Dr. Arshad Ayyaz
Positions
Assistant Professor
Affiliations
Full Member
Arnie Charbonneau Cancer Institute
Full Member
The Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases
Contact information
Web presence
Phone number
Office: 403.220.8134
Location
Office: BI238D
Background
Educational Background
Postdoc - Stem Cells and Cancer Genetics, Mount Sinai Hospital Toronto, 2021
Postdoc - Immunity and Regeneration Biology, Buck Institute for Research on Aging California, 2015
PhD - Molecular and Cell Biology, University of Strasbourg, 2012
MS - Integrated Cell Biology, Louis Pasteur University France, 2008
Biography
Following his doctoral training in mucosal immunity under Dr. Dominique Ferrandon at the Institut de Biologie Moléculaire et Cellulaire (University of Strasbourg, France), Dr. Arshad Ayyaz pursued postdoctoral fellowships at the Buck Institute for Research on Aging in Novato, California, with Dr. Heinrich Jasper, and at Mount Sinai Hospital in Toronto, Canada, under the guidance of Dr. Jeff Wrana. His research during these fellowships focused on the interplay between immune and regenerative responses during tissue repair. This work led to the discovery of several new stem cell types and unveiled a novel, conserved mechanism of intestinal regeneration regulated by immune cell-derived developmental cues. Furthermore, findings of Dr. Ayyaz highlighted how deviations in the finely orchestrated somatic regeneration process contribute to human disease development and adversely affect clinical outcomes.
Research
Areas of Research
- Understanding the mechanisms of immune escape in tumor initiating colorectal cancer cells
- Colorectal Cancer
- Stem Cells
- Immunotherapy Resistance
- Immune Escape
- Genomic Stress
Last decade has seen immunotherapy emerging as revolutionary anti-cancer treatment. Indeed, early clinical trials found a subset of patients with difficult-to-treat melanoma and lung cancer achieve long-term stable response. Subsequent studies found that these hypermutated cancers express ample peptide neo-antigens and are therefore readily detected as ‘non-self’ and eliminated by the therapeutically stimulated cytotoxic lymphocytes. However, most cancers contain relatively stable genome and do not respond to this treatment. For example, about 85% of all colorectal cancers (CRCs) show microsatellite stability, leading to poor response to immunotherapy. Consequently, a median 5-years survival in CRC patients with metastatic disease remains 12.5% making it a leading cause of cancer deaths globally. Thus, there is an urgent need to understand how transformed tissues evade immunity and find new ways to treat cancer patients. Tumor cells with stem cell-like properties that have long been associated with poor prognosis are now emerging as major players in resistance against immunotherapy, as shown by multiple pre-clinical studies. These cells, often referred to as tumor-initiating cells (TICs), can escape lymphocyte detection despite antigen editing, immune checkpoint inhibition or targeted T cell therapy, suggesting that tumor-mediated intrinsic processes, rather than lymphocyte dysfunction, drive immune escape in several tumors.
Our work is focused on understanding how regenerative somatic cells survive immune surveillance during genotoxic stress, what suppresses accumulation of somatic mutations under these conditions, how rare oncogenic genomic alterations escape these checkpoints, and what components of these mechanisms are hijacked by the transformed tissues which promotes their own growth and survival. We are using 3D organoids, tumor organoid-immune cell co-cultures, single cell-multiomics, functional genomics and targeted genome editing approaches to address these questions. Results from these studies are expected to provide novel therapeutic targets that could be used to develop better combination immunotherapeutic treatments that will improve clinical outcome in cancer patients.
Participation in university strategic initiatives
Courses
| Course number | Course title | Semester |
|---|---|---|
| CMMB 403 | Developmental Biology of Animals | Fall 2024 |
| CMMB 413 | Human Genetics | Winter 2024 |
| CMMB 507, 528, 530 | Undergraduate Independent Research Project |
Projects
Research interests
Human body is exposed to a large variety of chemical, biological and physical hazards, such as toxins, pathogens, pharmaceuticals, radiation and physical injury, just to name a few. These hazards induce damage to our organs and tissues and thereby adversely influence their function that is vital for survival. Therefore, an episode of tissue injury is generally followed by a rapid and highly organized process of tissue repair and regeneration, and cells that are specialized to perform this duty are called somatic stem cells. These regenerative cells are highly dynamic in nature and respond to several internal and external stimuli, which includes genomic alterations, morphogen signals, inflammatory cytokines, growth factors, metabolites and microbial products.
My laboratory is focused on understanding the molecular, genetic and epigenetic basis of stem cell response during normalcy and stress. To achieve this goal, we are using state-of-the-art genome editing, single cell multiomic technologies, transgenic animal models, and several in vivo and ex vivo 3D tissue culture techniques. Findings from these studies are relevant in regeneration medicine.
Disruption in stem cell function is a single most consequential alteration that associates with many degenerative diseases of the human intestine. This includes inflammatory bowel disease, dysplasia, fibrosis and colon cancer. We are using genetic disease models, transgenic animals, tissues collected from patients and clinical data to understand the mechanisms of disease initiation and progression and identify new ways to improve treatments in the clinic.
Teaching interests
My teaching philosophy is built upon universal principles of equity, diversity and inclusivity, collaborative learning, student engagement and effective feedback.
Publications
More Information
Publications
- Ayyaz A, Kumar S, Sangiorgi B, Ghoshal B, Gosio J, Ouladan S, Fink M, Barutcu S, Trcka D, Shen J, Chan K, Wrana JL and Gregorieff A. Single-cell transcriptomes of the regenerating intestine reveal a revival stem cell. Nature 569 (7754), 121-125 (2019).
- Morral C*, Ayyaz A*, Kuo HC*, Fink M, Verginadis I, Daniel AR, Burner DN, Driver LM, Satow S, Hasapis S, Ghinnagow R, Luo L, Ma Y, Attardi LD, Koumenis C, Minn A, Wrana JL, Lee CL, Kirsch DG. p53 Promotes Revival Stem Cells In The Regenerating Intestine After Severe Radiation Injury. Nature Communications 15: 3018 (2024). [*equal contribution]
- Dervovic D, Chen ELY, Malik A, Afiuni S, Boucher J, Berman JM, Teng K, Ayyaz A, Lu YQ, Narimatsu M, Mbamalu, Loganathan S, Martinez S, Tsai R, Lee JB, Zhang L, Wrana J, Roux PP, Jackson HW, Schramek D. In vivo CRISPR screens reveal Serpinb9 and Adam2 as regulators of immune therapy response in lung cancer. Nature Communications 14: 3150 (2023).
- Baghdadi MB, Ayyaz A, Coquenlorge S, Chu B, Kumar S, Streutker C, Wrana JL, Kim TH. Enteric glial cell heterogeneity regulates intestinal stem cell niches. Cell Stem Cell 29 (1): 86-100 (2022).
- Ayyaz A, Hongjie L and Jasper H. Haemocytes control stem cell activity in the drosophila intestine. Nature Cell Biology 17, 736-748 (2015).
- Ayyaz A, Attisano L and Wrana JL. Recent advances in understanding contextual TGFβ signaling. F1000 Research 6 (F1000 Faculty Rev.): 749 (2017).
- Goldsmith JR, Spitofsky N, Zamani A, Hood R, Boggs A, Li X, Li M, Reiner E, Ayyaz A, Etwebi Z, Lu L, Rivera Guzman J, Bou-Dargham MJ, Cathoupolis T, Hakonarson H, Sun H, Wrana JL, Gonzalez MV, Chen YH. TNFAIP8 controls murine intestinal stem cell homeostasis and regeneration by regulating microbiome-induced akt signaling. Nature Communications 11, Article number: 2591 (2020).
- Sousa-Victor P, Ayyaz A, Yayashi R, Qi Y, Madden DT, Lunyak VV, and Jasper H. Piwi is required to limit exhaustion of aging somatic stem cells. Cell Reports 20 (11): 2527-2537 (2017).
- Rahme BS, Lestradet M, Venanzio GD, Ayyaz A, Yamba MW, Lazzaro M, Liegeois S, Vescovi EG, Ferrandon D. The fliR gene contributes to the virulence of S. marcescens in a Drosophila intestinal infection model. Scientific Reports 12, 3068 (2022).
- Ayyaz A and Jasper H. Intestinal inflammation and stem cell homeostasis in aging Drosophila melanogaster. Frontiers in Cellular and Infection Microbiology 3:98 (2013).
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