Research

Pangburn, Michael, Ph.D.

← BACK  



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:
The part of the human innate immune system called the complement system. The mechanisms of activation and systems that control activation of complement as well as mechanisms of target identification by the complement system.

Complement Technology, Inc.
Complement Technology, Inc. was formed to continue supplying the medical research community with the highest quality reagents for complement research. CompTech has purchased the entire complement business from Advanced Research Technologies, Inc. of San Diego, California. CompTech and ART have established a formal ongoing relationship to guarantee a smooth transition. The owners and operators of CompTech have a combined experience of 65 years in the complement field. We plan to continue to be the lowest cost supplier of the highest quality reagents available. We will expand the line of reagents to meet the changing needs of research. We would welcome suggestions on how best to do this.

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.
  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 otherproteins 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 30 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 22 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 80 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. At present not a single drug exists for either suppressing nor enhancing this system.


Selected Papers and Abstracts: