Fletcher B. Taylor, Jr., M.D.
Distinguished Career Scientist
My 101
Infections can affect a patient on a sliding scale, from mildly ill to deathly sick. Doctors routinely use antibiotics to treat them, but when an infection survives and finds its way into the bloodstream it can cause sepsis and the situation gets serious very quickly.
Sepsis is caused when a patient’s defense mechanisms, like the inflammatory system and blood clotting, are turned on high in order to kill the infection. Unfortunately, the process makes the damage even worse. Sepsis kills about half a million people every year.
In my lab, we studied the pathophysiology of sepsis, or why the body overreacts to infections in the bloodstream, by studying bacteria like E. coli and B. anthracis. By studying how the body’s natural defenses are activated, we learned more about the different kinds of sepsis and how best to treat them.
One treatment we developed by using an animal model of E. coli sepsis was used to treat severe sepsis in humans. The drug Xigris, or activated protein C, was used to reduce sepsis deaths by 20 percent. (The drug is no longer available.)
By delving into the many overlapping negative effects of E. coli in the bloodstream, we found that many could be lethal on their own, much less when combined. By studying every facet of the infection and how it changes the body, we looked at different variants of sepsis. Even forms treated by Xigris could be better addressed with different treatment categories.
Research
Sepsis, or septic shock, kills approximately 500,000 people worldwide each year. Antibiotics remain a first line of defense for those suffering from infections, such as pneumonia, which can enter the bloodstream and cause sepsis. Once past the barriers guarding the bloodstream, bacteria and viruses can directly damage the blood vessels supplying the various organs, but worse yet, these organisms can trick the patient’s own inflammatory and blood clotting defenses into overreacting and making the damage even worse.
Our group studied the pathophysiology of sepsis caused by organisms ranging from E. coli to B. anthracis using the baboon as a model of the human diseases caused by these organisms. We used monoclonal antibodies and related antagonists against the naturally occurring mediators and regulators of the inflammatory hemostatic and tissue repair networks to manipulate the host’s innate response to these organisms.
Using the baboon model of E. coli sepsis, we developed a treatment of severe sepsis in humans using activated protein C (Xigris, Eli Lilly; no longer available) that reduced the relative mortality by 20 percent. In order to improve these results, we focused on two lines of investigation. First, we studied the effect of high concentrations of activated protein C given earlier and over a much shorter time, thus reducing the total amount of enzyme required. This attenuated the initial metabolic inflammatory disturbance in the target cells, which is one of the principal effects of Xigris. Second, we studied the natural history of E. coli sepsis that consists of a sequence of partially overlapping pathophysiologic processes, any one of which can be lethal. This smorgasbord of processes may account for why Xigris worked in some cases but not in others. Analysis of both plasma and tissues using mRNA, antigen, enzyme activity and genetic analysis over the course of the response may lead to earlier and more specific diagnosis and more appropriate treatment of severe sepsis.
One cannot treat effectively unless one can diagnose, and one cannot diagnose unless one knows severe sepsis in all its guises.
Brief CV
Education
B.S., Stanford University, 1952
M.D., University of California School of Medicine, 1956
Surgical Internship, Southern Pacific Hospital, San Francisco, 1956-1957
Surgical & Pathology Residency, Southern Pacific Hospital, San Francisco, 1957-1958
Research Fellow (Anatomy & Biochemistry), London Hospital, London, England, 1958-1959
San Francisco Heart Association Research Fellow (Cardiovascular Research), University of California Medical Center (Postdoctoral Training in Protein Chemistry and Fibrinolysis), 1959-1960
Medical Residency, University of California, Medical Center of San Francisco, 1960-1962
Research Physician, Steps I & II (Protein Chemistry and Fibrinolysis under Dr. M . Morales and J. Botts), University of California School of Medicine of San Francisco, 1960-1964
M.S., University of Pennsylvania, 1973
Honors and Awards
1968 Cochems prize for Outstanding Research (Cardiovascular/Thromboembolic Problems), awarded by University of Colorado, Drs. S. Sherry & M. Debakey
1969 Pasteur lecture, Paris, France
1970 Election to membership in the American Society for Clinical Investigation
1970-1976 Consultant in Coagulation and Haemostasis, NASA
1971-1976 Member, NHLBI SCOR Review Panel for Thrombotic and Hemorrhagic Diseases
1977 Chairman, Nominating Committee, American Heart Association, Dallas, TX
1977-1981 Advisory Committee of the American Red Cross Blood Program, Red Cross Research Lab, Bethesda, MD
1978 Chairman, Planning Committee, American Heart Association, Dallas, TX
1979 George Lynn Cross Research Professor, awarded by University of Oklahoma
1979-1993 Chairman, Institutional Review Board, OUHSC
1982-1992 Chairman, Assistant Member Evaluation Committee, OMRF
1985 H.A. and Mary K. Chapman Chair in Medical Research
2006 Distinguished Career Scientist, OMRF
Other Activities
Consulting physician at Veteran’s Administration Medical Center and University Hospital (both in Oklahoma City); reviewer for medical and biological publications including Blood, Journal of Clinical Investigation, Shock, Journal of Critical Care Medicine.
Joined OMRF Scientific Staff in 1982.
Publications
Recent Publications
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 130:2678-2681, 2017 December, PMID: 29021229, PMCID: PMC5731087
Frej C, Linder A, Happonen KE, Taylor FB, Lupu F, Dahlbäck B. Sphingosine 1-phosphate and its carrier apolipoprotein M in human sepsis and in Escherichia coli sepsis in baboons. J Cell Mol Med 20:1170-81, 2016 June, PMID: 26990127, PMCID: PMC4882985
Silasi-Mansat R, Zhu H, Georgescu C, Popescu N, Keshari RS, Peer G, Lupu C, Taylor FB, Pereira HA, Kinasewitz G, Lambris JD, Lupu F. Complement inhibition decreases early fibrogenic events in the lung of septic baboons. J Cell Mol Med 19:2549-63, 2015 November, PMID: 26337158, PMCID: PMC4627561
Selected Publications
Silasi-Mansat R, Zhu H, Popescu NI, Peer G, Sfyroera G, Magotti P, Ivanciu L, Lupu C, Mollnes TE, Taylor FB, Kinasewitz G, Lambris JD, Lupu F. Complement inhibition decreases the procoagulant response and confers organ protection in a baboon model of E. coli sepsis. Blood 116:1002-1010, 2010. [Abstract]
Samis JA, Stewart KA, Nesheim ME, Taylor FB Jr. Time-dependent association between coagulation factor inactivation and increased elastase during experimental sepsis. J Thromb Haemost 7:1032-1034, 2009. [Abstract]
Mehta A, Brewington R, Chatterji M, Zoubine M, Kinasewitz GT, Peer GT, Chang ACK, Taylor FB and Shnyra A. Infection-induced modulation of M1 and M2 phenotypes in circulating monocytes: Role in immune monitoring and early prognosis of sepsis. Shock 22:423-430, 2004. [Abstract]
Taylor FB and Kinasewitz G. Activated protein C in sepsis. J Thromb Haemost 2:708-717, 2004. [Abstract]
Siegler RL, Obrig TG, Pysher TJ, Tesh VL, Denkers ND and Taylor FB. Response to Shiga toxin 1 and 2 in a baboon model of hemolytic uremic syndrome. Pediatr Nephrol 18:92-96, 2003. [Abstract]
Taylor F, Jr. comment of "Drotrecogin Alfa (activated) (recombinant human protein C, rhAPC) reduces host coagulopathy response in patients with severe sepsis." Thromb Haemost 90:560-561, 2003. [Abstract]
Contact
Cardiovascular Biology Research Program, MS 45
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, OK 73104
Phone: (405) 271-2400
Fax: (405) 271-7417
E-mail: Fletcher-Taylor@omrf.org
For media inquiries, please contact OMRF’s Office of Public Affairs at news@omrf.org.
News from the Taylor lab
On Saturday, University of Central Oklahoma senior Meagan McLain will walk across the stage at commencement. The 24-year-old will shake hands, receive her diploma and toss her cap in the air. And with her newly minted degree in marketing, she’ll think of all that lies ahead for her: a career, a family, a life. But […]
Rayna DuBose came to say thank you. And thank you and thank you and thank you. “OMRF, the scientists and doctors—it’s good to meet the people who helped save me,” she said. “I just wanted to say thank you. I can’t say it enough.” DuBose, a 24-year-old Virginian, spoke Tuesday to more than 100 Oklahoma […]
The Oklahoma Medical Research Foundation will honor a pair of scientists and a board member at its annual honors and awards banquet Tuesday. For the first time in OMRF’s 61-year history, the event will be held in Tulsa, at historic Cain’s Ballroom. OMRF will award Linda Thompson, Ph.D., the Edward L. and Thelma Gaylord Prize […]
At its semiannual board meeting Thursday, the Oklahoma Medical Research Foundation added two new members to its board of directors: Tulsa Mayor Kathryn Taylor and James Morris II, a retired Oklahoma City insurance executive. The board also honored OMRF researchers Swapan Nath, Ph.D., and Fletcher Taylor Jr., M.D. An attorney, Kathryn Taylor began her legal […]
At its annual honors and awards banquet this evening, the Oklahoma Medical Research Foundation will name a pair of scientists as endowed chairs and add two new members to its board of directors. Xiao-Hong Sun, Ph.D., will be installed as the Eli Lilly Distinguished Chair in Biomedical Research, while Gary Gorbsky, Ph.D., will become the […]
The law firm of Kilpatrick Stockton has made a $100,000 contribution to the Oklahoma Medical Research Foundation (OMRF), the organizations announced today. Kilpatrick Stockton’s substantial gift will help OMRF establish a magnetic resonance imaging (MRI) facility for mice, the first of its kind in Oklahoma. The new facility, which will be completed in 2004, will […]
The Oklahoma Medical Research Foundation announced today that Fletcher B. Taylor, Jr., M.D., who has spent more than two decades as a scientist at OMRF, has endowed a chair at the foundation. Taylor’s gift will establish the Alvin Chang Chair in Cardiovascular Biology. The chair is named in honor of Taylor’s longtime senior research assistant, […]
