Osnat Herzberg


Herzberg Group


Email: osnat@umd.edu

Call: (240) 314-6245


  • Ph.D., Chemistry, Weizmann Institute of Science, Israel, 1982
  • M.S., Chemistry, Weizmann Institute of Science, Israel, 1976
  • B.S., Chemistry, Technion, Israel, 1971


Dr. Osnat Herzberg is a structural biologist interested in the relationship between the function and structure of proteins and how protein-ligand interactions can guide drug discovery. The Herzberg lab uses X-ray crystallography and other biophysical, biochemical, and cellular approaches to better understand various experimental systems.


Current projects in the Herzberg lab include studies of genetic factors that contribute to inflammatory bowel diseases; understanding the structure and function of myovirus phage CBA120 proteins, a bacteriophage that kills pathogenic E. coli; and, drug discovery for combating the parasitic diseases giardiasis and amebiasis. 

From crystals to electron density map to structure.
A tailspike protein structure is shown at the bottom.
Structural changes in the Gasdermin B polymorphism loop. The polymorphism of IBS associated protein leads to a more rigid structure (right) than that present in the healthy population (left).

The inflammatory bowel diseases (IBD), Crohn’s disease and ulcerative colitis, are human complex trait diseases caused by multiple genetic variants and environmental factors. The Herzberg lab is working to identify genetic variants known as single nucleotide polymorphisms (SNPs) that are associated with these diseases. They hope to determine how these variants alter proteins that contribute to disease. This is a collaborative project involving Dr. John Moult’s group. Dr. Moult’s group is identifying candidate disease variants by computational methods and the Herzberg group is carrying out experimental studies to validate these findings. One particular protein, called gasdermin B, has variants that have been implicated in IBD. Studies by the Herzberg lab revealed that protein changes associated with different SNPs alter the flexibility of a protein loop region and these changes have the potential to alter protein-protein interactions. Dr. Herzberg’s lab also discovered that gasdermin B can bind to lipid molecules that are critical to maintaining the integrity of the gut wall. It remains to be determined whether and how the gasdermin B variant found in IBD patients affects the lipid composition of the gut wall. 

The parasites Giardia lamblia and Entamoeba histolytica cause severe intestinal diseases and are major health hazards in undeveloped and developing countries. Moreover, disease outbreaks in the developed world are associated with drug resistance, which is rapidly spreading, and many patients do not tolerate these standard-of-care drugs. The Herzberg lab is developing less toxic drugs that are not prone to drug resistance. The Herzberg group is optimizing the properties of a drug called fumagillin, which is used in the European Union to treat immune compromised patients suffering from the parasitic infection microsporidiosis, in order to develop new and better antigiardiasis and antiamebiasis therapeutics. Compound optimization is facilitated by the unique capabilities of the group that integrate all aspects of preclinical studies, including medicinal chemistry, biochemistry, molecular biology, cellular biology, and animal studies.

Image of Giardia lamblia trophozoites highlighting in fluorescent green one of the ATP producing enzymes studied by the group.


Computational models in the service of X-ray and cryo-electron microscopy structure determination.
Structure and function of bacteriophage CBA120 ORF211 (TSP2), the determinant of phage specificity towards E. coli O157:H7.
Discovery and Preclinical Development of Antigiardiasis Fumagillol Derivatives.
Structure and tailspike glycosidase machinery of ORF212 from E. coli O157:H7 phage CBA120 (TSP3).
Intracellular Delivery of an Antibody Targeting Gasdermin-B Reduces HER2 Breast Cancer Aggressiveness.
Target highlights from the first post-PSI CASP experiment (CASP12, May-August 2016).
Reply to HU et al.: On the interpretation of gasdermin-B expression quantitative trait loci data.
A protein-protein interaction dictates Borrelial infectivity.
Gene polymorphism linked to increased asthma and IBD risk alters gasdermin-B structure, a sulfatide and phosphoinositide binding protein.
Discovery of novel antigiardiasis drug candidates.
Structural basis for the binding specificity of human Recepteur d'Origine Nantais (RON) receptor tyrosine kinase to macrophage-stimulating protein.
Crystal structure of ORF210 from E. coli O157:H1 phage CBA120 (TSP1), a putative tailspike protein.
Structural basis for inactivation of Giardia lamblia carbamate kinase by disulfiram.
Crystal structures of carbamate kinase from Giardia lamblia bound with citric acid and AMP-PNP.
Crystal structure of the Sema-PSI extracellular domain of human RON receptor tyrosine kinase.
Pliable DNA conformation of response elements bound to transcription factor p63.
Protein characterization of a candidate mechanism SNP for Crohn's disease: the macrophage stimulating protein R689C substitution.
Structures of p63 DNA binding domain in complexes with half-site and with spacer-containing full response elements.
High-throughput Giardia lamblia viability assay using bioluminescent ATP content measurements.
Structure of oxalacetate acetylhydrolase, a virulence factor of the chestnut blight fungus.