Jonathan S. Dordick

Institute Professor, Departments of Chemical and Biological Engineering and Biological Sciences Rensselaer Polytechnic Institute

  • Troy NY

Applies biological principles to advance bioengineering and biomanufacturing, stem cell engineering, and drug discovery

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Spotlight

2 min

With “Herd Immunity” Unlikely, Antivirals To Play Key Role in COVID-19 Management

According to The New York Times, the prospects for reaching “herd immunity” in the fight against COVID-19 are increasingly dim. Subsequently, the virus “will most likely become a manageable threat that will continue to circulate in the United States for years to come.” Therefore, long-term management of the SARS-CoV-2 virus, which causes COVID-19, will be increasingly important. As with influenza, and mosquito-borne viruses, like Zika, developing better antivirals for such perennial threats will have to be a part of the plan. Rensselaer Polytechnic Institute researchers Jonathan Dordick, a chemical engineer, and Robert Linhardt, a biochemist are developing one promising antiviral approach that uses a decoy to trap the virus before it can infect a cell. This decoy strategy has shown promise in combating a number of viruses, including SARS-CoV-2, dengue, Zika, and influenza A. Dordick and Linhardt, who is internationally recognized for his creation of synthetic heparin, focus on viruses that use glycoproteins to latch onto human cells, a trait common to many viruses, including coronaviruses. They study how viruses gain entry into human cells at the molecular level and identify safe, effective compounds to offer as a decoy. In their most recent test of this viral decoy strategy on mammalian cells, Dordick and Linhardt demonstrated that a compound derived from edible seaweeds substantially outperforms remdesivir, the current standard antiviral used to combat COVID-19. Heparin, a common blood thinner, and a heparin variant stripped of its anticoagulant properties, performed on par with remdesivir in inhibiting SARS-CoV-2 infection in mammalian cells. Both compounds bind tightly to the spike protein on the surface of SARS-CoV-2, the same strategy the team employed in their previous viral work. Dordick and Linhardt are available to speak on the viral decoy strategy and the need for more effective antivirals in future pandemic control.

Jonathan S. Dordick

2 min

A New Way to Fight Pandemics: Use Decoys to Trap the Viruses that Cause Them

With a vaccine for SARS-CoV-2 still months into the future, it’s clear that we need better antivirals to hold COVID-19 and future pandemics at bay. One strategy uses a decoy to block viruses at the point where they latch onto human cells, stopping infection before it can begin. To infect a cell, a virus must first latch onto a specific target on the cell surface, slice through the cell membrane, and insert its own genetic instructions, hijacking the cellular machinery within to produce replicas of the virus. But the virus could just as easily be persuaded to lock onto a decoy molecule, provided that molecule offers the same fit as the cellular target. Once bound to a decoy, the virus would be neutralized, unable to infect a cell or free itself, and would eventually degrade. This decoy strategy has shown promise in combating a number of viruses, including SARS-CoV-2, dengue, Zika, and influenza A. Two prominent researchers at Rensselaer Polytechnic Institute — Jonathan Dordick, a chemical engineer, and Robert Linhardt, internationally recognized for his creation of synthetic heparin — focus on viruses that use glycoproteins to latch onto human cells, a trait common to many viruses including coronaviruses. Their work studies how viruses gain entry into human cells at the molecular level and identifies safe, effective compounds to offer as a decoy. In their most recent test of this viral decoy strategy on mammalian cells, Dordick and Linhardt demonstrated that a compound derived from edible seaweeds substantially outperforms remdesivir, the current standard antiviral used to combat COVID-19. Heparin, a common blood thinner, and a heparin variant stripped of its anticoagulant properties, performed on par with remdesivir in inhibiting SARS-CoV-2 infection in mammalian cells. Both compounds bind tightly to the spike protein on the surface of SARS-CoV-2, the same strategy the team employed in their previous viral work. In 2019, the team created a trap for dengue virus, attaching specific aptamers — molecules the viral latches will bind to — precisely to the tips and vertices of a five-pointed star made of folded DNA. Floating in the bloodstream, the trap lights up when sprung, creating the world’s most sensitive test for mosquito-borne diseases. Dordick and Linhardt are available to speak on the viral decoy strategy, similar antiviral research efforts, and the need for more effective antivirals in future pandemic control.

Jonathan S. Dordick

2 min

Rensselaer Team Seeks Alternative Approach to Controlling Viruses

As researchers worldwide scramble to formulate a vaccine to combat COVID-19, a team at Rensselaer Polytechnic Institute is pursuing a potentially powerful solution to pandemic control: a viral trap that is easily adapted to different classes of viruses, enabling a “plug-and-play” approach to virus detection and antiviral activity.   Jonathan Dordick, an endowed professor of chemical and biological engineering at Rensselaer, and Robert Linhardt, an endowed professor of chemistry and chemical biology, said the team is exploring how their work — in the areas of viral detection, therapy, and inhibition — could be used against COVID-19 and other viruses in the future. Their team views such innovative approaches as a vital hedge against the growing threat of global pandemics.   The viral trap works by mimicking the latch points on a human cell that a virus must bind to before infecting a person by disgorging its genetic instructions into the cell. In research on the Dengue virus with Xing Wang, now a professor of chemistry at the University of Illinois, recently published in Nature Chemistry, the team folded a snippet of DNA into a five-pointed star, and attached decoy latch points that align perfectly with the virus’ own molecular grappling hooks. The result was the world’s most sensitive test for Dengue, and a novel means of capturing and ultimately killing the virus.   In previous research, the team demonstrated the same approach for Influenza A, and it can likely be expanded to other viruses like COVID-19.   In another approach, Dordick demonstrated how enzymes incorporated into paint, can form a catalytic coating capable of killing the Influenza A Virus. The research, published in Applied Microbiology and Biotechnology, suggests enzyme systems could further be incorporated into swabs, wipes, or coatings, to target and kill various viruses, including COVID-19.  

Jonathan S. Dordick
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Areas of Expertise

Drug Discovery
Biomanufacturing
Biochemical Engineering
Biochemistry
Chemistry
Bioengineering
Stem Cell Engineering

Biography

Jonathan S. Dordick is Institute Professor of Chemical and Biological Engineering at Rensselaer Polytechnic Institute where he is also the Senior Advisor to the President for Strategic Initiatives. Prof. Dordick served as the Vice President for Research from 2012-2018, the Director of Rensselaer’s Center for Biotechnology & Interdisciplinary Studies from 2008-2012, and as Department Chairman of Chemical and Biological Engineering at Rensselaer (1998-2002) and Chemical and Biochemical Engineering at the University of Iowa (1995-1998).

Prof. Dordick received his B.A. degree in Biochemistry and Chemistry from Brandeis University and his Ph.D. in Biochemical Engineering from the Massachusetts Institute of Technology. He has held chemical engineering faculty appointments at the University of Iowa (1987-1998), where he also served as the Associate Director of the Center for Biocatalysis and Bioprocessing, and Rensselaer Polytechnic Institute (1998-present) where he also holds joint appointments in the departments of Biomedical Engineering and Biological Sciences. Prof. Dordick’s research group includes chemical engineers, bioengineers, materials scientists, biologists, chemists, microbiologists and computational and AI scientists all focused on gaining a quantitative understanding of biological principles and applying them to advance bioengineering and biomanufacturing, stem cell engineering, and drug discovery.

Prof. Dordick has received numerous awards, including the Food, Pharmaceutical and Bioengineering Award of the American Institute of Chemical Engineers, Marvin J. Johnson Award and the Elmer Gaden Award both of the American Chemical Society, the International Enzyme Engineering Award, and an NSF Presidential Young Investigator Award. He is an elected Fellow of the National Academy of Inventors, the American Chemical Society, the American Association for the Advancement of Science, and the American Institute of Medical and Biological Engineers. He presently serves on the Scientific Advisory Boards for several biotechnology companies and venture capital firms, and has cofounded several companies, including EnzyMed (now part of Albany Molecular Research, Inc.), Solidus Biosciences, Inc., and Redpin Therapetuics. He has also served on multiple White House-sponsored panels and committees in biomanufacturing. Dr. Dordick has published over 370 papers and is an inventor/co-inventor on over 40 patents and patent applications.

Media

Education

Massachusetts Institute of Technology

Ph.D.

Biochemical Engineering

1986

Massachusetts Institute of Technology

M.S.

Biochemical Engineering

1983

Brandeis University

B.A.

Biochemistry and Chemistry

1980

Media Appearances

Jonathan Dordick Named Fellow of National Academy of Inventors

American Institute for Medical and Biological Engineering  online

2015-01-21

Jonathan Dordick is the vice president for research and the Howard P. Isermann Professor of Chemical and Biological Engineering at Rensselaer. He is a faculty member in the Howard. P. Isermann Department of Chemical and Biological Engineering at Rensselaer, and holds joint appointments in the departments of Biomedical Engineering, Materials Science and Engineering, and Biology. He is a past director of the Rensselaer Center for Biotechnology and Interdisciplinary Studies.

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Enzyme coating kills bacteria in food packaging

The Engineer  online

2013-04-03

Engineering researchers at Rensselaer Polytechnic Institute have developed a new method to kill pathogenic bacteria in food handling and packaging. The development is claimed to represent an alternative to the use of antibiotics or chemical decontamination in food supply systems.

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Nano-collaboration focus of symposium

WAMC  radio

2013-04-03

Collaboration is the focus of a two-day National Academy of Sciences symposium at Hudson Valley Community College in Troy, and nano-technology is at the center of the discussion because of the work at Rensselaer Polytechnic Institute in Troy, the College of Nano-Scale Science and Engineering in Albany and Global Foundries in Malta, Saratoga County. Working together in the nano field is vital according to professor Jonathan Dordick, vice president of research at RPI.

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Articles

Heavy Heparin: A Stable Isotope‐Enriched, Chemoenzymatically‐Synthesized, Poly‐Component Drug

Angewandte Chemie

Brady F Cress, Ujjwal Bhaskar, Deepika Vaidyanathan, Asher Williams, Chao Cai, Xinyue Liu, Li Fu, Vandhana M-Chari, Fuming Zhang, Shaker A Mousa, Jonathan S Dordick, Mattheos AG Koffas, Robert J Linhardt

2019

Heparin is a highly sulfated, complex polysaccharide and widely used anticoagulant pharmaceutical. In this work, we chemoenzymatically synthesized perdeuteroheparin from biosynthetically enriched heparosan precursor obtained from microbial culture in deuterated medium. Chemical de‐N‐acetylation, chemical N‐sulfation, enzymatic epimerization, and enzymatic sulfation with recombinant heparin biosynthetic enzymes afforded perdeuteroheparin comparable to pharmaceutical heparin. A series of applications for heavy heparin and its heavy biosynthetic intermediates are demonstrated, including generation of stable isotope labeled disaccharide standards, development of a non‐radioactive NMR assay for glucuronosyl‐C5‐epimerase, and background‐free quantification of in vivo half‐life following administration to rabbits. We anticipate that this approach can be extended to produce other isotope‐enriched glycosaminoglycans.

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Remodeling of Glycosaminoglycans During Differentiation of Adult Human Bone Mesenchymal Stromal Cells Toward Hepatocytes

Stem Cells and Development

Paiyz E. Mikael, Charles Willard, Aurvan Koyee, Charmaine-Grace Barlao, Xinyue Liu, Xiaorui Han, Yilan Ouyang, Ke Xia, Robert J. Linhardt, and Jonathan S. Dordick

2019

There is a critical need to generate functional hepatocytes to aid in liver repair and regeneration upon availability of a renewable, and potentially personalized, source of human hepatocytes (hHEP). Currently, the vast majority of primary hHEP are obtained from human tissue through cadavers. Recent advances in stem cell differentiation have opened up the possibility to obtain fully functional hepatocytes from embryonic or induced pluripotent stem cells, or adult stem cells. With respect to the latter, human bone marrow mesenchymal stromal cells (hBMSCs) can serve as a source of autogenetic and allogenic multipotent stem cells for liver repair and regeneration. A major aspect of hBMSC differentiation is the extracellular matrix (ECM) composition and, in particular, the role of glycosaminoglycans (GAGs) in the differentiation process. In this study, we examine the influence of four distinct culture conditions/protocols (T1–T4) on GAG composition and hepatic markers. α-Fetoprotein and hepatocyte nuclear factor-4α were expressed continually over 21 days of differentiation, as indicated by real time quantitative PCR analysis, while albumin (ALB) expression did not begin until day 21. Hepatocyte growth factor (HGF) appears to be more effective than activin A in promoting hepatic-like cells through the mesenchymal–epithelial transition, perhaps due to the former binding to the HGF receptor to form a unique complex that diversifies the biological functions of HGF. Of the four protocols tested, uniform hepatocyte-like morphological changes, ALB secretion, and glycogen storage were found to be highest with protocol T2, which involves both early- and late-stage combinations of growth factors. The total GAG profile of the hBMSC ECM is rich in heparan sulfate (HS) and hyaluronan, both of which fluctuate during differentiation. The GAG profile of primary hHEP showed an HS-rich ECM, and thus, it may be possible to guide hBMSC differentiation to more mature hepatocytes by controlling the GAG profile expressed by differentiating cells.

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Designer DNA architecture offers precise and multivalent spatial pattern-recognition for viral sensing and inhibition

bioRxiv

Paul S Kwon, Shaokang Ren, Seok-Joon Kwon, Megan E Kizer, Lili Kuo, Feng Zhou, Fuming Zhang, Domyoung Kim, Keith Fraser, Laura D Kramer, Nadrian C Seeman, Jonathan S Dordick, Robert J Linhardt, Jie Chao, Xing Wang

2019

DNA, when folded into nanostructures of customizable shapes, is capable of spacing and arranging external ligands in a desired geometric pattern with nanometer-precision. This allows DNA to serve as an excellent, biocompatible scaffold for complex spatial pattern-recognizing displays. In this report, we demonstrate that a templated designer DNA nanostructure achieves multi-ligand display with precise spatial pattern-recognition, representing a unique strategy in synthesizing potent viral sensors and inhibitors. Specifically, a star-shaped DNA architecture, carrying five molecular beacon-like motifs, was constructed to display ten dengue virus envelope protein domain-III (ED3)-binding aptamers into a 2D pattern precisely matching the pentagonal arrangement of ED3 clusters on the dengue viral surface. The resulting spatial pattern recognition and multivalent interactions achieve high dengue-binding avidity, conferring direct, highly-sensitive, facile, low-cost, and rapid sensing as well as potent viral inhibition capability. Our molecular-platform design strategy could be adapted to detect and combat other disease-causing pathogens, including bacteria and microbial-toxins, by generating the requisite ligand patterns on customized DNA nanoarchitectures.

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