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The William Harvey Research Institute - Faculty of Medicine and Dentistry

Dr Manikandan Subramanian

Manikandan

Senior Lecturer in Cardiovascular Inflammation

Centre: Biochemical Pharmacology

Email: m.subramanian@qmul.ac.uk
Twitter: @@Mani_CVD

Profile

Mani obtained his medical degree and clinical training from Kilpauk Medical College, India. He then pursued PhD in Immunology at the National Institute of Immunology followed by post-doctoral research at Columbia University Medical Center, New York, USA. Subsequently, Mani worked as an Associate Research Scientist in the Department of Medicine at Columbia University Medical Center before establishing his independent research laboratory in India as a Senior Scientist and Assistant Professor at the Institute of Genomics and Integrative Biology, New Delhi. His research was supported by grants from the Department of Biotechnology, Department of Science and Technology, Council of Scientific and Industrial Research, and an Intermediate Fellowship from the Wellcome Trust-DBT India Alliance. He joined the William Harvey Research Institute as a Senior Lecturer in Cardiovascular Inflammation in June 2020 to establish a research group focusing on understanding the mechanistic basis of impaired inflammation resolution response during dyslipidemia and to developing novel therapeutic strategies

Research

Cardiovascular diseases including myocardial infarction, stroke, and heart failure is the leading cause of death worldwide. One of the fundamental pathological process underlying these clinical conditions is the formation of an atherosclerotic plaque, which is characterized by the build-up of fat and fat-filled cells in the vascular wall. A subset of these atherosclerotic plaques progress to an advanced stage and display heightened inflammation, large areas of necrosis, and thin fibrous cap, pathological features that make them vulnerable to plaque rupture and adverse clinical outcomes. 

Our laboratory uses a combination of cell biology tools, animal models of obesity and atherosclerosis, as well patient samples for understanding the mechanistic basis of advanced atherosclerotic plaque progression with the ultimate goal of identifying therapeutic targets and drugs that would prevent rupture of atherosclerotic plaques via plaque stabilization.

Major research themes:

1. Understanding the immune and inflammatory mechanisms that lead to advanced atherosclerosis progression and associated complications.

2. Understanding the mechanistic basis of accelerated atherosclerosis progression in people with obesity.

3. Development of therapeutic strategies to promote inflammation resolution and stabilization of atherosclerotic plaques.

Key Publications

  • Yurdagul A Jr, Subramanian M, Wang X, Crown SB, Ilkayeva OR, Darville L, Kolluru GK, Rymond CC, Gerlach BD, Zheng Z, Kuriakose G, Kevil CG, Koomen JM, Cleveland JL, Muoio DM, Tabas I, (2020), Macrophage Metabolism of Apoptotic Cell-Derived Arginine Promotes Continual Efferocytosis and Resolution of Injury. Cell Metab. 2020 Mar 3;31(3):518-533.e10
  • Proto JD, Doran AC, Gusarova G, Yurdagul A Jr, Sozen E, Subramanian M, Islam MN, Rymond CC, Du J, Hook J, Kuriakose G, Bhattacharya J, Tabas I, (2018), Regulatory T Cells Promote Macrophage Efferocytosis During Inflammation Resolution. Immunity. 2018 Oct 16;49(4):666-677.e6.
  • Wang Y*, Subramanian M*, Yurdagul A Jr*, Barbosa-Lorenzi VC, Cai B, de Juan-Sanz J, Ryan TA, Nomura M, Maxfield FR, Tabas I, (2017), Mitochondrial Fission Promotes the Continued Clearance of Apoptotic Cells by Macrophages. Oct 5;171(2):331-345.e22. (*, equal first authors).
  • Subramanian M*, Proto J, Matsushima GK, Tabas I*, (2016), Deficiency of AXL in Bone Marrow-Derived Cells Does Not Affect Advanced Atherosclerotic Lesion Progression. Sci Rep. Dec 13; 6:39111. (*, Corresponding author).
  • Cai B, Thorp E, Doran A, Subramanian M, Lin CS, Fredman G, Tabas I, (2016), MerTK Cleavage Limits Pro-Resolving Mediator Biosynthesis and Exacerbates Tissue Inflammation. Proc Natl Acad Sci USA. Jun 7;113(23):6526-31.
  • Kamaly N, Fredman G, Fojas J, Subramanian M, Choi W, Zepeda K, Vilos C, Yu M, Gadded S, Wu J, Milton J, Leitao R, Rosa L, Hasan M, Gao H, Nguyen V, Harris J, Tabas I, Farokhzad OC, (2016), Targeted Interleukin-10 Nanotherapeutics Developed with a Microfluidic Chip Enhance Resolution of Inflammation in Advanced Atherosclerosis. ACS Nano. May 24;10(5):5280-92.
  • Subramanian M*, Ozcan L, Ghorpade S, Ferrante AW Jr., Tabas I*, (2015), Suppression of Adaptive Immune Cell Activation Does Not Alter Innate Immune Adipose Inflammation or Insulin Resistance in Obesity. Plos One. Aug 28;10(8): e0135842. (*, Corresponding author).
  • Subramanian M, Thorp E, Tabas I, (2015), Identification of a Non-Growth Factor Role for GM-CSF in Advanced Atherosclerosis: Promotion of Macrophage Apoptosis and Plaque Necrosis Through IL-23 Signaling. Circ Res. Jan 16;116(2): e13-24. (Accompanied by an editorial: Circ Res. 2015; 116:222-224)
  • Subramanian M*, Hayes C, Thorp E, Matsushima GK, Herz J, Liu K, Lakshmana MK, Tabas I*, (2014), An AXL/LRP-1/RANBP9 Complex Mediates DC Efferocytosis and Antigen Cross-Presentation In Vivo. J Clin Invest. Mar 3;124(3):1296-308. (*, corresponding author).
  • Westphalen K, Gusarova GA, Islam MN, Subramanian M, Cohen TS, Prince AS, Bhattacharya J, (2014), Sessile Alveolar Macrophages Communicate with Alveolar Epithelium to Modulate Immunity. Feb 27;506(7489):503-6. 
  • Kamaly N, Fredman G, Subramanian M, Gadde S, Pesic A, Cheung L, Fayad ZA, Langer R, Tabas I, Farokhzad OC, (2013), Development and In Vivo Efficacy of Targeted Polymeric Inflammation-Resolving Nanoparticles. Proc Natl Acad Sci USA. Apr 16; 110(16):6506-11.
  • Subramanian M*, Thorp E, Hansson GK, Tabas I*, (2013), Treg-Mediated Suppression of Atherosclerosis Requires MYD88 Signaling in DCs. J Clin Invest. Jan 2;123(1):179-88. (*, Corresponding author).
  • Liao X, Sluimer JS, Wang Y, Subramanian M, Brown K, Pattison SJ, Robbins J, Martinez J, Tabas I, (2012), Macrophage Autophagy Plays a Protective Role in Advanced Atherosclerosis. Cell Metab. Apr 4;15(4):545-53.

Review articles

  • Singhal A and Subramanian M*, (2017), Colony Stimulating Factors (CSFs): Complex Roles in Atherosclerosis. Cytokine. Oct 24. pii: S1043-4666(17)30317-4. (*, Corresponding author).
  • Subramanian M and Tabas I, (2014), A New RIDDle in DC-Mediated Cross-Presentation.  Nature Immunology 15(3):213-5.
  • Subramanian M* and Tabas I, (2014), Dendritic Cells in Atherosclerosis. Semin Immunopathol. Jan; 36(1):93-102. (*, Corresponding author).
  • Thorp E, Subramanian M, Tabas I, (2011), The Role of Macrophages and Dendritic Cells in the Clearance of Apoptotic Cells in Advanced Atherosclerosis. Eur J Immunol. 4(9):2515-8.

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