inflammasome-derived IL-1b and the IL-1R1\/MYD88 signaling axis regulate the production of GM-CSF by CD4+<\/sup> T cells and \u03b3\u03b4 T cells. J Immunol<\/i><\/strong>. 2012 Apr 1;188(7):3107-15.\u00a0 *<\/sup>JI Author Choice Article.<\/p>\n

Lukens JR<\/strong>, Dixit VD, Kanneganti TD.\u00a0 Inflammasome activation in obesity-related inflammatory diseases and autoimmunity.<\/a> Discovery Medicine<\/i><\/strong>. 2011 Jul;12(62):65-74.<\/p>\n

Shaw PJ, Barr MJ, Lukens JR<\/strong>, McGargill MA, Chi H, Mak TW, Kanneganti TD.\u00a0 Signaling via the RIP2 adaptor protein in central nervous system-infiltrating dendritic cells promotes inflammation and autoimmunity.<\/a> Immunity<\/i><\/strong>. 2011 Jan 28;34(1):75-84.<\/p>\n

Shaw PJ, Lukens JR<\/strong>, Burns S, Chi H, McGargill MA, Kanneganti TD.\u00a0 Cutting edge: Critical role for PYCARD\/ASC in the development of experimental autoimmune encephalomyelitis.<\/a> J Immunol<\/i><\/strong>. 184(9):4610-4614, 2010.<\/p>\n

Lassen MG, Lukens JR<\/strong>, Dolina JS, Brown MG, Hahn YS.\u00a0 Intrahepatic IL-10 maintains NKG2A+Ly49- liver NK cells in a functionally hyporesponsive state.<\/a> J Immunol<\/i><\/strong>. 184(5):2693-2701, 2010.<\/p>\n

Lukens JR<\/strong>, Dolina JS, Kim TS, Tacke RS, Hahn YS. Liver is able to activate na\u00efve CD8+ T cells with dysfunctional anti-viral activity in the murine system.<\/a> PLoS One<\/i><\/strong>. 4(10):e7619, 2009.<\/p>\n

Lukens JR<\/strong>, Cruise MW<\/a>, Lassen MG<\/a>, Hahn YS<\/a>. Blockade of PD-1\/B7-H1 interaction restores effector CD8+ T cell responses in a hepatitis C virus core murine model.<\/a> J Immunol<\/i><\/strong>. 180(7):4875-4884, 2008.<\/p>\n

Hwang ML, Lukens JR<\/strong><\/a>,<\/strong> Bullock TN<\/a>. 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.<\/a> J Immunol<\/i><\/strong>. 179(9):5829-5838, 2007.<\/p>\n

Cruise MW, Lukens JR<\/strong>, Nguyen AP, Lassen MG, Waggoner SN, Hahn YS.\u00a0 Fas ligand is responsible for CXCR3 chemokine induction in CD4+ T cell-dependent liver damage.<\/a> J Immunol<\/i><\/strong>. 176(10):6235-6244, 2006.<\/p>\n

Cruise MW, Melief HM, Lukens J<\/strong>, Soguero C, Hahn YS.<\/a> Increased Fas ligand expression of CD4+ T cells by HCV core induces T cell-dependent hepatic inflammation.<\/a> J Leukoc Biol<\/i><\/strong>. 78(2):412-425, 2005.<\/p>\n

Cruise MW, Lukens JR<\/strong>, Hahn YS.\u00a0 Hepatitis C virus\u2019s immune evasion strategies. Curr Immunol Rev<\/i><\/strong>. 1(3):223-236, 2005.<\/p>\n

Holub JM, O’Toole-Colin K, Getzel A, Argenti A, Evans MA, Smith DC, Dalglish GA, Rifat S, Wilson DL, Taylor BM, Miott U, Glersaye J, Lam KS, McCranor BJ, Berkowitz JD, Miller RB, Lukens JR<\/strong>, Krumpe K, Gupton JT, Burnham BS. Lipid-lowering effects of ethyl 2-phenacyl-3-aryl-1H-pyrrole- 4-carboxylates in rodents.<\/a> Molecules<\/i><\/strong>. 9(3):134-157, 2004.<\/p>\n

Gupton J, Clough S, Miller R, Lukens J<\/strong>, Henry C, Kanters R, Sikorski J.\u00a0 The application of vinylogous iminium salt derivatives to the synthesis of ningalin B hexamethyl ether.\u00a0 Tetrahedron<\/i><\/strong>. 59:207-215, 2003.
\nContact<\/strong><\/p>\n

John Lukens, Ph.D.
\nAssistant Professor
\nDepartment of Neuroscience
\nCenter for Brain Immunology and Glia
\nUniversity of Virginia
\n409 Lane Road, MR4- 6102
\nCharlottesville VA 22908
\nLab: \u00a0434-924-7781
\nOffice: \u00a0434-924-7782
\nJohn.Lukens@virginia.edu<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

Assistant Professor B.S., 2003 University of Richmond Ph.D., 2008 University of Virginia Postdoctoral Research, 2008-2014 St. Jude Children’s Research Hospital John.Lukens@virginia.edu Lukens Lab website   Research in the Lukens Laboratory Our laboratory is focused on understanding how immunological pathways contribute to neurodegenerative, neurodevelopmental, mental and behavior disorders. 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