Mathieu Crupi

Laboratory Website (Under Construction)

Announcement: Zachary Dugas is the first Master’s student to join the Crupi lab!
We are currently looking to recruit new students for 2027 at the Master’s and PhD level

Zachary is from Ottawa (ON, Canada) and completed his Honours Bachelor of Medical Sciences (BMSc) with Double Majors in Microbiology & Immunology and Physiology at Western University. He previously worked as a summer student at the Children’s Hospital of Eastern Ontario Research Institute and the Ottawa Hospital Research Institute investigating innovative approaches to recruit tumour-infiltrating lymphocytes for preclinical studies. His current research project in the Crupi Lab now focuses on the characterizing a metabolic kinase involved in facilitating or preventing viral infection. In his free time, Zachary enjoys playing soccer, golf, volleyball and piano.

Research Interests

Newfoundland and Labrador has among the highest rates of hereditary cancer syndromes in Canada, where families face elevated lifetime risk and where standard treatments often fall short. Our translational research program aims to serve these patients at the forefront. We work at the intersection of immunology, virology, and molecular engineering, with a focus on oncolytic viruses and immune-cell engagers, two complementary strategies for making tumours visible to the immune system and driving a durable anti-tumour response. A major goal of the lab is to engineer viruses that express novel transgenes directly within the tumour microenvironment so that the immune system can be recruited, activated and retargeted to the tumour. Our goal is to produce personalized biotherapeutics tailored to the specific vulnerabilities of these cancers, moving ideas from vector design and in vitro validation through to preclinical models and biomanufacturing. Above all, we are committed to generating therapies that are affordable and accessible for the people of Newfoundland and Labrador and all other Canadians.

Ongoing Project: Characterizing the involvement of different kinases in pro-viral or anti-viral pathways. How do two closely related forms of the same kinase produce opposite outcomes for different viruses in identical cells? We use a plethora of methodologies to interrogate this question, including:

• Synthetic biology and cloning
• Super-resolution and live-cell confocal microscopy
• Virological techniques
• CRISPR editing
• Electron microscopy
• Proximity-dependent labelling and mass spectrometry
• RNA sequencing
• Seahorse metabolic profiling

Our findings may elucidate new ways to restrict pathogenic viruses or enhance production of oncolytic viruses and/or virus-based vaccine platforms. The Crupi lab aims to train the next generation of scientists in transferable techniques that are in demand across academia, industry, government and biotechnology.

Ongoing Project: The hypoxic tumour microenvironment is a major barrier to effective cancer therapy, driving resistance and immune evasion. We have identified unique vulnerabilities that can potentially render these hypoxic regions susceptible to oncolytic virus therapies. Can we encode antibody-based approaches in viruses to increase immune recruitment and activation, while simultaneously increasing viral spread inside tumours? Here, we are exploring a combination of different techniques, including:

• Synthetic biology and cloning
• Flow Cytometry
• Virological techniques
• Spheroid/organoid co-cultures
• Nanoluciferase killing assays
• Tumour coring and preclinical models
• Immunoblotting and ELISAs
• Cytokine Arrays and ELISpots

Tumour spheroid models co-cultured with immune cells in a hypoxic chamber or with hypoxia- mimetic drugs led to upregulation of novel targets. Through CRISPR depletion, anti-viral targets were identified in colorectal and pancreatic cancers. We are now engineering oncolytic viruses capable of overcoming these barriers in the tumour microenvironment by encoding antibody-based approaches that boost immune-mediated bystander killing of tumour cell populations generally resistant to oncolytic virus spread.

Professional Experience

2026-Present: Assistant Professor of Immunology & Infectious Disease, Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL

2023-2026: Personalized Biotherapeutics Lead, Boreal Biomanufacturing (formerly known as the Biotherapeutics Manufacturing Centre), Ottawa Hospital Research Institute, Ottawa, ON, Canada

• CAR T Therapy Technology Transfer / Travelling Internship (Conconi Family Immunotherapy Lab, Deeley Research Centre, Victoria, BC, Canada)
• TIL Therapy Technology Transfer / Travelling Internship (Le Centre hospitalier de l'Université de Montréal, Montréal, QU, Canada)

2018-2023: Postdoctoral Fellow, Cancer Research Program / Biochemistry, Microbiology and Immunology, University of Ottawa and Ottawa Hospital Research Institute, Ottawa, ON, Canada

Education

PhD in Pathology and Molecular Medicine, Specialization in Cancer Research, Terry Fox Foundation Training Program in Transdisciplinary Cancer Research in Partnership with CIHR, Queen’s University, Kingston, ON, Canada

• Travelling Fellowship for TIRF Imaging and Super-Resolution Microscopy (Department of Chemistry & Biology), Toronto Metropolitan University / MaRS / SickKids, Toronto, ON, Canada

BScH in Biology Major, Honours in Genetics & Diseases, Queen’s University, Kingston, ON, Canada

Publications (since 2020)

Mediratta K, Mocǎnițǎ M, Popatia AM, O’Dwyer C, Kirkby M, Moga SS, Han P, Humber J, Hu H, Abdisalam S, Diab MD, Sinha A, Crupi MJF, Massad S, El-Sahli S, Shrestha A, Ariana A, Gadde S, Lee S-H, Benoit YD, Ardolino M, Li X, Lavoie JR, Liu Z, D’Costa VM, Wang L. (2026). Clinically approved ALDH inhibitor combined with a chemotherapeutic agent enables selective targeting of triple-negative breast cancer stem cells via PD-L1 blockade. Scientific Reports. 16:69314.

Boulton S, Singh S, Organ B, Thomas J, Rezaei R, Gill R, Vallati S, Guo Q, Dave J, Petryk J, Tanese De Souza C, Austin B, He X, Gingrich A, Crupi MJF, Singaravelu R, Ilkow CS, Bell JC. (2026). Oncolytic vaccinia virus encoding constitutively active EPAC remodels the tumor microenvironment to enhance therapeutic efficacy with chemotherapy and surgery. Journal for ImmunoTherapy of Cancer. 14(1): e013832.

Orofiamma LA, Delos Santos RC, Mehrabi A, Leshchyshyn N, Hesketh GG, Rahmani S, Patel A, Fekri F, Ata R, Ratcliffe CDH, Crupi MJF, Mulligan LM, Park M, Gingras AC, Antonescu CB. (2025). Cargo-selective regulation of clathrin-mediated endocytosis by AMP-activated Protein Kinase. iScience. 28(8): 113131.

Taha Z*, Crupi MJF*, Alluqmani N, MacKenzie D, Vallati S, Whelan JT, Fareez F, Alwithenani A, Petryk J, Chen A, Spinelli MM, Ng K, Sobh J, Tanese de Souza C, Bharadwa PR, Lee TKH, Huang BZ, Kassas O, Thomas DA, Huang BZ, Kassas O, Poutou J, Gilchrist VH, Boulton S, Thomson M, Marius R, Hooshyar M, McComb S, Arulanandam R, Ilkow CS, Bell JC*, Diallo JS*. [*=co-first] [*=co-senior]. (2024). Complementary dual-virus strategy drives synthetic target and cognate T-cell engager expression for endogenous-antigen agnostic immunotherapy. Nature Communications. 15:7267. 

Wong B, Birtch R, Bergeron A, Ng K, Maznyi G, Spinelli M, Chen A, Landry A, Crupi MJF, Arulanandam R, Ilkow CS, Diallo JS. (2024). High throughput screen identifies lysosomal acid phosphatase 2 (ACP2) to regulate IFN-1 responses to potentiate oncolytic VSV∆51 activity. Scientific Reports 14(1):28284.

Walker TJ, Reyes-Alvarez E, Hyndman BD, Sugiyama MG, Oliveira LCB, Rekab AN, Crupi MJF, Cabral-Dias R, Guo Q, Dahia PLM, Richardson DS, Antonescu CN, Mulligan LM. (2024). Loss of tumor suppressor TMEM127 drives RET-mediated transformation through disrupted membrane dynamics. eLife. 12: RP89100.

Hodgins JJ, Abou-Hamad J, O’Dwyer CE, Hagerman A, Yakubovich E, Tanese de Souza C, Marotel M, Buchler A, Fadel S, Park MM, Fong-McMaster C, Crupi MJF, Makinson OJ, Kurdieh R, Rezaei R, Dhillon HS, Ilkow CS, Bell JC, Harper ME, Rotstein BH, Auer RC, Vanderhyden BC, Sabourin LA, Bourgeois-Daigneault MC, Cook DP, Ardolino M. (2024). More than a ligand: PD-L1 promotes oncolytic virus infection via a metabolic shift that inhibits the type I interferon pathway. Journal of Experimental Medicine. 221(7):e20221721.

Wong B, Birtch R, Rezaei R, Jamieson T, Crupi MJF, Diallo JS, Ilkow CS. (2023). Optimal delivery of RNA interference by viral vectors for cancer therapy. Molecular Therapy. 31(11): 3127-3145.

Boulton S, Poutou J, Gill R, Alluqmani N, He X, Singaravelu R, Crupi MJF, Petryk J, Austin B, Angka L, Taha Z, Teo I, Singh S, Jamil R, Marius R, Martin N, Jamieson TJ, Azad T, Diallo JS, Ilkow CS, Bell JC. (2023). A T Cell-targeted multi-antigen poxvirus vector vaccine generates robust cellular and humoral immunity against SARS-CoV-2 infection. Molecular Therapy – Methods & Clinical Development. 31:101110.

Martin NT*, Crupi MJF*, Taha Z, Poutou JP, Whelan J, Vallati S, Petryk J, Marius M, Austin B, Azad T, Boulanger M, Burgess T, Sanders I, Victoor C, Dickinsin B, Diallo JS, Ilkow CS, Bell JC [*=co-first]. (2023). Engineering rapalog-inducible genetic switches based on Split-T7 polymerase to regulate oncolytic virus-driven production of tumour-localized IL-12 for anti-cancer immunotherapy. Pharmaceuticals. 16:709.

Azad T, Rezaei R, Singaravelu R, Pelin A, Boulton S, Petryk J, Onsu KA, Martin NT, Hoskin V, Ghahremani M, Marotel M, Marius R, He X, Crupi MJF, Hoang HD, Nik-Akhtar A, Ahmadi M, Zamani NK, Golshani A, Alain T, Greer P, Ardolino M, Dickinson BC, Tai LH, Ilkow CS, Bell JC. (2023). Synthetic virology approaches to improve the safety and efficacy of oncolytic virus therapies. Nature Communications 14:3035.

Taha Z, Crupi MJF, Alluqmani N, Fareez F, Ng K, Sobh J, Lee E, Chen A, Thomson M, Spinelli MM, Ilkow CS, Bell JC, Arulanandam R, Diallo JS. (2023). Syngeneic mouse model of human HER2+ metastatic breast cancer for the evaluation of trastuzumab emtansine combined with oncolytic rhabdovirus. Frontiers in Immunology 14:1181014.

Boulton S, Crupi MJF, Siddharth S, Carter-Timofte ME, Azad T, Organ BC, He X, Gill R, Neault S, Jamieson T, Dave J, Kurmasheva N, Austin B, Petryk J, Singaravelu R, Huang BZ, Franco N, Babu K, Parks R, Ilkow CS, Olagnier D, JC Bell. (2023). EPAC Inhibition Induces Broad Spectrum Inhibition of Virus Infectivity via Remodelling of Actin Complexes. Journal of Medicinal Chemistry. 299(6): 104749.

Surendran A*, Jamalkhah M*, Poutou J*, Birtch R*, Lawson C*, Dave J, Crupi MJF, Mayer J, Taylor V, Petryk J, Tanese De Souza C, Moodie N, Billingsley JL, Austin B, Cormack N, Blamey N, Rezaei R, McCloskey CW, Fekete EEF, Birdi HK, Neault S, Jamieson TR, Wylie B, Tucker S, Azad T, Vanderhyden B, Tai LH, Bell JC, Ilkow CS [*=co-first]. (2023). Fatty acid transport protein inhibition sensitizes breast and ovarian cancers to oncolytic virus therapy via lipid modulation of the tumor microenvironment. Frontiers in Immunology. 14:1099459.

Moulin C, Crupi MJF, Ilkow CS, Bell JC, Boulton S. (2023) Extracellular vesicles and viruses: two intertwined entities. International Journal of Molecular Sciences. 24(2): 1036.

Crupi, MJF, Taha, Z, Janssen, T, Petryk, J, Boulton S, Alluqmani N, Jirovec, A, Kassas, O, Vallati, S, Lee, E, Huang, BZ, Khan, ST, He, X, Marius, R, Austin, B, Duong, J, Pelin, A, Neault, S, Azad, T, McComb, S, Auer, R, Ilkow, CS, Diallo, JS, and Bell, JC. Oncolytic virus driven T-cell-based combination immunotherapy platform for colorectal cancer. Frontiers in Immunology. (2022) 13:1029269.

Whelan JT*, Singaravelu R*, Wang F*, Pelin A*, Tamming LA, Pugliese G, Martin NT, Crupi MJF, Petryk J, Austin B, He X, Marius R, Duong J, Carter J, Fekete EEF, Alluqmani N, Chen A, Boulton S, Huh M, Tang MY, Taha Z, Scut E, Diallo JS, Azad T, Lichty BD, Ilkow CS, Bell JC [*=co-first]. (2022). CRISPR-mediated rapid arming of poxvirus vectors enables facile generation of novel immunotherapeutic STINGPOX. Frontiers in Immunology. 13:1050250.

Taha Z*, Arulanandam R*, Maznyi G, Godbout E, Carter-Timofte ME, Kurmasheva N, Reinert LS, Chen A, Crupi MJF, Boulton S, Laroche G, Phan A, Rezaei R, Alluqmani N, Jirovec A, Acal A, Brown EEF, Singaravelu R, Petryk J, Idorn M, Potts KG, Todesco H, John C, Mahoney DJ, Ilkow CS, Giguere P, Alain T, Cote M, Paludan SR, Olagnier D, Bell JC, Azad T, Diallo JS [*=co-first] (2022). Identification of FDA-approved Bifonazole as SARS-CoV-2 blocking agent following a bioreporter drug screen. Molecular Therapy. 30(9):2998-3016.

Wedge ME*, Jennings VA*, Crupi MJF*, Poutou J*, Jamieson T, Pelin A, Pugliese G, Tanese de Souza C, Petryk J, Laight BJ, Boileau M, Taha Z, Alluqmani N, McKay HE, Pikor L, Khan ST, Azad T, Rezaei R, Austin B, He X, Mansfield D, Pelin A, Rose E, Brown EEF, Crawford N, Alkayyal A, Surendran A, Singaravelu R, Roy DG, Migneco G, McSweeney B, Cottee ML, Jacobus EJ, Keller BA, Geoffrion M, Rayner KJ, Chatterjee A, Auer RC, Diallo JS, Gibbings D, tenOever BR, Melcher A, Bell JC and Ilkow CS [*=co-first] (2022). Virally programmed extracellular vesicles sensitize cancer cells to oncolytic virus and small molecule therapy. Nature Communications. 13(1): 1898.

Boulton S*, Poutou J*, Martin NT*, Azad T*, Singaravelu R*, Crupi MJF*, Jamieson T*, He X, Marius R, Petryk J, Tanese de Souza C, Austin B, Taha Z, Whelan J, Khan ST, Pelin A, Rezaei R, Surendran A, Tucker S, Brown EEF, Dave J, Diallo JS, Auer R, Angel JB, Cameron DW, Cailhier JF, Lapointe R, Potts K, Mahoney DJ, Bell JC**, Ilkow CS**. [*=co-first] [** = co-senior]. (2021). Single-dose replicating poxvirus vector-based RBD vaccine drives robust humoral and T cell immune response against SARS-CoV-2 infection. Molecular Therapy. 30(2):1-12.

Azad T*, Singaravelu R*, Taha Z, Jamieson TR, Boulton S, Crupi MJF, Martin NT, Brown EEF, Poutou J, Ghahremani M, Pelin A, Nouri K, Rezaei R, Marshall CB, Enomoto M, Arulanandam R, Alluqmani N, Samson R, Gingras AC, Cameron DW, Greer PA, Ilkow CS, Diallo JS, Bell JC [*=co-first]. (2021). Nanoluciferase complementation-based bioreporter reveals the importance of N-linked glycosylation of SARS-CoV-2 S for viral entry. Molecular Therapy. 29(6): 1984-2000.

Azad T*, Rezaei R*, Singaravelu R*, Jamieson T, Crupi MJF, Surendran A, Poutou J, Taklifi P, Cameron DW, Ilkow CS [*=co-first]. (2021). A high-throughput NanoBiT-based serological assay detects SARS-CoV-2 seroconversion. Nanomaterials. 11: 807.

Azad T*, Janse van Rensburg HJ*, Morgan J*, Rezaei R*, Crupi MJF*, Chen R, Ghahremani M, Jamalkhah M, Forbes N, Ilkow CS, Bell JC [*=co-first]. (2021). Luciferase-based biosensors in the era of the COVID-19 pandemic. ACS Nanoscience Au. 1: 15-37.

Brown, EEF*, Rezaei R*, Jamieson TR*, Dave J*, Martin NT, Singaravelu R, Crupi MJF, Boulton S, Tucker S, Duong J, Pelin A, Yasavoli-Shrahi H, Taha Z, Arulanandam R, Surendran A, Ghahremani M, Austin B, Matar C, Diallo JS, Bell JC, Ilkow CS, Azad T [*=co-first]. (2021). Characterization of Critical Determinants of ACE2–SARS CoV-2 RBD Interaction. International Journal of Molecular Sciences. 22(5): 2268.

Azad T*, Singaravelu R*, Crupi MJF*, Jamieson T*, Dave J, Brown EEF, Rezaei R, Taha Z, Boulton S, Martin NT, Surendran A, Poutou J, Ghahremani M, Nouri K, Whelan JT, Duong J, Tucker S, Diallo JS, Bell JC, Ilkow CS [*=co-first]. (2020). Implications for SARS-CoV-2 Vaccine Design: Fusion of Spike Glycoprotein Transmembrane Domain to Receptor-Binding Domain Induces Trimerization. Membranes. 10(9):215.

Moodley S, Lian EY, Crupi MJF, Hyndman BD, Mulligan LM. (2020). RET51-isoform specific interaction with ezrin promotes cell motility and chemotaxis in lung adenocarcinoma cells. Lung Cancer. 142: 123-131.

Crupi MJF, Maritan SM, Reyes-Alvarez E, Lian E, Hyndman BD, Rekab AN, Moodley S, Antonescu CN, Mulligan LM. (2020). GGA3-mediated recycling of the RET receptor tyrosine kinase contributes to cell migration and invasion. Oncogene. 39: 1361–1377.