What We Do
The tumor microenvironment (TME) plays a crucial role in cancer progression and resistance to treatments, including immunotherapy. The TME consists of various components, such as stromal cells, tumor cells, immune cells, and the extracellular matrix. The complex interactions between these elements influence how tumors grow and how they respond to therapies. Recent studies have highlighted the significant variation among individual cells within the TME, revealing extensive cellular diversity. However, one key question remains: How do these heterogeneous cells communicate with each other? We believe that the way these cells interact not only shapes their behavior but also affects the effectiveness of immunotherapy in cancer patients. To explore this, our lab uses advanced multi-omics techniques and CRISPR screening while maintaining the spatial structure of the TME. This approach helps us investigate how cells within the TME communicate and how these interactions impact the outcomes of immunotherapy such as immune checkpoint blockade therapy and CAR T cell therapy.
WHO WE ARE
REZA MIRZAEI
Principal Investigator
Assistant Professor at the Department of Oncology
Scientist at AHS
Reza earned his PhD in Immunology from Tehran University, where he focused on enhancing dendritic cell-based immunotherapy for cancer patients. During his postdoctoral work in Dr. Wee Yong’s lab at the University of Calgary, he studied the brain tumor microenvironment using integrative single-cell spatial transcriptomics. His research uncovered critical insights, including regulators of brain tumor-initiating cells, mechanisms of resistance to PD-1 blockade therapy, and the identification of new macrophage subsets in brain tumors. At Memorial Sloan Kettering Cancer Center and Mount Sinai in New York, Reza applied CRISPR screening to explore how the tumor microenvironment and cell interactions shape the effectiveness of immunotherapy such as CAR T cell therapy.
VIJAY PAL SINGH
Lab Manager
Vijay holds master’s degrees in Human Nutrition and Applied Microbiology, one of which he earned from the University of Alberta. He has published his research in peer-reviewed journals and received several prestigious awards, including the DORA European Union Research Fellowship and multiple gold medals for academic excellence. With over seven years of experience in microbiology, molecular biology, and virology, Vijay brings invaluable expertise to the Mirzaei Lab.
WHAT WE HAVE DONE
Selected publications:
- 1-Mirzaei R*, McNeil R, D’Mello C, Sarkar S, Wong B, Visser F, Poon C, Bose P, Yong VW*. Spatially resolved single-cell analysis uncovers protein kinase C-expressing microglia with anti-tumor activity in glioblastoma. *Corresponding author https://www.biorxiv.org/content/10.1101/2023.12.04.570023v2
- 2-Mirzaei R, D’Mello C, Nikolic A, Kumar M, Liu M, Sarkar S, Bose P, Gallo M, Yong VW. Single cell spatial analysis identifies regulators of brain tumor initiating cells. Cancer Research. 2023 May 15;83(10):1725-1741.
- 3-Mirzaei R, Yong VW. Microglia – T cell conversations in brain cancer progression. In press. Trends Mol Med. 2022 Sep 5;S1471-4914(22)00211-8.
- 4-Mirzaei R, Gordon A, Zemp F, Kumar M, Sarkar S, Luchman H, Bellail A, Hao C, Mahoney D, Dunn J, Bose P, Yong VW. PD-1 independent of PD-L1 ligation promotes glioblastoma growth through the NFB pathway. Science Advances. 2021 Nov 5;7(45):eabh2148.
- 5-Dzikowski L*, Mirzaei R*, Sarkar S, Kumar M, Bose P, Bellail A, Hao C, Yong VW. Fibrinogen in the glioblastoma microenvironment contributes to the invasiveness of brain tumor-initiating cells. Brain Pathol. 2021 Sep;31(5):e12947. *Co-first author.
- 6-Mirzaei R, Sarkar S, Dzikowski L, Rawji KS, Khan L, Faissner A, Bose P, Yong VW. Brain tumor-initiating cells export tenascin-C associated with exosomes to suppress T cell activity. OncoImmunology. 2018 Aug 6;7(10):e1478647.
- 7-Sarkar S, Yang R*, Mirzaei R*, Rawji K, Poon C, Mishra MK, Zemp FJ, Bose P, Kelly J, Dunn JF, Yong VW. Control of brain tumor growth by reactivating myeloid cells with niacin. Sci Transl Med. 2020 Apr 1;12(537):eaay9924. *Co-second author.
- 8-Kaushik DK, Bhattacharya A, Mirzaei R, Rawji KS, Ahn Y, Rho JM, Yong VW. Enhanced glycolytic metabolism supports transmigration of brain-infiltrating macrophages in multiple sclerosis. J Clin Invest. 2019 May 21;129(8):3277-3292.
- 9-Sarkar S, Mirzaei R, Zemp FJ, Wei W, Senger DL, Robbins SM, Yong VW. Activation of NOTCH Signaling by Tenascin-C Promotes Growth of Human Brain Tumor-Initiating Cells. Cancer Res. 2017 Jun 15;77(12):3231-3243.
- 10-Mirzaei R, Sarkar S, Yong VW. T Cell Exhaustion in Glioblastoma: Intricacies of Immune Checkpoints. Trends Immunol. 2017 Feb;38(2):104-115.
JOIN US
If you are passionate about the tumor microenvironment and immunotherapy, and eager to tackle challenging questions, we encourage you to reach out. We are always looking for candidates for PhD and postdoctoral positions. Candidates should send a statement of interest and CV to rmirzaei@ualberta.ca
WHERE WE ARE
We are part of the Cross Cancer Institute and affiliated with the Department of Oncology at the University of Alberta in Edmonton, Alberta, Canada.