2004-2007: BSc (Biotechnology, Zoology, Chemistry), NIZAM College, Osmania University, Hyderabad, Telangana, India 

2007-2009: MSc (Biochemistry), Osmania University, Hyderabad, Telangana, India 

2011-2017: PhD (Biology), Academy of Scientific and industrial research (AcSIR), Ghaziabad, Uttar Pradesh. (Research Work carried out at CSIR-Indian Institute of Chemical Technology), Hyderabad, India. 

2017-2023: Post doctoral Research Associate, cardiovascular research Center, University of Virginia, Charlottesville, VA. 

2023-2025: Research Scientist, Cardiovascular Research Center, University of Virginia, Charlottesville, VA. 

Research Areas: Pro-inflammatory and senescence pathways in cardiovascular diseases (CVD), with a focus on atherosclerosis and myocardial infarction, using novel SMC- and EC-lineage tracing conditional knockout mouse models. 

Collaboration Opportunities: Seahorse-based metabolic assays, grant proposal development, and small-molecule drug screening in cardiovascular and cancer cell and animal models. 

Our lab investigates how inflammaging plays a key role in cardiovascular diseases, including atherosclerosis and myocrdial infarction by using SMC, EC-lineage atracing mouse models. We focus on the role of cellular senescence in SMC, EC and test both senolytics and anti-inflammatory molecules to modulate plaque progression, Fibrous cap maintenance, and tissue remodeling. By uncovering how these interventions influence aging pathways, we aim to develop strategies that promote cardiovascular health and extend healthy lifespan by conducting the late-stage intervention studies to better mimic the clinical trials.  

• Investigating the dichotomous beneficial and detrimental roles of pro-inflammatory signaling (e.g., IL1β–NFκB–NLRP3) in early versus advanced atherosclerosis. 

• Defining the roles of replicative (TERT pathway) versus stress-induced premature senescence in early and late stages of atherosclerosis. 

• Utilizing novel SMC- and EC-specific lineage-tracing and conditional knockout mouse models, and scRNAseq, and ultrasound imaging techniques. 

• Evaluating senolytics and small-molecule inhibitors in cardiovascular and cancer models. 

• Applying Seahorse metabolic assays and integrating omics approaches for translational insights. 

Full list of publications: https://scholar.google.com/citations?user=qh0mnnUAAAAJ 

SELECTED PUBLICATIONS 

1. Karnewar S, Karnewar V, Deaton R, Shankman LS, Benavente ED, Williams CM, Bradley X, Alencar GF, Bulut GB, Kirmani S, Baylis RA, Zunder ER, den Ruijter HM, Pasterkamp G, Owens GK. IL-1β inhibition partially negates the beneficial effects of diet-induced lipid lowering. https://www.ahajournals.org/doi/10.1161/ATVBAHA.124.320800 (Arterioscler Thromb Vasc Biol. 2024). IF 8.7 

1. Karnewar S, Karnewar V, Shankman LS, Owens GK. Treatment of advanced atherosclerotic mice with ABT-263 reduced indices of plaque stability and increased mortality. JCI Insight. 2024 Jan 23;9(2):e173863. doi: 10.1172/jci.insight.173863. PMID: 38258907; PMCID: PMC10906456. IF 8.0 

1. Karnewar S, Pulipaka S, Katta S, Panuganti D, Neeli PK, Thennati R, Jerald MK, Kotamraju S. Mitochondria-targeted esculetin mitigates atherosclerosis in the setting of aging via the modulation of SIRT1-mediated vascular cell senescence and mitochondrial function in Apoe-/- mice. Atherosclerosis. 2022 Jul 20; 356:28-40. IF 6.8 

1. Karnewar S, Neeli PK, Panuganti D, Sasikumar Kotagiri, Sreevidya Mallappa, Jain N, JM Kumar, Kotamraju S. Metformin regulates mitochondrial biogenesis and senescence through AMPK mediated H3K79 methylation: Relevance in age-associated vascular dysfunctions. BBA Molecular Basis of Disease. 2018; 1864: 1115-1128. IF 6.2 

1. Karnewar S, Vasamsetti SB, Gopoju R, Kanugula AK, Ganji SK, Sripadi P, Rangaraj N, Tupperwar N, JM Kumar, Kotamraju S: Mitochondria-targeted esculetin alleviates mitochondrial dysfunction by AMPK- mediated nitric oxide and SIRT3 regulation in endothelial cells: potential implications in atherosclerosis. Scientific Reports. 2016; 6, 24108. IF 5.1 

1. Shamsuzzaman S, Deaton RA, Salamon A, Doviak H, Serbulea V, Milosek VM, Evans MA, Karnewar S, Saibaba S, Alencar GF, Shankman LS, Walsh K, Bekiranov S, Kocher O, Krieger M, Kull B, Persson M, Michaëlsson E, Bergenhem N, Heydarkhan-Hagvall S, Owens GK. Novel Mouse Model of Myocardial Infarction, Plaque Rupture, and Stroke Shows Improved Survival With Myeloperoxidase Inhibition. Circulation. 2024 Jun 17. doi: 10.1161/CIRCULATIONAHA.123.067931. Epub ahead of print. PMID: 38881440. IF 38 

1. Aherrahrou R, Baig F, Theofilatos K, Lue D, Beele A, Örd T, Kaikkonen MU, Aherrahrou Z, Cheng Q, Ghosh SKB, Karnewar S, Karnewar V, Finn AV, Owens GK, Joner M, Mayr M, Civelek M. Secreted Protein Profiling of Human Aortic Smooth Muscle Cells Identifies Vascular Disease Associations. Arterioscler Thromb Vasc Biol. 2024 Apr;44(4):898-914. doi: 10.1161/ATVBAHA.123.320274. Epub 2024 Feb 8. PMID: 38328934; PMCID: PMC10978267. IF 8.7 

1. Benavente ED, Karnewar S, Buono M, Mili E, Hartman RJG, Kapteijn D, Slenders L, Daniels M, Aherrahrou R, Reinberger T, Mol BM, de Borst GJ, de Kleijn DPV, Prange KHM, Depuydt MAC, de Winther MPJ, Kuiper J, Björkegren JLM, Erdmann J, Civelek M, Mokry M, Owens GK, Pasterkamp G, den Ruijter HM. Female Gene Networks Are Expressed in Myofibroblast-Like Smooth Muscle Cells in Vulnerable Atherosclerotic Plaques. Arterioscler Thromb Vasc Biol. 2023 Aug 17. doi: 10.1161/ATVBAHA.123.319325. Epub ahead of print. PMID: 37589136. IF 8.7 

1. Alexandra AC Newman, Vlad Serbulea, Richard A. Baylis, Laura S. Shankman, Xenia Bradley, Alencar GF, Owsiany KM, Deaton AR, Karnewar S, Shamsuzzaman S, Liang Guo, Aloke Finn, Renu Virmani, Olga A. Cherepanova, Gary K. Owens*. The fibrous cap of atherosclerotic lesions arises from multiple cellular origins through PDGFRB- and bioenergetic-dependent mechanisms. Nat Metab 3, 166–181 (2021). https://doi.org/10.1038/s42255-020-00338-8. IF 20.8 

1. Gamze B. Bulut, Gabriel F. Alencar, Katherine M. Owsiany, Anh T. Nguyen, Santosh Karnewar, Ryan M. Haskins, Lillian K. Waller, Olga A. Cherepanova, Rebecca A. Deaton, Laura S. Shankman, Susanna R. Keller, and Gary K. Owens. KLF4-dependent perivascular plasticity contributes to adipose tissue inflammation. Arterioscler Thromb Vasc Biol. 2021 Jan; 41(1):284-301. doi: 10.1161/ATVBAHA.120.314703. Epub 2020 Oct 15. PMID: 33054397; PMCID: PMC7769966. IF 10.5 

1. Alencar GF, Owsiany KM, Karnewar S, Sukhavasi K, Mocci G, Nguyen AT, Williams CM, Shamsuzzaman S, Mokry M, Henderson CA, Haskins R, Baylis RA, Finn AV, McNamara CA, Zunder ER, Venkata V, Pasterkamp G, Björkegren J, Bekiranov S, Owens GK. Stem Cell Pluripotency Genes Klf4 and Oct4 Regulate Complex SMC Phenotypic Changes Critical in Late-Stage Atherosclerotic Lesion Pathogenesis. Circulation. 2020 Nov 24;142(21):2045-2059. IF 38 

1. Gayathri T, Karnewar S, Kotamraju S, Singh SP. High Affinity Neutral Bodipy Fluorophores for Mitochondrial Tracking. ACS Med Chem Lett. 2018 Jun 20;9(7):618-622. doi: 10.1021/acsmedchemlett.8b00022. PMID: 30034589; PMCID: PMC6047038. IF 4.0 

1. Katta S, Karnewar S, Panuganti D, Jerald MK, Sastry BKS, Kotamraju S. Mitochondria-targeted esculetin inhibits PAI-1 levels by modulating STAT3 activation and miR-19b via SIRT3: Role in acute coronary artery syndrome. J Cell Physiol. 2018 Jan;233(1):214-225. doi: 10.1002/jcp.25865. Epub 2017 May 3. PMID: 28213977. IF 4.5 

1. Vasamsetti SB, Karnewar S, Gopoju R, Gollavilli PN, Narra SR, Kumar JM, Kotamraju S. Resveratrol attenuates monocyte-to-macrophage differentiation and associated inflammation via modulation of intracellular GSH homeostasis: Relevance in atherosclerosis. Free Radic Biol Med. 2016 Jul;96:392-405. doi: 10.1016/j.freeradbiomed.2016.05.003. Epub 2016 May 5. PMID: 27156686. IF 5.6 

1. S. B. Vasamsetti, S. Karnewar, A. K. Kanugula, A. T. Raj, J. M. Kumar, S. Kotamraju: Metformin inhibits monocyte-to-macrophage differentiation via AMPK mediated inhibition of STAT3 activation: Potential role in atherosclerosis. Diabetes. 2015 Jun; 64(6):2028-41. IF 8.6 

CARDIOVASCULAR DRUG DISCOVERY LAB (CAP) 

PI- Dr. Santosh Karnewar 

Our long-term goal is to identify novel therapeutic targets in cardiovascular diseases, particularly atherosclerosis, myocardial infarction, and stroke. We focus on understanding the mechanisms driving atherosclerosis and developing interventions for age-associated disease. Special emphasis is placed on the role of inflammation and aging (Inflammaging) and its impact on disease progression and therapy. 

Our lab will investigate the cellular and molecular mechanisms that drive disease progression, emphasizing age-associated atherosclerosis and the inflammatory processes that exacerbate vascular pathology. By combining advanced SMC and EC- lineage tracing mouse models, scRNASeq, cy-TOF, and Ultrasound echo techniques, and mechanistic studies, we aim to understand how smooth muscle cells, endothelial cells, and immune cells contribute to plaque development, progression, and regression. Our recent work has highlighted the complex roles of senescence and IL-1β–dependent pro-inflammatory signaling in late-stage atherosclerosis. Furthermore, our novel mouse model of myocardial infarction, plaque rupture, and stroke will play key role in our studies.  Unlike traditional Apoe-/- and Ldlr-/- models, these mice develop spontaneous plaque rupture, MI, stroke, and increased mortality in response to Western diet (WD) feeding, closely mimicking human coronary artery disease (CAD) in aged patients.  

Cellular senescence accumulates in the vascular wall with age and drives atherosclerosis by promoting inflammation through the senescence-associated secretory phenotype (SASP). Senolytic agents, which selectively eliminate senescent cells, have shown promise in reducing plaque burden and vascular inflammation in early-stage disease. However, in advanced atherosclerosis, removing senescent vascular cells can destabilize plaques and impair smooth muscle–mediated repair, increasing cardiovascular risk. These findings highlight the complex, stage-dependent role of senescence and the need for precision-targeted senolytic/senomorphic therapies in atherosclerosis. 

By leveraging these novel lineage-tracing mouse models, we aim to investigate the role of IL-1β–NFκB–NLRP3 signaling and stress-induced premature senescence (SIPS) versus replicative senescence in smooth muscle cells, endothelial cells, and immune cells to identify novel therapeutic strategies for treating heart attack and stroke.