Florea Lupu, Ph.D.

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.

Education
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

Other Activities
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.

Memberships
Romanian Society for Cell Biology, 1982
European Vascular Biology Organization, 1986
International Society for Haemostasis and Thrombosis, 1991
International Society for Fibrinolysis and Thrombolysis, 1992
Royal Microscopical Society, 1994
European Immunocytochemistry Club, 1994
American Society of Hematology, 2002
American Society for Investigative Pathology, 2003
Histochemical Society, 2003
American Thoracic Society, 2011
American Association of Immunologists, 2013
American Heart Association, 2013

Joined OMRF scientific staff in 2001

View more publications

Recent Publications

Puy C, Moellmer SA, Pang J, Vu H, Melrose A, Lorentz CU, Tucker EI, Shatzel JJ, Keshari RS, Lupu F, Gailani D, McCarty OJT. Coagulation factor XI regulates endothelial cell permeability and barrier function in vitro and in vivo. Blood, 2024 August, PMID: 39158072

Riecan M, Domanska V, Lupu C, Patel M, Vondrackova M, Rossmeisl M, Saghatelian A, Lupu F, Kuda O. Tissue-specific sex-dependent difference in the metabolism of fatty acid esters of hydroxy fatty acids. Biochim Biophys Acta Mol Cell Biol Lipids:159543, 2024 August, PMID: 39097081

Wu ML, Wheeler K, Silasi R, Lupu F, Griffin CT. Endothelial Chromatin-Remodeling Enzymes Regulate the Production of Critical ECM Components During Murine Lung Development. Arterioscler Thromb Vasc Biol, 2024 June, PMID: 38868942

Selected Publications

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.

Cardiovascular Biology Research Program, MS 45
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, OK 73104

Phone: (405) 271-7462
Fax: (405) 271-7417
E-mail: Florea-Lupu@omrf.org

For media inquiries, please contact OMRF’s Office of Public Affairs at news@omrf.org.

Robert Silasi-Mansat, Ph.D.
Research Assistant Professor

Cristina Lupu, Ph.D.
Staff Scientist

Ravi Keshari, Ph.D.
Associate Staff Scientist

Tomohiro Abe, Ph.D.
Postdoctoral Scientist

Mia Pederson-Rambo
Project Coordinator I

News from the Lupu lab

Fighting a Killer

March 20, 2023

February Two days before he almost died, Ryan Eisner felt great. In fact, if you’d asked him, Eisner, then about to begin his junior year as a point guard for the Drew University basketball team in New Jersey, would’ve told you he was in the best shape of his life. But when a seemingly routine […]

OMRF receives $3.1 million to study sepsis

February 22, 2022

Research ultimately could help combat a leading cause of death globally.

Walking the walk: Sepsis survivor overcomes illness, amputation

September 10, 2020

Sept. 13 is World Sepsis Day, established to raise awareness of the deadly condition.

Discovery could help treat Tylenol overdoses

June 12, 2018

New research from OMRF has pinpointed the cause of liver bleeding during acetaminophen overdose, as well as a possible treatment.

OMRF honors Everest, five scientists

April 13, 2018

At its annual honors and awards ceremony on Thursday, OMRF presented Christy Everest with its Board of Directors Distinguished Service Award.

OMRF receives four grants totaling more than $5 million

August 8, 2017

The grants cover a range of areas, including colitis and colon cancer, sepsis, genomic tools, and outreach strategies for clinical trials.

OMRF collaborates with GSK to develop novel treatments for severe inflammatory diseases

July 24, 2017

This collaboration is part of GSK’s “Discovery Partnerships with Academia” (DPAc) efforts.

OMRF researcher tests new approach for treating deadly blood infection

July 18, 2017

Lupu’s findings were published in the Proceedings of the National Academy of Sciences.

Investigating the role of obesity in arthritis

February 21, 2017

Osteoarthritis, or OA, is the most common form of disability in the U.S.

OMRF discoveries could lead to better treatment for lymphedema

December 7, 2015

There is currently no cure for lymphedema but new research might help manage it.

Military academy students complete summer of research at OMRF

July 21, 2015

Muskogee physician keeps father’s memory alive with scholar program.

OMRF receives $14.5 million grant to continue anthrax studies

August 13, 2014

Grant renewal adds years 11-15 of funding for anthrax research projects

OMRF discovery could stop deadly blood vessel hemorrhaging

December 13, 2013

A protein is key to the structural integrity surrounding blood vessels.

Scientists discover novel functions of platelets

September 3, 2013

Researchers found the answer to a long-standing medical mystery in platelets.

$2.1 million grant to help study deadly blood poisoning

January 3, 2012

Scientists seek treatment options for sepsis, which kills thousands annually

Collaboration yields cancer finding

January 19, 2011

OMRF and OU teamed up to discover new information about cancer.

Researchers turn years of heart science on its ear

January 3, 2011

McEver finds new information about a protein vital to the immune response

OMRF discovery could stop organ damage and death in sepsis and trauma

June 22, 2010

Discovery may help lower deaths from severe sepsis and traumatic injuries.

OMRF scientists discover promising new path for treating traumas

October 26, 2009

Antibody could slow internal bleeding, fluid build-up

OMRF Receives $10 Million Grant

September 30, 2003

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 […]