Dr. Stephen H. Safe is being honored with the 2019 SOT Merit Award for his breakthrough research developments and his devotion to advancing toxicology through mentorship and instruction.
After completing a PhD in bioorganic chemistry at the University of Oxford in England, Dr. Safe spent several years as a research officer for the National Research Council of Canada. He then began his teaching career at the University of Guelph in Ontario, Canada, after which he took a position at Texas A&M University, where he has remained since 1981. Currently, Dr. Safe is a distinguished professor in Texas A&M’s Department of Veterinary Physiology and Pharmacology.
Dr. Safe has been an innovator in the toxicological field since the start of his career. His research is expansive and includes such subjects as the TEF-TEQ concept for dioxin-like chemicals and novel nuclear receptor mediated cancer chemotherapy agents. His laboratory was one of the earliest implementers of cell and biology techniques to investigate mechanisms of chemical toxicity. Further, his work on dioxins and their effect on endocrine systems was instrumental in developing the concept of endocrine disruption. The impact of this research is quantifiable; Dr. Safe has more than 770 publications, and his work has been cited more than 70,000 times, making him the most highly cited toxicologist on Google Scholar with an h-impact factor of 122.
Dr. Safe is one of Texas A&M’s most decorated professors. In the early 1990s, he helped establish the toxicology curriculum within the Department of Veterinary Physiology and Pharmacology by assembling faculty and students to create a program that would become renowned in the field. These efforts attest to Dr. Safe’s impact on both the university and the discipline of toxicology. More than 115 graduate students who have trained in the Safe laboratory have gone on to have thriving careers after graduation, and numerous respected members of SOT are his former trainees.
In addition to the many other scientific professional societies in which he participates, Dr. Safe has long been a member of SOT. He is a Burroughs Wellcome Toxicology Scholar (1989), is a past Chair of the SOT Education and Continuing Education Committees, and was the 2007 recipient of the SOT Distinguished Toxicology Scholar Award.
EDITOR'S SIDEBAR: Merit Award Lecture at SOT 58th Annual Meeting and ToxExpo
Dr. Stephen H. Safe will give the Merit Award Lecture on Tuesday, March 12, 2019, from 12:30 pm to 1:30 pm, in Ballroom II of the Baltimore Convention Center during the SOT 58th Annual Meeting and ToxExpo. The topic of Dr. Safe's lecture is “Receptor Schizophrenia: Molecules That Regulate Cellular Homeostasis and Disease and Are Important Drug Targets.” The lecture abstract is as follows:
The aryl hydrocarbon receptor (AhR) was initially identified as the intracellular protein that binds and mediates the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and structurally related compounds. Subsequent studies with AhR knockout animal models have demonstrated that this receptor plays an important role in maintaining cellular homeostasis in multiple tissues and in pathophysiology. The AhR binds TCDD but also structurally diverse ligands, which include pharmaceuticals, health-promoting phytochemicals, and microbial metabolites. These compounds are selective AhR modulators (SAhRMs) and exhibit tissue/cell-specific AhR agonist and antagonist activities and can be used as drugs to target the AhR and its functions in multiple diseases, including cancer. The functions of the AhR and its ligands in both cellular homeostasis and disease are not unique and are also observed for many members of the nuclear receptor superfamily, which include steroid hormone receptors and adopted orphan and orphan receptors. In our studies on SAhRMs derived from 1,1-bis (3’-indolyl) methane (DIM), a series of synthetic analogs typified by 1,1-bis (3’-indolyl) -1- (p-hydroxyphenyl) methane (DIM-C-pPhOH) were characterized as AhR-inactive; they target the orphan nuclear receptor 4A1 (NR4A1, Nur77, TR3), and other analogs interact with NR4A2 (Nurr1). Like the AhR, endogenous ligands for NR4A1 and NR4A2 have not been identified, and ongoing studies show that both NR4A receptors are important in maintaining cellular homeostasis and in pathophysiology. Selective NR4A1 modulators such as DIM-C-pPhOH and related compounds are being investigated as potential drugs for treating metabolic diseases, arthritis, immune dysfunction, neurological and cardiovascular problems, and cancer. DIM-C-pPhOH and a series of more potent second-generation analogs exhibit cell/tissue-specific NR4A1 antagonist and agonist activities, and this presentation will highlight some of the potential clinical applications of bis-indole-derived NR4A1 ligands and focus primarily on their inhibition of NR4A1-dependent pro-oncogenic pathways and genes in solid tumors.
