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Taylor, Fletcher B.

Fletcher B. Taylor, Jr., M.D.

Fletcher B. Taylor, Jr., M.D.

Distinguished Career Scientist

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’re studying 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 can understand 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 is now used to treat severe sepsis in humans. The drug Xigris, or activated protein C, has been used to reduce sepsis deaths by 20 percent, but we’re continuing to refine our discovery to make it more effective. By delving into the many overlapping negative effects ofE. coli in the bloodstream, we’ve 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 are looking at different variants of sepsis. Even forms that already treated by Xigris could be better addressed with different treatment categories.

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.

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 studies 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 use 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) that has reduced the relative mortality by 20 percent. In order to improve these results, we focused on two lines of investigation. First, we are studying 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 attenuates the initial metabolic inflammatory disturbance in the target cells, which is one of the principal effects of Xigris. Second, we are studying 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 works 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 will 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.

Recent Publications

Kim PY, Kim PY, Taylor FB, Jr., Nesheim ME. Thrombin-activatable fibrinolysis inhibitor is activated in vivo in a baboon model of Escherichia coli induced sepsis. J Thromb Thrombolysis 33:412-415, 2012. [Abstract]

Taylor FB, Jr., Kinasewitz GT, Lupu F. Pathophysiology, staging and therapy of severe sepsis in baboon models. J Cell Mol Med 16:672-682, 2012. [Abstract]

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]

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]

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

Barbara Irish
Administrative Assistant