Jeffrey Hudgens

Research Chemist

Hudgens Group



Call: (240) 314-6485


  • National Research Council Postdoctoral Fellow (NRC/NRL), Chemical Division, Naval Research Laboratory Washington, DC, 1975–1977
  • Ph.D., Physical Chemistry, University of Illinois at Urbana–Champaign, 1976      
  • B.S., Chemistry, Miami University, 1971


Dr. Jeffrey Hudgens investigates the precision of hydrogen-deuterium exchange mass spectrometry (HDX-MS) and its application to the measurement of protein-ligand and glycoprotein-ligand interactions, the dynamical structures of mAbs, lipid-protein complexes, and membrane protein interactions. In addition to these fundamental determinations of the relationship between biomolecular structure and function, Dr. Hudgens also invents new apparatus and methods that improve HDX-MS methodology, especially as related to biopharmaceutical analysis. These improvements and insights will enable HDX-MS to be used in comparability studies of innovator and biosimilar drugs, thus advancing biopharmaceutical development and regulation.


Dr. Hudgens focuses on the development of advanced techniques for accurate and precise characterization of higher-order-structure (HOS) in biotherapeutics, particularly monoclonal antibodies. Industry and regulators use knowledge of HOS to establish consistency in drug manufacturing, to detect process-related drug-product variations, and to compare biosimilars to innovator reference products.   

Diagram showing the steps of the HDX-MS Interlaboratory Comparison Project

Determination of the Reproducibility of HDX-MS

The NIST HDX-MS Interlaboratory Comparison Project is designed to measure reproducibility and to facilitate the harmonization of HDX-MS. An understanding of HDX-MS reproducibility has become critical as proteolytic fragmentation HDX-MS measurements of the same (and similar) mAbs are conducted over periods of years and in multiple locations.

Sequence coverage of FcγRIIa.  (A) Amino acid sequence coverage of FcγRIIa with regions with detected peptides shown in red and regions without detected peptides shown in black.  (B) Sequence coverage mapped onto PDB 3RY6 FcγRIIa structure.  FcγRIIa termini not included in crystal structure were appended as representations, joined using blue asterisks to PDB 3RY6 structure.  Representation of C-terminus is shown in lipid bilayer for reference.

To answer the question of HDX-MS precision, NIST has determined the precision of HDX-MS by the analysis of 78,900 peptide measurements by 15 laboratories of the Fab fragment of NISTmAb. The reporting laboratories reside in four countries, at six pharmaceutical companies, four universities, NIST, and a private foundation. This project is finalizing its reports, which will be published as a manuscript and a data set that can be mined by other investigators.

Studies of Membrane Proteins

Membrane proteins represent ~60 % of all drug targets. The interactions of mAbs with membrane-bound FcgR receptors govern their effector mechanism and binding characteristics.  Hudgens studies membrane proteins entrained in phospholipid bicelles, liposomes, and nanodiscs. Previously, HDX-MS of entrained proteins required labor-intensive manual removal of phospholipids. The Hudgens lab has reported an automated procedure for phospholipid removal, which should increase the productivity of HDX-MS studies of membrane proteins. The lab is using this phospholipid removal method during their studies of the effects of glycan complexes.


HDX-MS and MD Simulations Provide Evidence for Stabilization of the IgG1-FcγRIa (CD64a) Immune Complex Through Intermolecular Glycoprotein Bonds.
Conformational gating, dynamics and allostery in human monoacylglycerol lipase.
Construction of a Dual Protease Column, Subzero (-30 °C) Chromatography System and Multi-channel Precision Temperature Controller for Hydrogen-Deuterium Exchange Mass Spectrometry.
Interlaboratory Comparison of Hydrogen-Deuterium Exchange Mass Spectrometry Measurements of the Fab Fragment of NISTmAb.
Hydrogen-Deuterium Exchange Mass Spectrometry (HDX-MS) Centroid Data Measured between 3.6 °C and 25.4 °C for the Fab Fragment of NISTmAb.
Automated Removal of Phospholipids from Membrane Proteins for H/D Exchange Mass Spectrometry Workflows.
Effects of Distal Mutations on the Structure, Dynamics and Catalysis of Human Monoacylglycerol Lipase.
Data on crystal organization in the structure of the Fab fragment from the NIST reference antibody, RM 8671.
Biophysical characterization and structure of the Fab fragment from the NIST reference antibody, RM 8671.
Conformational Changes in Active and Inactive States of Human PP2Cα Characterized by Hydrogen/Deuterium Exchange-Mass Spectrometry.
Mapping of the Allosteric Site in Cholesterol Hydroxylase CYP46A1 for Efavirenz, a Drug That Stimulates Enzyme Activity.
Mapping Protein-Ligand Interactions with Proteolytic Fragmentation, Hydrogen/Deuterium Exchange-Mass Spectrometry.
Characterization of AlgMsp, an alginate lyase from Microbulbifer sp. 6532A.
A novel mechanism for regulating the activity of proliferating cell nuclear antigen by a small protein.
Effects of desialylation on human α1-acid glycoprotein-ligand interactions.
Surface mediated assembly of small, metastable gold nanoclusters.
Reaction network governing diphosphine-protected gold nanocluster formation from nascent cationic platforms.
Predictive gold nanocluster formation controlled by metal-ligand complexes.
Reaction mechanism governing formation of 1,3-bis(diphenylphosphino)propane-protected gold nanoclusters.
Gold cluster formation with phosphine ligands: etching as a size-selective synthetic pathway for small clusters?