Thomas Fuerst

Professor

Fuerst Group

Contact

Email: tfuerst@umd.edu

Call: (240) 314-6507

Education

  • Ph.D., Molecular Genetics, Cornell University, 1984
  • MBA, Science, Technology and Innovation, George Washington University, 1992
  • B.A., Biochemistry, University of California at Berkeley, 1980

Profile

Dr. Fuerst’s research is focused on the development of next-generation vaccines and protein-based therapeutics for infectious disease and cancer. The Fuerst group brings together an assemblage of scientific disciplines including virology, immunology, analytical chemistry, cell biology, structural biology, computational biology, and protein engineering. The multidisciplinary programs include:  (1) a structure-based vaccine design program focused on enveloped viruses, (2) a scaffold-based protein therapeutics program focused on cancer targets, and, (3) an immunoadjuvant and delivery program focused on polyphosphazene-based macromolecular delivery systems.

CURRENT RESEARCH

Antigenic domains mapped to the surface of E2.  Antigenic domains are colored and labeled on the neutralizing phase of the E2 protein.

The structure-based vaccine program identifies viral proteins that can be used in vaccines to promote protective immune responses. Hepatitis C virus (HCV), a major human pathogen and a leading cause of liver cirrhosis, liver failure, and hepatocellular carcinoma, is the principal focus of this program. Multiple research studies have suggested that different arms of the immune response are needed for controlling acute and chronic HCV infection. The Fuerst group is defining conserved portions of HCV proteins that can promote protective antibody responses against multiple HCV strains. This novel approach relies on the fundamental principles of structural vaccinology, which involves understanding the nature of neutralizing determinants at the atomic level and applying these insights to develop vaccines that induce protective responses.

Polyphosphazene immunoadjuvant and
drug delivery technologies.

The scaffold-based therapeutic program is developing powerful new classes of protein-based molecules, referred to as SMART molecules, as multi-component protein machines with the potential to undergo changes in conformation in response to binding, which activates a targeted response. SMART molecules can act with low toxicity and have fewer off-target reactions. The group is developing the technology using HRAS, one of the most frequently mutated oncogenes associated with numerous cancers. The SMART molecules under development are expected to sense subtle differences between normal versus oncogenic states in HRAS and compute different therapeutic responses.

The immunoadjuvant and delivery program is customizing a platform for synthesizing multifunctional, biodegradable classes of polymers well-suited for protein stabilization, antigen presentation, and delivery of macromolecules. The research group uses a unique class of polymer called polyphosphazene, which has specialized structural characteristics including a biodegradable backbone. Polyphosphazenes can undergo self-assembly with vaccine antigens and protein therapeutics, and they have unique targeting capabilities, including environmentally-triggered controlled release. Projects within this program focus on immunoadjuvant properties of polyphosphazenes for vaccine delivery and targeted nanoparticle delivery for protein-based therapeutics.

Publications
2021
An Antigenically Diverse, Representative Panel of Envelope Glycoproteins for Hepatitis C Virus Vaccine Development.
Structural and Biophysical Characterization of the HCV E1E2 Heterodimer for Vaccine Development.
Immunopotentiating and Delivery Systems for HCV Vaccines.
Supramolecular assembly of Toll-like receptor 7/8 agonist into multimeric water-soluble constructs enables superior immune stimulation in vitro and in vivo.
Engineering subtilisin proteases that specifically degrade active RAS.
Intracellular Delivery of Active Proteins by Polyphosphazene Polymers.
Design of a native-like secreted form of the hepatitis C virus E1E2 heterodimer.
2020
Crystal Structure of a Bivalent Antibody Fab Fragment.
Structure-Based Design of Hepatitis C Virus E2 Glycoprotein Improves Serum Binding and Cross-Neutralization.
In Vivo and In Vitro Potency of Polyphosphazene Immunoadjuvants with Hepatitis C Virus Antigen and the Role of Their Supramolecular Assembly.
2019
Protein-loaded soluble and nanoparticulate formulations of ionic polyphosphazenes and their interactions on molecular and cellular levels.
Antigenicity and Immunogenicity of Differentially Glycosylated Hepatitis C Virus E2 Envelope Proteins Expressed in Mammalian and Insect Cells.
In vivo combination of human anti-envelope glycoprotein E2 and -Claudin-1 monoclonal antibodies for prevention of hepatitis C virus infection.
2018
Structural basis for broad neutralization of ebolaviruses by an antibody targeting the glycoprotein fusion loop.
Hydrolytically Degradable PEGylated Polyelectrolyte Nanocomplexes for Protein Delivery.
Designing a B Cell-Based Vaccine against a Highly Variable Hepatitis C Virus.
2017
Biodegradable "Smart" Polyphosphazenes with Intrinsic Multifunctionality as Intracellular Protein Delivery Vehicles.
2016
Global mapping of antibody recognition of the hepatitis C virus E2 glycoprotein: Implications for vaccine design.
Affinity maturation of a broadly neutralizing human monoclonal antibody that prevents acute hepatitis C virus infection in mice.
Molecular-Level Interactions of Polyphosphazene Immunoadjuvants and Their Potential Role in Antigen Presentation and Cell Stimulation.