Sean C. Murphy, MD, PhD

Clinical and Research Background

Dr. Murphy’s work focuses on the immune response to complex infectious diseases and on diagnostic test development. The major focus of the laboratory is malaria infection of humans and animal models by Plasmodium parasites. There is currently no approved vaccine to prevent malaria infection. However, for the past 40 years, it has been known that humans and animals can be protected against later infections when experimentally immunized with repeated doses of attenuated Plasmodium sporozoites, the form of the parasite that is transmitted by female Anopheles mosquitoes. The protective immune responses induced by these kind of immunizations remain largely unknown because it is extremely difficult to simultaneously monitor responses against hundreds of potential antigens. Using novel high-throughput T cell screening technologies developed in collaboration with Dr. Brad Stone, Dr. Murphy’s group studies the complex poly-specific T cell repertoire induced by Plasmodium sporozoites using mouse models of malaria infection. The laboratory is also exploring novel methods to experimentally induce broadly protective immune responses against malaria using synthetic biology-based T cell vaccines.

A major goal of this work is to identify protective antigens in mice, validate the orthologous antigens in human subjects and develop unprecedented multi-component subunit vaccines that target the pre-erythrocytic stage of malaria infection. Such vaccines could accelerate elimination and eventual eradication of malaria, a major goal worldwide. The tools that the Murphy Lab are developing for antigen discovery and vaccination may also find use more broadly for other infectious and autoimmune diseases in need of vaccines and therapeutics. Our group is exploring several such possibilities using small animal models and livestock in an effort to improve both human and livestock health.

In collaboration with Dr. Jim Kublin (Fred Hutch Cancer Research Center) and the Seattle Biomed Malaria Clinical Trials Center (MCTC, http://seattlebiomed.org/mctc), Dr. Murphy helps to conduct controlled human malaria infection (CHMI) studies in Seattle that are aimed at identifying effective malaria drug and vaccine candidates in humans. These Phase I/II studies are used to make early decisions about such candidates prior to initiating larger Phase II/III studies in malaria-endemic regions. The samples obtained in these studies are also used to identify correlates of immunity and to probe for new antigens. The Seattle MCTC center is the only West Coast-based CHMI facility in the US that was purpose-built to conduct these studies. Dr. Murphy serves as a clinical investigator in these studies. In addition, the quantitative reverse transcription PCR (qRT-PCR) assays developed by Dr. Murphy are conducted by the Department of Laboratory Medicine under Dr. Murphy’s direction in support of early diagnosis in these CHMI studies. The qRT-PCR assays supported by UW are recognized as some of the most sensitive and robust molecular diagnostic assays for malaria in the world—the assays allow for detection of malaria parasites in human blood up to 3-4 days earlier than by conventional blood smears. Dr. Murphy’s group is also promoting a quality improvement initiative to implement external quality assurance amongst a network of CHMI centers that perform molecular malaria testing in the US, Europe, Africa and Australia.