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Niranjana Natarajan, PhD, is an assistant professor of medicine in the Division of Rheumatology and Clinical Immunology at the University of Pittsburgh School of Medicine. Dr. Natarajan’s work focuses on understanding how immune cells drive inflammation in chronic diseases, particularly in the context of cardiovascular and autoimmune conditions.
Dr. Natarajan earned her doctorate from Johns Hopkins University and joined the division in July 2024, with a secondary appointment in the Department of Immunology. She completed a postdoctoral fellowship at the University of Pittsburgh Vascular Medicine Institute, working in the lab of Partha Dutta, DVM, PhD, associate professor of Medicine and Immunology. She has also been a postdoctoral scholar at Harvard University in the Department of Stem Cell and Regenerative Biology.
“I’ve always been fascinated by how immune cells communicate with their environment to drive health or disease,” says Dr. Natarajan. “My has been focused on investigating the immune system’s complex role in systemic inflammation and chronic disease progression, specifically in the cardiovascular system.”
Investigating Macrophages in Heart Failure with Preserved Ejection Fraction
Dr. Natarajan’s current research, supported by a National Institutes of Health K99/R00 grant, is focused on heart failure with preserved ejection fraction (HFpEF).
HFpEF is a condition in which the heart retains its pumping ability but struggles to relax and fill properly, leading to symptoms of heart failure. HFpEF accounts for about half of all heart failure cases and is frequently associated with comorbidities like obesity, diabetes, and hypertension. Effective treatments for HFpEF have remained elusive.
“HFpEF is a complex syndrome, and we don’t fully understand what drives it,” says Dr. Natarajan. “My research aims to uncover how macrophages contribute to heart remodeling and identify potential therapeutic targets.”
Dr. Natarajan’s research is trying to understand how inflammation and macrophages influence deleterious changes in the heart’s cellular structure and function. These changes include the activation of fibroblasts — a type of cell in the heart that can transform into myofibroblasts. This transformation leads to the excessive production of cardiac fibrosis and ultimately impairs the heart’s diastolic dysfunction.
Dr. Natarajan’s work is also exploring the molecular mechanisms driving these changes, particularly how macrophages communicate with fibroblasts. This research includes investigating complement signaling, which is an important immune system pathway, and assessing the role of the NLRP3 inflammasome — a protein complex involved in inflammation — in regulating fibroblast activity.
Using two animal models of HFpEF, Dr. Natarajan is working to understand the effects of depleting macrophages with clodronate liposomes to see if reducing inflammation can prevent or reverse harmful cellular changes in the heart.
“By targeting macrophages and the pathways they activate, we hope to identify ways to mitigate the damage and improve heart function in HFpEF,” says Dr. Natarajan.
By linking inflammation to heart remodeling, Dr. Natarajan’s research has the potential to identify new therapeutic targets and inform the development of effective treatments.
Linking Macrophages and Atherosclerosis
In addition to her work on HFpEF, Dr. Natarajan was the first author of a recent study published by the Dutta Lab and collaborators in Nature Communications that explored the role of macrophages in atherosclerosis. The study focused on how macrophages drive inflammation through mitochondrial DNA (mtDNA) production.
“Macrophages are meant to protect the body, but in certain conditions, they can go rogue,” says Dr. Natarajan. “In this study, we showed that excessive mtDNA production by macrophages acts as a signal that triggers chronic inflammation, accelerating plaque growth and destabilizing arterial walls.”
A key molecule, VCAM-1, was identified as a driver of this harmful process.
In their research, Dr. Natarajan and colleagues showed that blocking either VCAM-1 or mtDNA synthesis significantly reduced inflammation and stabilized plaques in preclinical models.
The findings from the study highlight potential therapeutic targets for preventing cardiovascular events.
“We’re learning how immune cells can sometimes contribute to disease progression, and understanding these pathways could lead to better interventions for patients with atherosclerosis,” says Dr. Natarajan.
Future Directions for Research
Dr. Natarajan is committed to advancing our understanding of the immune system’s role in chronic diseases and developing new strategies to treat inflammation-driven conditions.
“The immune system is such a powerful driver of health and disease,” says Dr. Natarajan. “I’m excited to keep exploring its potential to shape better treatments for patients.”
References and Further Reading
Other Related Publications Co-Authored by Dr. Natarajan
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