Blood clotting plays an important role in the body. We depend on clotting to help close wounds and keep us from bleeding too much. But when we clot more than normal, it can lead to heart attack, stroke, or other diseases of the cardiovascular system.
We look not only at blood itself but also at the way it interacts with the inside lining of the blood vessels, called the endothelium. This thin layer of cells works with the blood, so the latter knows when to clot—or not. In particular, we study the process that controls the start of blood clotting at the point where the blood and the vessel wall interact.
We also study the changes that lead to the formation of unwanted and/or excessive blood clots during sepsis. Sepsis is a serious blood infection that kills approximately 11 million people worldwide each year. It occurs when the body must fight a severe infection that has spread through the body via the bloodstream. If a patient develops sepsis, they will likely suffer widespread blood clotting coupled with a state of low blood pressure called “shock.” This condition can develop either because of the body’s own defense system or from toxic substances made by infectious agents, such as bacteria and viruses, like the SARS-CoV-2 that causes the potentially deadly COVID-19.
The main focus of our work is directed to the pathophysiology and therapy of sepsis. In particular we look at the steps involved in the progression of sepsis and how they lead to organ damage and, many times, death. Our group studies bacterial sepsis that occurs from exposure to Escherichia coli, Staphylococcus aureus or anthrax and the sequence of overlapping disease conditions involved, any one of which can be lethal. Furthermore, we are testing new therapies targeting the contact phase pathways that initiate blood clotting, and the complement activation mechanisms and immune responses associated with these pathways. Both lines of investigation aim to provide in-depth knowledge on potentially new drugs that will prevent organ damage and death in septic patients. A new research project is directed toward the identification of biomarkers that can predict the stage and the outcome of sepsis and can help the physician apply the most appropriate treatment. By learning more about the way sepsis infection develops and spreads, we hope to find ways to diagnose the condition earlier and develop more effective ways to treat it.
Another line of research focuses on what triggers the normal blood clotting system. We study a protein on the surface of vascular cells that is responsible for telling the blood to clot. This protein, known as tissue factor, is strictly regulated by a natural inhibitor called tissue factor pathway inhibitor (TFPI). We also discovered a novel protein called ADTRP that could play a role in the modulation of TFPI function. By looking at the ways that TFPI is regulated in the vessels, we hope to identify new proteins involved in the process and increase our understanding of blood clotting.
M.S., Faculty of Biology, University of Cluj, Romania, 1975
Ph.D., Institute of Cellular Biology and Pathology, Bucharest, Romania, 1986
Honors and Awards
1983 Fulbright Fellow, US Council for International Exchange of Scholars
1994 Young Investigator Award of American Health Association
2018 H. Allen & Mary K. Chapman Chair in Medical Research, Oklahoma Medical Research Foundation
Serves as Associate Editor of the Journal of Cellular and Molecular Medicine.
Reviews articles submitted to Blood, Blood Advances, Proceedings of National Academy of Sciences of U.S.A., Journal of Cell Biology, Journal of Biological Chemistry, Journal of Cellular and Molecular Medicine, Circulation, Circulation Research, Journal of Thrombosis and Haemostasis, Thrombosis and Haemostasis, Arteriosclerosis Thrombosis and Vascular Biology, Haemostasis, etc.
Reviews grants submitted to National Institutes of Health, American Heart Association, British Heart Foundation, Science Foundation of Ireland, Wellcome Trust, Austrian National Science Foundation, and European Union.
American Heart Association -2013
American Association of Immunologists – 2013
American Thoracic Society - 2011
Histochemical Society – 2003
American Society for Investigative Pathology – 2003
American Society of Hematology – 2002
European Immunocytochemistry Club – 1994
Royal Microscopical Society – 1994
International Society for Fibrinolysis and Thrombolysis – 1992
International Society for Haemostasis and Thrombosis – 1991
European Vascular Biology Organization – 1986
Romanian Society for Cell Biology – 1982
Joined OMRF Scientific Staff in 2001.
Jiang Y, Tang Y, Hoover C, Kondo Y, Huang D, Restagno D, Shao B, Gao L, Michael McDaniel J, Zhou M, Silasi-Mansat R, McGee S, Jiang M, Bai X, Lupu F, Ruan C, Marth JD, Wu D, Han Y, Xia L. Kupffer cell receptor CLEC4F is important for the destruction of desialylated platelets in mice. Cell Death Differ, 2021 November, PMID: 33993195, PMCID: PMC8564511
Keshari RS, Popescu NI, Silasi R, Regmi G, Lupu C, Simmons JH, Ricardo A, Coggeshall KM, Lupu F. Complement C5 inhibition protects against hemolytic anemia and acute kidney injury in anthrax peptidoglycan-induced sepsis in baboons. Proc Natl Acad Sci U S A 118, 2021 September, PMID: 34507997, PMCID: PMC8449412
Chaftari P, Qdaisat A, Chaftari AM, Maamari J, Li Z, Lupu F, Raad I, Hachem R, Calin G, Yeung SJ. Prognostic Value of Procalcitonin, C-Reactive Protein, and Lactate Levels in Emergency Evaluation of Cancer Patients with Suspected Infection. Cancers (Basel) 13, 2021 August, PMID: 34439240, PMCID: PMC8393196
Silasi R, Keshari RS, Regmi G, Lupu C, Georgescu C, Simmons JH, Wallisch M, Kohs TCL, Shatzel JJ, Olson SR, Lorentz CU, Puy C, Tucker EI, Gailani D, Strickland S, Gruber A, McCarty OJT, Lupu F. Factor XII plays a pathogenic role in organ failure and death in baboons challenged with Staphylococcus aureus. Blood. 2021 Jul 15;138(2):178-189. doi: 10.1182/blood.2020009345. PMID: 33598692; PMCID: PMC8288658.
Keshari RS, Silasi R, Popescu NI, Georgescu C, Chaaban H, Lupu C, McCarty OJT, Esmon CT, Lupu F. Fondaparinux pentasaccharide reduces sepsis coagulopathy and promotes survival in the baboon model of Escherichia coli sepsis. J Thromb Haemost. 2020 Jan;18(1):180-190. doi: 10.1111/jth.14642. Epub 2019 Oct 16. PMID:31549765; PMCID: PMC6940562.
Silasi R, Keshari RS, Lupu C, Van Rensburg WJ, Chaaban H, Regmi G, Shamanaev A, Shatzel JJ, Puy C, Lorentz CU, Tucker EI, Gailani D, Gruber A, McCarty OJT, Lupu F. Inhibition of contact-mediated activation of factor XI protects baboons against S aureus-induced organ damage and death. Blood Adv. 2019 Feb 26;3(4):658-669. doi: 10.1182/bloodadvances.2018029983. Erratum in: Blood Adv. 2020 Aug 11;4(15):3741. PMID: 30808684; PMCID: PMC6391670.
Popescu NI, Silasi R, Keshari RS, Girton A, Burgett T, Zeerleder SS, Gailani D, Gruber A, Lupu F, Coggeshall KM. Peptidoglycan induces disseminated intravascular coagulation in baboons through activation of both coagulation pathways. Blood. 2018 Aug 23;132(8):849-860. doi: 10.1182/blood-2017-10-813618. Epub 2018 Jun 19. PMID: 29921614; PMCID: PMC6107880.
Keshari RS, Silasi R, Lupu C, Taylor FB Jr, Lupu F. In vivo-generated thrombin and plasmin do not activate the complement system in baboons. Blood. 2017 Dec 14;130(24):2678-2681. doi: 10.1182/blood-2017-06-788216. Epub 2017 Oct 11. PMID: 29021229; PMCID: PMC5731087.
Keshari RS, Silasi R, Popescu NI, Patel MM, Chaaban H, Lupu C, Coggeshall KM, Mollnes TE, DeMarco SJ, Lupu F. Inhibition of complement C5 protects against organ failure and reduces mortality in a baboon model of Escherichia coli sepsis. Proc Natl Acad Sci U S A. 2017 Aug 1;114(31):E6390-E6399. doi:10.1073/pnas.1706818114. Epub 2017 Jul 18. PMID: 28720697; PMCID: PMC5547645.
Cristina Lupu, Ph.D.
Ravi Shankar Keshari, Ph.D.
Assistant Staff Scientist
Robert Silasi-Mansat, Ph.D.
Associate Staff Scientist
Girija Regmi, Ph.D.
Senior Research Technician
Hala Chaaban, M.D.
Gary T. Kinasewitz, M.D.
Administrative Assistant IV
News from the Lupu lab
The Oklahoma Medical Research Foundation announced today that it has received a $10 million grant from the National Institutes of Health. “This is yet another important step in the emergence of Oklahoma as a center of biomedical excellence,” said OMRF President Dr. J. Donald Capra. “Five years ago, this state had never seen a $10 […]