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.
Cell. 2018 Feb 22;172(5):1050-1062.e14
Cell. 2018 Jan 11;172(1-2):176-190.e19
A CD103+ Conventional Dendritic Cell Surveillance System Prevents Development of Overt Heart Failure during Subclinical Viral Myocarditis.
Immunity. 2017 Nov 21;47(5):974-989.e8
Sci Rep. 2017 Aug 09;7(1):7653
JCI Insight. 2017 Jul 20;2(14):
S-Nitrosoglutathione Reductase (GSNOR) Deficiency Confers Improved Survival and Neurological Outcome in Experimental Cerebral Malaria.
Infect Immun. 2017 Jul 03;:
Erratum: CCL19-CCR7-dependent reverse transendothelial migration of myeloid cells clears Chlamydia muridarum from the arterial intima.
Nat Immunol. 2017 May 18;18(6):705
CCL19-CCR7-dependent reverse transendothelial migration of myeloid cells clears Chlamydia muridarum from the arterial intima.
Nat Immunol. 2016 Sep 26;
Circ Res. 2016 May 13;118(10):1454-6
c-Myb Regulates Proliferation and Differentiation of Adventitial Sca1+ Vascular Smooth Muscle Cell Progenitors by Transactivation of Myocardin.
Arterioscler Thromb Vasc Biol. 2016 May 12;
Scientist, Toronto General Hospital Research Institute (TGHRI)
Assistant Professor, Departments of Laboratory Medicine and Pathobiology and Immunology, University of Toronto