Charles Shoemaker

Charles Shoemaker
Professor
Development and application of therapeutic biomolecules, novel antitoxin therapeutics, molecular helminthology

Professor Shoemaker currently leads research focused on the development and application of therapeutic biomolecules for treating a wide variety of diseases. Most of our therapeutic agents employ single domain antibody (sdAb) binding agents consisting of the VH region of heavy-chain-only Abs (VHHs) from immunized alpacas which have been selected for their ability to neutralize critical pathogen functions. These simple, stable agents are engineered in a variety of ways to produce agents having excellent therapeutic efficacies in animal models. Employing these VHH-based neutralizing agents (VNAs) we have developed novel antitoxin agents for the prevention and treatment of a wide variety of toxin exposures including Botulinum neurotoxins, anthrax and ricin, and toxin-mediated diseases such as from Clostridium difficile and pathogenic E. coli infections. We are also working to develop VNAs targeting several microbial and viral pathogens. Dr. Shoemaker and Dr. Patrick Skelly co-lead the Molecular Helminthology Laboratory in which research is directed to the development of therapeutics and vaccines for parasitic worm infections, often applying our recombinant antibody technologies. Therapeutic targets are identified through studies characterizing the complex host/parasite relationship in nematode and trematode diseases infecting billions of people in the developing world and causing serious economic losses in the animal industries.

Prior to arriving at Tufts in 2003, Dr. Shoemaker led the Animal Health Research Unit at the government-owned research company, AgResearch, in New Zealand. This team of over 60 scientists and staff worked to reduce the impact of disease on the animal industry and to leverage this knowledge for human health benefits. Research in the Animal Health Unit primarily centered on internal parasites and bovine tuberculosis. Dr. Shoemaker had joined AgResearch in 1995 from Harvard University, where his research focused on applying biotechnology to reduce the burden of worm parasitic diseases on the developing world, particularly schistosomiasis.

Dr. Shoemaker received his PhD in Biochemistry at the University of Iowa and was a postdoctoral fellow at the Massachusetts Institute of Technology in the laboratory of Nobel Laureate, Dr. David Baltimore. In 1980, Chuck was one of the original scientists at the formation of Genetics Institute, Inc., a highly successful biotechnology company in Boston that was later acquired by American Home Products and is now part of Wyeth. While at Genetics Institute, he was the leader of several drug development projects that resulted in several protein pharmaceutical agents now on the market such as two currently used to treat hemophilia. Chuck left Genetics Institute to join the faculty at Harvard in 1987.


Education

  • PhD - University of Iowa - 1979
  • BS - University of NH - 1975
  1. Vazquez-Cintron, E.J., Beske, P.H., Tenezaca, L., Tran, B.Q., Oyler, J.M., Glotfelty, E.J., Angeles, C.A., Syngkon, A., Mukherjee, J., Kalb, S.R., Band, P.A., McNutt, P.M., Shoemaker, C.B., Ichtchenko, K. 2017. Engineering Botulinum Neurotoxin C1 as a Molecular Vehicle for Intra-Neuronal Drug Delivery. Scientific Reports.
  2. Krautz-Peterson, G., Debatis, M., Tremblay, J.M., Oliveira, S.C., Da’dara, A.A., Skelly, P.J., Shoemaker, C.B. 2017. Schistosoma mansoni Infection of Mice, Rats and Humans Elicits a Strong Antibody Response to a Limited Number of Reduction-Sensitive Epitopes on Five Major Tegumental Membrane Proteins. PLoS Neglected Tropical Diseases.
  3. Dinh, T.L., Ngan, K.C., Shoemaker, C.B., Walt, D.R. 2017. Rapid and ultrasensitive detection of botulinum neurotoxin serotype A1 in human serum and urine using single-molecule array method. Forensic Toxicology.
  4. Vrentas, C.E., Moayeri, M., Keefer, A.B., Greaney, A.J., Tremblay, J., O'Mard, D., Leppla, S.H., Shoemaker, C.B. 2016. A diverse set of single-domain antibodies (VHHs) against the anthrax toxin lethal and edema factors provides a basis for construction of a bispecific agent that protects against anthrax infection. Journal of Biological Chemistry.
  5. Schmidt, D.J., Beamer, G., Tremblay, J.M., Steele, J.A., Kim, H.B., Wang, Y., Debatis, M., Sun, X., Kashentseva, E.A., Dmitriev, I.P., Curiel, D.T., Shoemaker, C.B., Tzipori, S. 2016. A tetraspecific VHH-based neutralizing antibody modifies disease outcome in three animal models of clostridium difficile infection. Clinical and Vaccine Immunology.
  6. Rudolph, M.J., Vance, D.J., Cassidy, M.S., Rong, Y., Shoemaker, C.B., Mantis, N.J. 2016. Structural analysis of nested neutralizing and non-neutralizing B cell epitopes on ricin toxin’s enzymatic subunit. Proteins: Structure, Function and Bioinformatics.
  7. Moayeri, M., Tremblay, J.M., Debatis, M., Dmitriev, I.P., Kashentseva, E.A., Yeh, A.J., Cheung, G.Y.C., Curiel, D.T., Leppla, S., Shoemaker, C.B. 2016. Adenoviral Expression of a Bispecific VHH-Based Neutralizing Agent That Targets Protective Antigen Provides Prophylactic Protection from Anthrax in Mice. Clinical and Vaccine Immunology.
  8. Herrera, C., Tremblay, J.M., Shoemaker, C.B., Mantis, N.J. 2015. Mechanisms of ricin toxin neutralization revealed through engineered homodimeric and heterodimeric camelid antibodies. Journal of Biological Chemistry.
  9. Moayeri, M., Leysath, C.E., Tremblay, J.M., Vrentas, C., Crown, D., Leppla, S.H., Shoemaker, C.B. 2015. A heterodimer of a VHH (variable domains of camelid heavy chain-only) antibody that inhibits anthrax toxin cell binding linked to a VHH antibody that blocks oligomer formation is highly protective in an anthrax spore challenge model. Journal of Biological Chemistry.
  10. Barrera, D.J., Rosenberg, J.N., Chiu, J.G., Chang, Y..-N., Debatis, M., Ngoi, S..-M., Chang, J.T., Shoemaker, C.B., Oyler, G.A., Mayfield, S.P. 2015. Algal chloroplast produced camelid VHH antitoxins are capable of neutralizing botulinum neurotoxin. Plant Biotechnology Journal.
  11. Ashour, J., Schmidt, F.I., Hanke, L., Cragnolini, J., Cavallari, M., Altenburg, A., Brewer, R., Ingram, J., Shoemaker, C., Ploegh, H.L. 2015. Intracellular expression of camelid single-domain antibodies specific for influenza virus nucleoprotein uncovers distinct features of its nuclear localization. Journal of Virology.
  12. Sheoran, A.S., Dmitriev, I.P., Kashentseva, E.A., Cohen, O., Mukherjee, J., Debatis, M., Shearer, J., Tremblay, J.M., Beamer, G., Curiel, D.T., Shoemaker, C.B., Tzipori, S. 2015. Adenovirus vector expressing Stx1/Stx2-neutralizing agent protects piglets infected with Escherichia coli O157: H7 against fatal systemic intoxication. Infection and Immunity.
  13. Mukherjee, J., Dmitriev, I., Debatis, M., Tremblay, J.M., Beamer, G., Kashentseva, E.A., Curiel, D.T., Shoemaker, C.B. 2014. Prolonged prophylactic protection from botulism with a single adenovirus treatment promoting serum expression of a VHH-based antitoxin protein. PLoS ONE.
  14. Rudolph, M.J., Vance, D.J., Cheung, J., Franklin, M.C., Burshteyn, F., Cassidy, M.S., Gary, E.N., Herrera, C., Shoemaker, C.B., Mantis, N.J. 2014. Crystal structures of ricin toxin's enzymatic subunit (RTA) in complex with neutralizing and non-neutralizing single-chain antibodies. Journal of Molecular Biology.
  15. Herrera, C., Vance, D.J., Eisele, L.E., Shoemaker, C.B., Mantis, N.J. 2014. Differential neutralizing activities of a single domain camelid antibody (VHH) specific for Ricin Toxin's Binding subunit (RTB). PLoS ONE.
  16. Kaliberov, S.A., Kaliberova, L.N., Buggio, M., Tremblay, J.M., Shoemaker, C.B., Curiel, D.T. 2014. Adenoviral targeting using genetically incorporated camelid single variable domains. Laboratory Investigation.
  17. Yang, Z., Schmidt, D., Liu, W., Li, S., Shi, L., Sheng, J., Chen, K., Yu, H., Tremblay, J.M., Chen, X., Piepenbrink, K.H., Sundberg, E.J., Kelly, C.P., Bai, G., Shoemaker, C.B., Feng, H. 2014. A novel multivalent, single-domain antibody targeting TcdA and TcdB prevents fulminant clostridium difficile infection in mice. Journal of Infectious Diseases.
  18. Vance, D.J., Tremblay, J.M., Mantis, N.J., Shoemaker, C.B. 2013. Stepwise engineering of heterodimeric single domain camelid VHH antibodies that passively protect mice from ricin toxin. Journal of Biological Chemistry.
  19. Shoemaker, C.B., Oyler, G.A. 2013. Persistence of Botulinum neurotoxin inactivation of nerve function. Current Topics in Microbiology and Immunology.
  20. Tremblay, J.M., Mukherjee, J., Leysath, C.E., Debatis, M., Ofori, K., Baldwin, K., Boucher, C., Peters, R., Beamer, G., Sheoran, A., Bedenice, D., Tzipori, S., Shoemaker, C.B. 2013. A single VHH-based toxin-neutralizing agent and an effector antibody protect mice against challenge with Shiga toxins 1 and 2.. Infection and immunity.

General Research Interests

Selected Research Projects

  1. VHH-based neutralizing agents for antitoxin therapy
  2. Botulism antidotes
  3. Characterizing the helminth host/parasite interface

Research Interests by Area

Infectious Diseases: Prevention and Control
  • Botulism antidotes and anti-toxins
Infectious Diseases: Genetics and Genomics
  • Helminth parasite genomics
Infectious Diseases: Pathogenesis/Host Response
  • Helminth host/parasite interface and interaction
  • Helminth parasite vaccines

Laboratory Personnel

Shoemaker/Skelly Lab:

  • Dr. Akram d'Adara
  • Dr. Junya Awata
  • Dr. Paroma Ghosh
  • Dr. Manal Elzoheiry
  • Ms. Jacque Tremblay
  • Ms. Michelle Debatis
  • Mr. Qiang Wang