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

Daniel Lingwood was born and raised in Toronto, Canada. He studied physiology at the University of Guelph (BSc) and completed his MSc examining the role of membrane lipids in regulating ion transport ATPases. His subsequent doctoral work at the Max Planck Institute for Molecular Biology and Genetics in Dresden, Germany, helped to define the Lipid Raft property as a cell membrane subcompartmentalization principle.  As a post-doctoral fellow at the Vaccine Research Center of NIH, Daniel further explored the ability of membranes to ‘alosterically’ modulate surface recognition processes now in the context of B cell activation by Influenza virus. This lead to the discovery that humans possess genomically-encoded antibody sequences that when properly oriented at the membrane surface, engage conserved sites of viral vulnerability and serve as substrates upon which broadly neutralizing antibodies can be developed.

 

Now as an Assistant Professor in Medicine at Harvard Medical School, Daniel uses membrane structure and function as a means to define B cell antigen recognition and inform vaccine design. In this context, the Lingwood laboratory studies B cell antibody responses to both HIV and influenza with the goal of 1) understanding how antigenic sites of vulnerability are initially perceived by specific germline B cell receptor (BCR) sequences and  2) how that recognition process can direct antibody affinity maturation toward production of broadly neutralizing anti-viral responses.

 

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

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 In press.

 

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 Signaling7: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. Nature489:566-570.

 

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.


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