Lingwood

Daniel Lingwood, PhD

Lab Info:

Principal Investigator: Daniel Lingwood, PhD

Lab Staff: 2 post doc, 1 PhD student, 2 techs

Office/Location: 400TS 768

Phone: (857) 268-7180

Email: dlingwood@mgh.harvard.edu

Category: Group Leaders, Members

Dr. Daniel Lingwood is an Assistant Professor in Medicine at Harvard Medical School and a Group Leader at the Ragon Institute of MGH, MIT and Harvard. He also serves as the Associate Director of the Harvard University Center for AIDS Research (CFAR) Advanced Technologies Core.

 

Dr. Lingwood defines basic principles of B-cell antigen recognition to inform the design of antibody vaccines. Through this work Dr. Lingwood’s lab has discovered that the antigen receptor of human B cells is sometimes constructed using specific genes that encode antigen-binding loops with ‘natural’ affinity for vaccine targets, akin to an innate-like receptor activity. Using a series of purpose-built human animal vaccine models, Dr. Lingwood’s group has demonstrated that this unconventional mode of human B-cell antigen recognition genetically ‘endows’ reproducible, vaccine-amplifiable antibody responses that engage a conserved site of viral vulnerability on influenza virus, leading to elicitation of broadly protective and broadly neutralizing antibodies (bnAb) against this pathogen. Dr. Lingwood’s laboratory is concomitantly defining how this principle of B-cell ‘pattern-recognition’ may genetically endow human bnAb responses against other vaccine targets including those on HIV.

 

Dr. Lingwood has been recognized as a Gilead Sciences Research Scholar in HIV and is the recipient numerous honors, including the NIH Director’s New Innovator Award.

 

Dr. Lingwood completed postdoctoral training at the Max Planck Institute for Molecular Cell Biology and Genetics in Dresden, Germany, and the Vaccine Research Center at the NIH. He received a PhD from the Max Planck Institute and a BSc and MSc from the University of Guelph in Guelph, Canada.

 

Specific Questions Asked

  • Do germline BCR-antigen interactions reconstituted in vitro accurately predict antibody response patterns in vivo?
  • How do viral envelope proteins distract BCR activity away from sites of vulnerability?
  • Can we design immunogens to stimulate specific B cell lineages, effectively launching ‘specific’ affinity maturation pathways that lead to broadly neutralizing anti-viral responses?

Selected Publications

Sangesland M, Ronsard L, Kazer SW, Bals J, Boyoglu-Barnum SB, Yousif AS, Barnes R, Feldman J, Quirindongo-Crespo M, McTamney P, Rohrer D, Lonberg N, Chackerian B, Graham BS, Kanekyio M, Shalek AK, and Lingwood D. 2019. Germline-encoded affinity for cognate antigen enables vaccine-amplification of a human broadly neutralizing response against influenza virus. Immunity, In press.

 

Villar, RF, Patel J, Weaver GC, Kanekiyo M, Wheatley AK, Yassine HM, Costello CE, Chandler KB, McTamney PM, Nabel GJ, McDermott AB,
Mascola JR, Carr SA and Lingwood D. 2016. Reconstituted B cell receptor signaling reveals carbohydrate-dependent mode of activation. Scientific Reports 6:36298.

 

Weaver GC, Villar RF, Kanekiyo M, Nabel GJ, Mascola JR, Lingwood D. 2016. In vitro reconstitution of B cell receptor-antigen interactions to evaluate potential vaccine candidates. Nature Protocols 11:193-213.

 

Lingwood, D. 2014. Lipocalin 2 as a membrane reorganizing agent. Science Signaling 7:p19.

 

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.

 

Lingwood, D, Binnington B, Róg T, Vattulainen I, Grzybek M, Coskun U, Lingwood CA, Simons K2011. Cholesterol modulates glycolipid conformation and receptor activity. Nature Chemical Biology 7:260-262.

 

Kaiser­­­­­ H-J, Surma MA, Mayer F, LeventalI, Grzybek M, Klemm RW, Da Cruz S, Meisinger C, Müller V, SimonsK, and Lingwood D. 2011. Molecular convergence of bacterial and eukaryotic surface order. J. Biol. Chem. 286:40631-40637.

 

Kaiser­­­­­­ H-J, Orłowski A, Róg T, Chai W, FeiziT, Lingwood D, Vattulainen I, Simons K. 2011. Sorting in model membranes by cholesterol-mediated hydrophobic matching. Proc. Natl. Acad. Sci. U.S.A. 108:16628-16633.

 

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

 

Levental I, Lingwood D, Grzybek M, Coskun U, Simons K. 2010. Palmitoylation regulates raft affinity for the majority of integral raft proteins. Proc. Natl. Acad. Sci. U S A. 107:22050-22054.

 

Lingwood D, Schuck S, Ferguson C, Gerl, M, Simons, K. 2009. Morphological homeostasis by autophagy. Autophagy 5:1039-1040.

 

Kaiser H-J, Lingwood D, Levental I, Sampaio J, Kalvodova L, Rajendran L, Simons K. 2009. Order of lipid phases in model and plasma membranes. Proc. Natl. Acad. Sci. U.S.A. 106:16645-16650.

 

Lingwood D, Schuck S, Ferguson C, Gerl M, Simons K.2009. Generation of cubic membranes by controlled homotypic interaction of membrane proteins in the endoplasmic reticulum. J. Biol. Chem. 284:12041-12048.

 

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.

 

Lingwood D, Simons K. 2007. Detergent resistance as a tool in membrane research. Nature Protocols 2:2159-2165.

 

Lingwood D, Harauz G, Ballantyne JS. 2005. Regulation of fish gill Na+-K+-ATPase by selective sulfatide-enriched raft partitioning during seawater adaptation. J Biol. Chem. 280:36545-36550.

 

Lingwood D, Fisher LJ, Callahan JW, Ballantyne JS. 2004. Sulfatide and Na+-K+-ATPase: a salinitysensitive relationship in the gill basolateral membrane of rainbow trout. J. Membr. Biol. 201:77-84.