I am currently a Visiting Lecturer in the Department of Biological Sciences at the University of Pittsburgh. Prior to joining the faculty at Pitt, I had the pleasure of teaching at Brigham Young University, Utah Valley University and Nazarbayev University in Astana, Kazakhstan. I was also a research associate in the Department of Immunology, in the University of Pittsburgh’s, School of Medicine for seven years prior to starting my teaching career. I enjoy both teaching and research and thoroughly enjoy interacting with the highly-motivated students at Pitt.
My research focused on the development of a vaccine to combat the protozoan parasite Trypanosoma cruzi. T. cruzi is the causative agent of Chagas’ disease and is most often transmitted to humans when blood-sucking reduviid bugs deposit infected feces or urine into or near a bite wound. The acute phase of Chagas disease is often mild or asymptomatic and infected individual rarely seek treatment. It is followed by a long asymptomatic phase that may be life-long. Approximately, a third of infected individuals will progress to chronic phase disease. Chronic Chagas disease is characterized by cardiac and/or gastrointestinal tract irregularity and enlargement and at this point, treatment options are limited. Patients generally die from congestive heart failure or heart attack.
The immune response to T. cruzi does not result in sterilizing immunity and infection with more than one strain is common in endemic areas. Efforts to eliminate the insect vector and serological screening of the blood bank, have succeeded at limiting the spread of the microbe in many countries where it is endemic, however, development of an effective vaccine is still the best hope of completely eliminating the parasite from human populations.
Norris et al. identified a185kDa glycoprotein on the surface of the microbe called the complement regulatory protein (CRP) that is highly immunogenic and correlated with protection. CRP is a GPI anchored protein that binds C3b and C4b of the alternative and classical complement pathways respectively, and restricts activation of the complement cascade. CRP-C3b binding also accelerates the decay of the C3 convertase; ultimately preventing formation of the membrane attack complex and lysis of the organism. Antibodies that interfere with CRP/C3b binding play an important role in keeping the microbe in check and preventing progression to chronic Chagas’ disease. An antigenically-variable domain located in the carboxyl terminus of CRP seems to function as a decoy domain used by the parasite to divert the immune response away from the functional C3b-binding domain. This strategy contributes to parasite persistence in the host. In murine vaccine trials, antibodies were generated in high quantity to this decoy domain but were ineffective at preventing infection by the parasite. My research focuses on identification of the C3b binding site on CRP with the aim of developing a vaccine that targets the immune response to this portion of the protein.