Research Discipline(s): Immunology, Cell Biology, Signal Transduction
Primary Title: Professor and Head, Department of Immunology, Max Rady College of Medicine
Additional Titles & Affiliations: Cross-appointed Professor, Biochemistry and Medical Genetics, Internal Medicine
RESEARCH TOPICS
Leukemia, Lymphoma
Research Summary
During an immune response, B cells dramatically reprogram to undergo extensive cell division, metabolic activation, functional differentiation and migration to various tissues. This cellular reprogramming depends on a complex network of cell surface receptors which activate intracellular signal transduction cascades. Disruption of these signaling networks and their intrinsic control mechanisms can contribute to a range of diseases including autoimmunity and B cell malignancies. Dr. Marshall’s research focuses on one key signaling network known as the PI3K signaling pathway, which modifies lipids to activate the plasma membrane and create docking sites for signal transduction to occur. The PI3K pathway is dysregulated in B cell malignancies and contributes to abnormal cell proliferation and survival in diseases such as chronic lymphocytic leukemia (CLL) and B cell lymphomas. By studying the lipid kinases, phosphatases and lipid binding proteins in this pathway, Dr. Marshall is discovering how this network controls functions such as B cell metabolic reprograming and migration, identifying new ways to therapeutically target this pathway in B cell malignancies. Dr. Marshall’s group also studies mechanisms by which B lymphocytes interact with other cells of the immune system, such as T lymphocytes, in the context of various diseases such as leukemia, lymphoma and autoimmunity.
Goals
Dr. Marshall's research goals are 1) to understand the signal transduction mechanisms controlling the cellular activities of B lymphocytes in health and disease, 2) to understand the mechanisms for cell-to-cell interactions that controlling the cellular activities of B lymphocytes in health and disease, 3) apply the fundamental discoveries regarding B cell biology to develop novel therapeutic strategies to disrupt pathological B cell activities in the context of leukemia, lymphoma and autoimmune diseases.
Research Biography
Dr. Aaron Marshall is Professor and Head of Immunology at the University of Manitoba and President of the Canadian Society for Immunology. Dr Marshall earned his PhD in Immunology at the University of Toronto and during a post-doctoral fellowship at the University of Washington he furthered his studies in the field of B lymphocyte molecular biology. His research program is centred on signal transduction pathways that control various aspects of normal and malignant B lymphocyte biology, including cell migration, adhesion, metabolic reprogramming and immune regulation. Dr. Marshall’s work has a particular focus on regulation and function of the phosphoinositide 3-kinase (PI3K) signaling pathway in the context of chronic lymphocytic leukemia and other B cell malignancies. Dr. Marshall has also worked with Manitoba CLL Clinic researchers to better understand immune dysfunction in CLL patients more broadly.
Achievements
- Canada Research Chair in Molecular Immunology
- President, Canadian Society for Immunology
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Featured Publications
- Wu X, Fajardo-Despaigne JE, Zhang C, Neppalli V, Banerji V, Johnston JB, Gibson SB, Marshall AJ. Altered T Follicular Helper Cell Subsets and Function in Chronic Lymphocytic Leukemia. Front Oncol. 2021 Apr 28;11:674492. doi: 10.3389/fonc.2021.674492. PMID: 33996605; PMCID: PMC8113764.
- Ali AY, Wu X, Eissa N, Hou S, Ghia JE, Murooka TT, Banerji V, Johnston JB, Lin F, Gibson SB, Marshall AJ. Distinct roles for phosphoinositide 3-kinases γ and δ in malignant B cell migration. Leukemia. 2018 Sep;32(9):1958-1969. doi: 10.1038/s41375-018-0012-5. Epub 2018 Jan 31. PMID: 29479062; PMCID: PMC6127087.
- Ali AY, Guan Q, Wu X, Hou S, Banerji V, Johnston JB, Wall D, Szwajcer D, Gibson SB, Marshall AJ. Expression and function of phosphoinositide 3-kinase delta in mesenchymal stromal cells from normal and leukaemic bone marrow. Br J Haematol. 2019 Jun;185(5):883-887. doi: 10.1111/bjh.15865. Epub 2019 Mar 14. PMID: 30873593.
- Ishdorj G, Streu E, Lambert P, Dhaliwal HS, Mahmud SM, Gibson SB, Banerji V, Marshall AJ, Johnston JB. IgA levels at diagnosis predict for infections, time to treatment, and survival in chronic lymphocytic leukemia. Blood Adv. 2019 Jul 23;3(14):2188-2198. doi: 10.1182/bloodadvances.2018026591. PMID: 31324639; PMCID: PMC6650736.
- Chowdhury SR, Peltier C, Hou S, Singh A, Johnston JB, Gibson SB, Marshall A, Banerji V. Ex Vivo Mitochondrial Respiration Parallels Biochemical Response to Ibrutinib in CLL Cells. Cancers (Basel). 2021 Jan 19;13(2):354. doi: 10.3390/cancers13020354. PMID: 33477957; PMCID: PMC7835851.
- Roy Chowdhury S, Bouchard EDJ, Saleh R, Nugent Z, Peltier C, Mejia E, Hou S, McFall C, Squires M, Hewitt D, Davidson L, Shen GX, Johnston JB, Doucette C, Hatch GM, Fernyhough P, Marshall A, Gibson SB, Dawe DE, Banerji V. Mitochondrial Respiration Correlates with Prognostic Markers in Chronic Lymphocytic Leukemia and Is Normalized by Ibrutinib Treatment. Cancers (Basel). 2020 Mar 11;12(3):650. doi: 10.3390/cancers12030650. PMID: 32168755; PMCID: PMC7139649.
