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Lili Wang

Research Chemist

Research Interests

My research mostly focuses on using quantitative flow cytometry to measure clinically and biomanufacturing relevant biological substances, cells, extracellular vesicles/exosomes, virus, proteins, DNA and RNA. Current effort includes development of additional reference fluorophore solutions and reference cell materials for standardizing flow cytometer intensity scale and performance characteristics in the unit of the equivalent number of reference fluorophores (ERF) and building sufficient measurement assurance in counting of bio-entities and biomarker expression analysis using flow cytometry. We provide an ERF value assignment service to the manufacturers of cytometer calibration particles under the flow cytometry quantitation consortium. The application of cell reference materials facilitates the quantitative measure of unknown biomarker expression in the unit of antibodies bound per cell (ABC), independent of the flow cytometers used. Additionally, we work closely with other international metrological institutions for the development of cell and other bio-entity counting reference materials. Examples of current projects include 1) characterization of biological reference materials including cell lines, engineered cell lines, primary cells, lyophilized cells, and exosomes; 2) quantifying expression of cell surface and intracellular biomarkers by estimating the antibodies bound per cell; 3) enumeration of cells with specific phenotypic characteristics and function, e.g. CD34+ stem cells and cytokine producing T cells; 4) harmonizing flow cytometry data across different cytometer platforms through panel design, antibody titration, instrument calibration, reference cell controls, and high dimensional data analysis.

Memberships and Committees

  • CLSI Committee on Validation of Assays Performed by Flow Cytometry, 2017-present
  • CDRH/FDA Hematology and Pathology Devices Panel Advisory Committee, Consultant, 2011- present
  • JCTLM Team Leader on Blood Cell Counting and Typing, 2009-present
  • ISAC Standards Committee Fluorescence Calibration Task Force, Co-chair, 2009-present
  • ICCS Quality and Standards Committee, 2016-present
  • USP CD34 – Positive Cells Expert Panel, 2010-2016
  • IFCC cTnI Standardization Working Group, 2007-present

Selected Publications

  1. Building Measurement Assurance in Flow Cytometry. Cytometry Part A, 95A, 626-630 (2019).
  2. Comparison of volumetric and bead-based counting of CD34 cells by single-platform flow cytometry. Cytometry Part B 96B: 508-513 (2019).
  3. Methodology for evaluating and comparing fluorescence measurement capabilities: Multi-site study of 23 flow cytometers. Cytometry Part A 93A, 1087-1091 (2018).
  4. Quantitative Fluorescence Measurements with Multicolor Flow Cytometry. Flow Cytometry Protocols, 4th Edition, Humana Press/Springer, New York, p93-110 (2018).
  5. Steps to Achieve Quantitative Measurements of microRNA Using Two-Step Digital Droplet PCR. PLoS ONE 12(11): e0188085 (2017).
  6. Assignment of the Number of Equivalent Reference Fluorophores to Dyed Microspheres. J. Res. Natl. Inst. Stand. Technol. 121, 269-286 (2016).
  7. Quantitative Flow Cytometry Measurements in Antibodies Bound per Cell Based on a CD4 Reference. Curr. Protoc. Cytom. 75:1.29.1-1.29.14 (2016).
  8. Consistent, multi-instrument single tube quantification of CD20 in antibody bound per cell based on CD4 reference. Cytometry Part B 90B: 159-167 (2016).
  9. Determination of CD4+ Cell Count per µL in Reconstituted Lyophilized Human PBMC Pre-labelled with Anti-CD4 FITC Antibody. Cytometry Part A 87A, 244-253 (2015).
  10. Quantification of Cells with Specific Phenotypes II: Determination of CD4 Expression Level on Lyophilized Human PBMC Surface Labeled with Anti-CD4 FITC Antibody. Cytometry Part A 87A, 254-261 (2015).
  11. Quantifying CD4 receptor protein in two human CD4+ lymphocyte preparations for quantitative flow cytometry. Clin Proteomics 11:43 (2014).
  12. Quantifying CD4 Receptor Density on Human T Lymphocytes Using Multiple Reaction Monitoring Mass Spectrometry. Anal Chem 85, 1773-1777 (2013).
  13. Breast cancer biomarker measurements and standards: progress on Her2. Proteomics Clin. Appl. 7, 17-29 (2013).
  14. Quantifying CD4 Receptor Density on Human T Lymphocytes Using Multiple Reaction Monitoring Mass Spectrometry. Anal Chem 85, 1773-1777 (2013).
  15. NIST/ISAC standardization study: variability in assignment of intensity values to fluorescence standard beads and in cross calibration of standard beads to hard dyed beads. Cytometry Part A, 81A, 785-796 (2012).
  16. Human CD4+ Lymphocytes for Antigen Quantification: Characterization Using Conventional Flow Cytometry and Mass Cytometry. Cytometry Part A 81A, 567-575 (2012).
  17. A Model for Harmonizing Flow Cytometry in Clinical Trials. Nature Immunology 11(11), 975-978 (2010).
  18. Development of a Candidate Secondary Reference Procedure (Immunoassay Based Measurement Procedure of Higher Metrological Order) for Cardiac Troponin I: 1. Antibody Characterization and Preliminary Validation. Clin Chem Lab Med 48(11), 1603-1610 (2010).
  19. Toward Quantitative Fluorescence Measurements with Multicolor Flow Cytometry. Cytometry 73A, 279-288 (2008).

NIST-NRC and NIH/NIST NRC Postdoctoral Fellowship Opportunities

  1. Quantitative Flow Cytometry Measurements; RO#: 50.64.41.B6740
  2. Multiplexed Assays for Cell-based Production of Biopharmaceuticals; RO#: 50.64.41.B8223
  3. Analytical Metrology for Isolating, Purifying and Characterizing Extracellular Vesicles (EVs) for Development and Delivery of Gene and Protein-Based Therapeutics; (RO#: 50.64.41.C0414)

Awards

  • CSTL Technical Achievement Award (2004)
  • CSTL Director's Cash-in-a-Flash Award (2007)
  • Emerald Honor Award from Minorities in Research/Career Communications Group (2007)
  • Department of Commerce Bronze Award (2015)

Publications

Workshop 9: Control Cells or Not

Author(s)
Paul Wallace, Jonni S. Moore, Derek Jones, Litwin Virginia, Lili Wang, Yanli Liu
“Control Cells or Not” was an educational workshop that used surveys, lectures, and discussions to identify problems and solutions related to using commercially

Workshop 13: Building Measurement Assurance in Flow Cytometry

Author(s)
Lili Wang, Stephen Perfetto, Robert Hoffman, John T. Elliott, Sheng Lin-Gibson, Steven Bauer, Heba Degheidy, Judith Arcidiacono, Litwin Virginia
Two workshops were held to identify measurement challenges and potential solutions for building measurement assurance for flow cytometry. This report summarizes

Comparison of volumetric and bead-based counting of CD34 cells by single-platform flow cytometry

Author(s)
Luisa Saraiva, Lili Wang, Martin Kammel, A. Kummrow, E Atkinson, J Y. Lee, B Yalcinkaya, M Akgoz, A Ruf, A Engel, Yu-Zhong Zhang, O O''Shea, M P. Sassi, C Divieto, T Lekishvili, J J. Campbell, Y Liu, J Wang, R Stebbings, Adolfas Gaigalas, P Rigsby, J Neukammer, S Vessillier
Background: Over 2000 people a year in the UK need a bone marrow or blood stem cell transplant. It is important to accurately quantify the haematopoietic stem

Methodology for evaluating and comparing fluorescence measurement capabilities: Multi-site study of 23 flow cytometers

Author(s)
David R. Parks, Wayne A. Moore, Ryan Brinkman, Yong Chen, Danilo Condello, Faysal E. Khettabi, John P. Nolan, Stephen P. Perfetto, Doug Redelman, Josef Spidlen, Jonathan V. Dyke, Lili Wang, James C. Wood
We developed measurement methods and analysis procedures to perform inter-instrument comparisons and used them to evaluate and compare the fluorescence
Created October 9, 2019, Updated April 15, 2020