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Geena Paramel

Position: Researcher School/office: School of Medical Sciences

Email: Z2VlbmEucGFyYW1lbDtvcnUuc2U=

Phone: +46 19 303801

Room: X2101

Research subject

Biomedicine

About Geena Paramel

Geena Paramel received her PhD in Medical science with specialization in biomedicine at Örebro University, Sweden on a thesis titled ‘Innate Immunity in Human Atherosclerosis and Myocardial Infarction: Role of CARD8 and NLRP3’ in 2017. After conducting postdoctoral studies in metabolism lab at Dalhousie University, Canada, Geena returned to Örebro University and is actively involved both in research and teaching.

Research

Geena Paramel is an active member of the Cardiovascular Research Center (CVRC) at Örebro University, where her research focuses on understanding the roles of both endogenous and exogenous factors in atherosclerosis. Her studies investigate how these factors regulate molecular and clinical changes in key innate immunity proteins, such as CARD8, NLRP3, and IL-1β, which contribute to the development and progression of atherosclerosis.
In addition to investigating molecular mechanisms, she conducts collaborative research with industries to develop innovative strategies, including drugs and small molecule inhibitors, to reduce inflammation, thrombosis, and vascular fibrosis. Genetic variation studies relevant to inflammatory diseases are also a significant aspect of her research. Geena’s research extends to understanding the role of neutrophil extracellular traps (NETs) in atherosclerosis, as NETs can promote inflammation and thrombosis within atherosclerotic plaques. She also explores how cholesterol crystals, a hallmark of vulnerable plaques, contribute to inflammation and damage in vascular cells. Additionally, her studies involve examining serotonin receptors, particularly the 5-HT2B receptor, which has been implicated in vascular inflammation and fibrosis, to understand its potential as a therapeutic target in cardiovascular diseases. In addition, she examines the role of platelets, which are critical in thrombosis and hemostasis, exploring their contribution to inflammatory processes and their interaction with other immune components, such as NETs and cholesterol crystals, in the development and progression of atherosclerosis.

Uptake-of-cholesterol-crystals

Uptake of cholesterol crystals in human aortic smooth muscle cells (cholesterol crystals, white; cell marker, Red; nucleus, blue) (A); Expression of CARD8 protein (DAB/brown) in the endothelial cells (vWF/Red) of human carotid atherosclerotic plaque (B); Neutrophil extracellular traps formation in response to IL33 (NETs, green; neutrophils, red) (C); Expression of serotonin receptor, HTR2B in human carotid atherosclerotic plaque (HTR2B, green; nucleus, blue; cell markers, vWF, SMA, CD68 in order top to bottom in red) (D).

Her research also utilizes cardiac spheroids to bridge the gap between traditional in vitro studies and complex human physiology, offering a unique platform to study heart disease mechanisms in a highly controlled yet biologically relevant environment. By leveraging these models, she is investigating the effects of various disease causing factors on cardiac health, unraveling how they induce pathological changes and disrupt normal heart function.

CS_Geena Paramel Video: Cultured human cardiac spheroid composed of cardiomyocytes, cardiac fibroblasts, and coronary endothelial cells.

Teaching

Geena Paramel is involved in teaching advanced level courses both at the School of Health and sciences and Medical sciences. She is the course coordinator for the Master level course, Research overview and design course (MC2034/BL2009/MC036A) and semester 7 in the medical program. Her teaching responsibilities in the International master program in the department of medical science includes literature review writing, lectures and holding Problem based learning (PBL) sessions.

Collaborations

Geena Paramel has ongoing collaboration with Dalhousie University, Canada, Karolinska Institute and Swedish biotech companies.

Active projects

Research groups

Publications

Articles in journals

Jedlina, L. , Paramel Varghese, G. , Soboleva, S. , Chutna Olin, O. , Marianne, H. , Fransén, K. , Lindstam, M. , Brewinska-Olchowik, M. & et al. (2024). Antithrombotic but not anticoagulant activity of the thrombin-binding RNA aptamer Apta-1. British Journal of Pharmacology. [BibTeX]
Fransén, K. , Hiyoshi, A. , Paramel Varghese, G. & Hurtig-Wennlöf, A. (2024). Association between C10X polymorphism in the CARD8 gene and inflammatory markers in young healthy individuals in the LBA study. BMC Cardiovascular Disorders, 24 (1). [BibTeX]
Kapetanaki, S. , Kumawat, A. K. , Paramel Varghese, G. , Persson, K. & Demirel, I. (2024). TMAO enhances TNF-α mediated fibrosis and release of inflammatory mediators from renal fibroblasts. Scientific Reports, 14 (1). [BibTeX]
Thazhathveettil, J. , Kumawat, A. K. , Demirel, I. , Sirsjö, A. & Paramel Varghese, G. (2024). Vascular smooth muscle cells in response to cholesterol crystals modulates inflammatory cytokines release and promotes neutrophil extracellular trap formation. Molecular Medicine, 30 (1). [BibTeX]
Wenglén, C. , Demirel, I. , Göthlin Eremo, A. , Grenegård, M. & Paramel Varghese, G. (2023). Targeting serotonin receptor 2B inhibits TGFβ induced differentiation of human vascular smooth muscle cells. European Journal of Pharmacology, 944. [BibTeX]
Kumawat, A. K. , Zegeye, M. M. , Paramel Varghese, G. , Baumgartner, R. , Gisterå, A. , Amegavie, O. , Hellberg, S. , Jin, H. & et al. (2022). Inhibition of IL17A Using an Affibody Molecule Attenuates Inflammation in ApoE-Deficient Mice. Frontiers in Cardiovascular Medicine, 9. [BibTeX]
Paramel Varghese, G. , Lindkvist, M. , Idosa, B. A. , Sebina, L. S. , Kardeby, C. , Fotopoulou, T. , Pournara, D. , Kritsi, E. & et al. (2022). Novel purine analogues regulate IL-1β release via inhibition of JAK activity in human aortic smooth muscle cells. European Journal of Pharmacology, 929. [BibTeX]
Kumawat, A. K. , Paramel Varghese, G. , Jayaprakash, K. & Demirel, I. (2021). Human Renal Fibroblasts, but Not Renal Epithelial Cells, Induce IL-1β Release during a Uropathogenic Escherichia coli Infection In Vitro. Cells, 10 (12). [BibTeX]
Paramel Varghese, G. , Karadimou, G. , Göthlin Eremo, A. , Ljungberg, L. , Hedin, U. , Olofsson, P. S. , Folkersen, L. , Paulsson Berne, G. & et al. (2020). Expression of CARD8 in human atherosclerosis and its regulation of inflammatory proteins in human endothelial cells. Scientific Reports, 10 (1). [BibTeX]
Kardeby, C. , Paramel Varghese, G. , Pournara, D. , Fotopoulou, T. , Sirsjö, A. , Koufaki, M. , Fransén, K. & Grenegård, M. (2019). A novel purine analogue bearing nitrate ester prevents platelet activation by ROCK activity inhibition. European Journal of Pharmacology, 857. [BibTeX]
Zegeye, M. M. , Lindkvist, M. , Fälker, K. , Kumawat, A. K. , Paramel Varghese, G. , Grenegård, M. , Sirsjö, A. & Ljungberg, L. U. (2018). Activation of the JAK/STAT3 and PI3K/AKT pathways are crucial for IL-6 trans-signaling-mediated pro-inflammatory response in human vascular endothelial cells. Cell Communication and Signaling, 16 (1). [BibTeX]
D'Souza, K. , Nzirorera, C. , Cowie, A. , Paramel Varghese, G. , Trivedi, P. , Eichmann, T. , Biswas, D. , Touaibia, M. & et al. (2018). Autotaxin-Lysophosphatidic Acid Signaling Contributed to Obesity-Induced Insulin Resistance in Muscle and Impairs Mitochondrial Metabolism. Journal of Lipid Research, 59 (10), 1805-1817. [BibTeX]
Paramel Varghese, G. , Folkersen, L. , Strawbridge, R. J. , Halvorsen, B. , Yndestad, A. , Ranheim, T. , Krohg-Sørensen, K. , Skjelland, M. & et al. (2016). NLRP3 Inflammasome Expression and Activation in Human Atherosclerosis. Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, 5 (5). [BibTeX]
Paramel, G. , Uporova, L. , Halfvarson, J. , Sirsjö, A. & Fransén, K. (2015). Polymorphism in the NLRP3 inflammasome-associated EIF2AK2 gene and inflammatory bowel disease. Molecular Medicine Reports, 11 (6), 4579-4584. [BibTeX]
Paramel, G. , Folkersen, L. , Strawbridge, R. J. , Elmabsout, A. , Särndahl, E. , Lundman, P. , Jansson, J. , Hansson, G. K. & et al. (2013). CARD8 gene encoding a protein of innate immunity is expressed in human atherosclerosis and associated with markers of inflammation. Clinical Science, 125 (8), 401-407. [BibTeX]
Paramel, G. , Fransén, K. , Hurtig-Wennlöf, A. , Bengtsson, T. , Jansson, J. & Sirsjö, A. (2013). Q705K variant in NLRP3 gene confers protection against myocardial infarction in female individuals. Biomedical Reports, 1 (6), 879-882. [BibTeX]

Articles, reviews/surveys

Paramel Varghese, G. , D’Souza, K. & Kienesberger, P. (2018). Lysophosphatidic Acid Signaling in Obesity and Insulin Resistance. Nutrients, 10 (4). [BibTeX]
Paramel, G. , Sirsjö, A. & Fransén, K. (2015). Role of genetic alterations in the NLRP3 and CARD8 genes in health and disease. Mediators of Inflammation. [BibTeX]

Conference papers

Lindkvist, M. , Paramel Varghese, G. , Rydberg Millrud, C. , Rattik, S. , Grönberg, C. , Liberg, D. & Fransén, K. (2024). Novel antibodies targeting IL1RAP affects markers of vascular inflammation and adhesion in endothelial cells. In: TOLL 2024 ABSTRACT E-BOOK. Paper presented at TOLL 2024 - Road to translation, Rotterdam, The Netherlands, April 17-20, 2024. (pp. 236-236). [BibTeX]
Thazhathveettil, J. , Kumawat, A. , Demirel, I. , Sirsjö, A. & Paramel, G. (2023). Cholesterol crystals uptake in vascular smooth muscle cells modulates local immune responses. In: Atherosclerosis. Paper presented at 91st Annual Meeting of the European-Atherosclerosis-Society (EAS 2023), Mannheim, Germany, May 21-24, 2023. (pp. S9-S9). Elsevier. [BibTeX]
Lindkvist, M. , Paramel Varghese, G. , Rydberg Millrud, C. , Rattik, S. , Grönberg, C. , Liberg, D. & Fransén, K. (2023). IL1RAP: a future target to reduce vascular inflammation and adhesion?. Paper presented at Chemical biology workshop - Drug and biomarker discovery Institute of Chemical Biology, National Hellenic Research Foundation, Athens, Greece, 23-25 November , 2023. [BibTeX]
Fotopolou, T. , Ansari, S. , Paramel Varghese, G. , Lindkvist, M. , Ramström, S. , Pournara, D. , Ifanti, E. , Kritsi, E. & et al. (2021). Study of the anti platelet/anti-thromobotic activity of 6-piperazinyl-purien analogues. Paper presented at 18th Hellenic Symposium on Medicinal Chemistry, 25-27 feb. 2021. [BibTeX]
Biswas, D. , Cowie, A. , Tozer, K. , Perez, L. J. , Trivedi, P. , Bartlett, J. J. , Duffley, L. , Dao, K. T. & et al. (2018). Adverse Cardiometabolic Outcomes in Obese Patients Correlates Strongly with Defective Branched-Chain Amino Acid Catabolism. In: Journal of Molecular and Cellular Cardiology. Paper presented at 37th Annual Conference of the North-American-Section (NAS) of the International-Society-for-Heart-Research (ISHR) - Cardiovascular Disease in Vulnerable Populations, Halifax, CANADA, MAY 29-JUN 01, 2018. (pp. 121-122). Elsevier. [BibTeX]
Fransén, K. , Paramel Varghese, G. , Jansson, J. , Eriksson, P. & Sirsjö, A. (2016). Molecular genetic aspects of the NLRP3 inflammasome in cardiovascular disease. Paper presented at Miami Winter symposium 2016, Miami, Florida, USA, 24-27 Jan., 2016. [BibTeX]

Doctoral theses, comprehensive summaries

Paramel Varghese, G. (2017). Innate immunity in human atherosclerosis and myocardial infarction: Role of CARD8 and NLRP3. (Doctoral dissertation). (Comprehensive summary) Örebro: Örebro University. [BibTeX]

Manuscripts

Kardeby, C. , Paramel Varghese, G. , Pournara, D. , Fotopoulou, T. , Sirsjö, A. , Koufaki, M. , Fransén, K. & Grenegård, M. A novel purine analogue bearing nitrate ester prevents platelet activation by ROCK activity inhibition. [BibTeX]
Paramel Varghese, G. , Göthlin Eremo, A. , Ljungberg, L. , Sirsjö, A. & Fransén, K. CARD8, a protein of innate immunity regulates the release of inflammatory cytokines in human endothelial cells. [BibTeX]
Lindkvist, M. , Paramel Varghese, G. , Göthlin Eremo, A. , Haque, A. , Rydberg Millrud, C. , Rattik, S. , Grönberg, C. , Liberg, D. & et al. IL-1RAP expression in human atherosclerosis : a future target of novel antibodies to reduce vascular adhesion and inflammation?. [BibTeX]
Paramel Varghese, G. , Zhang, B. , Khalaf, H. , Ljungberg, L. U. , Sirsjö, A. , Bengtsson, T. & Fransén, K. Poryphyromonas gingivalis induces IL-1β in aortic smooth muscle cells : possible role of gingipains?. [BibTeX]