SBRI - Research: Scientists: Patrick Duffy

Mission
Dr. Duffy and his colleagues are developing vaccines against malaria. He directs the Malaria Program at SBRI, leads an International Malaria Research Training Program for young African scientists, and coordinates two international consortia to develop vaccines for pregnant women and young children. In 2005, Dr. Duffy received one of 43 prestigious Grand Challenges in Global Health grants from the Gates Foundation, targeted at identifying the immune responses that prevent severe disease and death due to Plasmodium falciparum malaria.

Research
Pregnancy Malaria Vaccine The Duffy and Fried labs made the seminal finding that pregnant women are infected by parasites that bind to the placental receptor chondroitin sulfate A, and they continue to collaborate to develop a vaccine based on this knowledge. The Duffy lab has completed the first whole genome expression studies of the human immune response to sequestered parasites, and has defined the molecular basis for preeclampsia caused by placental malaria. They have pioneered the use of functional genomics tools to characterize the distinct features of placental parasites, and to identify the infected red cell surface proteins that may be developed as pregnancy malaria vaccines. In 2003, Dr. Duffy and a consortium of laboratories launched a Pregnancy Malaria Initiative with support from the Bill & Melinda Gates Foundation to identify the necessary antigens for a malaria vaccine to protect women during pregnancy. The consortium is focused on assessing a limited number of parasite proteins as candidates for a vaccine that could be given before pregnancy to protect first-time mothers and their babies.

Immunity to Severe Malaria in African Children With support from the GCGH Program, an international consortium led by the Duffy lab is identifying the immune responses that protect African children from severe malaria. African children may only suffer one or two episodes of severe malaria before developing resistance, and earlier studies showed that antibody purified from the serum of immune adult Africans could cure young children with malaria. The consortium is identifying the parasite forms and parasite proteins that may be targeted by protective antibody, as a key step in developing vaccines to protect young children from severe malaria and death. The clinical research is centered at the MOMS Morogoro laboratory, and the consortium has also established a Genome Science Center at Sokoine University in Morogoro for microarray and bioinformatics studies.

Severe Malarial Anemia With support from the US Department of Defense, Dr. Duffy and his colleagues are seeking to identify antigens for a vaccine that prevents severe anemia due to malaria. Proteomics and microarray tools are used to identify blood stage surface proteins in parasites collected in MOMS-Muheza, which are subsequently assessed as targets of naturally occurring protective antibodies acquired by individuals in malaria-endemic areas.

Liver Stage Malaria Dr. Duffy is collaborating with the Krzych lab at Walter Reed Army Institute of Research, the Koelle lab at UW, and the Kappe lab at SBRI to develop a vaccine against liver stage parasites. The laboratory of Dr. Urszula Krzych at Walter Reed has optimized in vitro culture of liver stage parasites, and these samples are analyzed in microarray and qPCR studies in Dr. Duffy’s lab to characterize the transcriptome of liver stage P. falciparum. Novel liver stage antigens are examined as targets of immune responses that correlate with protection in animals or humans, in collaboration with Krzych and Koelle. Proteins expressed by liver stage parasites may be used in vaccines to block malaria infection. Novel genes are also assessed by genetic replacement to determine whether they are essential for liver stage development, and whether the resulting knock-out parasites may be useful as whole attenuated parasite vaccines to block infection, in collaboration with Kappe.

Training Programs in East Africa The Duffy lab leads an International Malaria Research Training Program that supports young Tanzanian scientists to conduct research in Seattle and at the lab in Tanzania. Each year, he and his colleagues organize regional scientific workshops in East Africa focused on diseases endemic to those countries. The training program is supported with funds from the Fogarty International Center (NIH) and the GCGH program.

Themes
*	Malaria Immunoepidemiology and Pathogenesis
*	Pregnancy Malaria Vaccines
*	Severe Malaria of Childhood
*	Liver Stage Malaria
Laboratory Accomplishments
*	Described the pathogenesis of pregnancy malaria.
*	Defined the benefits of antibodies that protect pregnant mothers and their fetuses from malaria.
*	Established the first microarray facility in East Africa.
*	Pioneered the use of functional genomics tools to study field parasites.

The National Institutes of Health (NIH), the Bill & Melinda Gates Foundation, the US Department of Defense, and the Fogarty International Center at NIH provide support for Dr. Duffy’s current research.