Dr Kendle Maslowski - Microbial and Metabolic Immune Modulation
Introduction
New therapies that target immune responses to kill tumours are an area of rapid growth and hope. While immune checkpoint blockade therapy has led to dramatic improvement for some patients, it still is not applicable for the majority of people affected by cancer. Challenges for immune therapies include poor immune infiltration of tumours, an inhibitory tumour microenvironment as well as immune-related toxicities.
The immune system protects us from infectious agents such as bacteria, viruses and fungi, as well as from malignant growth of our own tissues. Our lab is interested in the intersection between anti-bacterial and anti-tumour responses. Our bodies have both positive (commensals) and negative (pathogenic) interactions with bacteria. On the one hand, microbes that form our gut microbiota are important for instructing and regulating our immune system; While on the other, pathogenic or opportunistic microbes can deviate and manipulate our immune responses to aid their survival and spread, and even be involved in pro-tumourigenic processes.
The concept of bacterial cancer therapy dates to William Coley, who developed ‘Coley’s toxins’, a preparation of heat killed bacteria injected into tumours. Our work largely focuses on the use of live-attenuated Salmonella as a cancer therapy; we are dissecting the mechanisms by which attenuated Salmonella treatment leads to tumour regression, looking at the adaptation of the bacteria to the tumour environment, and the effects on cancer cells and on immune responses. With a detailed mechanistic understanding of bacterial therapy, we aim to achieve optimal engineering of Salmonella to advance towards clinical application.
EmailLab Report
Key Publications
Copland A, Mackie GM, Scarfe L, Lecky DAJ, Gudgeon N, McQuade R, Ono M, Barthel M, Hardt W-D, Ohno H, Dimeloe S, Bending D, Maslowski KM. Salmonella cancer therapy metabolically disrupts tumours at the collateral cost of T cell immunity. bioRxiv. 2023;10.1101/2023.01.12.523780:2023.2001.2012.523780.
Mackie GM, Copland A, Takahashi M, Nakanishi Y, Everard I, Kato T, Oda H, Kanaya T, Ohno H, Maslowski KM. Bacterial cancer therapy in autochthonous colorectal cancer affects tumor growth and metabolic landscape. JCI Insight. 2021;6.
Maslowski KM. Metabolism at the centre of the host-microbe relationship. Clin Exp Immunol. 2019;197:193-204.
Allam R, Maillard MH, Tardivel A, Chennupati V, Bega H, Yu CW, Velin D, Schneider P, Maslowski KM. Epithelial NAIPs protect against colonic tumorigenesis. J Exp Med. 2015;212:369-383
Maslowski KM, Vieira AT, Ng A, Kranich J, Sierro F, Yu D, Schilter HC, Rolph MS, Mackay F, Artis D, Xavier RJ, Teixeira MM, Mackay CR. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature. 2009;461:1282-1286.
Biography
Education and qualifications
2011: PhD, University of New South Wales, Sydney, Australia; Supervisor: Prof Charles Mackay, Project: The role of GPR43 in the immune system: a novel connection between diet, gut microbiota and immune function
2006: BSc with Honours, Molecular Biology, Murdoch University, Perth, Australia
2005: BSc, Molecular Biology, Murdoch University, Perth, Australia
Appointments
2023-present: Beatson Research Fellow, CRUK Career Development Fellow, CRUK Scotland Institute, Glasgow, UK
2022-2023: Associate Professor and CRUK Career Establishment Fellow, Institute of Immunology and Immunotherapy, University of Birmingham, UK
2017-2022: Birmingham Fellow and CRUK Career Establishment Fellow, Institute of Immunology and Immunotherapy, University of Birmingham, UK
2014-2017: Postdoctoral Researcher with Prof Hiroshi Ohno, RIKEN, Centre for Integrative Medical Sciences, Yokohama, Japan
2011-2014: Postdoctoral Researcher with Prof Jürg Tschopp, Department of Biochemistry, University of Lausanne, Switzerland
2007-2007: Research Assistant with Prof Charles Mackay, Garvan Institute of Medical Research, Sydney, Australia
Recent Publications
2023
Copland A, Mackie GM, Scarfe L, Lecky DAJ, Gudgeon N, McQuade R, Ono M, Barthel M, Hardt W-D, Ohno H, Dimeloe S, Bending D, Maslowski KM. Salmonella cancer therapy metabolically disrupts tumours at the collateral cost of T cell immunity. bioRxiv. 2023;10.1101/2023.01.12.523780:2023.2001.2012.523780.
Fisch D, Pfleiderer MM, Anastasakou E, Mackie GM, Wendt F, Liu X, Clough B, Lara-Reyna S, Encheva V, Snijders AP, Bando H, Yamamoto M, Beggs AD, Mercer J, Shenoy AR, Wollscheid B, Maslowski KM, Galej WP, Frickel EM. PIM1 controls GBP1 activity to limit self-damage and to guard against pathogen infection. Science. 2023;382(6666):eadg2253.
2022
Bishop EL, Gudgeon NH, Mackie GM, Chauss D, Roberts J, Tennant DA, Maslowski KM, Afzali B, Hewison M, Dimeloe S. 1,25-Dihydroxyvitamin D3 suppresses CD4(+) T-cell effector functionality by inhibition of glycolysis. Immunology. 2022;166:299-309.
Bombaci G, Sarangdhar MA, Andina N, Tardivel A, Yu EC, Mackie GM, Pugh M, Ozan VB, Banz Y, Spinetti T, Hirzel C, Youd E, Schefold JC, Taylor G, Gazdhar A, Bonadies N, Angelillo-Scherrer A, Schneider P, Maslowski KM, Allam R. LRR-protein RNH1 dampens the inflammasome activation and is associated with COVID-19 severity. Life Sci Alliance. 2022;5.
Elliot TAE, Jennings EK, Lecky DAJ, Rouvray S, Mackie GM, Scarfe L, Sheriff L, Ono M, Maslowski KM, Bending D. Nur77-Tempo mice reveal T cell steady state antigen recognition. Discov Immunol. 2022;1:kyac009.
2021
Elliot TAE, Jennings EK, Lecky DAJ, Thawait N, Flores-Langarica A, Copland A, Maslowski KM, Wraith DC, Bending D. Antigen and checkpoint receptor engagement recalibrates T cell receptor signal strength. Immunity. 2021;54:2481-2496.e2486.
Mackie GM, Copland A, Takahashi M, Nakanishi Y, Everard I, Kato T, Oda H, Kanaya T, Ohno H, Maslowski KM. Bacterial cancer therapy in autochthonous colorectal cancer affects tumor growth and metabolic landscape. JCI Insight. 2021;6.
Scarfe L, Mackie GM, Maslowski KM. Inflammasome-independent functions of NAIPs and NLRs in the intestinal epithelium. Biochem Soc Trans. 2021;49:2601-2610.
2020
Sasaki N, Miyamoto K, Maslowski KM, Ohno H, Kanai T, Sato T. Development of a Scalable Coculture System for Gut Anaerobes and Human Colon Epithelium. Gastroenterology. 2020;159:388-390.e385.
2019
Maslowski KM. Metabolism at the centre of the host-microbe relationship. Clin Exp Immunol. 2019;197:193-204.
2018
Chennupati V, Veiga DF, Maslowski KM, Andina N, Tardivel A, Yu EC, Stilinovic M, Simillion C, Duchosal MA, Quadroni M, Roberts I, Sankaran VG, MacDonald HR, Fasel N, Angelillo-Scherrer A, Schneider P, Hoang T, Allam R. Ribonuclease inhibitor 1 regulates erythropoiesis by controlling GATA1 translation. J Clin Invest. 2018;128:1597-1614.
2015
Allam R, Maillard MH, Tardivel A, Chennupati V, Bega H, Yu CW, Velin D, Schneider P, Maslowski KM. Epithelial NAIPs protect against colonic tumorigenesis. J Exp Med. 2015;212:369-383
Vieira AT, Macia L, Galvão I, Martins FS, Canesso MC, Amaral FA, Garcia CC, Maslowski KM, De Leon E, Shim D, Nicoli JR, Harper JL, Teixeira MM, Mackay CR. A Role for Gut Microbiota and the Metabolite-Sensing Receptor GPR43 in a Murine Model of Gout. Arthritis Rheumatol. 2015;67:1646-1656.
Sellin ME, Maslowski KM, Maloy KJ, Hardt WD. Inflammasomes of the intestinal epithelium. Trends Immunol. 2015;36:442-450.
2014
Scott C, Bonner J, Min D, Boughton P, Stokes R, Cha KM, Walters SN, Maslowski K, Sierro F, Grey ST, Twigg S, McLennan S, Gunton JE. Reduction of ARNT in myeloid cells causes immune suppression and delayed wound healing. Am J Physiol Cell Physiol. 2014;307:C349-357.
Sellin ME, Müller AA, Felmy B, Dolowschiak T, Diard M, Tardivel A, Maslowski KM, Hardt WD. Epithelium-intrinsic NAIP/NLRC4 inflammasome drives infected enterocyte expulsion to restrict Salmonella replication in the intestinal mucosa. Cell Host Microbe. 2014;16:237-248.
2013
Zaiss MM, Maslowski KM, Mosconi I, Guenat N, Marsland BJ, Harris NL. IL-1β suppresses innate IL-25 and IL-33 production and maintains helminth chronicity. PLoS Pathog. 2013;9:e1003531.
Michallet MC, Rota G, Maslowski K, Guarda G. Innate receptors for adaptive immunity. Curr Opin Microbiol. 2013;16:296-302.
2012
Macia L, Thorburn AN, Binge LC, Marino E, Rogers KE, Maslowski KM, Vieira AT, Kranich J, Mackay CR. Microbial influences on epithelial integrity and immune function as a basis for inflammatory diseases. Immunol Rev. 2012;245:164-176
2011
Kranich J, Maslowski KM, Mackay CR. Commensal flora and the regulation of inflammatory and autoimmune responses. Semin Immunol. 2011;23:139-145.
Maslowski KM, Mackay CR. Diet, gut microbiota and immune responses. Nat Immunol. 2011;12:5-9.
2009
Maslowski KM, Vieira AT, Ng A, Kranich J, Sierro F, Yu D, Schilter HC, Rolph MS, Mackay F, Artis D, Xavier RJ, Teixeira MM, Mackay CR. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature. 2009;461:1282-1286.
