Dr Manikandan Subramanian

Profile

ORCID iD: 0000-0002-2608-3890

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

Group members

Dr Umesh Dhawan (Postdoctoral Research Associate); Aarushi Singhal (PhD student); Purbasha Bhattachary (PhD student - External) 

Summary

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

1. Bhattacharya P, Dhawan UK, Hussain MT, Singh P, Bhagat KK, Singhal A, Austin-Williams S, Sengupta S, Subramanian M. Efferocytes release extracellular vesicles to resolve inflammation and tissue injury via prosaposin-GPR37 signaling. Cell Reports. 2023 Jul 25;42(7):112808.
2. Dhawan UK, Margraf A, Lech M, Subramanian M. Hypercholesterolemia promotes autoantibody production and a lupus-like pathology via decreased DNase-mediated clearance of DNA. J Cell Mol Med. 2022 Oct;26(20):5267-5276
3. Manickam V, Dhawan UK, Singh D, Gupta M, Subramanian M, (2022), Pomegranate Peel Extract Decreases Plaque Necrosis and Advanced Atherosclerosis Progression in Apoe -/- mice. Front. Pharmacol. 2022 Jun 1;13:888300.
4. Dhawan UK, Bhattacharya P, Narayanan S, Manickam V, Aggarwal A, Subramanian M, (2021), Hypercholesterolemia Impairs Clearance of Neutrophil Extracellular Traps and Promotes Inflammation and Atherosclerotic Plaque Progression. Arterioscler Thromb Vasc Biol. doi: 10.1161/ATVBAHA.120.316389.
5. 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
6. 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. Cell. Oct 5;171(2):331-345.e22. (*, equal first authors).
7. 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).
8. 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.
9. 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)
10. 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).
11. 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. Nature. Feb 27;506(7489):503-6.
12. 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.
13. 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).
    
    Review articles
    
    
14. Perretti M, Subramanian M. Resolution pharmacology - A fresh approach to the clinical management of human inflammatory diseases. Semin Immunol. 2022 Dec 22;65:101669.
15. Bhattacharya P, Kanagasooriyan R, Subramanian M, (2022), Tackling inflammation in atherosclerosis: Are we there yet and what lies beyond? Curr Opin Pharmacol. 2022 Aug 26;66:102283.
16. Subramanian M, Marelli-Berg FM, (2021), CD36 pumps fat to defang killer T cells in tumors. Cell Metab. Aug 3;33(8):1509-1511.
17. Dhawan UK, Singhal A, Subramanian M, (2021), Dead cell and debris clearance in the atherosclerotic plaque: Mechanisms and therapeutic opportunities to promote inflammation resolution. Pharmacol Res. Jun 2;170:105699.

Collaborators

Internal

• Professor Mauro Perretti (WHRI)
• Professor Amrita Ahluwalia (WHRI)

External

• Professor Catherine Godson, University College Dublin, Ireland
• Professor Shantanu Sengupta, CSIR-Institute of Genomics and Integrative Biology, India

Disclosures

No disclosures.