Natalia de Val, PhD - Frederick National Laboratory for Cancer Research - Director, Electron Microscopy Laboratory. Team Lead, Cryo-EM at the Center for Molecular Microscopy

Natalia de Val

PhD

Frederick National Laboratory for Cancer Research

Director, Electron Microscopy Laboratory. Team Lead, Cryo-EM at the Center for Molecular Microscopy

FREDERICK, MD | United States

Main Specialties: Biology

Additional Specialties: Electron Microscopy, Structural biology, Vaccine development


Top Author

Natalia de Val, PhD - Frederick National Laboratory for Cancer Research - Director, Electron Microscopy Laboratory. Team Lead, Cryo-EM at the Center for Molecular Microscopy

Natalia de Val

PhD

Introduction

I am a Biochemist/Protein engineering specialist, with 11-year experience in single particle Cryo-Electron Microscopy, protein expression and purification, as well as immunogenic design efforts for vaccine achievement.
At my current position as the Director of the Electron Microscopy Laboratory and the Team Lead for the Cryo-Electron Microscopy facility at the Center for Molecular Microscopy (CMM), Center for Cancer Research (CCR) and National Cancer Institute (NCI), I am responsible for the management of a wide portfolio of projects related mainly to cancer and HIV. Our goal at the CMM is to provide structural biology information that will help to develop vaccines and cures for infectious diseases as AIDS. Cryo-Electron Microscopy (Cryo-EM) is a technique which allows for direct visualization of samples in solution, preserved in their native hydrated state. Direct visualization allows us to fully understand the true nature of particles in solution which helps our collaborators effectively troubleshoot problems and correlate morphological and structural variations across different protein complexes. Within the last few years, several key advances have allowed for better and better resolution: first, a new type of camera (direct electron detectors) has been introduced, which allows for much better signal to noise ratio; and second, more computing power coupled with new algorithms for processing images has allowed researchers to tease more information out of existing electron microscopic images. For the first time, it is possible to acquire near-atomic resolution information from Cryo-Electron Microscopy.

Primary Affiliation: Frederick National Laboratory for Cancer Research - FREDERICK, MD , United States

Specialties:

Additional Specialties:

Research Interests:

Education

Oct 2007
Ph.D

Publications

32Publications

945Reads

722Profile Views

1265PubMed Central Citations

Structures and operating principles of the replisome.

Science 2019 02 24;363(6429). Epub 2019 Jan 24.

Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

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http://www.sciencemag.org/lookup/doi/10.1126/science.aav7003
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http://dx.doi.org/10.1126/science.aav7003DOI Listing
February 2019
89 Reads
31.477 Impact Factor

Rational Design of DNA-Expressed Stabilized Native-Like HIV-1 Envelope Trimers.

Cell Rep 2018 Sep;24(12):3324-3338.e5

Imperial College London, Department of Medicine, Division of Infectious Diseases, Section of Virology, Norfolk Place, London W2 1PG, UK. Electronic address:

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https://linkinghub.elsevier.com/retrieve/pii/S22111247183133
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http://dx.doi.org/10.1016/j.celrep.2018.08.051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6167709PMC
September 2018
14 Reads
7.210 Impact Factor

Hidden Lineage Complexity of Glycan-Dependent HIV-1 Broadly Neutralizing Antibodies Uncovered by Digital Panning and Native-Like gp140 Trimer

https://doi.org/10.3389/fimmu.2017.01025

Frontiers in Immunology

Germline precursors and intermediates of broadly neutralizing antibodies (bNAbs) are essential to the understanding of humoral response to HIV-1 infection and B-cell lineage vaccine design. Using a native-like gp140 trimer probe, we examined antibody libraries constructed from donor-17, the source of glycan-dependent PGT121-class bNAbs recognizing the N332 supersite on the HIV-1 envelope glycoprotein. To facilitate this analysis, a digital panning method was devised that combines biopanning of phage-displayed antibody libraries, 900 bp long-read next-generation sequencing, and heavy/light (H/L)-paired antibodyomics. In addition to single-chain variable fragments resembling the wild-type bNAbs, digital panning identified variants of PGT124 (a member of the PGT121 class) with a unique insertion in the heavy chain complementarity-determining region 1, as well as intermediates of PGT124 exhibiting notable affinity for the native-like trimer and broad HIV-1 neutralization. In a competition assay, these bNAb intermediates could effectively compete with mouse sera induced by a scaffolded BG505 gp140.681 trimer for the N332 supersite. Our study thus reveals previously unrecognized lineage complexity of the PGT121-class bNAbs and provides an array of library-derived bNAb intermediates for evaluation of immunogens containing the N332 supersite. Digital panning may prove to be a valuable tool in future studies of bNAb diversity and lineage development.

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August 2017
11 Reads

Open and closed structures reveal allostery and pliability in the HIV-1 envelope spike.

Nature 2017 07 12;547(7663):360-363. Epub 2017 Jul 12.

Department of Integrative Structural and Computational Biology, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, International AIDS Vaccine Initiative Neutralizing Antibody Center, and Collaboration for AIDS Vaccine Discovery, The Scripps Research Institute, La Jolla, California 92037, USA.

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http://dx.doi.org/10.1038/nature23010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538736PMC
July 2017
63 Reads
30 Citations
42.351 Impact Factor

Glycine Substitution at Helix-to-Coil Transitions Facilitates the Structural Determination of a Stabilized Subtype C HIV Envelope Glycoprotein.

Immunity 2017 05;46(5):792-803.e3

IAVI Neutralizing Antibody Center at The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Scripps Center for HIV/AIDS Vaccine Immunology & Immunogen Discovery (CHAVI-ID), La Jolla, CA 92037, USA. Electronic address:

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http://dx.doi.org/10.1016/j.immuni.2017.04.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5439057PMC
May 2017
48 Reads
13 Citations
21.561 Impact Factor

Tailored Immunogens Direct Affinity Maturation toward HIV Neutralizing Antibodies.

Cell 2016 Sep;166(6):1459-1470.e11

Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02129, USA. Electronic address:

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http://dx.doi.org/10.1016/j.cell.2016.08.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5018249PMC
September 2016
36 Reads
55 Citations
32.242 Impact Factor

Structures of Ebola virus GP and sGP in complex with therapeutic antibodies.

Nat Microbiol 2016 Aug 8;1(9):16128. Epub 2016 Aug 8.

Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California 92037, USA.

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http://dx.doi.org/10.1038/nmicrobiol.2016.128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5003320PMC
August 2016
55 Reads
19 Citations

Thermostability of Well-Ordered HIV Spikes Correlates with the Elicitation of Autologous Tier 2 Neutralizing Antibodies

10.1371/journal.ppat.1005767

PLOS Pathogens

In the context of HIV vaccine design and development, HIV-1 spike mimetics displaying a range of stabilities were evaluated to determine whether more stable, well-ordered trimers would more efficiently elicit neutralizing antibodies. To begin, in vitro analysis of trimers derived from the cysteine-stabilized SOSIP platform or the uncleaved, covalently linked NFL platform were evaluated. These native-like trimers, derived from HIV subtypes A, B, and C, displayed a range of thermostabilities, and were “stress-tested” at varying temperatures as a prelude to in vivo immunogenicity. Analysis was performed both in the absence and in the presence of two different adjuvants. Since partial trimer degradation was detected at 37°C before or after formulation with adjuvant, we sought to remedy such an undesirable outcome. Cross-linking (fixing) of the well-ordered trimers with glutaraldehyde increased overall thermostability, maintenance of well-ordered trimer integrity without or with adjuvant, and increased resistance to solid phase-associated trimer unfolding. Immunization of unfixed and fixed well-ordered trimers into animals revealed that the elicited tier 2 autologous neutralizing activity correlated with overall trimer thermostability, or melting temperature (Tm). Glutaraldehyde fixation also led to higher tier 2 autologous neutralization titers. These results link retention of trimer quaternary packing with elicitation of tier 2 autologous neutralizing activity, providing important insights for HIV-1 vaccine design

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August 2016
19 Reads

Presenting native-like trimeric HIV-1 antigens with self-assembling nanoparticles.

Nat Commun 2016 06 28;7:12041. Epub 2016 Jun 28.

Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, California 92037, USA.

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http://dx.doi.org/10.1038/ncomms12041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4931238PMC
June 2016
41 Reads
21 Citations
10.742 Impact Factor

Uncleaved prefusion-optimized gp140 trimers derived from analysis of HIV-1 envelope metastability.

Nat Commun 2016 06 28;7:12040. Epub 2016 Jun 28.

Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California 92037, USA.

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http://dx.doi.org/10.1038/ncomms12040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4931249PMC
June 2016
39 Reads
31 Citations
10.742 Impact Factor

Affinity Maturation of a Potent Family of HIV Antibodies Is Primarily Focused on Accommodating or Avoiding Glycans.

Immunity 2015 Dec;43(6):1053-63

Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Scripps Center for HIV/AIDS Vaccine Immunology & Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address:

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http://www.cell.com/immunity/pdf/S1074-7613(15)00459-8.pdf
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http://linkinghub.elsevier.com/retrieve/pii/S107476131500459
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http://dx.doi.org/10.1016/j.immuni.2015.11.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4692269PMC
December 2015
25 Reads
79 Citations
21.561 Impact Factor

Structure-Guided Redesign Increases the Propensity of HIV Env To Generate Highly Stable Soluble Trimers.

J Virol 2015 Dec 30;90(6):2806-17. Epub 2015 Dec 30.

IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California, USA Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California, USA

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http://dx.doi.org/10.1128/JVI.02652-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810649PMC
December 2015
19 Reads
39 Citations
4.440 Impact Factor

Model Building and Refinement of a Natively Glycosylated HIV-1 Env Protein by High-Resolution Cryoelectron Microscopy.

Structure 2015 Oct 17;23(10):1943-1951. Epub 2015 Sep 17.

Department of Integrative Structural and Computational Biology, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address:

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http://dx.doi.org/10.1016/j.str.2015.07.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4618500PMC
October 2015
20 Reads
32 Citations
5.620 Impact Factor

Cleavage-independent HIV-1 Env trimers engineered as soluble native spike mimetics for vaccine design.

Cell Rep 2015 Apr 16;11(4):539-50. Epub 2015 Apr 16.

IAVI Neutralizing Antibody Center at the Scripps Research Institute, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address:

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http://dx.doi.org/10.1016/j.celrep.2015.03.047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4637274PMC
April 2015
13 Reads
68 Citations
7.210 Impact Factor

Well-ordered trimeric HIV-1 subtype B and C soluble spike mimetics generated by negative selection display native-like properties.

PLoS Pathog 2015 Jan 8;11(1):e1004570. Epub 2015 Jan 8.

IAVI Neutralizing Antibody Center at The Scripps Research Institute, La Jolla, California, United States of America; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California, United States of America; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, United States of America.

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http://dx.doi.org/10.1371/journal.ppat.1004570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287557PMC
January 2015
18 Reads
51 Citations

Murine anti-vaccinia virus D8 antibodies target different epitopes and differ in their ability to block D8 binding to CS-E.

PLoS Pathog 2014 Dec 4;10(12):e1004495. Epub 2014 Dec 4.

Division of Cell Biology, La Jolla Institute for Allergy and Imunology (LIAI), La Jolla, California, United States of America.

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http://dx.doi.org/10.1371/journal.ppat.1004495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4256255PMC
December 2014
19 Reads
4 Citations

Vaccine-elicited primate antibodies use a distinct approach to the HIV-1 primary receptor binding site informing vaccine redesign.

Proc Natl Acad Sci U S A 2014 Feb 3;111(7):E738-47. Epub 2014 Feb 3.

International AIDS Vaccine Initiative Neutralizing Antibody Center, Departments of Integrative Structural and Computational Biology and Immunology and Microbial Science, and Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037.

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http://www.pnas.org/content/111/7/E738.full.pdf
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http://www.pnas.org/cgi/doi/10.1073/pnas.1319512111
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http://dx.doi.org/10.1073/pnas.1319512111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3932900PMC
February 2014
12 Reads
46 Citations
9.810 Impact Factor

Cryo-EM structure of a fully glycosylated soluble cleaved HIV-1 envelope trimer.

Science 2013 Dec 31;342(6165):1484-90. Epub 2013 Oct 31.

National Resource for Automated Molecular Microscopy, The Scripps Research Institute, La Jolla, CA 92037, USA.

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http://dx.doi.org/10.1126/science.1245627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3954647PMC
December 2013
47 Reads
326 Citations
31.480 Impact Factor

Native cysteine residues are dispensable for the structure and function of all five yeast mitotic septins.

Proteins 2013 Nov 19;81(11):1964-79. Epub 2013 Aug 19.

Division of Biochemistry, Biophysics and Structural Biology, Department of Molecular and Cell Biology, University of California, Berkeley, California, 94720-3202.

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http://dx.doi.org/10.1002/prot.24345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3880206PMC
November 2013
12 Reads
4 Citations
2.630 Impact Factor

A next-generation cleaved, soluble HIV-1 Env trimer, BG505 SOSIP.664 gp140, expresses multiple epitopes for broadly neutralizing but not non-neutralizing antibodies.

PLoS Pathog 2013 Sep 19;9(9):e1003618. Epub 2013 Sep 19.

Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York, United States of America ; Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

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http://dx.doi.org/10.1371/journal.ppat.1003618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3777863PMC
September 2013
59 Reads
302 Citations

Structural analysis of haemin demetallation by L-chain apoferritins.

J Inorg Biochem 2012 Jul 9;112:77-84. Epub 2012 Mar 9.

Institute of Life Sciences, University of Louvain, Place Croix du Sud, 1348 Louvain-la-Neuve, Belgium.

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http://dx.doi.org/10.1016/j.jinorgbio.2012.02.031DOI Listing
July 2012
16 Reads
4 Citations
3.444 Impact Factor

EPR studies of recombinant horse L-chain apoferritin and its mutant (E 53,56,57,60 Q) with haemin.

Biometals 2007 Feb 12;20(1):21-6. Epub 2006 May 12.

Unit of Biochemistry, Department of Chemistry, Université Catholique de Louvain, Bâtiment Lavoisier, 1 Place Louis Pasteur, 1348, Louvain-la-Neuve, Belgium.

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http://dx.doi.org/10.1007/s10534-006-9010-6DOI Listing
February 2007
11 Reads
2.503 Impact Factor

Mass spectrometry studies of demetallation of haemin by recombinant horse L chain apoferritin and its mutant (E 53,56,57,60 Q).

FEBS Lett 2006 Nov 24;580(26):6275-80. Epub 2006 Oct 24.

Department of Biochemistry, Université Catholique de Louvain, Bâtiment Lavoisier, 1 Place Louis Pasteur, 1348 Louvain-la-Neuve, Belgium.

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http://dx.doi.org/10.1016/j.febslet.2006.10.034DOI Listing
November 2006
13 Reads
3.170 Impact Factor

Optical and EPR spectroscopic studies of demetallation of hemin by L-chain apoferritins.

J Inorg Biochem 2006 Aug 16;100(8):1426-35. Epub 2006 Jun 16.

Université catholique de Louvain, Unit of Biochemistry, Place Louis Pasteur 1, B-1348 Louvain-la-Neuve, Belgium.

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http://dx.doi.org/10.1016/j.jinorgbio.2006.03.015DOI Listing
August 2006
14 Reads
1 Citation
3.444 Impact Factor

Top co-authors

Natalia de Val
Natalia de Val

Frederick National Laboratory for Cancer Research

30
Andrew B Ward
Andrew B Ward

The Scripps Research Institute

23
Ian A Wilson
Ian A Wilson

The Scripps Research Institute

12
Dennis R Burton
Dennis R Burton

The Scripps Research Institute

8
Richard T Wyatt
Richard T Wyatt

The Scripps Research Institute

8
John P Moore
John P Moore

Weill Medical College of Cornell University

8
Rogier W Sanders
Rogier W Sanders

Academic Medical Center

7
Javier Guenaga
Javier Guenaga

IAVI Neutralizing Antibody Center at The Scripps Research Institute

6
Gabriel Ozorowski
Gabriel Ozorowski

Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery

6
Max Crispin
Max Crispin

Oxford Glycobiology Institute

5