Biology Department Emeritus Faculty

Daniel A. Kirschner

Professor Emeritus

Department

Biology

Research

Our current research interests are focused on the structure and dynamic membrane interactions in abnormal nerve myelin, in which alterations have resulted from experimental, pathological, or genetic conditions. To link structure and composition at the molecular, macromolecular and tissue levels in the nervous system, our studies in these areas have utilized x-ray diffraction, microscopy at the light and ultrastructural levels, a variety of protein and lipid biochemical techniques, and molecular modeling.

What holds myelin together, and how are its constituents targeted in diseases? To characterize the molecular organization of lipids and proteins in nerve myelin membranes, and to define the molecular interactions of its membrane arrays, we have correlated biophysical and biochemical results from different types of specimens (e.g., whole unfixed or fixed tissue from a phylogenetic range of vertebrates, tissue homogenates, tissue fractions and model lipid/protein systems). Among the questions we addressed were: how does the organization of proteins and lipids in myelin account for the inter-membrane interactions of the membranes? What is the structural basis of demyelination? Our findings are relevant to understanding the process of membrane disruption and delamination which occurs in demyelinating diseases such as multiple sclerosis and certain peripheral neuropathies. Our findings have also helped to explain how specific mutations in myelin adhesion proteins or in lipid biosynthetic pathways affect the stability and functionality of the myelin.

Selected Publications

  • Visigalli D, Capodivento G, Basit A, Fernández R, Hamid Z, Pencová B, Gemelli C, Marubbi D, Pastorino C, Luoma AM, Riekel C, Kirschner DA, Schenone A, Fernández JA, Armirotti A, Nobbio L (2020) . Frontiers in Neurology: Neuromuscular Diseases. 11:903. doi: 10.3389/fneur.2020.00903
  • Baumann A, Denninger AR, Domin M, Demé B, Kirschner DA (2022) . BioRxiv doi: 10.1101/2021.12.17.473245v3. Current Research in Structural Biology 4:231-245. doi: 10.1016/ j.crstbi.2022.06.00
  • Snow AD, Castillo GM, Nguyen BP, Choi PY, Cummings JA, Cam J, Hu Q, Lake T, Pan W, Kastin AJ, Kirschner DA, Wood SG, Rockenstein E, Masliah E, Lorimer S, Tanzi RE, Larsen L (2019) . Scientific Reports, Feb 6;9(1):561. doi: 10.1038/s41598-019-38645-0.
  • Colombo L, Stoilova T, Deme B, Inouye H, Booth R, Del Favero E, Rondelli V,Kirschner DA, Cantu L, and Salmona M (2017).Scientific Reports, Jul 14;7(1):5510. doi:10.1038/s41598-017-05582-9
  • Inouye H, Kuo F-H, Denninger, AR, Weinhause B, Burghammer M,Kirschner DA(2017).J Structural Biology, Dec;200(3):229-243. doi:10.1016/j.jsb.2017.07.001
  • Ahmed SS, Schattgen S, Frakes AE, Sikoglu EM, Su Q, Li J, Hampton TG, Denninger A,Kirschner DA, Kaspar B, Matalon R, Gao G (2016).Molecular Therapy24(6):1030-41. doi: 10.1038/mt.2016.68. Epub 2016 Apr 4.
  • Inouye H,Kirschner DA(2016).Brain Research, Oct 28. pii: S0006-8993(15)00808-2. doi: 10.1016/j.brainres.2015.10.037.
  • Denninger AR, Breglio A, Maheras KJ, LeDuc G, Cristiglio V, Demé B, Gow A,Kirschner DA.(2015).Biophys J.Oct 6;109(7):1387-1397. doi: 10.1016/j.bpj.2015.08.012. PubMed PMID: 26445439.
  • Luoma AM, Kuo F, Cakici O, Crowther MN, Denninger AR, Avila RL, Brites P,Kirschner DA(2015).Free Radicals in Biology & Medicine, 84:296-310. doi: 10.1016/j.freeradbiomed.2015.03.012.
  • Heinecke KA, Luoma AM, d’Azzo A,Kirschner DA, Seyfried TN (2015).ASN Neuro,Jan-Feb 20157:1759091415568913,first published onFebruary 18, 2015;doi:10.1177/1759091415568913.
  • Denninger AR, Demé, B, Cristiglio V, LeDuc G, Feller WB,Kirschner DA(2014).Acta Crystallographica D70:3198-3211.doi: 10.1107/S1399004714023815.
  • Inouye H, Liu J, Makowski L, Palmisano M, Burghammer M, Riekel C,Kirschner DA(2014).PLoS ONE9(7):e100592. doi: 10.1371/journal.pone.0100592. http://hdl.handle.net/2345/bc-ir:103602
  • Krishnan R, Tsubery H, Proschitsky MY, Asp E, Lulu M, Gilead S, Gartner M, Waltho JP, Davis PJ, Hounslow AM,Kirschner DA, Inouye H, Myszka DG, Wright J, Solomon B, Fisher RA (2014).Journal of Molecular Biology426(13):2500-19. doi: 10.1016/j.jmb.2014.04.015. Epub 2014 Apr 22..
  • Da Silva TF, Eira J, Lopes A, Malheiro AR, Sousa V, Luoma AM, Avila RL, Wanders R, Just W,Kirschner DA, Sousa MM, Brites P (2014),J Clinical Investigation124(6):2560-70. doi: 10.1172/JCI72063. Epub 2014 Apr 24.
  • Ahmed SS, Li H, Cao C, Sikoglu EM, Denninger AR, Su Q, Eaton S, Liso A, Xie J, Szucs S, Zhang H, Moore C,Kirschner DA, Seyfried TN, Flotte TR, Matalon R, and Gao G (2013).Molecular Therapy21(12):2136-47. doi: 10.1038/mt.2013.138. Epub 2013 Jul 2.
  • Patzkó A, Bai Y, Saporta MA, Katona I, Wu XY, Wrabetz L, Feltri ML, Wang S, Dillon LM, Kamholz J,Kirschner DA, Sarkar F, Shy ME (2012).Brain135:3551-66. doi: 10.1093/brain/aws299.
  • Saporta MAC, Shy BR, Patzko A, Bai Y, Pennuto M, Ferri C, Tinelli E, Saveri P,Kirschner DA, Crowther M, Southwood C, Gow A, Wu X, Feltri ML, Wrabetz L, Shy ME (2012).Brain135:2032-2047. doi: 10.1093/brain/aws140.
  • Jiang H, Kiebish MA,Kirschner DA, Han X (2012) Multi-dimensional mass spectrometry-based shotgun lipidomics and its application for analysis of PEX7 mouse brain lipidome. InLipidomics – Technologies and Applications(K Ekroos, ed.), Wiley-VCH, Weinheim, Germany.
  • Gilardini A, Avila RA, Luckett R, Lu J, Oggioni N, Rodruguez-Menendez V. Bossi M, Canta A, Cavaletti G,Kirschner DA(2012).NeuroToxicology 33:1-7. doi: 10.1016/j.neuro.2011.10.010.
  • Echeverria V, Zeitlin R, Burgess S, Patel S, Barman A, Thakur G, Mamcarz M, Wang L, Sattelle DB,Kirschner DA, Mori T, Leblanc R, Prabhakar R, and Arendash GW (2011).J Alz Dis23:1-19. (link to PubMed abstract).
  • Avila RA, Inouye H, Feltri ML, Wrabetz L,Kirschner DA(2010). J Biol Chem, Oct 11. 285(53):42001-12.
  • Inouye, H., Gleason, K.A., Decatur, S.M.,Kirschner, D.A.2010..Proteins: Structure, Function, and Bioinformatics78: 2306–2321.
  • Kirschner, D.A., Avila, R.L., Luoma, A., Enzmann, G.U., Agrawal, D., Inouye, H., Bunge, M.B., Kocsis, J.D., Peters, A., Whittemore, S. 2010..Journal of Neuroscience Research88: 712–723.
  • Verheijen, M.H., Camargo, N., Nadra, K., de Preux, A.-S., Verdier, V., Luoma, A.M., Crowther, M., Inouye, H., Shimano, H., Chen, S., Brouwers, J., Helms, B.J., Feltri, M.L., Wrabetz, L.,Kirschner, D.A., Chrast, R., Smit, A.B. 2009..Proceedings of the National Academy of Sciences of the United States of America106: 21383–8.
  • Agrawal, D., Hawk, R., Avila, R.L., Inouye, H.,Kirschner, D.A.2009.Journal of Structural Biology168: 521–526.
  • Kirschner, D.A., Karthigesan, J., Bizzozero, O.A., Kosaras, B., Inouye, H. 2009..Neuron Glia Biology4: 59–70.
  • Inouye, H., andKirschner, D.A.2008. Myelin: A one-dimensional biological “crystal” for x-ray and neutron scattering. In:Molecules: Aggregation, Nucleation, CrystallizationBeyond Medical and Other Implications(Eds. J. Sedzik, P. Riccio), World Scientific Publishing, Singapore.
  • Flores, A.I., Narayanan, S.P., Morse, E., Shick, H.B., Avila, R.L.,Kirschner, D.A., and Macklin, W.B. 2008..The Journal of Neuroscience: The Official Journal of the Society for Neuroscience28: 7174–83.
  • Kirschner, D.A., Gross, A.A., Hidalgo, M., Inouye, H., Gleason, K., Abdelsayed, G., Castillo, G.M., Snow, A.D., Pozo-Ramajo, A., Petty, S.A., and Decatur, S.M. 2008..Current Alzheimer Research5: 288–307.
  • Luo, X.Y., Cerullo, J., Dawli, T., Priest, C., Haddadin, Z., Kim, A., Inouye, H., Suffoletto, B.P., Avila, R.L., Lees, J.P., Sharma, D., Xie, B., Costello, C.E., andKirschner, D.A.2008..Journal of Structural Biology162: 170–183.
  • Luo, X., Inouye, H., Sharma, D., Lee, D., Avila, R.L., Salmona, M., andKirschner, D.A.2007..Biophysical Journal93: 3515–3528.
  • Luo, X.Y., Sharma, D., Inouye, H., Lee, D., Avila, R.L., Salmona, M., andKirschner, D.A.2007..Neurochemical Research32: 197–209.
  • Yin, X., Baek, R.C.,Kirschner, D.A., Peterson, A., Fujii, Y., Nave, K.A., Macklin, W.B., and Trapp, B.D. 2006..Journal of Cell Biology172: 469–478.
  • Wrabetz, L., D’Antonio, M., Pennuto, M., Dati, G., Tinelli, E., Fratta, P., Previtali, S., Imperiale, D., Zielasek, J., Toyka, K., Avila, R.A.,Kirschner, D.A., Messing, A., Feltri, M.L., and Quattrini, A. 2006..Journal of Neuroscience26: 2358–2368.
  • Inouye, H., Sharma, D., Goux, W.J., andKirschner, D.A.2006..Biophysical Journal90: 1774–1789.
  • Shinchuk, L. M., Sharma, D., Blondelle, S.Y., Reixach, N., Inouye, H., andKirschner, D.A.2005.Proteins: Structure, Function, and Bioinformatics61: 579–589.
  • Sharma, D., Shinchuk, L.M., Inouye, H., Wetzel, R., andKirschner, D.A.2005..Proteins: Structure, Function, and Bioinformatics61: 398–411.
  • Avila, R.A., Inouye, H., Baek, R., Yin, X., Trapp, B.D., Feltri, M.L., Wrabetz, L., andKirschner, D.A.2005..Journal of Neuropathology & Experimental Neurology64: 976–990.
  • Kirschner, D.A., Wrabetz, L., and Feltri, M.L. 2004. The P0 Gene. In:Myelin Biology and Disorders 1, (Ed. R.A. Lazzarini et al.), Elsevier/Academic Press, NY, pp. 523–545.
  • Inouye, H., Bond, J.E., Deverin, S.P., Lim, A., Costello, C.E., andKirschner, D.A.2002..Biophysical Journal83: 1716–1727.
  • Thompson, A.J., Cronin, M.S., andKirschner, D.A.2002.Journal of Neuroscience Research67(6): 766–771.

Invited Talks

2015

  • “CIDP and Myelin Structural Biology”, Invited lectures (12) as Visiting Professor in Department of Neurological, Neuropsychological, Morphological & Movement Sciences, University of Verona Medical School, Verona, Italy
  • "From Macro to Nano: Focusing on Nerve Myelin—Nature's Multilayer Membrane Assembly", Invited colloquium, Physics Department, ֱ College (10/14)

2014

  • “Myelin Structural Biology: Probing the Boundaries of Wrap”, Invited talk, ֱ Physics of Living Systems Hangout, MIT (4/10)

2013

  • “@ & Between the Nodes: What X-rays & Neutrons Reveal About Nerve Myelin”, Invited talk, IBMC, Porto, Portugal (5/9)

2012

  • “Nerve Myelin Between the Nodes: What X-rays & Neutrons Reveal“, invited speaker, A.I. DuPont Hospital for Children, Nemours Translational Science Research Seminar Series, Wilmington, Delaware (10/25)
  • “Neutron Diffraction from Myelin: Redux >Forty Years”, invited speaker, Symposium: “Structural Dynamics and Dynamical Structures: Future and Challenges of Neutron Scattering in Biology”, Institute Laue-Langevin, Grenoble, France (10/3-10/5).
  • “Novel Molecular Views of Nerve Myelin Using Microbeam X-ray Diffraction and Neutron Diffraction”, invited talk, American Crystallographic Association, annual meeting, ֱ (7/30).
  • “Myelin Structural Biology: Molecular Organization and Dynamic Interactions”, Symposium on Membrane Biology, invited lecture, Acibadem University Medical School, Istanbul, Turkey (5/30)

2011

  • “A Sabbatical Report: Advances in Structural Biology: My Adventures in Milano & Grenoblewith X-rays & Neutrons, i Gelati & les Croissants, Ciao & Bonjour”, seminar, Biology Dept, BC (11/1)
  • “Nerve Myelin: A New Rap On An Old Wrap – Pushing the Boundaries of Analysis”, invited seminar, Department of Physiology and Biophysics, ֱ University (10/18)
  • “New Raps on A Phylogenetically Old Wrap: From Molecules to Myelinopathies”, invited lecture at the BioCenter Oulu Doctoral Programme Advanced Course in Structural Biology, University of Oulu, Oulu, Finland (5/31)
  • “En(w)raptures of Myelin”, invited lecture in “Protein Structure & Disease”, Brandeis University (3/28)

2010

  • “Assessing Myelin Development and Structure in Animal Models of Human Disorders “ Istituto di Richerche Farmacologiche Mario Negri”, Milano, Italy (10/11)
  • “Structure Determination by X-ray Diffraction”, invited lecture in Biological Chemistry (Bi435), ֱ College (4/30)
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