Dr. John M. Essigmann for the Founders’ Award of the Division of Chemical Toxicology of the American Chemical Society
By Deyu Li, University of Rhode Island.
Dr. John M. Essigmann is the winner for the 2021 Founders Award by the Division of Chemical Toxicology of the American Chemical Society. Dr. Essigmann has made significant contributions to the field of chemical toxicology. Currently, Dr. Essigmann is the William R. and Betsy P. Leitch Professor in the Departments of Chemistry and Biological Engineering at Massachusetts Institute of Technology. He recently transitioned from Director of the MIT Center for Environmental Health Sciences to Deputy Director. He has been the PI of the MIT Training Grant in Toxicology for almost 25 years and MIT Superfund Program’s Associate Director.
Overall, the theme of Dr. Essigmann’s research is to define the mechanisms underlying the responses of cells to DNA damaging agents. His research interests include chemical and biochemical mechanisms underlying mutation and cancer, antiviral chemotherapy, DNA repair, biological networks perturbed by toxic agents. Visit his lab website. His lab has made major impacts in the following areas:
- studying aflatoxin B1 (AFB1) and sterigmatocystin as fungal products contaminate food supplies, damage DNA and potently induce cancer in humans;
- developing the site-specifically modified genome as a tool to define the type, amount and genetic requirements for mutations and toxicity of DNA lesions;
- applying evolutionary theory to force extinction of pathogenic viruses in biological systems and inventing programmable anticancer agents that hijack transcription factors and block DNA repair.
Dr. Essigmann has won numerous awards for his scientific, teaching and service achievements. He was the recipient of awards from the American Chemical Society, American Association for Cancer Research, Society of Toxicology, and American Society for Microbiology. He has also been recognized by the Mutation Research Award given jointly by the ACS and the Environmental Mutagenesis and Genomics Society, the Arthur C. Smith Award, a Susan B. Komen Breast Cancer Foundation Award, an NIH R35 Outstanding Investigator Award, an R37 MERIT Award, and the Gold Medal presented by Princess Chulabhorn of Thailand for contributions to research and teaching in the developing world. Below are some detailed descriptions of his seminal accomplishments.
Aflatoxin B1 and sterigmatocystin are produced by fungi that contaminate food supplies and induce cancer in humans, mainly in the developing world. Dr. Essigmann’s doctoral thesis with Gerald Wogan dealt with the modification of nucleic acids during carcinogenesis. This work led to the identification of aflatoxin-DNA adducts, to the identification of the electrophilic epoxide that produced adducts, and helped to show the relevance of adduction to carcinogenic risk. His work also demonstrated the excretion of aflatoxin-DNA adducts in urine, which inspired colleagues at Johns Hopkins University to use adducts in urine for non-invasive body burden measurements in humans. Recently, Essigmann, with Larry Loeb, applied duplex consensus sequencing to an animal model of AFB1 induced liver cancer. The mutational patterns observed were of extraordinarily high detail and allowed bioinformatic connections to be made between the mutational spectra of aflatoxin in mice and mutational patterns seen in human hepatocellular carcinomas in areas of the world where people are exposed to this toxin. His lab is working with epidemiologists to translate measurement of those patterns as early warning signals for liver cancer (liver cancer is untreatable now, so early detection leading to surgical intervention is a leading approach to the problem of human liver cancer).
His laboratory is best known for the placement of DNA adducts of known structure at specific places in the genomes of replicating viral or plasmid vectors. This far, his group has defined the biological properties in living cells of over 100 DNA lesions, including those of alkylated bases (e.g., O6-methylguanine and 1,N6-ethenoadenine), aflatoxin, oxidants (e.g., 7,8-dihydro-8-oxoguanine, or 8-oxoG), aromatic amines (e.g., 4-aminobiphenyl), toxic metals, base halogenation products, mutagenic drugs and nitrofurans. By studying the biological properties of adducts in cells of different DNA repair and replication backgrounds, his lab was able to make precise statements regarding the biological systems that protect against, or confer susceptibility, to various types of DNA damage.
John’s lab has always been alert to find the “translational opportunities” in basic science. Mutagens can accelerate the process of population diversification. With Larry Loeb and J. Mullins, he contaminated the nucleotide pool of mammalian cells with nucleotides that had known mutagenic properties. Early experiments showed that HIV could be pushed to extinction in a cell culture system using 5-substituted cytosine derivatives. This work led directly to a drug candidate (KP-1212/KP-1461) in Phase II clinical trial as an antiviral agent. His lab also developed programmable anticancer agents that displace transcription factors from their promoters and block DNA repair. Several agents were designed in which a DNA damaging nitrogen mustard was tethered as “warhead” to a ligand for a steroid receptor that is over-expressed in cancer cells. These agents show good anticancer properties, and one (11-beta dichloro) shows promise as an agent to treat the debilitating cysts formed in animal models of polycystic kidney disease.
Dr. Essigmann made significant impacts on training students and serving the community. He chaired MIT’s Committee on Undergraduate Admissions and Financial Aid and MIT’s Taskforce on Minority Student Achievement. He has also served the Head of House (faculty resident) for Simmons Hall at MIT for many years. Dr. Essigmann has led the MIT T32 training program for almost 25 years, working with 18 faculty members from 7 departments who have research and teaching interests in the area of toxicology. Many of the student and postdoctoral scholars trained from his lab are faculty members in the US and other countries. Not limited to domestic service, for over 20 years he has taught in Thailand during the summers and helped found a certified predoctoral training program there that attracts students from 14 countries. This exercise keeps him focused on applications of toxicology research to developing world problems. John also taught biochemistry with Dr. JoAnne Stubbe for twenty years with a specific focus on the use of knowledge of organic chemistry rules to make seemingly complicated metabolic pathways understandable. Dr. Essigmann has participated and gave talks in our annual division meetings. He has published more than 200 papers. Among them, many were published in Chemical Research in Toxicology, the flagship journal of our division. It should be noted John’s 1988 field-defining review article with Ashis Basu was “Page 1 of Volume 1” of the inaugural issue of Chemical Research in Toxicology. This paper has inspired so many young chemical toxicologists at the time and now 30 years later.
With the outstanding achievements in science, his service to the Chemical Toxicology community, and his tireless devotion to mentoring junior faculty members and students, Dr. John Essigmann is a well-deserved winner of the Founders Award supported by the Division of Chemical Toxicology.