Dr Marcel Doerflinger, Lab Head | WEHI Researcher Profile

Q: Defining novel treatment paradigms for tuberculosis

Mycobacterium tuberculosis (Mtb) chronically infects phagocytes in the lung, and our project aims at developing novel RNA-based therapeutics that disarm Mtbs armoury of virulence factors and induce apoptosis to boost immunity.

Q: Deciphering the role and regulation of Caspases in COVID-19 disease

Programmed cell death and inflammation appear to be involved in COVID-19 disease outcomes, and our project aims to identify which key players contribute to or mitigate pathology and present avenues for therapeutic intervention.

Q: Developing and assessing novel therapies against chronic HIV infection

Despite the success of antiretroviral therapy (ART) in suppressing acute HIV infection, there is no curative intervention that rids the body of the latent HIV reservoir. Our strategy of inducing cell death to kill this ‘needle in a haystack’ aims to overcome the lifelong treatment of patients with a pill every day.

Q: Host-directed therapies for Dengue disease.

Dengue fever is a vector borne viral disease and an increasing global health threat that necessitates the urgent development of new therapies. The most severe symptoms of Dengue appear to a result of dysregulated host immune response, and our work aims to understand the host factors that drive disease and toidentify novel treatment targets.

Q: Developing new diagnostics and therapeutics for HTLV-1

HTLV-1 is a virus that causes severe disease sequelae including leukemia, myelopathy and secondary bacterial lung infections. HTLV-1 is highly endemic in remote indigenous communities in rural Australia, There is no treatment and no point-of-care diagnostic tests available to detect this pathogen in the field.

Q: Immune profiling in adult and pediatric cancer patients

Cancer patients are at increased risk of infection due to immunesupression as a result of their chemotherapy. Tests that can identify the patients at risk of severe infectious complications will enable rapid and customized treatment.

About

Dr Doerflinger completed a Master of Science Degree with focus on Biochemistry and Immunology at the University of Stuttgart, Germany. Dr Doerflinger then moved to Australia in February 2012 to undertake PhD studies under the supervision of Associate Professor Hamsa Puthalakath at La Trobe University, and their work on cell death regulation resulted in several first author publications.

In 2016, they took up a position as Postdoctoral Fellow in the Pellegrini laboratory at WEHI, where they expanded their skillset and career focus towards translational outcomes and have built productive collaborative networks nationally (such as The Peter Doherty Institute, Hudson Institute, La Trobe University, Peter MacCallum Cancer Centre, MCRI and The Florey) and internationally (Austria, Germany, Japan, US).

Dr Doerflinger has recently been appointed Laboratory Head at WEHI and in this role oversees the PC3 facility within the Infectious Diseases and Immune Defense division. This is the basis to lead a comprehensive research program in which Dr Doerflinger continues to uncover the regulatory processes of programmed cell death processes and their contribution to shaping immune responses to infection.

Education

Publications

Selected publications from Dr Marcel Doerflinger

M. Bader S, Calleja DJ, Devine SM, Kuchel NW, Lu BGC, Wu X, Birkinshaw RW, Bhandari R, Loi K, Volpe R, Khakham Y, Au AE, Blackmore TR, Mackiewicz L, Dayton M, Schaefer J, Scherer L, Stock AT, Cooney JP, Schoffer K, Maluenda A, Kleeman EA, Davidson KC, Allison CC, Ebert G, Chen G, Katneni K, Klemm TA, Nachbur U, Georgy SR, Czabotar PE, Hannan AJ, Putoczki TL, Tanzer M, Pellegrini M, Lechtenberg BC, Charman SA, Call MJ, Mitchell JP, Lowes KN, Lessene G, Doerflinger M, Komander D. A novel PLpro inhibitor improves outcomes in a pre-clinical model of long COVID. Nature Communications. 2025;16(1):10.1038/s41467-025-57905-4

M. Bader S, Scherer L, Schaefer J, Cooney JP, Mackiewicz L, Dayton M, Georgy SR, Davidson KC, Allison CC, Herold MJ, Strasser A, Pellegrini M, Doerflinger M. IL-1β drives SARS-CoV-2-induced disease independently of the inflammasome and pyroptosis signalling. Cell Death & Differentiation. 2025;:10.1038/s41418-025-01459-x

Reynolds GK, Williams L, Anderson MA, Dowling MR, Minson A, Dickinson MJ, Thursky KA, Harrison SJ, Slavin MA, Doerflinger M, Teh BW. Predicting Risk of Infection in Patients Receiving CAR-T for Aggressive Lymphoma: A Study Exploring the Utility of Immune Profiling. Blood. 2024;144(Supplement 1):10.1182/blood-2024-203133

Reynolds GK, Williams L, Anderson MA, Dowling MR, Minson A, Dickinson MJ, Thursky KA, Harrison SJ, Slavin MA, Doerflinger M, Teh BW. Longitudinal Cytokine Expression in Aggressive Lymphoma Patients Treated with CAR-T: Applications of Immune Profiling to CAR-T. Blood. 2024;144(Supplement 1):10.1182/blood-2024-202836

Wang TT, Hirons A, Doerflinger M, Morris KV, Ledger S, Purcell DFJ, Kelleher AD, Ahlenstiel CL. Current State of Therapeutics for HTLV-1. Viruses. 2024;16(10):10.3390/v16101616

Muhi S, Buultjens AH, Porter JL, Marshall JL, Doerflinger M, Pidot SJ, O’Brien DP, Johnson PDR, Lavender CJ, Globan M, McCarthy J, Osowicki J, Stinear TP. Mycobacterium ulcerans challenge strain selection for a Buruli ulcer controlled human infection model. PLOS Neglected Tropical Diseases. 2024;18(5):10.1371/journal.pntd.0011979

M. Bader S, Cooney JP, Bhandari R, Mackiewicz L, Dayton M, Sheerin D, Georgy SR, Murphy JM, Davidson KC, Allison CC, Pellegrini M, Doerflinger M. Necroptosis does not drive disease pathogenesis in a mouse infective model of SARS-CoV-2 in vivo. Cell Death & Disease. 2024;15(1):10.1038/s41419-024-06471-6

Muhi S, Marshall JL, O’Brien DP, Johnson PDR, Ross G, Ramakrishnan A, Mackay LK, Doerflinger M, McCarthy JS, Jamrozik E, Osowicki J, Stinear TP. A human model of Buruli ulcer: Provisional protocol for a Mycobacterium ulcerans controlled human infection study.Wellcome Open Research. 2024;9:10.12688/wellcomeopenres.22719.2

Garnish SE, Martin KR, Kauppi M, Jackson VE, Ambrose R, Eng VV, Chiou S, Meng Y, Frank D, Tovey Crutchfield EC, Patel KM, Jacobsen AV, Atkin-Smith GK, Di Rago L, Doerflinger M, Horne CR, Hall C, Young SN, Cook M, Athanasopoulos V, Vinuesa CG, Lawlor KE, Wicks IP, Ebert G, Ng AP, Slade CA, Pearson JS, Samson AL, Silke J, Murphy JM, Hildebrand JM. A common human MLKL polymorphism confers resistance to negative regulation by phosphorylation. Nature Communications. 2023;14(1):10.1038/s41467-023-41724-6

Arandjelovic P, Kim Y, Cooney JP, Preston SP, Doerflinger M, McMahon JH, Garner SE, Zerbato JM, Roche M, Tumpach C, Ong J, Sheerin D, Smyth GK, Anderson JL, Allison CC, Lewin SR, Pellegrini M. Venetoclax, alone and in combination with the BH3 mimetic S63845, depletes HIV-1 latently infected cells and delays rebound in humanized mice. Cell Reports Medicine. 2023;4(9):10.1016/j.xcrm.2023.101178