A quarter of all deaths in Canada are caused by complications associated with cardiovascular disease. The main cause of vascular disease is atherosclerosis, or build-up of plaque in the arteries. Atherosclerosis is an inflammatory disease. One subset of inflammatory cells, macrophages, play an important role in atherosclerosis progression. How these cells gather in plaques, however, is not clear. Macrophages can appear in plaques through recruitment of their monocyte precursors from the bloodstream. Our recently published data shows macrophages also proliferate or divide locally within the plaque. We are currently pursuing three main research streams:
- Investigating the role of lesional macrophage proliferation in atherosclerosis.Which process - monocyte influx or macrophage proliferation - is more important? What are the mechanisms that drive proliferation? How does the balance between the two processes change with co-morbidities and treatment? Does one process influence the other? Which of the two is the better therapeutic target? The answers to these question are likely to identify new therapeutic targets in treating atherosclerosis.
- Determining the contribution of embryonic- versus bone marrow-derived macrophages in atherosclerosis.Some macrophages develop from hematopoietic stem cells, while others develop prior to birth and independent of the bone marrow. We ask the important question whether functional differences exist between these different macrophage populations and to what extent each population contributes to disease.
- Determining the molecular mechanisms that regulate macrophage accumulation in atherosclerosis.In addition to growth factors, hematopoiesis is tightly controlled at the transcriptional level. One such transcription factor, c-Myb, has been demonstrated to play an important role in the survival, proliferation, and differentiation of hematopoietic cells. We are currently studying the role of c-Myb in regulating inflammation in atherosclerosis.
c-Myb Exacerbates Atherosclerosis through Regulation of Protective IgM-Producing Antibody-Secreting Cells.
Cell Rep. 2019 May 21;27(8):2304-2312.e6
Publisher Correction: Self-renewing resident cardiac macrophages limit adverse remodeling following myocardial infarction.
Nat Immunol. 2019 May;20(5):664
Hypertension. 2019 Jan 14;:HYPERTENSIONAHA11811828
Self-renewing resident cardiac macrophages limit adverse remodeling following myocardial infarction.
Nat Immunol. 2019 Jan;20(1):29-39
Induction of Autonomous Memory Alveolar Macrophages Requires T Cell Help and Is Critical to Trained Immunity.
Cell. 2018 Oct 20;:
Monocyte and Macrophage Dynamics in the Cardiovascular System: JACC Macrophage in CVD Series (Part 3).
J Am Coll Cardiol. 2018 Oct 30;72(18):2198-2212
Clin Sci (Lond). 2018 Jun 29;132(12):1253-1256
Cell. 2018 May 31;173(6):1549
Stem Cells Dev. 2018 May 02;:
Cell. 2018 Feb 22;172(5):1050-1062.e14
Senior Scientist, Toronto General Hospital Research Institute (TGHRI)
Assistant Professor, Departments of Laboratory Medicine and Pathobiology and Immunology, University of Toronto