Hypercholesterolemia impairs clearance of neutrophil extracellular traps and promotes inflammation and atherosclerotic plaque progression
Arteriosclerosis, Thrombosis, and Vascular Biology · 41(10), 2021
63 Cited by
Immunology · Inflammation Resolution
Inflammation
Resolution
Immunologist · The Francis Crick Institute, London
Uncovering how the body switches off inflammation — across cardiovascular disease, lupus, and fungal immunity — to reveal new therapeutic opportunities.
Macrophage DNases clear NET-DNA in the atherosclerotic plaque. Impaired DNase responses let NETs persist and drive plaque progression — restoring DNase 1 reduces necrotic core and inflammation.
Circulation Research 2025 ↗
225+
Citations
7
h-index
6
i10-index
10+
Publications
Published in
Leading peer-reviewed journals
Research Focus
Areas of study
Cardiovascular Disease
How impaired clearance of dead cells and NETs drives atherosclerotic plaque progression.
Inflammation Resolution
Signalling programs and vesicles through which immune cells actively end inflammation.
Lupus & Autoimmunity
Defective efferocytosis and immune dysregulation underlying systemic autoimmune disease.
Fungal Immunity
How innate immunity senses fungal pathogens and tips toward protection or pathology.
Advancing health through the biology of inflammation resolution.
Umesh Dhawan
Postdoctoral Researcher · London, UK
Selected Work
Publications
Efferocytes release extracellular vesicles to resolve inflammation and tissue injury via prosaposin–GPR37 signaling
Cell Reports · 42(7), 2023
48 Cited by
Dead cell and debris clearance in the atherosclerotic plaque: mechanisms and therapeutic opportunities to promote inflammation resolution
Pharmacological Research · 170, 2021
43 Cited by
Pomegranate peel extract decreases plaque necrosis and advanced atherosclerosis progression in Apoe−/− mice
Frontiers in Pharmacology · 13, 2022
33 Cited by
Figure adapted (cropped) from the article · CC BY 4.0
Macrophage DNases limit neutrophil extracellular trap–mediated defective efferocytosis in atherosclerosis
Circulation Research · 137(10), 2025
16 Cited by
Hypercholesterolemia promotes autoantibody production and a lupus-like pathology via decreased DNase-mediated clearance of DNA
Journal of Cellular and Molecular Medicine · 26(20), 2022
9 Cited by
Figure adapted (cropped) from the article · CC BY 4.0
TRIB3 links endoplasmic reticulum stress to impaired efferocytosis in atherosclerosis
Circulation Research · 137(12), 2025
5 Cited by
β1-Integrin-mediated uptake of chondrocyte extracellular vesicles regulates chondrocyte homeostasis
International Journal of Molecular Sciences · 25(9), 2024
4 Cited by
Figure adapted (cropped) from the article · CC BY 4.0
In Preparation
Unpublished manuscripts
Current work not yet in the peer-reviewed record — new mechanisms in antifungal immunity and the metabolism of inflammation resolution.
Under revision · Science
Macrophages dismantle fungal hyphae through ARPC5-dependent actin rings
Macrophages build Arp2/3 actin rings around hyphae that sequester Dectin-1 and SHIP-1, packaging fungal cell-wall fragments into immunologically silent extracellular vesicles — revealing how antifungal inflammation is switched off.
Dhawan U et al.
Read more ↗
In preparation
Macrophages recycle mitochondria from engulfed apoptotic cells to fuel sustained efferocytosis
Macrophages salvage mitochondria from the apoptotic cells they engulf, repolarize them, and wire them into their own network — supplying the energy for continual dead-cell clearance and driving inflammation resolution.
Dhawan U et al.
Read more ↗
In preparation
Pharmacological enhancement of efferocytosis for inflammation resolution
A high-throughput phenotypic screen of FDA-approved and Tocris bioactive compounds identifies and validates small molecules that boost macrophage efferocytosis — a foundation for drug repurposing toward pro-resolving therapies.
Dhawan U et al.
Read more ↗
Macrophages dismantle fungal hyphae through ARPC5-dependent actin rings that package cell-wall fragments into immunologically silent extracellular vesicles
Pathogenic fungi are encased in rigid polysaccharide cell walls that contain potent pathogen-associated molecular patterns (PAMPs) but cannot be degraded by mammalian enzymes. During infection, fungi form large hyphae that are too large to be phagocytosed, leaving the mechanisms that eliminate persistent inflammatory cell wall material unknown. Here, we identify an actin-dependent mechanism by which macrophages dismantle fungal hyphal cell walls. Macrophages assemble specialized ARPC5-containing Arp2/3-dependent actin rings around hyphae that sequester the antifungal receptor Dectin-1 together with the inhibitory phosphatase SHIP-1, thereby limiting inflammatory signalling while packaging fungal cell wall fragments into multivesicular bodies for release as immunologically silent extracellular vesicles that disseminate to the lungs and circulation.
ARPC5-deficient macrophages fail to dismantle hyphae, resulting in Dectin-1-dependent inflammation and the release of pro-inflammatory extracellular vesicles. Consistently, macrophage-specific deletion of Arpc5 in experimental aspergillosis impairs fungal cell wall processing and causes Dectin-1-dependent mortality. These findings reveal that post-mortem management of fungal PAMPs is essential for maintaining immune tolerance during fungal infection.
Live imaging
Macrophages recycle mitochondria from engulfed apoptotic cells to fuel sustained efferocytosis and inflammation resolution
Every day, tissue macrophages eliminate 200–400 billion apoptotic cells to maintain tissue homeostasis and prevent secondary necrosis, which would otherwise release damage-associated molecular patterns (DAMPs) and drive chronic inflammation. Because apoptotic cells are often comparable to or larger than the macrophages that engulf them, continuous efferocytosis imposes an extraordinary bioenergetic burden — and how macrophages sustain this lifelong demand has remained a fundamental unanswered question.
Here, we uncover a mechanism in which macrophages selectively acquire mitochondria from engulfed apoptotic cells, restore their membrane potential through repolarization, and integrate these functional organelles into their own mitochondrial network. The recycled mitochondria enhance oxidative metabolism and ATP production, providing the energy to sustain subsequent rounds of efferocytosis, while the remaining cargo is directed to lysosomal degradation. Disrupting mitochondrial acquisition or repolarization compromises clearance, causing accumulation of dying cells, secondary necrosis, and heightened inflammation — establishing intercellular mitochondrial recycling as a fundamental driver of inflammation resolution.
Pharmacological enhancement of efferocytosis for inflammation resolution
Defective efferocytosis — the inefficient clearance of apoptotic cells — is a hallmark of numerous chronic inflammatory diseases, including cardiovascular disease, autoimmune disorders, fibrosis, and neurodegeneration. Despite its central role in maintaining tissue homeostasis, no approved therapies are specifically designed to enhance macrophage efferocytosis.
To address this unmet need, I developed a high-throughput phenotypic screening platform to identify small molecules that enhance macrophage efferocytosis. By screening FDA-approved drug libraries together with a curated Tocris bioactive compound collection, I identified and experimentally validated multiple compounds that significantly improve the efficiency of apoptotic cell clearance.
This work establishes a foundation for drug repurposing to therapeutically enhance inflammation resolution. Ongoing studies focus on defining the molecular mechanisms underlying these compounds and evaluating their translational potential — leveraging clinically tractable molecules with established safety profiles to accelerate the development of novel pro-resolving therapies.
About
Biography
Dr. Umesh Kumar Dhawan was born in Dausa, Rajasthan (India), and raised in the small rural village of Rampura Khurd with limited access to education. He studied at the local government school until the fifth standard, travelled daily to a neighbouring village to continue through the eighth standard, and later moved to Dausa city to complete his secondary education.
These early challenges shaped his resilience, discipline, and belief in the transformative power of education. Fascinated by biology, he pursued a Bachelor's degree in Biotechnology at the University of Rajasthan, followed by a Master's degree in Biotechnology at the University of Allahabad after qualifying the Combined Biotechnology Entrance Examination (CEEB). His postgraduate education was supported by a fellowship from the Department of Biotechnology (DBT), Government of India.
He later qualified the CSIR-UGC NET, DBT-Junior Research Fellowship (DBT-JRF), and GATE examinations and began his doctoral research at CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB), New Delhi, under the supervision of Dr. Manikandan Subramanian. He was subsequently awarded the prestigious Queen Mary University of London Principal's Studentship, enabling him to continue his Ph.D. research at the William Harvey Research Institute, where he earned a Ph.D. in Cardiovascular Medicine. He then completed postdoctoral training at Queen Mary University of London before joining the Francis Crick Institute, London, as a Postdoctoral Fellow.
Dr. Dhawan's research focuses on understanding how the immune system resolves inflammation and maintains tissue homeostasis. His discoveries have revealed fundamental mechanisms governing the clearance of neutrophil extracellular traps (NETs), apoptotic cells, and fungal pathogens, providing new insights into macrophage biology, inflammation resolution, and chronic inflammatory diseases.
From a small village in Rajasthan to one of the world's leading biomedical research institutes, his journey reflects the power of perseverance, scientific curiosity, and opportunity. His long-term vision is to establish an internationally recognised research programme in India dedicated to understanding inflammation resolution and immune homeostasis while mentoring the next generation of scientists, particularly those from rural and underrepresented communities.
His story carries a simple message: where you begin does not define how far you can go.
Circulation Research
Cell Reports
ATVB
Pharmacological Research
Frontiers in Pharmacology
J Cellular & Molecular Medicine
Int. J. Molecular Sciences
Contact
Get in touch
Interested in collaboration, a talk, or a question about the research? Send a message below, or reach me directly.
Email
umesh.dhawan@crick.ac.uk
Institution
The Francis Crick Institute, London
Google Scholar
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ORCID
0009-0001-5395-5527 ↗
LinkedIn
in/umesh-dhawan-phd ↗