Eric Toth

Assistant Research Professor

Toth Group



Call: (240) 314-6516


  • Postdoctoral Fellowship, University of California, Los Angeles (UCLA), and Harvard Medical School, 2000-2004
  • Ph.D., Biochemistry, UCLA, 1999
  • B.A., Biochemistry (Honors), University of Pennsylvania, 1992


Dr. Eric Toth applies biochemical and biophysical techniques, including X-ray crystallography, to accelerate the development of agents that modulate the function of a wide array of potential therapeutic targets. These efforts include the development of next-generation protein therapeutics, novel vaccines, and small molecule inhibitors of biologically important proteins.


Therapeutic Protein Design and Development

One area of research in Dr. Toth’s laboratory is the engineering of well-characterized proteins to develop new properties for use as therapeutics, sensors, or novel reagents. The development of a protein-based therapeutic directed against cancer-causing Ras protein is a proof-of-principle project currently underway. This project is a collaborative effort conducted by a team composed of Dr. Toth, Dr. John Orban (UMCP Department of Chemistry and Biochemistry) and Dr. Phil Bryan (Potomac Affinity Proteins), with contributions from Dr. Silvia Muro (IBBR) and the Ras Initiative (NCI-Frederick).

General paradigm for engineering next-generation protein therapeutics.

Mutations in one of the three RAS genes are involved in roughly a third of all human cancers, but therapeutic interventions have limited clinical efficacy. The goal of this project is to engineer a highly specific, highly regulated protease capable of destroying mutated human Ras proteins. The long-term objectives are to develop a “smart” therapeutic and to create a platform for future engineering of enzymatic machines to treat drug-resistant cancers and other diseases.

Hepatitis C vaccine

The Toth lab is part of a multi-institutional team, led by IBBR director Dr. Thomas Fuerst, which is developing a vaccine to prevent hepatitis C viral infection. Funded by a $6 million NIH grant, the effort takes a structure-based vaccine design approach to engineer vaccine candidates that elicit a broadly neutralizing immune response. Dr. Toth’s lab is developing novel methods for producing and isolating candidate vaccine antigens for biochemical and immunological testing.

Hepatitis C virus (HCV) is a major cause of severe liver disease and cancer with a global burden of nearly 185 million infected individuals. HCV is an RNA virus that mutates rapidly, making both treatment and vaccine development challenging for this pathogen. While HCV-specific antiviral agents provide effective therapy, a successful treatment does not prevent reinfection. In addition, the high cost of these drugs restricts access, particularly in developing nations where disease burden is greatest, further underscoring the need for a vaccine.

The biological dimer of hNQO1 with two active sites, one at each end of the dimer interface. One monomer is colored magenta while the other monomer is colored blue. Two FAD molecules present at each active site are shown orange and an E6a molecule is shown in green. The inset shows the surface area buried upon FAD-E6a interaction. (BMC Struct. Biol. (2016). 16,1).

Structure-Based Drug Design  

Dr. Toth has led efforts to determine crystal structures of several important drug targets in complex with novel lead compounds aimed at combating cancer and neurological diseases. These efforts include targeting malignant melanoma through disruption of the interaction of p53 with S100B, combating acute myeloid leukemia and other cancers with novel naphthoquinones that inhibit NQO1 (see inset), and targeting neurological disorders by developing inhibitors of the kynurenine pathway of tryptophan degradation.

Induction of broadly neutralizing antibodies using a secreted form of the hepatitis C virus E1E2 heterodimer as a vaccine candidate.
Structural and Biophysical Characterization of the HCV E1E2 Heterodimer for Vaccine Development.
Engineering subtilisin proteases that specifically degrade active RAS.
Design of a native-like secreted form of the hepatitis C virus E1E2 heterodimer.
Structure-Based Design of Hepatitis C Virus E2 Glycoprotein Improves Serum Binding and Cross-Neutralization.
Crystal structures of human 3-hydroxyanthranilate 3,4-dioxygenase with native and non-native metals bound in the active site.
Structure-based design of N-substituted 1-hydroxy-4-sulfamoyl-2-naphthoates as selective inhibitors of the Mcl-1 oncoprotein.
A direct interaction between NQO1 and a chemotherapeutic dimeric naphthoquinone.
Hydroxylated Dimeric Naphthoquinones Increase the Generation of Reactive Oxygen Species, Induce Apoptosis of Acute Myeloid Leukemia Cells and Are Not Substrates of the Multidrug Resistance Proteins ABCB1 and ABCG2.
Small Molecule Inhibitors of Ca(2+)-S100B Reveal Two Protein Conformations.
Covalent small molecule inhibitors of Ca(2+)-bound S100B.
Interaction of apurinic/apyrimidinic endonuclease 2 (Apn2) with Myh1 DNA glycosylase in fission yeast.
Structure of human apurinic/apyrimidinic endonuclease 1 with the essential Mg2+ cofactor.
Coordination of MYH DNA glycosylase and APE1 endonuclease activities via physical interactions.
The crystal structure of human quinolinic acid phosphoribosyltransferase in complex with its inhibitor phthalic acid.
A unique IBMPFD-related P97/VCP mutation with differential binding pattern and subcellular localization.
Structure-Based Discovery of a Novel Pentamidine-Related Inhibitor of the Calcium-Binding Protein S100B.
Hsp70 is a novel posttranscriptional regulator of gene expression that binds and stabilizes selected mRNAs containing AU-rich elements.
Target binding to S100B reduces dynamic properties and increases Ca(2+)-binding affinity for wild type and EF-hand mutant proteins.
Crystal structure of human methyl-binding domain IV glycosylase bound to abasic DNA.