Daniel Lingwood

Daniel Lingwood, PhD

Principal Investigator


Core Member

Ragon Institute of MGH, MIT and Harvard

Contact


857.268.7180

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Programing vaccine antibody responses

Research Overview

The Lingwood lab studies vaccine ‘resistant’ pathogens such as influenza virus and HIV, which often trigger non-protective antibody responses. The goals of our laboratory are to define the molecular decision-making rules that the immune system uses to establish antibody targets and to apply vaccines that rework these rules to refocus antibody attention upon the conserved ‘Achilles heels’ of these viruses.

The Lingwood Lab’s research centers on defining how fundamental principles of B cell antigen recognition control epitope-targeting by the antibodies elicited by vaccines. We have described how gene-encoded antigen ‘pattern’ recognition motifs exist within the human antibody repertoire through this work. Our research centers on defining how fundamental principles of B cell antigen recognition control epitope-targeting by the antibodies elicited by vaccines. We have defined how gene-encoded antigen ‘pattern’ recognition motifs exist within the human antibody repertoire and can, within purpose-built humanized mouse systems, serve as natural substrates for refocusing humoral immunity upon ‘universal’ vaccine targets on influenza virus, HIV, and gram-negative bacteria.  We have also recently described a biological buffer system which sets the circulating level of interleukin-6 (IL-6) to regulate the output of these antibody responses and more broadly, innate immune reactions. Using a series of genetic models to manipulate the buffer-system in vivo, we now demonstrate that coordinated shifts in the buffer equilibrium regulate pro-inflammatory IL-6 signaling to enable novel anti-viral immunity at the respiratory surface.

Recognition and Media

The Lingwood Lab has been awarded a number of grants and honors in pursuit of our research. These include: NIH Director’s New Innovator Award; William F. Milton Award (Harvard University), The Gilead Research Scholars Program in HIV; and multiple R01s.

About

Daniel’s training has been at the interface of cell surface communication and membrane structure and function—an education that has engendered a unique perspective on solving vaccinology problems. Daniel has defined how key features of 2D molecular interactions in the membrane plane enable natural pattern recognition by human BCRs. He and his lab now demonstrate this principle serves as a natural substrate for vaccine-amplifying broadly protective anti-viral and anti-bacterial humoral responses in humanized mice.

Selected Publications

Lipid rafts as a membrane organizing principle

Lingwood D, Simons, K.

Science, 2010. 27:46-50

Cholesterol modulates glycolipid conformation and receptor activity

Lingwood, D, Binnington B, Róg T, Vattulainen I, Grzybek M, Coskun U, Lingwood CA, Simons K.

Nature Chemical Biology, 2011. 7:260-262

Structural and Genetic Basis for Development of Broadly Neutralizing Influenza Antibodies

Lingwood, D, McTamney PM, Yassine HM, Whittle JR, Guo X, Boyington JC, Wei C-J, Nabel G.

Nature, 2012 489:566-570

In vitro reconstitution of B cell receptor-antigen interactions to evaluate potential vaccine candidates

Weaver GC, Villar RF, Kanekiyo M, Nabel GJ, Mascola JR, Lingwood D. 2016

Nature Protocols, 2016 11:193-213

Germline-encoded affinity for cognate antigen enables vaccine-amplification of a human broadly neutralizing response against influenza virus.

Sangesland M, Ronsard R, Kazer SW, Bals J, Boyoglu-Barnum S, Yousif, AS, Barnes R, Feldman J, Quirindongo-Crespo M, McTamney PM, Rohrer D, Lonberg N, Chackerian B, Graham BS, Kanekiyo M, Shalek AS, and Lingwood D. 2019.

Immunity, 2019. 51:1-15

A single human VH gene allows for a broad-spectrum antibody response targeting bacterial lipopolysaccharides in the blood

Sangesland M, Yousif A, Ronsard L, Kazer SW, Zhu AL, Gatter GJ, Hayward MR, Barnes R, Quirindongo-Crespo M, Rohrer D, Lonberg N, Kwon D, Shalek AK and Lingwood D.

Cell Reports, 2020. 32:108065

Defining and manipulating B cell immunodominance hierarchies to elicit broadly neutralizing antibody responses against influenza virus

Amitai A, Sangesland M, Barnes R, Rohrer D, Lonberg N, Lingwood D*, and Chakraborty A*.

Cell Systems. 2020, 11: 573-588.

The persistence of interleukin-6 is regulated by a blood buffer system derived from dendritic cells

Yousif AS, Ronsard R, Shah P, Omatsu T, Sangesland M, Bracamonte Moreno T, Lam EC, Vrbanac VD, Balazs AB, Reinecker H-C, and Lingwood D.

Immunity, 2021. 54:235-246

Lab Team

Nathania Hartojo

Research Technician I

Faez Amokrane Nait Mohamed

Research Fellow

Thalia Bracamonte Moreno

Research Technician II

Vintus Okonkwo

Research Technologist

Larance Ronsard

Research Fellow

Maya Sangesland

Research Fellow

Daniel Tapia

Research Fellow