Ernesto Freire

About

Ernesto Freire received his PhD from the University of Virginia. He is a professor in the Department of Biology at Johns Hopkins University and holds a joint appointment in the Department of Biophysics and Biophysical Chemistry at JHMI. His research interests include the structure-based thermodynamics of molecular recognition and function, with a focus on drug development for important diseases. His work has contributed to the development of a thermodynamic platform for small molecule drug discovery and optimization, aimed at achieving high binding affinity, selectivity, and appropriate pharmacokinetics. Additionally, he has developed experimental approaches and thermodynamic algorithms to evaluate and predict the long-term stability of monoclonal antibodies, which are the fastest growing segment in the pharmaceutical industry. His research also involves the development of analytical methods and software for analyzing calorimetry data to study the structural stability of proteins, including monoclonal antibodies, antibody drug conjugates, and other antibody constructs. His collaborative work includes characterizing antibody binding to targets associated with infectious diseases such as malaria and SARS-CoV-2, contributing to the identification of broadly neutralizing antibodies and understanding protein interactions relevant to disease mechanisms.

Research topics

• Chemistry
• Biochemistry
• Biology
• Biophysics
• Thermodynamics
• Nuclear chemistry
• Immunology
• Crystallography
• Chemical physics
• Molecular biology

Selected publications

• Impact of Surface Polyethylene Glycol (PEG) Density on Biodegradable Nanoparticle Transport in Mucus <i>ex Vivo</i> and Distribution <i>in Vivo</i>

  ACS Nano · 2015-08-24 · 552 citations

  article

  Achieving sustained drug delivery to mucosal surfaces is a major challenge due to the presence of the protective mucus layer that serves to trap and rapidly remove foreign particulates. Nanoparticles engineered to rapidly penetrate mucosal barriers (mucus-penetrating particles, "MPP") have shown promise for improving drug distribution, retention and efficacy at mucosal surfaces. MPP are densely coated with polyethylene glycol (PEG), which shields the nanoparticle core from adhesive interactions…

  PublisherDOI

• A human monoclonal antibody prevents malaria infection by targeting a new site of vulnerability on the parasite

  Nature Medicine · 2018-03-19 · 312 citations

  letterOpen access
  PublisherOA PDFDOI

• Crystal structures of trimeric HIV envelope with entry inhibitors BMS-378806 and BMS-626529

  Nature Chemical Biology · 2017-08-21 · 127 citations

  articleOpen access
  PublisherOA PDFDOI

• The β20–β21 of gp120 is a regulatory switch for HIV-1 Env conformational transitions

  Nature Communications · 2017-10-14 · 115 citations

  articleOpen access

  The entry of HIV-1 into target cells is mediated by the viral envelope glycoproteins (Env). Binding to the CD4 receptor triggers a cascade of conformational changes in distant domains that move Env from a functionally "closed" State 1 to more "open" conformations, but the molecular mechanisms underlying allosteric regulation of these transitions are still elusive. Here, we develop chemical probes that block CD4-induced conformational changes in Env and use them to identify a potential control sw…

  PublisherOA PDFDOI

• Small-Molecule CD4-Mimics: Structure-Based Optimization of HIV-1 Entry Inhibition

  ACS Medicinal Chemistry Letters · 2016-01-19 · 104 citations

  articleOpen access

  The optimization, based on computational, thermodynamic, and crystallographic data, of a series of small-molecule ligands of the Phe43 cavity of the envelope glycoprotein gp120 of human immunodeficiency virus (HIV) has been achieved. Importantly, biological evaluation revealed that the small-molecule CD4 mimics (4-7) inhibit HIV-1 entry into target cells with both significantly higher potency and neutralization breadth than previous congeners, while maintaining high selectivity for the target vi…

  PublisherOA PDFDOI

Recent grants

• Cooperative Interactions in Proteins

  NSF · $1.1M · 2007–2012

• NIH Grant R01NS024520

  NIH · $1.5M · 1997

• NIH Grant R01GM057144

  NIH · $6.3M · 2013

Frequent coauthors

• Joseph Sodroski

  Dana-Farber Cancer Institute

  123 shared

• Arne Schön

  Johns Hopkins University

  117 shared

• Navid Madani

  99 shared

• Irwin Chaiken

  Drexel University

  89 shared

• Amos B. Smith

  University of Pennsylvania

  72 shared

• Simon Cocklin

  Drexel University

  68 shared

• Jeffrey C. Klein

  Johns Hopkins University

  59 shared

• Zhihai Si

  Akebia Therapeutics (United States)

  41 shared

Similar researchers at Johns Hopkins University

• Steven L. Salzbergh-191
• Rachel Greenh-114
• Margaret Johnsonh-92