Philip R. Dormitzer, MD, PhD

Research Overview

The goal of Philip Dormitzer's current research is to develop a second-generation rotavirus vaccine. Because rotavirus is the most important cause of childhood gastroenteritis and is responsible for approximately 6% of deaths of children under age five, it is a major target for vaccine development.

In rotavirus infection, a large subviral particle is translocated across a membrane and into the cytoplasm. However, protective antibodies against this triple-layered, non-enveloped virus can block its entry into cells. Dormitzer's work focuses on the outer capsid proteins VP4 and VP7, which are the targets of neutralizing antibodies and make up the viral entry apparatus.

Dormitzer and colleagues have used biochemical and structural techniques to study its entry into cells. They have purified and crystallized the major "moving" parts of the entry apparatus and, so far, have determined structures of the hemagglutination and membrane interaction domains of VP4 using X-ray crystallography and NMR spectroscopy. The purified proteins function in simple in vitro systems to recapitulate aspects of rotavirus uncoating, protease activation, and membrane interaction.

Recently, Dormitzer and colleagues have demonstrated that recombinantly produced outer capsid proteins can mediate entry of rotavirus subviral particles. Employing a combination of biochemical, structural, functional, and "recoating" genetics approaches, they are working to dissect the rotavirus entry pathway. They will apply the results of these studies to engineer optimized antigens for use in a potential vaccine against rotavirus.

About Philip Dormitzer

Philip Dormitzer received MD and PhD degrees from Stanford University School of Medicine.? He completed an internship and residency in Internal Medicine at Massachusetts General Hospital and a fellowship in Infectious Diseases through the Harvard Combined Infectious Diseases Program.? He is board certified in Internal Medicine and Infectious Diseases.

In 2003 Dr. Dormitzer received a New Scholar Award in Global Infectious Disease from the Ellison Medical Foundation.

Key Publications

• Dormitzer PR, Nason EB, Prasad BV, Harrison SC. Structural rearrangements in the membrane penetration protein of a non-enveloped virus Dormitzer PR, Nason EB, Prasad BVV, Harrison SC. Nature 2004; 430: 1053-1058.
• Dormitzer PR, Sun Z-Y J, Blixt O, Paulson J, Wagner G, Harrison SC. The specificity and affinity of sialic acid binding by the rhesus rotavirus VP8* core. Journal of Virolology 2002; 76: 10512-10517.
• Dormitzer PR, Sun Z-Y J, Wagner G, Harrison SC. The rhesus rotavirus VP4 sialic acid binding domain has a galectin fold with a novel carbohydrate binding site. EMBO Journal 2002; 21: 885-897.