Jean Gariépy

At A Glance

• Dr. Jean Gariépy’s team focuses on the design and evaluation of DNA aptamers, vaccines and protein-based therapeutics in the areas of oncology and inflammatory diseases.
• Students typically develop and test new biologics or vaccines as part of their training.
• The more recent focus of the laboratory is in the area of immune checkpoint modulators.

Short Bio

Dr. Jean Gariépy was originally trained as a peptide chemist and biophysicist at the University of Alberta (Ph.D.), and as a peptide/protein engineer at Stanford University, in the areas of bacterial toxins and infectious diseases (as a postdoctoral fellow). He is the Director of the Molecular Targeting and Therapeutics Laboratory at the Sunnybrook Research Institute (SRI), and the SRI Research Chair in Biomolecular Engineering. Dr. Gariépy has had a long standing interest in developing new technologies in the field of biotherapeutics, being cited as an inventor or co-inventor on 8 granted patents and on more than 20 patent applications. He co-founded and was a director [2000-2008] and CSO [2000-2009] of Molecular Templates, Inc. (MTI; MTEM; www.moleculartemplates.com; Austin, Texas), a well-funded, NASDAQ-listed company that focuses on the development of protein-based biotherapeutics (Engineered Toxin Bodies) in the area of Oncology. Dr. Gariépy more recently co-founded, is a director and the CSO of D5Pharma, a Toronto-based discovery company focusing on the development of an immune checkpoint modulator in the field of asthma. More recently, his group has developed and is studying the mechanism of action of several novel protein-based biologics that behave as powerful immune checkpoint agonists. Finally, his group has been developing a preventive vaccine against metastatic cancer.

Research Synopsis

Molecular Engineering and the Development of Targeted Biological Therapies

Our laboratory is interested in developing both in vivo imaging modalities and targeted therapies directed at inflammatory diseases and cancer (breast, colon, prostate, ovarian, lung, and pancreas). Our research program is a fine balance of both basic and applied research projects aimed at understanding how peptides, proteins and oligonucleotide templates work and how they can be engineered or utilized in developing directed therapies against tumor cells (either through the design of cancer vaccines, DNAaptamers and immune checkpoint protein biologics.) or as novel anti-inflammatory agents.

The spectrum of approaches taken by our group to address our design and discovery programs ranges from protein engineering, combinatorial protein or DNA library design/screening, cell biology/microscopy techniques to yeast genetics and mouse models.

Because of the broad nature of our molecular engineering efforts, projects in our laboratory are usually tailored to a student’s expectations and aptitudes.

Recent Publications

P53 MUTATIONS AND CLINICAL OUTCOMES

• Fischer,N, Prodeus,A., Malkin, D. and Gariépy,J.  (2016). p53 Oligomerization Status Modulates Cell Fate Decisions Between Growth, Arrest and Apoptosis. Cell Cycle 2016 Dec;15(23):3210-3219.
• Fischer NW, Prodeus A, Tran J, Malkin D, Gariépy J.(2018) Association Between the Oligomeric Status of p53 and Clinical Outcomes in Li-Fraumeni Syndrome. J Natl Cancer Inst. 2018 Jun 27. doi: 10.1093/jnci/djy114.
• Fischer NW, Prodeus A, and Gariépy J (2018) Survival in males with glioma and gastric adenocarcinoma correlates with mutant p53 residual transcriptional activity. JCI Insight. 2018 Aug 9;3(15). pii: 121364. doi: 10.1172/jci.insight.121364. [Epub ahead of print].  Link to video

CANCER VACCINES

• Sean O. Ryan, Michael S. Turner, Jean Gariépy, and Olivera J. Finn (2010). Tumor Antigen Epitopes interpreted by the Immune System as Self or abnormal-Self differentially affect cancer vaccine responses. Cancer Res. Jul 15; 70(14):5788-96. 
• Abdul-Wahid, A., Cydzik, M., Prodeus, A., Alwash, M., Stanojcic, M., Thompson, M., Huang, E.H.-B.,and Gariépy, J. (2016). Induction of Antigen-Specific TH9 Immunity Accompanied by Mast Cell Activation Block Tumor Cell Engraftment. Int J Cancer 139(4):841-53.
• Scheid, E., Major, P., Bergeron, A., Finn, O.J., Salter, R.D. Eady, R., Yassine-Diab, B., Favre, D., Peretz, Y., Landry, C.,  Hotte, S., Mukherjee, S.,  Dekaban, G.A., Fink, C., Foster, P.J., Gaudet, J., Gariépy, J,  Sekaly, R., Lacombe, L., Fradet,Y. and Foley,R. (2016). Tn-MUC1 Dendritic Cell Vaccination: A Preclinical Study in Rhesus Macaques and Phase I/II Trial in Patients with Non-Metastatic Castrate Resistant Prostate Cancer. Cancer Immunol Res. 4(10):881-892.

APTAMERS AS THERAPEUTIC AGENTS

• Catia Ferreira, Melissa Cheung, Sotiris Missailidis,  Stuart Bisland, and Jean Gariépy, J. (2009). Phototoxic aptamers selectively enter and kill epithelial cancer cells.  Nucleic Acids Research 37: 866-876.
• Erik Orava and Jean Gariépy (2013) A short DNA aptamer that recognized TNF-alpha and blocks its activity in vitro.  ACS Chem Biol 8(1):170-8.

IMMUNE CHECKPOINT BIOLOGICS

• Matus, E Sparkes A, Gariépy, J., (2020). A soluble activator that favors the ex-vivo expansion of CD8+CD27+ T-cells. JCI Insight. 5(22): e141293.

• Ma YV, Sparkes A, Romão E, Saha S, Gariépy, J., (2021). Agonistic nanobodies and antibodies to human VISTA. MAbs. 2021 Jan-Dec;13(1):2003281. doi: 10.1080/19420862.2021.2003281.

• Prodeus A, Abdul-Wahid A, Sparkes A, Fischer N, Marzena Cydzik   M, Chiang N, Alwash M, Ferzoco A, Vacaresse N, Julius M, Gorczysnki RM, and Gariépy J. (2017) VISTA.COMP: an engineered checkpoint receptor agonist that potently suppresses T-cell mediated immune responses. JCI Insight 2(18):e94308.
• Prodeus, A., Cydzik, M., Huang, E.H.-B.,  Khatri, I., Gorczynski, R., and Gariépy, J. (2014). Agonistic CD200R1 DNA Aptamers are Potent Immunosuppressants that Prolong Allogeneic Skin Graft Survival. Molecular Therapy Nucleic Acids. 3:e190.
• Prodeus, A., Abdul-Wahid, A., Fischer, N.W., Huang, E. H.-B., Cydzik, M., and Gariépy, J. (2015). Targeting the PD-1/PD-L1 immune evasion axis with DNA aptamers as a novel therapeutic strategy for the treatment of disseminated cancers. Molecular  Therapy-Nucleic Acids 4:e237. 

Graduate Students

Esther Matus