Paul Spearman, M.D.

Paul Spearman
Chief Research Officer

Chief Research Officer
Children’s Healthcare of Atlanta

Professor
Division of Infectious Disease
Department of Pediatrics
Emory University School of Medicine

Nahmias-Schinazi Research Professor and Vice Chair for Research

Director
Children’s Center for Vaccines and Immunology

Research

The Spearman laboratory focuses on HIV assembly, HIV pathogenesis, and immune responses relevant to HIV vaccine development. The HIV Gag protein forms the shell of the developing virion, and must traffic to its site of assembly through interactions with specific cellular pathways. Endosomal trafficking plays a prominent role in HIV assembly. We have described the interaction of Gag with the AP-3 adaptor complex, and are defining the role of this interaction in productive trafficking of Gag. The role of vesicular trafficking of Gag along microtubules is under intensive investigation at present. The form of Gag that interacts specifically with adaptors and regulators of vesicular trafficking is being dissected using mutants of Gag that fail to form multimers or fail to interact with cellular trafficking factors. The viral Vpu protein assists in particle release through overcoming a host cell restriction. The identification of this cellular restriction factor is essential to understanding this mechanism, and is a focus of the laboratory. Neutralizing antibodies directed against HIV can be elicited by vaccination, but lack breadth of activity against diverse isolates. The basic mechanisms of neutralization of HIV must be better understood in order to overcome this problem. We are dissecting the B cell repertoire that develops in infected individuals, and developing novel monoclonal antibodies from humans and from immunized mice in order to better understand the basis of HIV neutralization.