Niraj Harish Tolia, Ph.D.

Host-Pathogen Interactions and Structural Vaccinology Section

Established in 2018

NIH Main Campus, Bethesda, MD

Niraj Harish Tolia, Ph.D. (He/Him/His)

Senior Investigator
Chief, Host-Pathogen Interactions and Structural Vaccinology Section
 

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Photo of Niraj Harish Tolia, Ph.D.

Major Areas of Research

  • Host-pathogen interactions: structure, function and mechanism
  • Mechanisms of protective antibody neutralization
  • Structural vaccinology for infectious diseases

Program Description

The mission of the Host-Pathogen Interactions and Structural Vaccinology Section (HPISV) is to define molecular mechanisms required for infectious diseases pathogenesis, and to elucidate the fundamental phenomena necessary to develop potent and durable vaccines through structural vaccinology. We utilize structural biology, biochemistry, biophysics, immunology, and microbiology to examine proteins and protein complexes associated with pathogenesis.

Infectious diseases vaccines could be significantly improved by structure-guided design of immunogens, which enables more precise targeting of well-defined epitopes that elicit protective responses, while also limiting immune responses that are non-protective or interfering. Our group pursues vaccine development by conducting research in three areas: 1) host-pathogen interactions; 2) neutralizing antibodies; and 3) structural vaccinology for infectious diseases. Through structural, functional, and mechanistic studies, we define critical host-pathogen interactions and the mechanisms of protective antibody neutralization. These studies enable structural vaccinology for malaria and COVID-19 and inform the design of novel effective antigens for vaccines.

Biography

Education

Ph.D., 2004, Cold Spring Harbor Laboratory School of Biological Sciences, NY

B.Sc., 1999, Imperial College, London

Dr. Tolia became the Chief of the Host-Pathogen Interactions and Structural Vaccinology section in the Laboratory of Malaria Immunology and Vaccinology in May 2018. He is a tenured Senior Investigator in the Division of Intramural Research, NIAID. He has pioneered the structural and biophysical studies of host-pathogen interactions, antibody neutralization and immunogen design for malaria. A major goal is to define how processes required for malaria parasite survival are mediated and can be exploited for preventative, therapeutic and diagnostic purposes. This work has direct implications for drug and vaccine development. His laboratory uses the tools of microbiology, cell biology, biochemistry, biophysics and structural biology to study proteins and complexes.

Dr. Tolia received his B.Sc. from Imperial College, and his Ph.D. from the Cold Spring Harbor Laboratory School of Biological Sciences as a Leslie Quick Jr. Fellow. He began his independent career as an Assistant Professor of Molecular Microbiology, and an Assistant Professor of Biochemistry and Molecular Biophysics at Washington University School of Medicine in November 2007. He was the recipient of an Investigator in the Pathogenesis of Infectious Disease Award from the Burroughs Wellcome Fund and his research was supported by grants from the National Institutes of Health, the Edward Mallinckrodt, Jr. Foundation, the American Heart Association, the W.M. Keck Foundation and the Children’s Discovery Institute.

Selected Publications

Patel PN, Dickey TH, Hopp CS, Diouf A, Tang WK, Long CA, Miura K, Crompton PD, Tolia NH. Neutralizing and interfering human antibodies define the structural and mechanistic basis for antigenic diversion. Nat Commun. 2022 Oct 6;13(1):5888.  

Dickey TH, Tang WK, Butler B, Ouahes T, Orr-Gonzalez S, Salinas ND, Lambert LE, Tolia NH. Design of the SARS-CoV-2 RBD vaccine antigen improves neutralizing antibody response. Sci Adv. 2022 Sep 16;8(37):eabq8276.  

Ma R, Lian T, Huang R, Renn JP, Petersen JD, Zimmerberg J, Duffy PE, Tolia NH. Structural basis for placental malaria mediated by Plasmodium falciparum VAR2CSA. Nat Microbiol. 2021 Mar;6(3):380-391.  

Urusova D, Carias L, Huang Y, Nicolete VC, Popovici J, Roesch C, Salinas ND, Dechavanne S, Witkowski B, Ferreira MU, Adams JH, Gross ML, King CL, Tolia NH. Structural basis for neutralization of Plasmodium vivax by naturally acquired human antibodies that target DBP. Nat Microbiol. 2019 Sep;4(9):1486-1496.  

Jimah JR, Salinas ND, Sala-Rabanal M, Jones NG, Sibley LD, Nichols CG, Schlesinger PH, Tolia NH. Malaria parasite CelTOS targets the inner leaflet of cell membranes for pore-dependent disruption. Elife. 2016 Dec 1;5:e20621.  

Batchelor JD, Zahm JA, Tolia NH. Dimerization of Plasmodium vivax DBP is induced upon receptor binding and drives recognition of DARC. Nat Struct Mol Biol. 2011 Jul 10;18(8):908-14.  

Visit PubMed for a complete publication listing.

Research Group

The Host-Pathogen Interactions and Structural Vaccinology Section (HPISV) seeks to uncover the fundamental phenomena necessary to develop the next generation of vaccines through structural vaccinology. Structure-guided design of immunogens to elicit well-defined immune responses will likely lead to significant improvements in vaccine efficacy and durability.

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