Dr. Leapman obtained his Bachelor's in Natural Sciences, and Ph.D. in physics from the University of Cambridge, UK. He was then trained as a postdoctoral fellow in the Department of Materials Science at the University of Oxford, UK, and in the Department of Applied and Engineering Physics at Cornell University, NY, where he contributed to the development of electron spectroscopy in the transmission electron microscope. He subsequently moved to NIH to adapt those techniques to characterize the structure and chemical composition of cells at a nanoscale. Dr. Leapman is Chief of NIBIB’s Laboratory of Cellular Imaging and Macromolecular Biophysics, and also heads the Supramolecular Structure and Function Section. He is currently Editor of the Journal of Microscopy (Oxford) and serves on editorial boards of other microscopy and nanotechnology journals, as well as on Scientific Advisory Committees.

Research Interests

Dr. Richard Leapman's research interests are in the development and application of quantitative electron microscopy and the application of novel nanoscale imaging methods to solve problems in structural and cellular biology. He has been particularly active in developing the techniques of electron energy loss spectroscopy (EELS) and combining it with x-ray spectroscopy and scanning transmission electron microscopy (STEM) to provide an unprecedented high spatial resolution for nanoanalysis of biological structures. Dr. Leapman has devised new methods for quantifying both elemental and chemical information obtained from inelastic electron scattering, a research area in which he has over one hundred publications. Recently, he and his group have extended the techniques of STEM and energy-filtered electron tomography to obtain three-dimensional structural and compositional information about cellular components.

Selected Publications

Sousa AA, Azari AA, Zhang G, Leapman RD (2011) Dual-axis electron tomography of biological specimens: Extending the limits of specimen thickness with bright-field STEM imaging. J Struct Biol. (in press). (http://www.ncbi.nlm.nih.gov/pubmed/21055473)

Aronova MA, Sousa AA, Leapman RD (2011) EELS characterization of radiolytic products in frozen samples. Micron 42, 252-256. (http://www.ncbi.nlm.nih.gov/pubmed/21111626.)

Fukunaga M, Li T-Q, van Gelderen P, de Zwart JA, Shmueli K, Yao B, Lee J, Maric D, Aronova MA, Zhang G, Leapman RD, Schenck JF, Merkle H, Duyn JH (2010) Layer-specific variation of iron content in cerebral cortex as a source of MRI contrast. Proc Natl Acad Sci U S A. 107, 3834-3839. (http://www.ncbi.nlm.nih.gov/pubmed/20133720)

Leapman RD (2010) Nanoparticles: Dissected with electrons. Nature Nanotechnol. 5, 480-481. (http://www.ncbi.nlm.nih.gov/pubmed/20606638)

Aronova MA, Sousa AA, Zhang G, Leapman RD (2010) Limitations of beam damage in electron spectroscopic tomography of embedded cells. J Microsc. 239, 223-32. (http://www.ncbi.nlm.nih.gov/pubmed/20701660)

Hohmann-Marriott MF, Sousa AA, Azari AA, Glushakova S, Zhang G, Zimmerberg J, Leapman RD (2009) Nanoscale 3D cellular imaging by axial scanning transmission electron tomography. Nature Methods 6, 729-732. (http://www.ncbi.nlm.nih.gov/pubmed/19718033)

Sousa AA, Aronova MA, Wu H, Sarin H, Griffiths GL, Leapman RD (2009) Determining molecular mass distributions and compositions of functionalized dendrimer nanoparticles. Nanomedicine. 4, 391-399. (http://www.ncbi.nlm.nih.gov/pubmed/19505242)

Sousa AA, Hohmann-Marriott MF, Zhang G, Leapman RD (2009) Monte Carlo electron-trajectory simulations in bright-field and dark-field STEM: implications for tomography of thick biological specimens. Ultramicroscopy 109, 213-221. (http://www.ncbi.nlm.nih.gov/pubmed/19110374)

Paravastu AK, Qahwash I, Leapman RD, Meredith SC, Tycko R (2009) Seeded growth of beta-amyloid fibrils from Alzheimer’s brain-derived fibrils produces a novel fibril structure. Proc Natl Acad Sci USA 106, 7443-7448. (http://www.ncbi.nlm.nih.gov/pubmed/19376973)

Chen KG, Leapman RD, Zhang G, Lai B, Valencia JC, Cardarelli CO, Vieira WD, Hearing VJ, Gottesman MM (2009) Melanosome dynamics affect drug resistance and sensitivity in malignant melanoma. J. Natl. Cancer Inst. 101, 1259-1271. (http://www.ncbi.nlm.nih.gov/pubmed/19704071)

Aronova MA, Kim, YC, Pivovarova NB, Andrews SB, Leapman RD (2009) Quantitative EFTEM mapping of low calcium concentrations in biological specimens. Ultramicroscopy 109, 201-212. (http://www.ncbi.nlm.nih.gov/pubmed/19118952 )

Trachtenberg S, Dorward LM, Speransky VV, Jaffe H, Andrews SB, Leapman RD (2008) Structure of the cytoskeleton of Spiroplasma melliferum BC3 and its interactions with the cell membrane. J. Mol. Biol. 378, 776-87. (http://www.ncbi.nlm.nih.gov/pubmed/18400234)

Chen X, Winters C, Azzam R, Li X, Galbraith JA, Leapman RD, Reese TS (2008) Organization of the core structure of the postsynaptic density. Proc Natl Acad Sci USA 105, 4453-4458. (http://www.ncbi.nlm.nih.gov/pubmed/18326622)

Paravastu AK, Leapman RD, Yau WM, Tycko R (2008) Molecular structural basis for polymorphism in Alzheimer’s beta amyloid fibrils. Proc Natl Acad Sci USA 105, 18349-18354. (http://www.ncbi.nlm.nih.gov/pubmed/19015532)

Sousa AA, Hohmann-Marriott M, Aronova MA, Zhang G, Leapman RD (2008) Determination of quantitative distributions of heavy-metal stain in biological specimens by annular dark-field STEM. J Struct Biol 162, 14-28. (http://www.ncbi.nlm.nih.gov/pubmed/18359249)

Aronova MA, Kim YC, Zhang G, Leapman RD (2007) Quantification and thickness correction of EFTEM phosphorus maps. Ultramicroscopy 107, 232-244. (http://www.ncbi.nlm.nih.gov/pubmed/16979822)

Leapman RD, Aronova MA (2007) Localizing specific elements bound to macromolecules by EFTEM. Methods in Cell Biol 79, 593-613. (http://www.ncbi.nlm.nih.gov/pubmed/17327176)

Aronova MA, Kim YC, Harmon R, Sousa AA, Zhang G, Leapman RD (2007) Three-dimensional elemental mapping of phosphorus by quantitative electron spectroscopic tomography (QuEST). J. Struct. Biol. 160, 35-48. (http://www.ncbi.nlm.nih.gov/pubmed/17693097)

Sousa AA, Aronova MA, Kim YC, Dorward LM, Zhang G, Leapman RD (2007) On the feasibility of visualizing ultrasmall gold labels in biological specimens by STEM tomography. J Struct Biol 159, 507-522. (http://www.ncbi.nlm.nih.gov/pubmed/17689263)

Sousa AA, Leapman RD (2007) Quantitative STEM mass measurement of biological macromolecules in a 300 kV TEM. J. Microsc. 228, 25-33. (http://www.ncbi.nlm.nih.gov/pubmed/17910694)

Chen KG, Valencia JC, Lai B, Zhang G, Paterson JK, Rouzaud F, Berens W, Wincovitch SM, Garfield SH, Leapman RD, Hearing VJ, Gottesman MM (2006) Melanosomal sequestration of cytotoxic drugs contributes to the intractability of malignant melanomas. Proc. Natl. Acad. Sci. USA. 103, 9903-9907. (http://www.ncbi.nlm.nih.gov/pubmed/16777967)

Chen X, Vande L, Leapman, RD, Nakagawa T, Petersen J, Phillips T, Dosemeci A, Sheng M, Reese T (2005) Mass of the postsynaptic density and enumeration of three key molecuels. Proc Natl Acad Sci USA 102, 11551-11556. (http://www.ncbi.nlm.nih.gov/pubmed/16061821

Petkova AT, Leapman RD, Guo Z, Yau W-M, Mattson MP, Tycko R (2005) Self-propagating, molecular-level polymorphism in Alzheimer’s ?-amyloid fibrils. Science 307, 262-265. (http://www.ncbi.nlm.nih.gov/pubmed/15653506)