Research

Pangburn, Michael, Ph.D.

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Contact: michael.pangburn@uthct.edu

Education:
B.S., Chemistry, 1969, Univ. of California at Los Angeles
Ph.D., Biochemistry, 1974, Univ. of Washington at Seattle

Research Interest:
My research focuses on the part of the human innate immune system called the complement system. Complement is a system of proteins and enzymes in human blood that form our first line of defense against infections. In most cases microorganisms are attacked and killed by complement within 15 min of first contact with blood. We study the mechanisms of activation, the systems that control activation of complement, mechanisms of target identification and errors of activation that lead to disease and pathology caused by complement proteins.

Complement Technology, Inc.
Complement Technology, Inc. was formed to supply the medical research community with the highest quality reagents for complement research. It was created as a spin-off from the research program of my laboratory at the University of Texas HSC at Tyler and now operates as an independent biotech company located in Tyler, Texas. Complement Technology, Inc. is the world’s primary supplier of proteins and enzymes of the human complement system. The owners and operators of Complement Technology, Inc. have a combined experience of more than 70 years in the complement field. The highly specialized reagents produced by Complement Technology, Inc. are used by medical researchers all over the world in the drug development industry, in the biotech industry and in medical research labs at universities and research foundations.

Current Projects:

  1. Current projects include the analysis of the proteins responsible for recognizing and initiating the attack on bacteria, viruses, parasites and fungi. How the complement system distinguishes between human cells and foreign microorganisms is not yet clear, but knowledge of how this is done is very important.
  2. A second but related project is the cloning and site-directed mutagenesis of one of the key proteins involved in this recognition step. By picking apart the protein we are beginning to understand why it allows an attack to proceed on microorganisms, but blocks it on our own cells and tissues. Errors by this proteins appear to lead misdirected attacks on human tissues in the diseases of age-related macular degeneration and the inherited form of hemolytic uremic syndrome. These are just a few of the known diseases where complement does not protect us as it normally does, but causes harm instead.
  3. A third project involves trying to measure the enzymatic properties of the central enzyme of the complement activation process - the C5 convertase. We want to understand its structure and why it is one of the slowest enzymes ever found in a biological system. Finally, we are using a new instrument, the BIAcore X, to study the interactions of each complement protein with other proteins and with enzymes with the goal of understanding how these proteins assemble into the complexes necessary for killing microoganisms.

Lay Summary:
Human blood contains an infection-fighting system of proteins called the complement system. There are over 34 proteins in this system and each performs a specific role in killing and removing bacteria, viruses, parasites and fungi (yeast infections) from our bodies. I have been studying these proteins for 32 years. My work involves purifying each protein from outdated plasma that we get from the local blood bank. Recently we have been getting some of these proteins by cloning DNA. We then mix certain components back together and try to learn which ones work together, how they combine and how they kill infectious organisms. We are also trying to understand why the complement system sometimes attacks our own tissues, such as in autoimmune diseases and after strokes or heart attacks where as much as half of the tissue damage can be caused by complement. We are using the knowledge gained about complement to develop drugs to stop the system when an attack is misdirected at our own tissues.

Research Overview:
Human blood contains many systems for fighting disease. One of the major systems for killing microorganisms such as bacteria, yeasts, viruses and parasites is referred to as the "complement system." This system got its name from the discovery over 90 years ago that antibodies alone could not kill bacteria. These same antibodies, however, mixed with non-immune plasma could kill. Thus it was said that something in the plasma "complemented" the antibodies. We now know that this system is made up of more than 34 different proteins that circulate in plasma or reside on cells. These proteins each have different functions in combating infections and in maintaining a normal immune response to antigens. My research is centered on understanding how each of these proteins performs its disease fighting role and why the destructive power of the complement system occasionally is directed at human tissues. The main focus of the lab is the alternative pathway of complement activation. This pathway of activation provides the host with an innate system of defense against infectious agents because it is capable of neutralizing a variety of potential pathogens on contact, prior to the production of antibodies. To investigate these reactions many of the proteins of the complement system are purified and used to analyze protein-protein interactions, to study mechanisms of activation and to understand how each of these reactions contributes to the overall process leading to killing of infectious organisms. Also in use are techniques of molecular biology to mutagenize and express complement proteins in order to study structural features which perform critical functions. Finally, my laboratory is interested in the development of drugs which would allow physicians to control the complement system. Recently the first drug that controls the complement system was approved for use in humans for the treatment of PNH and it has had dramatic results. Many drugs are currently at various stages of development by many drug companies for either suppressing or enhancing the complement system.


Selected Papers and Abstracts: