HMS Virology

Virology Faculty Member - Daniel Lingwood Ph.D.

Daniel Lingwood

Assistant Professor of Medicine, HMS

Ragon Institute of MGH, MIT and Harvard
400 Technology Square | Room 768 |
Cambridge, MA 02139
Lab phone: 857-268-7198
Tel: 857-268-7180
Email: dlingwood@mgh.harvard.edu
Lab Members: 1 postdoc; 2 technicians



Our research centers on defining biochemical and biophysical principles of antigen recognition to inform on the design of viral vaccines.

The mechanism by which the germline B cell receptor (BCR) engages antigen prior to development of immunological memory is not well understood. New antigen-specific BCR sequences can arise through VDJ recombination and stochastic diversification of the germline antibody repertoire, however, conserved features in humoral responses to some viruses has prompted us to hypothesize that the adaptive immune system is also endowed with innate-like pattern recognition motifs that de-randomize the epitope upon which antibody responses center. This has lead to our discovery that humans possess genetically-encoded B cell receptor (BCR) sequences that naturally engage conserved sites of viral vulnerability, serving as substrates for the development of pan-neutralizing humoral responses. Interestingly, this pattern recognition depends critically on membrane surface orientation of antibody paratopes, highlighting an unexpected physical contribution to innate-like antigen recognition. We now use a combination of reconstituted BCR signaling and immunization studies to examine how this kind of pattern-recognition and B cell surface organization can be exploited to engender effective humoral responses, primarily to influenza virus and HIV.

Questions we currently exploring:

1) Can reconstituted BCR-antigen interactions predict and rank-order vaccine activity prior to use?
2) Do other conserved BCR motifs in addition to the specific germline V sequences serve as pattern-recognition motifs?
3) How does pattern-recognition shape humoral responses to vaccine targets?
4) How are vaccine antigens physically presented to the naïve BCR in vivo?



Last Update: 5/12/2015



Publications

Selected Publications

1. Lingwood, D. 2014. Lipocalin 2 as a Membrane Reorganizing Agent. Science Signaling Sci. Signal. 7:pe19. PMID: 25118326

2. Lingwood, D, McTamney PM, Yassine HM, Whittle JR, Guo X, Boyington JC, Wei C-J, Nabel G. 2012. Structural and Genetic Basis for Development of Broadly Neutralizing Influenza Antibodies. Nature 489:566-570. PMID: 22932267

3. Lingwood, D, Binnington B, Róg T, Vattulainen I, Grzybek M, Coskun U, Lingwood CA, Simons K 2011. Cholesterol modulates glycolipid conformation and receptor activity. Nature Chemical Biology 7:260-262. PMID: 21460830

4. Lingwood D, Simons, K. 2010. Lipid rafts as a membrane organizing principle. Science 27:46-50. PMID: 20044567

5. Lingwood D, Ries J, Schwille P, Simons, K. 2008. Plasma membranes are poised for activation of raft phase coalescence at physiological temperature. Proc. Natl. Acad. Sci. U.S.A. 105:10005-10010. PMID: 18621689



© 2016 President and Fellows
of Harvard College