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Message from the Division Chair, F. Peter Guengerich
Greetings for 2008. We are well into the new year, and a lot of things are happening in the Chemical Toxicology Division. Our Chair-Elect, Lisa Peterson, has been working with me on a couple of important projects. We now have a Finance Committee, which Pete Dedon chairs. A concentrated fund-raising effort is being made, and we have already had success. The Finance Committee is now actively engaged in the budget making process at the start of the year, including the program at the national meeting. We will have some changes this year, which I think will be for the better.
A short course will be associated with the ACS ProSpectives Conference on Drug Toxicity in May (see the description below in this newsletter), with Pete Dedon, Dan Liebler, and I contributing. Our Short Course Committee has developed a separate course entitled "Chemical Toxicology: A Chemist's Roadmap to Reducing Bioactivation Liabilities in Drug Candidates" to be offered at the August ACS National Meeting in Philadelphia.
Kent Gates and the Program Committee have developed a great program for the August National Meeting. One feature will be the Founders' Award symposium, honoring Larry Marnett. In addition to Marnett, the speakers chosen by him will be Ned Porter, Rafael Radi, Lisa Peterson, and John Essigmann.
I am also pleased to announce that Kaushik Mitra has agreed to serve as Program Chair for 2009-2010. In the course of Division history we have had great service in this post, including Ken Gates (current Chair). We are enthusiastic about Kaushik and also hope that he will be able to stimulate more participation in the program from our industrial members.
We are planning to have an option for including posters and talks from the ACS National Meeting on the Division website (after the meeting). Access will require a password and the time that they are posted will be limited (4 to 6 weeks). The rules for whether posted presentations can be submitted for publication (and manuscripts) will vary among ACS and other journals, but Chemical Research in Toxicology will have no restrictions. The choice of posting is up to the poster/talk authors. More to follow.
Speaking of Chemical Research in Toxicology , congratulations on the 20th anniversary. If you didn't see the January 2008 Anniversary issue, with its collection of reviews, check it out. Also check out the cover, even if you don't get the print subscription. I also add that the new web version has many interesting new features. The journal website also has a direct link to the TOXI Division website.
That reminds me to mention the website (which Tom Spratt continues to manage). We have a section on Job Listings , which we would like to expand. I note current openings in both academic and industry groups. If you have a position open, post here. If you want a job, look here.
Scott Daniels chairs the Membership Committee. We are always hoping to add more members to the Division. We welcome all, but we would particularly like to have more from the industrial sector and foreign countries, especially in Asia.
This is still early but we will have electronic balloting this year, which will save time and mailing costs. A slate of nominees will be in place by our August meeting.
Well, that's all I have for the first quarter. As always, any ideas for improving the Division are welcome.
Fred Guengerich, Chair
Division's Founders Award Goes to Lawrence Marnett
 The Division of Chemical Toxicology is pleased to announce awarding of the first annual Founder's Award to Dr. Larry Marnett, Prof. of Chemistry, Biochemistry, and Pharmacology at Vanderbilt University. The award recognizes Dr. Marnett's achievements in the field of chemical toxicology, a field in which he has been a pioneer and unifying force. The award is given to a TOXI member whose scientific activities have emphasized innovative research in the general field of chemical toxicology. The award was established by the Division to honor the vision and contributions of individuals who worked to get to the division started in the mid-1990s.
Professor Marnett's research in chemical toxicology has focused on chemical and biochemical transformations within the body which may lead to cancer, but has also involved mechanistic studies on the bioactivation of exogenous chemicals by non cytochrome P-450 oxygenases involved in lipid peroxidation and prostaglandin biosynthesis. He has been a pioneer in the field of endogenous carcinogenesis and was one of the first to recognize that DNA damage could result from endogenous lipid peroxidation and the ensuing free radical chemistry. Many of Marnett's investigations have focused on the properties of a small three carbon molecule, malondialdehyde, which is a product of mammalian endogenous lipid peroxidation. He and his coworkers have shown how it is formed, and importantly, the nature of its DNA binding. Their interdisciplinary research on the characteristics of the primary DNA guanine-malonaldehyde revealed much about the mechanisms of mutagenesis and carcinogenesis of this molecule.
Marnett has also made many contributions to our understanding of the fundamental biochemical and chemical mechanisms of prostaglandin biosyntheses and modes of action. Much of his activity has focused on cyclooxygenases (COX), key enzymes in this process. Early in the course of this research he recognized and showed that benzo[a]pyrene, a carcinogenic polycyclic aromatic hydrocarbon, could be oxidized through the hydroperoxidase activity of COX. A leading authority on COX, Marnett and his group have also generated significant data on the structural requirements of inhibitors for these isozymes, which, among other activities, play such an important role in inflammatory processes.
Dr. Marnett received a B.S. in Chemistry from Rockhurst College and a Ph.D. in Chemistry from Duke University under the direction of Professor Ned Porter. Doctoral students will be interested to learn that the initial direction of his research career grew out of the necessity of generating an original research proposition in order to pass his Ph. D. organic chemistry prelims at Duke in the early 1970's. In reading an article on the free radical theory of aging by William Pryor, he learned that malondialdehyde was generated from membrane polyunsaturated fatty acid oxidation but the chemistry of its formation was unknown He proposed a mechanism and research to test it. During the course of this process he read a number of Professor Bengt Samuelsson's papers on prostaglandin biosynthesis and became excited by them. Eventually, this led him to a postdoctoral position in Samuelsson's lab at the Karolinska Institute in Stockholm. There, Marnett began a long-term interest in the chemistry and biology of lipid oxidation by cyclooxygenases. After a second postdoc with Professor Paul Schaap at Wayne State University, he joined the Chemistry faculty at Wayne and initiated research programs on both DNA damage and mutation by malondialdehyde and COX-catalyzed hydroperoxidations. Much of this activity gave rise to what we now recognize as chemical toxicology. Visit his Laboratory's Website for mopre information of his current research.
In addition to these noteworthy accomplishments, Prof. Marnett is well-known as the founding and current Editor of Chemical Research in Toxicology, a highly successful ACS Journal that has just celebrated its 20th year. Marnett's activities as Editor have provided not only a tremendous stimulus for research in the field, but very high quality and innovative forum for the publication of research in mechanistic chemical toxicology. Marnett was also one of the founders of the Division of Chemical toxicology and served as its Treasurer until this year.
Dr. Marnett is a native of Kansas. Prior to his current position and Vanderbilt, he was a Professor of Chemistry at Wayne State University. He holds the Mary Geddes Stahlman Professor of Cancer Research Chair in the Vanderbilt School of Medicine, and is the Director of the Vanderbilt Institute of Chemical Biology. He holds professorial appointments in Biochemistry, Chemistry and Pharmacology at Vanderbilt. The award will be presented at the ACS meaning in Philadelphia in August of 2008. A symposium will honor Dr. Marnett's accomplishments.
Richard N. Loeppky, Editor
Kaushik Mitra, Our Next Program Chair
 Kaushik Mitra, Senior Research Chemist in the Department of Drug Metabolism at Merck Research Laboratories in Rahway, N.J. has been appointed by the Executive Committee to be the next Program Chair for the Division. His term will begin in January. Kaushik became active in TOXI as a doctoral student in organic chemistry at the University of Missouri. He, along with Paul Henderson, Shauna Sturla, and Scott Daniels, all current Executive Committee members, represent a new generation of TOXI leaders whose activities began when they were either grad students or postdocs. Following his Ph. D. at Missouri with Kent Gates (1999), Mitra took a postdoctoral position with John Essigmann at MIT. He then joined Merck. He is our first Program Chair from industry and we are very pleased that Merck is also giving him the opportunity to serve the Division in this capacity. He will certainly bring new perspectives to our programming. He welcomes programming suggestions and can be contacted at: kaushik_mitra@merck.com. He has been an elected member of the Executive Committee and active in the Division in several activities including service on the Program Committee.
Division Connected Conferences and Short Courses
TOXI Division members are associated with two short courses and an ACS ProSpective conference. The second short course (Chemical Toxicology: A Chemist's Roadmap to Reducing Bioactivation Liabilities in Drug Candidates) will provide for Division funding because all of the lecturers are donating their service. All proceeds above costs will go to TOXI.
ACS ProSpective Conference
Mechanisms of Chemically-Induced Toxicity for Medicinal Chemistry
May 18-20, 2008 in Philadelphia
Fred Guengerich has organized an ACS ProSpectives Conference, along with Jim MacDonald of Schering-Plough, to be held May 18-20 in Philadelphia. This conference will feature presentations by a number of the members of our Division and others, focusing on mechanisms of toxicity of drugs and drug candidates. If you are interested in the field, this is an important meeting to attend. There will also be a short course.
Sessions will be held on reactive metabolites and alternative mechanisms, with an emphasis on specific chemical groups and methods of screening. Numerous case studies will be given throughout the program by scientists from Pfizer, Schering Plough, and Merck, among others.
Abstracts are being accepted for Poster Presentations. (Deadline May 15, 2008). You can register for this two-day conference on-line.
Short Courses in Drug Metabolism and Chemical Toxicology
Philadelphia, Saturday of National ACS meeting, August 16, 2008
Chemical Toxicology: A Chemist's Roadmap to Reducing Bioactivation Liabilities in Drug Candidates
The course is geared towards medicinal chemists, but could also benefit graduate students/post-docs considering a career in the drug industry or to industrial drug metabolism scientists looking to broaden their knowledge base.
Introduction to bioactivation concepts (Guengerich, Vanderbilt) (8:30-11:30 AM)
-Enzymes, including non-CYP enzymes involved in bioactivation
-Cytochrome P450 mechanisms of catalysis and relevance to bioactivation
-The balance of bioactivation vs. detoxication within enzyme systems
-Important polymorphisms and species- or gender-dependent enzyme expression
-Mechanism based CYP inhibition
LUNCH BREAK (11:30-1:00 PM)
Methodologies and strategies for the assessment of bioactivation mediated toxicity (Humphreys, BMS) (1:00-3:00 PM)
-Models for assessment of bioactivation and genotoxicity potential
-Small molecule and large molecule covalent binding assays
-Strategies for incorporating information into drug discovery efforts
-Methods to investigate metabolism mediated toxicity (in vivo methods to determine if metabolism is involved in toxicity, newer -omics methods as predictive tools)
Integrating reactive metabolite liability considerations into drug design during SAR development (Kaushik Mitra and Christine Fandozzi, Merck) (3:00-5:00 PM)
-Structure based liabilities/chemical classes associated with bioactivation
-Strategies and case studies of drug design aimed at reducing bioactivation (cover reducing mechanism-based CYP inhibition, reducing protein and DNA adduct formation)
For more information on the course visit the ACS webpage.
Service on NIH study sections
In response to a recent initiative from the NIH entitled "New National Registry for Society-Recommended Reviewers" the Division of Chemical Toxicology is developing a list of those of its members who would be appropriate to recommend for service on NIH study sections, either as ad-hoc or chartered members. I have personally served NIH in this way many times; it is very important to our entire scientific system and, I might add, a learning experience. You really can't write great grants unless you see how others do it. I know the current CSR Director, Toni Scarpa, from my first term as a study section member. You also meet a lot of interesting people in the field. I recall that I first met a number of the current members of our Division at study section meetings.
It is highly important that the breadth of expertise encountered in our discipline of chemical toxicology be reflected across a range of relevant study sections. In general, appropriateness is based on current and historical support of an individual's work by NIH (or equivalent) mechanisms, publication record, ability to present a concise informative summary before a normally diverse group of individuals and willingness to serve when called. There is some flexibility in the above because of the wide range of mechanisms for funding at the NIH. Thus Division members from industry may be appropriate on certain study sections even though they may be expected to have little track record of NIH support. More detailed requirements/expectations can be found on the NIH web site. If you feel that you would be an appropriate individual who could be recommended by the Division, please forward, by e-mail, your NIH bio-sketch, or equivalent vitae to the Secretary, Tom Spratt, . For the Secretary's convenience, please employ the e-mail "Subject" title as "NIH Reviewer". Please include a list of areas of expertise and, if you can identify any, chartered study sections that would be most relevant to your interests. Thanks.
Fred Guengerich, Chair, Division of Chemical Toxicology
Fund Rising Initiatives
The Division of Chemical Toxicology has recently embarked on a major fund raising effort to ensure the future of TOXI programming activities at the national meetings of the American Chemical Society. The effort was initiated by the Finance Committee consisting of Peter Dedon (Committee Chair), Lisa Peterson, Trevor Penning, Kent Gates, Carmelo Rizzo, Scott Daniels, Lawrence Sayre and Fred Guengerich. The Committee was charged with developing a fund raising strategy to prevent shortfalls in the budget with the growing costs of ongoing activities of the Division in education, training, and scientific exchange at the national ACS meetings. Unfortunately, TOXI dues and the allocation from ACS are insufficient to cover the entire cost of speaker travel and registration, the highly popular poster session social event, and student and postdoc travel awards. This has become increasingly important in light of the wide-ranging interests of TOXI's > 1000 members.
TOXI is well on the way to a target goal of raising $20,000 annually. The effort is in its early stages but so far has been quite successful, with major donations provided by Merck, Millennium, Abbott Labs, Pfizer, and Bristol-Myers Squibb. These companies and other companies have recognized the benefits of supporting TOXI programming, including access to graduate students and postdoctoral scientists who are among the best-educated and best-trained scientists in the world, potential collaborative interactions with academic scientists from universities and institutes around the world, an avenue for dissemination of novel research findings, and access to high quality training programs and workshops on chemical toxicology.
The $20,000 annual target will sustain the activities of the TOXI Division as we strive to promote research and training in chemical toxicology. In addition to companies interested in supporting TOXI, the Finance Committee invites all TOXI members to consider making a donation of any size to the fund raising effort, with the added benefit of possible matching donations from employers! Please contact Carmelo Rizzo (c.rizzo@vanderbilt.edu), TOXI Treasurer, for information about how to make a donation.
Peter C. Dedon, Massachusetts Institute of Technology
New Publications Committee Formed
The Division of Chemical Toxicology has formed a new publications committee. The mission of the committee is to facilitate the publication of all the initiatives sponsored by the Division that might generate revenue to help sustain it. Revenue streams being discussed with ACS include the following:
- Publication of Division sponsored symposia in the "ACS Symposium Series" where the royalties generated would go to the Division.
- Proposed publication of ACS-Proceedings-on line. This venue will provide access to Powerpoint presentations of oral presentations at National Meetings; that will be copyrighted to ACS and password protected. Members of the division would have free access to their division symposia as a member benefit. This could increase membership to the Division. Access to all other proceedings by members and non-members alike will require a fee with royalties coming back to the division.
- Publication of Ebooks for an international audience in areas of chemical toxicology.
Individuals that have agreed to serve on this Committee are as follows:
- Chair, Trevor M. Penning, Ph.D.
- Larry J. Marnett, Ph.D. Editor-in-Chief Chemical Research in Toxicology
- Thomas Spratt, Ph.D., Secretary
- Kent Gates, Ph.D., Program Chair
If you have suggestions for TOXI sponsored publications please contact Trevor M. Penning at penning@pharm.med.upenn.edu.
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