Prof Christopher Goodnow

Deputy Director, Lab Head - Immunogenomics

Conjoint/Adjunct Role(s)

The Bill and Patricia Ritchie Foundation Chair
NHMRC Australia Fellow
Adjunct Professor, John Curtin School of Medical Research, Australian National University
President, Australasian Society for Immunology

Chris Goodnow holds The Bill and Patricia Ritchie Foundation Chair and is NHMRC Australia Fellow, Head of the Immunogenomics lab and Deputy Director at the Garvan Institute of Medical Research in Sydney, Australia. He is known particularly for research using mouse molecular genetics that has illuminated how the body’s immune system learns to distinguish “self” from “not-self” so that it does not attack our own body or cause cancer while fighting off infections.

With an American father and Australian mother, Goodnow grew up in Washington DC before moving to Sydney as a teenager. He trained in veterinary medicine and surgery, immunochemistry, and immunology at the University of Sydney and in molecular biology at Stanford University. After doctoral studies begun at the Walter and Eliza Hall Institute in Melbourne and performed at Sydney University, he joined the faculty of Stanford University Medical School and the Howard Hughes Medical Institute in 1990. To pioneer large-scale genetic analysis of the immune system, he joined the faculty at the Australian National University in 1997 as Professor and Director of the Medical Genome Centre, leading its development into a Major National Research Facility, the Australian Phenomics Facility.

In 2015 Chris joined the Garvan Institute to translate genomic analysis of the human immune system into understanding the cause and treatment of immune disorders. He is also President of the Australasian Society for Immunology 2015-2016. His research contributions have been recognised by a number of awards, including American Association of Immunologists (AAI) Pharmingen Investigator Award, AAI Distinguished Lecturer, Australasian Society for Immunology Burnet Orator, Gottschalk Medal, Health Minister’s Prize, Centenary Medal, Ramaciotti Medal, GSK Award for Research Excellence, Fellow of the Australian Academy of Science, Fellow of the Royal Society, and Member of the US National Academy of Sciences.

Goodnow employs genome-wide mutation analysis as a principle tool to understand self-nonself discrimination by the immune system and illuminate the pathogenesis of autoimmune diseases, allergic diseases, immune deficiency diseases and cancer.  In inbred laboratory mice, he and his collaborators conduct large-scale genetic screens to reveal new genes and mechanisms of immune disease, successfully integrating whole exome and whole genome sequence analysis with cellular immunology. Recently he and his collaborators have embarked on a parallel approach to analyse immunological disease in humans, taking into account the much higher numbers of accumulated mutations in the human genome, by integrating whole exome or genome sequence analysis, immune cell analysis by flow cytometry and deep sequencing, and the capacity to test disease causation and mechanisms in mice.

Research Interests

Self-nonself discrimination by the immune system
The pathogenesis of autoimmune diseases, allergic diseases, immune deficiency diseases and cancer
Integration of whole exome and whole genome sequence analysis with cellular immunology

Awards and Honours

2013 - Member of the US National Academy of Science
2012 - Glaxo-Smith-Kline Award for Research Excellence
2010 - The Ramaciotti Medal
2010 - NHMRC Australia Fellow
2009 - Fellow of the Royal Society
2007 - Ramaciotti Major Research Award
2006 - ARC Federation Fellow
2006 - Centenary Medal
2005 - ISI Highly Cited Researcher
2005 - Health Minister’s Prize for Excellence in Medical Research
2002 - Fellow of the Australian Academy of Science
2001 - Gottschalk Medal, Australian Academy of Science
1998 - American Association of Immunologists Pharmingen Investigator Award
1992 - Searle Scholar
1990 - Investigator of the Howard Hughes Medical Institute
1989 - Medical Foundation Postdoctoral Fellowship
1986 - NH & MRC Biomedical Research Scholarship
1984 - Honours Class I with B.V.Sc. degree; Honours Class I and University Medal with B.Sc.(Vet) degree
1979 - John Gurner and Frederick Ebsworth Prize for Biology, University of Sydney

Education

1990 - PhD, University of Sydney - Australia
1984 - BVSc Hons I, and BSc(Vet) Hons I and University Medal, University of Sydney - Australia

Selected Publications

Highlights from 212 publications:

Goodnow CC & Ohashi PS. Immunological Tolerance. In Fundamental Immunology 7th Edition 2013. Editor Paul WE, Chapter 32, pp 765-794, NLM 101591462.

Wang JQ, Beutler B, Goodnow CC* & Horikawa K*. 2016. Inhibiting TLR9 and other UNC93B1-dependent TLRs paradoxically increases accumulation of MYD88L265P plasmablasts in vivoBlood (in press). *Equal senior and corresponding authors.

Reed JH, Jackson J, Christ D, Goodnow CC. 2016. Clonal redemption of autoantibodies by somatic hypermutation away from self-reactivity during human immunization. J Exp Med. 213:1255-65.

Andrews TD, Jeelall Y, Talaulikar D, Goodnow CC, Field MA. 2016. DeepSNVMiner: a sequence analysis tool to detect emergent, rare mutations in subsets of cell populations. PeerJ. 4:e2074.

Hillhouse EE, Liston A, Collin R, Desautels E, Goodnow CC, Lesage S. 2016. TCR transgenic mice reveal the impact of type 1 diabetes loci on early and late disease checkpoints. Immunol Cell Biol. Apr 5. doi: 10.1038/icb.2016.27. 

Dooley J, Tian L, Schonefeldt S, Delghingaro-Augusto V, Garcia-Perez JE, Pasciuto E, Di Marino D, Carr EJ, Oskolkov N, Lyssenko V, Franckaert D, Lagou V, Overbergh L, Vandenbussche J, Allemeersch J, Chabot-Roy G, Dahlstrom JE, Laybutt DR, Petrovsky N, Socha L, Gevaert K, Jetten AM, Lambrechts D, Linterman MA, Goodnow CC, Nolan CJ, Lesage S, Schlenner SM, Liston A. 2016. Genetic predisposition for beta cell fragility underlies type 1 and type 2 diabetes. Nature Genetics 48:519-27.

Field MA, Cho V, Andrews TD, Goodnow CC. 2015. Reliably Detecting Clinically Important Variants Requires Both Combined Variant Calls and Optimized Filtering Strategies. PLoS One. 10:e0143199.

Field MA, Andrews TD, Cho V, Cook MC, Enders A, Vinuesa C & Goodnow CC. 2015. Reducing the search space for causal genetic variants with VASP: Variant Analysis of Sequenced Pedigrees. Bioinformatics 31(14):2377-9.

Miosge L, Field MA, Sontani Y, Cho E, Johnson S, Palkova A, Balakishnan B, Liang R, Zhang Y, Lyon S, Beutler B, Whittle B, Betram E, Enders A, Goodnow CC* & Andrews TD* 2015. Comparison of predicted and actual consequences of missense mutations. Proc Natl Acad Sci USA 112:E5189-98. *Equal senior and corresponding authors.

Hu DY, Yap JY, Wirasinha RC, Howard DR, Goodnow CC, Daley SR. 2015. A timeline demarcating two waves of clonal deletion and Foxp3 up-regulation during thymocyte development. Immunol Cell Biol. 94(4):357-66.

Ramiscal RR, Parish IA, Lee-Young RS, Babon JJ, Blagih J, Pratama A, Martin J, Hawley N, Cappello JY, Nieto PF, Ellyard J, Kershaw NJ, Sweet RA, Goodnow CC, Jones RG, Febbraio MA, Vinuesa C, Athanasopoulos V. 2015. Attenuation of AMPK signaling by ROQUIN promotes T follicular helper cell formation. Elife. Oct 23;4. pii: e08698.

Wertz IE, Newton K, Kusam S, Seshasayee D, Lam C, Zhang J, Popovych N, Helgason E, Schoeffler A, Jeet S, Ramamoorthi N, Kategaya L, Newman RJ, Horikawa K, Dugger D, Sandoval W, Mukund S, Zindal A, Martin F, Quan C, Tom J, Fairbrother WJ, Townsend M, Warming S, DeVoss J, Dueber E, Caplazi P, Lee WP, Goodnow CC, Balazs M, Yu K, Kolumam G and Dixit VM. 2015. Phosphorylation and linear ubiquitination regulate A20 inhibition of inflammatory signaling. Nature 528:370-375.

Kayagaki N, Stowe IB, Lee BL, O’Rourke K, Anderson K, Warming S, Cuellar T, Haley B, Roose-Girma M, Phung QT, Liu PS, Lill JR, Li H, Wu J, Kummerfeld S, Zhang J, Lee WP, Snipas SJ, Salvesen GS, Morris LX, Fitzgerald L, Zhang Y, Bertram EM, Goodnow CC & Dixit VM. 2015. Gasdermin-D mediates LPS-induced non-canonical inflammasome signaling downstream of caspase-11. Nature (Article) 526:666-671.

Tangye SG, Brink R, Goodnow CC, Phan TG. 2015. SnapShot: Interactions between B Cells and T Cells. Cell 162:926-926.e1.

Lee CE, Fulcher DA, Whittle B, Chand R, Fewings N, Field M, Andrews D, Goodnow CC, Cook MC. Autosomal dominant B cell deficiency with alopecia due to a mutation in NFKB2 that results in non-processible p100. Blood 2014; Sep 18. pii: blood-2014-06-578542.

Sabouri Z, Schofield P, Horikawa K, Spierings E, Kipling D, Randall KL, Langley D, Roome B, Vazquez-Lombardi R, Rouet R, Hermes JR, Chan TD, Brink R, Dunn-Walters D, Christ D* and Goodnow CC*. Redemption of autoantibodies on anergic B cells by V-region glycosylation and mutation away from self-reactivity. Proc Natl Acad Sci USA 2014; 111:E2567-75. *Equal senior and corresponding authors. Accompanied by expert commentary: Haynes BF, Verkoczy L, Kelsoe G. “Redemption of autoreactive B cells” Proc Natl Acad Sci U S A 111(25):9022-3.

EndersA*, Short A, Miosge LA, Bergmann H, Sontani Y, Bertram EM, Whittle B, Balakishnan B, Yoshida K, Sjollema G, Field MA, Andrews TD, Hagiwara H & Goodnow CC*. Zinc-finger protein ZFP318 is essential for expression of IgD, the alternatively spliced Igh product made by mature B lymphocytes. Proc Natl Acad Sci USA 2014; 111:4513-4518. *Equal senior and corresponding authors.

Wang JQ, Jeelall YS, Beutler B, Horikawa K* & Goodnow CC*. Consequences of the recurrent MYD88L265P somatic mutation for B cell tolerance. J Exp Med 2014; 211:413-426. * Equal senior and corresponding authors.

Altin JA, Daley SR, Howitt J, Rickards HJ, Batkin AK, Horikawa K, Prasad SJ, Nelms KA, Kumar S, Wu LC, Tan S-S, Cook MC* & Goodnow CC*. Ndfip1 mediates peripheral tolerance to self and exogenous antigen by inducing cell cycle exit in responding CD4+ T cells. Proc Natl Acad Sci USA 2014; 111:2067-2074. * Equal senior and corresponding authors.

Daley SR, Hu DY & Goodnow CC. Helios marks strongly self-reactive CD4+ cells in two major waves of thymic deletion distinguished by induction of PD-1 or NF-κB. J Exp Med 2013; 210:269-85.

Jeelall YS, Wang JQ, Law HD, Domaschenz H, Fung HK, Kallies A, Nutt SL, Goodnow CC*, Horikawa K*. Human lymphoma mutations reveal CARD11 as the switch between self-antigen-induced B cell death or proliferation and autoantibody production. J Exp Med. 2012; 209:1907-17. *Equal senior authors.

Andrews TD, Whittle B, Field MA, Balakishnan B, Zhang Y, Shao Y, Cho V, Kirk M, Singh M, Xia Y, Hager J, Winslade S, Sjollema G, Beutler B, Enders A, Goodnow CC. Massively parallel sequencing of the mouse exome to accurately identify rare, induced mutations: an immediate source for thousands of new mouse models. Open Biol. 2012; 2:120061.

Teh CE, Daley SR, Enders A, Goodnow CC. T-cell regulation by casitas B-lineage lymphoma (Cblb) is a critical failsafe against autoimmune disease due to autoimmune regulator (Aire) deficiency. Proc Natl Acad Sci USA 2010; 107:14709-14.

Randall KL, Lambe T, Johnson A, Treanor B, Kucharska E, Domaschenz H, Whittle B, Tze LE, Enders A, Crockford TL, Bouriez-Jones T, Alston D, Cyster JG, Lenardo MJ, Mackay F, Deenick EK, Tangye SG, Chan TD, Camidge T, Brink R, Vinuesa CG, Batista FD, Cornall RJ, Goodnow CC. Dock8 mutations cripple B cell immunological synapses, germinal centers and long-lived antibody production. Nature Immunol. 2009; 10:1283-91. Accompanied by expert commentary: “B cell memory: how to start and when to end” N Pelletier1 & MG McHeyzer-Williams, Nature Immunology 10, 1233 – 1235.

Wu Z, Jia X, de la Cruz L, Su X, Marzolf B, Troisch P, Zak D, Hamilton A, Whittle B, Yu D, Sheahan D, Bertram E, Aderem A, Otting G, Goodnow CC* & Hoyne GF. Memory T cell RNA rearrangement programmed by heterogeneous nuclear ribonucleoprotein hnRNPLL.  Immunity 2008; 29:863-875. *corresponding author and equal senior author (cover article).

Siggs OM, Miosge LA, Yates AL, Kucharska EM, Sheahan D, Brdicka T, Weiss A, Liston A, Goodnow CC. Opposing functions of the T cell receptor kinase ZAP-70 in immunity and tolerance differentially titrate in response to nucleotide substitutions. Immunity 2007; 27:912-26.

Yu D, Tan A, Hu X, Athanasopoulos V, Hutloff A, Lam KP, Simpson N, Giles KM, Leedman PJ, Goodnow CC* & Vinuesa CG*. Roquin represses autoimmunity by limiting T cell Inducible CoStimulator mRNA.  Nature 2007; 450:299-305. *Equal senior authors.

Goodnow CC. Multistep pathogenesis of autoimmune disease. Cell 2007; 130:25-35.

Nijnik A, Woodbine L, Marchetti C Dawson S, Lambe T, Liu C, Rodrigues N, Crockford TL, Cabuy E, Vindigni A, Enver T, Bell JI, Slijepcevic P, *Goodnow CC, *Jeggo PA, *Cornall R. DNA repair is limiting for haematopoietic stem cells during ageing.  Nature (Article) 2007; 447:686-90. *Equal senior authors. Accompanied by expert commentary: “Ageing: from stem to stern.” Brunet A, Rando TA. Nature. 2007 449:288-91.

Horikawa K, Martin SW, Pogue SL, Peng K, Takatsu K & Goodnow CC. Enhancement and suppression of signaling by the conserved tail of IgG memory-type B cell antigen receptors.  J Exp Med 2007; 204:759-69.

Blery M, Tze L, Miosge LA, Jun JE, Goodnow CC. Essential role of membrane cholesterol in accelerated BCR internalization and uncoupling from NF-kB in B cell clonal anergy. J Exp Med. 2006; 203:1773-83.

Vinuesa CG, Cook MC, Angelucci C, Athanasopoulos V, Rui L, Hill KM, Yu D, Domaschenz H, Whittle B, Lambe T, Roberts IS, Copley RR, Bell JI, Cornall RJ & Goodnow CC. A RING-type ubiquitin ligase family member essential to repress follicular helper T cells and autoimmunity.  Nature (Article) 2005; 435: 452-458.

Liston A, Lesage S, Gray D, O’Reilly L, Strasser A, Fahrer A, Boyd RL, Wilson J, Baxter AG, Gallo E, Crabtree GR, Peng K, Wilson SR & Goodnow CC. Generalised resistance to thymic deletion in the NOD mouse: a polygenic trait characterized by defective induction of BIM. Immunity 2004; 21:817-30.

Liston A, Lesage S, Wilson J, Peltonen L, Goodnow CC. Aire regulates negative selection of organ-specific T cells. Nature Immunol 2003; 4, 350-354.

Jun, J.E., Wilson, L.E., Vinuesa, C.G., Lesage, S., Blery, M., Miosge, L.A., Cook, M.C., Kucharska, E.M., Hara, H., Penninger, J.M., Domaschenz, H., Hong, N.A., Glynne, R.J., Nelms, K.A., and Goodnow, C.C. Identifying the MAGUK protein CARMA-1 as a central regulator of humoral immune responses and atopy by genome-wide mouse mutagenesis. Immunity 2003: 18:751-762.

Martin SW, Goodnow CC. Burst-enhancing role of the IgG membrane tail as a molecular determinant of memory.  Nature Immunol. 2002; 3:182-8.

Glynne, R., Akkaraju, S., Healy, J.I., Rayner, J., Goodnow, C.C*. & Mack, D. How self-tolerance and the immunosuppressive drug FK506 prevent B cell mitogenesis. Nature 2000; 403:672-676. (*Corresponding senior author).

Cornall, R.J.,  Cyster, J.G., Hibbs, M.L., Dunn, A.R., Otipoby, K.L., Clark, E.A.  & Goodnow, C.C. Polygenic autoimmune traits:  Lyn, CD22, and SHP-1 are limiting elements of a biochemical pathway regulating BCR signaling and selection.  Immunity 1998; 8, 497-508.

Dolmetsch, R.E., Lewis, R.S*, Goodnow, C.C*. & Healy, J.I. Differential activation of transcription factors induced by Ca2+ response amplitude and duration.  Nature 1997; 386, 855-858. (*Equal senior authors)

Healy, J.I., Dolmetsch, R.E., Timmerman, L.A., Cyster, J.G.,  Thomas, M.L., Crabtree, G.R., Lewis, R.S. & Goodnow, C.C. Different nuclear signals are activated by the B cell receptor during positive versus negative signaling.  Immunity 1997; 6, 419-428.

Rathmell, J.C., Townsend, S.E., Xu, JC, Flavell, R.A. & Goodnow, C.C.  Expansion or elimination of B cells in vivo:  dual roles for CD40- and Fas (CD95)-ligands modulated by the B cell antigen receptor.  Cell 1996; 87, 319-329.

Shokat, K.M. & Goodnow, C.C. Antigen-induced B cell death and elimination during germinal center immune responses  Nature 1995; 375, 334-338.

Cyster, J.G., Hartley, S.B.  & Goodnow C.C. Competition for follicular niches excludes self-reactive cells from the recirculating B cell repertoire.  Nature  1994; 371, 389-395.  (IF 29.3, cited 399)

Hartley, S.B., Cooke, M.P., Fulcher, D.A., Harris, A.W., Cory, S., Basten, A. & Goodnow, C.C. Elimination of self-reactive B lymphocytes proceeds in two stages:  arrested development and cell death.  Cell  1993; 72, 325-335.

Hartley, S.B., Crosbie, J., Brink, R., Kantor, A.B., Basten, A. & Goodnow, C.C. Elimination from peripheral lymphoid tissues of self-reactive B lymphocytes recognizing membrane-bound antigens.  Nature 1991; 353, 765-769.

Goodnow, C.C.,  Crosbie, J.,  Jorgensen, H.,  Brink, R.A.  &  Basten, A. Induction of self-tolerance in mature peripheral B lymphocytes.  Nature  1989; 342, 385-391.

Goodnow, C.C.,  Crosbie, J.,  Adelstein, S.,  Lavoie, T.B.,  Smith-Gill, S.J.,  Brink, R.A.,  Pritchard-Briscoe, H.,  Wotherspoon, J.W.,  Loblay, R.H.,  Raphael, K.,  Trent, R.J.  & Basten, A. Altered immunoglobulin expression and functional silencing of self-reactive B-lymphocytes in transgenic mice Nature 1988; 334, 676-682.  (reprinted as “Pillars of Immunology” article 2009, J Immunol. 183: 5439–5441.)

Prof Christopher Goodnow