Volume 32
Issue 1, 2013
ISSX President’s Message: 2013 ISSX Meeting Schedule Follows Strategy By Bill J. Smith, ISSX President I am frequently asked by members, “How does the Society select meeting locations?” Since there is never a simple answer to this question, I thought it was a good substrate for the President’s Winter Message. To answer these questions, I will provide a bit of the history and thinking behind the three meetings that ISSX will organize alone or as a collaborator in 2013. Each meeting this year aligns with one or more aspects of our strategic plan and supports the ISSX Mission: ISSX is an international association of scientists that promotes the understanding of the interactions of medicines and chemicals with living systems. Let’s start with the joint New England Drug Metabolism Discussion Group (NEDMDG)/ISSX Workshop entitled, “The Role of Drug Metabolism in Immune-Mediated Drug Toxicity: Molecular, Clinical and Mechanistic Aspects,” to be held April 17–19 in
Cambridge, MA, USA. Several years ago, Steve Wrighton (past ISSX Treasurer) noted that total attendance to ISSX meetings declined in years when we held a single international meeting. He proposed that in those years we organize a small workshop to provide a benefit to ISSX members who might be unable to attend an international meeting. This workshop also aligns with two other aspects of our strategic plan: first, to identify collaborators willing to share ideas, finances, and to tap into the members of both groups and second, to organize meetings at a location where there is a high density of academic, industry, and government researchers who attend ISSX meetings. The collaboration with NEDMDG and the Cambridge, MA location are a perfect fit with this strategy. This workshop was conceived in 2011 by Charles Crespi, ISSX Treasurer, who works in the Boston area and is also active locally in NEDMDG.
ISSX is a supporting partner in a small student workshop in Kaifeng, Henan Province, in Central China to be held May 17–20 and organized by the Chinese Society for the Study of Xenobiotics (CSSX). This partnership follows a consistent strategy of ISSX to fulfill our international mission to facilitate the association of scientists in the field to share research findings. Yuichi Sugiyama (past ISSX President) sought to develop consistent interactions in China because the number of researchers in the sciences spanned by ISSX is growing rapidly. CSSX has been an exemplary partner in this regard. All ISSX Presidents succeeding Yuichi have continued to follow this strategy. ISSX will sponsor several faculty to attend and support this CSSX meeting. Continued on page 10
IN THIS ISSUE 1 2 3
ISSX President’s Message Book Review: Activation and Detoxification Enzymes Follow Your Passion
Invites Members to 4 ISSX Organize Scientific Meetings
5
Workshop: Immune-Mediated Drug Toxicity: Molecular, Clinical and Mechanistic Aspects
International ISSX Meeting 11 10th Announcement
17 New Member Listing
Book Review ACTIVATION AND DETOXIFICATION ENZYMES Functions and Implications Author: Chang-Hwei Chen Springer Science and Business Media, Germany 177pp, ISBN 978-1-4614-1048-5, 2012
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Over the past few years there appears to have been an upsurge in the number of books published that address the rudiments of drug (foreign compound) metabolism and disposition. This is not a bad thing, as for many years the availability of texts at this basic level was lacking. The present book fits into this category and the author emphasizes this point, when he states that, “an organized, concise overview is needed for the readers who are initially exposed to this important subject, particularly for students and researchers in the areas of biomedical sciences, biochemistry, nutrition, pharmacology and chemistry” (back cover and preface, vii/viii). The book is divided into 16 chapters, covering the sources of foreign compounds, a general overview of lipophilic compounds and their conversion into more water soluble species, the enzyme systems involved in these conversion reactions, their induction and inhibition and genetically predisposed variation in their efficacy, a mention of reactive intermediates, and effects of dietary and various enzyme modulators. As expected, and appreciated, many chemical structures and tabulated data, substantial references and an
adequate index complement the text. The book is firmly constructed, with a readable print font, good quality paper and stout binding. The purist might point to a few syntactic misdemeanours but they are of little consequence. Both chapters 14 (pages 137–144) and 15 (pages 145–154) are entitled, “Catalytic reactions of Phase II enzymes,” and this oversight also occurs within the “Contents” pages (pages xiii/xiv). Needless to say, the first chapter deals with Phase I enzymes, but, unfortunately, such errata do not inspire confidence. As one may expect, the text concentrates on the “usual suspects” as far as catalytic reactions are concerned and only gives a paragraph each to “peripheral” enzymes such as xanthine oxidase, peroxidases or azoreductases, but nevertheless they are mentioned. The items listed in Table 11.1 (page 105) are sub-divided into, “Part 1” and “Part 2,” but explanation of this in the text appears to be missing. Is this a division of the mentioned vegetables into Cruciferous crops and others? Also, there is discussion of the potential effects of brussel sprouts on cytochromes P450 activity but no reference to possible effects on flavin monooxygenases (e.g. Cashman et al., Biochem. Pharmacol., 1999, 58, 1047–1055). There is also a slight concern about statements without obvious reference, such as, “diets that promote oxidant scavenging by inducing detoxification enzymes have been reported to have positive influence on human health conditions such as aging associated
degenerative changes” (page 104). The chapters are constructed, perhaps not intentionally, but nonetheless in an unfortunate and obfuscating manner, where references occur only at the ends of the chapters (in a bibliography) so that it is uncertain and confusing as to which actually refers to any specific point within the text—this is frustrating and hinders verification and further investigation. This book succeeds in delivering a broad overview of the subject with a bias towards food components and the consequences of anutrient intake—certainly an interesting aspect. If another introductory text is required then this is satisfactory for those just embarking on a career into the fascinating but complex world of drug and foreign compound metabolism.
Reviewed by
Steve Mitchell Faculty of Medicine Imperial College London London SW7 2AZ, UK
Book ordering information: Springer –Verlag GmbH Tiergartenstrasse 17 69121 Heidelberg Germany. Tel: +49 (0) 6221-487-8134 Fax: +49 (0) 6221-487-68134 Web: www.springer.com
Springer Science and Media, LLC, 233 Spring Street New York, NY 10013, USA
ISSX CAREER CENTER Find the right candidates for open positions through the ISSX Career Center: www.issx.org/career.
Follow Your Passion By Dr. Allen Cato, III, ISSX Newsletter Editor “I’ve certainly taken a circuitous educational route to get to where I am today,” declares Emily Scott, Ph.D. That indirect route for Scott has proven fascinating, and it began with her sailing the high seas and diving to collect marine specimens for research. Those of you fortunate enough to have attended the 18th North American Regional ISSX Meeting in Dallas, Texas, USA, or to have read the previous edition of the ISSX Newsletter, likely recognize Dr. Scott as a recipient of the North American New Investigator Award in honor of James R. Gillette. During the winding road of Scott’s career, she has studied brittle star hemoglobin, elucidated the structure and function of various human cytochrome P450 enzymes, and worked on a protein linked to prostate and breast cancers. Along the way, she and her husband managed to start a family and they now have two daughters, which may help to explain why one of her favorite props to educate people about her research is a child’s toy.
learn X-ray crystallography and generate some of the first membrane P450 structures. Scott’s next move would take her even further from her days of sailing the high seas and entrench her firmly in the P450 research that recently earned her the ISSX New Investigator award. She Emily Scott, Ph.D. moved from the gulf coast to Kansas to join the Department of Medicinal Chemistry faculty at the University of Kansas, where her research has continued to progress by leaps and bounds. “I was fortunate to get into the P450 field at a stage of tremendous new opportunity in the structure and function of these amazing enzymes,” Scott states. “There is still just so much to be done, so many opportunities, that it’s hard to know what to do next sometimes.” But somehow she always seems to figure it out.
As you may have surmised, Scott’s B.S. degree is in marine biology. Under influential mentor Dr. Donald Harper, she spent several excursions in the Gulf of Mexico diving and collecting marine samples for NSF-funded expeditions lasting weeks at a time. Those samples included brittle stars, a close relative of starfish. She became interested in one brittle star species whose tube feet are red because of the presence of hemoglobin. This Dirk Pitt–like introduction to real-world science both taught her the challenges of doing real-world research and inspired her curiosity about heme proteins.
Another area of research in the Scott lab is P450s and lung cancer. A nicotine byproduct metabolized by CYP2A13 in human lung results in two products linked to lung cancer Continued on page 10
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Yet another twist in the road of Scott’s career occurred when she contemplated postdoctoral options. She yearned to continue heme protein research, but wanted to consider an aspect different from reversible oxygen binding. That motivation led her to membrane cytochrome P450 enzyme research in Dr. James Halpert’s lab at UTMB Pharmacology and Toxicology. While there, she also had the opportunity to collaborate with Scripps researchers Drs. Eric Johnson and David Stout—a mentor trifecta that allowed her to
Recent research has focused on CYP17A1, a drug target for treatment of prostate and breast cancers. CYP17A1 generates androgen steroid hormones, a key part of normal masculine physiology, but also a key supporter of metastatic prostate cancer. The Scott lab recently determined the first structure of CYP17A1, providing a starting point for new-drug design. Their current focus is on determining how the enzyme performs two distinct reactions—but only one of which leads to prostate cancer. So how is this linked to breast cancer? Estrogens are made from androgens, thus, this approach may also be effective for estrogen-responsive breast cancer.
Issue 1, 2013
Thus, for her doctoral studies, she left behind her maritime adventures to focus on heme protein biochemistry at Rice University. There, mentors John Olson and Quentin Gibson not only provided excellent technical training in myoglobin and hemoglobin, but also set excellent personal examples and challenged her to take her research further.
CYP17A1 Enzyme
ISSX Invites Members to Organize Scientific Meetings ISSX meetings provide invaluable opportunities for learning, networking, and exploring new ideas. Organizing an ISSX scientific meeting is a significant responsibility but also a tremendously valuable experience. Those who have previously organized ISSX scientific meetings earn the gratitude of their contemporaries and add a highly impressive credit to their curriculum vitae. A general overview of the meeting organization process of ISSX follows. Those interested in organizing an ISSX meeting should also review the document "Guidelines for the Organization of ISSX Meetings� located on our web site and contact the ISSX Executive Director for more detailed information. The Scientific Affairs Committee (SAC) of ISSX oversees the planning, development, and content of the scientific program portion of ISSX meetings. The SAC additionally works to identify individuals to organize our meetings in our three regions worldwide: North America, Asia Pacific, and Europe. International ISSX Meetings are held every three years and may be planned to convene in any region.
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Individuals who wish to organize an ISSX meeting should submit a proposal at least 4-5 years in advance of the contemplated date of the meeting. The initial proposal should be submitted to the ISSX Executive Director who will review it and send copies to the chair and members of the SAC. The SAC will review the proposal and communicate comments to the chair of the Meeting Organizing Committee (MOC). The MOC should address the concerns of the SAC and submit a revised proposal if requested. The SAC will review the revised proposal and, once all issues have been resolved to their satisfaction, shall send written approval of the proposal. Once the proposal has been approved in writing, indicating that no significant unresolved issues remain, the proposal will be submitted to the ISSX Council for review. Once a meeting is approved, the professional staff of ISSX will negotiate and enter into agreements with meeting venues (as well as with all suppliers providing goods and services to the meeting).
Following approval by the SAC, the ISSX Council will have the opportunity to raise questions regarding meeting proposals and can interact with the MOC until there are no significant unresolved issues. Once a meeting proposal is approved by Council, it will be added to the official ISSX Meetings Calendar. Preliminary discussions between the SAC and prospective meeting chairpersons will address the following to be included in a written proposal from the prospective organizer to the SAC. 1. T he names and present positions of proposed core members of the MOC and the meeting's Scientific Advisory Board. 2. The provisional intentions for the Scientific Program. 3. T he number of attendees anticipated, by category (member, non-member, student). Proposed meeting budgets will be developed by the Executive Director in consultation with the Meeting Organizers. Proposed meeting budgets must be reviewed by and have final approval of the Finance Committee. Approved meeting budgets will be combined into the overall ISSX operating budget to be reviewed and formally approved by Council. A penultimate program that lists all speakers and titles of their presentations should be provided to the SAC approximately 16 months before the meeting. The SAC will review the program, provide suggestions to the MOC, and approve the revised finalized program in a timely manner, such that the final program can be distributed 12 months before the meeting. ISSX is served by our professional staff team in our Washington, DC headquarters. They manage all of the logistical details of our meetings including abstract management, communications, venue, registration, and much more. This frees the scientific chair and the meeting organizing committee to focus on the scientific content of the meeting. Continued on page 9
We Invite You to Attend the Workshop: Immune-Mediated Drug Toxicity: Molecular,Clinical and Mechanistic Aspects Organized by the New England Drug Metabolism Discussion Group and the International Society for the Study of Xenobiotics April 17-19, 2013 | Boston Marriott Cambridge Hotel Pre-Workshop: The pre-workshop is designed to provide important background for three focus areas of the main workshop, the formation of reactive intermediates from drugs, the adaptive immune system and the innate immune system. The composition, function and consequences of these biological processes are complex and will not be covered in detail in the main workshop. The pre-workshop is ideal for drug metabolism scientists who wish to have more background information on the immune system and immunologists who wish to have more background information on drug metabolism systems. Workshop: Idiosyncratic drug induced liver injury (IDILI) is a significant cause of morbidity and mortality. IDILI events can derail clinical drug development programs and lead to drug withdrawal. However, the underlying mechanisms are currently poorly understood. There is growing evidence that the immune system plays an important role in mediating or modulating some forms of IDILI. This workshop will explore the latest advances in understanding the roles of bioactivation, adaptive immunity, innate immunity and cellular signaling in IDILI. This workshop will be of interest to those in the fields of pharmacokinetics, drug metabolism, drug safety assessment and immunology.
Registration Fees Pre-Workshop Session | Wednesday, April 17, 2013 Non-Student/Postdoc Student/Postdoc
$75.00 $50.00
Non-Student/Postdoc Student/Postdoc
$375.00 $275.00
Corning Life Sciences, Tewksbury, MA, USA
Thomas Baillie
Robert Roth Michigan State University, East Lansing, MI, USA
Steven Tannenbaum
University of Washington, Seattle, WA, USA
Massachusetts Institute of Technology, Cambridge, MA, USA
Radford Decker
Jack Uetrecht
Sunovion Pharmaceuticals, Inc., Marlborough, MA, USA
University of Toronto, Toronto, Ontario, Canada
Chandra Prakash
Nancy Wong
Biogen Idec, Cambridge, MA, USA
Eisai Inc., Andover, MA, USA
Zhiyang Zhao Amgen, Cambridge, MA, USA
Accommodations Hotel rooms have been reserved at the Boston Marriott Cambridge at a special rate for NEDMDG/ISSX Workshop attendees. Located 5 miles from Boston Logan International Airport - BOS, the hotel is easily accessible by public transportation, taxi, and rental car. Visit www.issx. org/workshop/accomodations for more information. • To obtain the special room rate of $209, exclusive of sales and occupancy taxes, book online by Tuesday, March 19. • If making reservations by phone at +1-617-494-6600, be sure to mention that you are a NEDMDG/ISSX Workshop attendee to obtain the attendee room rate. Our specially-negotiated room rate is $209, exclusive of sales and occupancy taxes.
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Registration is Open! www.issx.org/workshop/registration
Charles Crespi, Workshop Chair
Issue 1, 2013
Workshop and Opening Welcome Reception
Workshop Organizing Committee
Workshop Program-at-a-Glance WEDNESDAY, APRIL 17, 2013 12:00 pm – 6:00 pm | Grand Ballroom Foyer | Registration Open 1:00 pm – 5:15 pm | Grand Ballroom Salon 5 Pre-Workshop Session 1:00 pm | Overview of Reactive Intermediate Formation and Potential Consequences, Thomas Baillie 2:15 pm | Introduction to Adaptive Immunity, Robert Balderas 3:30 pm | Refreshment Break 3:50 pm | Introduction to Innate Immunity, Gyongi Szabo 5:30 pm – 7:30 pm | Grand Ballroom Salon 3 | Opening Welcome Reception with Exhibitors
THURSDAY, APRIL 18, 2013 7:00 am – 5:00 pm | Grand Ballroom Foyer | Registration Open 8:30 am – 9:30 am | Grand Ballroom Salon 4 Welcome and Plenary Session 8:30 am | Welcome from Workshop Organizing Committee Chair, Charles Crespi 8:45 am | Definition and Significance of IDILI, Clinical Cases, Neil Kaplowitz
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9:30 am – 11:50 am | Grand Ballroom Salon 4 SESSION 1: Mechanisms – Bioactivation
1:20 pm – 5:40 pm | Grand Ballroom Salon 4 SESSION 2: Mechanisms—Adaptive Immunity 1:20 pm | Adaptive Immunity and IDILI, Jack Uetrecht 2:00 pm | Genetic Determinants of IDILI—HLA Polymorphisms, Paul Watkins 2:40 pm | Overcoming Liver Tolerance to Adaptive Immune Mediated Injury, Angus W. Thomson 3:20 pm | Refreshment Break with Exhibitors in Grand Ballroom Salon 3 3:40 pm | Hypersensitivity Reactions in Skin: Possible Reaction to IDILI, Dean Naisbitt 4:30 pm | Late-Breaking Talks from Posters 5:00 pm | Case Study—Direct Interactions of Drugs (Abacavir) with HLA, Michael Norcross
FRIDAY, APRIL 19, 2013 7:00 am – 5:00 pm | Grand Ballroom Foyer | Registration Open 8:30 am – 11:30 am | Grand Ballroom Salon 4 SESSION 3: Mechanisms—Cell Signaling and Cell Responses 8:30 am | In vitro Model Systems for Studying Heptotoxicity, Nandita Shangari 9:10 am | Perspectives on the Role of Mitochondria in Organ Toxicity, James Dykens 9:50 am | Refreshment Break with Exhibitors in Grand Ballroom Salon 3
9:30 am | Hepatocellular Activation of IDILI-Associated Drugs, B. Kevin Park
10:10 am | Case Studies for Immune Mediated Drug Toxicity, The AstraZeneca Experience, Tommy B. Andersson
10:10 am | Refreshment Break with Exhibitors in Grand Ballroom Salon 3
10:50 am | Case Study—Pfizer Experience, Jessica Whritenour
10:30 am | Reactive Intermediates versus Covalent Modifiers: Similarities and Differences in Chemical Properties and Toxicological Potential, Thomas Baillie
11:30 am – 1:00 pm | Grand Ballroom Salon 3 | Lunch on Own and Visit Posters
11:10 am | Case Study—Assessing Heptotoxicity Risk Considering Dose and Fraction Covalently Bound, Steve Clark 11:50 am – 1:20 pm | Grand Ballroom Salon 3 | Lunch on Own and Visit Posters
1:00 pm – 4:15 pm | Grand Ballroom Salon 4 SESSION 4: Mechanisms – Innate Immunity 1:00 pm | Animal Models / TLR, Cynthia Ju 1:40 pm | I nflammatory Stress Hypothesis--Role of Interferon-gamma, Robert Roth
2:20 pm | Systems Analysis of Acetaminophen-induced Liver Injury Under Conditions of Bacterialinduced Inflammatory Stress, Steven R. Tannenbaum
3:20 pm | Views of Future Directions and Discussion, B. Kevin Park and Paul Watkins
3:00 pm | Refreshment Break and Poster Removal in Grand Ballroom Salon 3
Abstract and Poster Presentations Poster presentations will be held in the Workshop Exhibit Hall on the following schedule: Poster Set-Up
Thursday, April 18
7:00 am – 8:00 am
Poster Presentations | Group 1
Thursday, April 18
11:50 am – 1:20 pm
Poster Presentations | Group 2
Friday, April 19
11:30 am – 1:00 pm
Poster Removal
Friday, April 19
3:00 pm – 3:20 pm
Opening Welcome Reception On Wednesday, April 17, 2013, attend the Opening Welcome Reception in the Exhibit Hall. Open to all registered attendees, the welcome reception includes hors d’oeuvres and refreshments as well as time for collegial networking. Don’t miss this chance to meet with friends and colleagues and to make new connections before the workshop program begins on Thursday, April 18.
Exhibition Information This workshop includes an exhibition of the products and services researchers need to advance their work. The exhibition begins with the welcome reception on Wednesday evening and continues until the workshop concludes. Meet with representatives from top suppliers and maximize the value of your attendance. Companies interested in exhibiting should download the exhibitor prospectus at www.issx.org/workshop/exhibits.
Current Exhibitors Celsis In Vitro Technologies Corning Life Sciences Cyprotex HepatoChem, Inc.
Hepregen Corporation Seventh Wave Laboratories Solvo Biotechnology
XenoBiotic Laboratories, Inc. XenoTech LLC Lablogic Systems, Inc.
Nominations are now being accepted for the following awards to be presented at the 10th International ISSX Meeting in Toronto, Ontario, Canada:
The Frederick J. Di Carlo Distinguished Service Award—Presented to an ISSX member from any region who has a record of important service to the Society and its goals. Visit www.issx.org/awards/nominations to learn more and submit a nomination by June 30, 2013.
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The R.T. Williams Distinguished Scientific Achievement Award—Sponsored by Charles Crespi and Family. Presented to an ISSX member or non-member from any region who has made substantial and seminal scientific contributions to the field over a sustained period. The focus of this award is the individual’s scientific accomplishments and it is intended to recognize the best in the field, internationally.
Issue 1, 2013
NOMINATE A COLLEAGUE FOR THE 10TH INTERNATIONAL ISSX MEETING AWARDS
International
Invitation to Attend the 10th International ISSX Meeting Dear Colleagues, On behalf of the Meeting Organizing Committee, it is my great pleasure to invite you to the premier international meeting on xenobiotics: the 10th International ISSX Meeting, to convene September 29–October 3, 2013 in Toronto, Ontario, Canada. This meeting provides a wonderful opportunity for members of the international scientific community to exchange ideas and expertise, to develop a common vision, and to create and nurture fruitful collaborations in fields related to the study of chemicals that are foreign to the body.
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Enjoy state-of-the-art scientific sessions, poster presentations and commercial exhibits in a relaxed and friendly environment. Proposed topics for a combination of keynote lectures, plenary sessions, parallel sessions and short course workshops at ISSX 2013 in Toronto include: systems pharmacology and xenobiotic-host interactions; drug-metabolizing enzymes as potential therapeutic targets; metabolism and pharmacokinetics
of traditional medicines; regulatory challenges in drug development and approval; toxicogenomic profiling; in vitro and cell-based systems for predicting human drug metabolism; cell type specific mechanisms of toxicity and adverse drug reactions; nuclear receptors as regulators of drug metabolism and therapeutic targets; novel biomarkers for xenobiotic-induced toxicity; utility of structural biology in predicting drug response, metabolism and ADRs; and many more. Please take this unique opportunity to expand and share your knowledge on the interaction of foreign chemicals with living systems, renew or develop friendships with your colleagues from around the world, and enjoy everything the wonderful city of Toronto has to offer. I look forward to seeing you in Toronto! Sincerely,
Denis M. Grant University of Toronto Chairman, Meeting Organizing Committee
ADVERTISE WITH ISSX The quarterly ISSX Newsletter is an online publication featuring Society updates, scientific articles of interest, book reviews, summaries of ISSX meeting proceedings, and more. This publication is designed to update the ISSX membership on the activities and events of the organization and to provide an information forum. The ISSX Newsletter reaches every ISSX.org site visitor as well as the ISSX membership. Visit www.issx.org/advertising today!
ISSX Invites Members to Organize Scientific Meetings Continued from page 4
Visit www.issx.org for more information, including the document “Guidelines for the Organization of ISSX Meetings,” for sample meeting proposals, and for the meeting proposal submission form. Please direct any inquiries to the ISSX Executive Director, Steven Kemp, at skemp@issx.org.
UPCOMING MEETINGS The Role of Drug Metabolism in Immune-Mediated Drug Toxicity: Molecular, Clinical and Mechanistic Aspects A joint workshop organized by the New England Drug Metabolism Discussion Group (NEDMDG) and ISSX Boston Marriott Cambridge Cambridge, Massachusetts, USA April 17–19, 2013
10th International ISSX Meeting The Westin Harbour Castle Hotel Toronto, Ontario, Canada September 29– October 3, 2013
5th Asia Pacific Regional ISSX Meeting Crowne Plaza Hotel | Tianjin, China May 17–19, 2014
29th JSSX and 19th North American Regional ISSX Meeting
Hilton San Francisco | San Francisco, California, USA October 19–23, 2014
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President’s Message
Follow Your Passion
Continued from page 1
Continued from page 3
The third meeting of the year will be the 10th International ISSX Meeting to be held September 29–October 3 in Toronto, Canada. Toronto was initially chosen as a location by the ISSX Council in 2008 because of the incredible success of the 7th International ISSX Meeting held in Vancouver, Canada in 2004 and organized by Frank Abbott and Wayne Riggs. The Vancouver meeting was the most heavily attended meeting in ISSX history. It has been almost a decade since the last International ISSX meeting was held in North America, so Toronto is a fitting selection for our 10th International Meeting. We also benefit from the strong academic presence there and Denis Grant (University of Toronto) has volunteered to serve as the meeting organizing chair. Toronto is a busy international hub with convenient connections from the North American, European, and Asia Pacific regions.
initiation. Inhibition of CYP2A13 could reduce the incidence of tobacco-related lung cancer. However, unlike the specialized P450 enzymes such as CYP17A1 above, CYP2A13 and many other human P450 enzymes each bind a large number of structurally diverse small molecules. Scott compares these types of P450 enzymes to a child’s shape-sorter toy—there are multiple shapes the enzyme’s active site can adopt to fit either round pegs or square ones or ovals. This makes these P450s very difficult to selectively inhibit. But if one can develop CYP2A13selective inhibitors, one could prevent formation of DNAdamaging products from nicotine in the lung.
There you have it, a quick summary of the history and thinking behind the meetings organized for this year. Now for your part, please plan on attending an ISSX conference this year and convince your colleagues to do the same! By doing so you are helping ISSX fulfill its mission. At its core, ISSX is a society that organizes great conferences and to continue this, we need your attendance. Finally, since you will be attending a meeting this year, please renew your membership which provides you with the benefit of significantly discounted meeting registration rates!
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Have a good winter, Bill J. Smith ISSX President
2013 ISSX Global Partner
Even during her independent research career, Scott recognizes supportive mentors, colleagues, and collaborators in and out of the P450/drug metabolism field. She finds that the international and the North American ISSX meetings are excellent places to get to know the thought leaders in the field and to discuss the latest research advances. She credits these colleagues with having set an amazing aggregate role model for the kind of mentor she strives to be. She seems to have put those skills to good use as she describes her own research group. “I have a great group. They are fun, but also generally very hard working. I think they work really well as a team, which I value highly. I can’t wait until an upcoming sabbatical to demote myself to senior postdoc in the lab and get back to more time working alongside them to learn new things.” On the “group news” section of Scott’s KU faculty webpage, it’s obvious that they have mixed in fun activities alongside the hard work. Ice skating, getting lost in Kansas corn mazes, camping and canoeing, bowling, stargazing—and of course Scott’s other passion, scuba diving—are interspersed among a long list of student presentations and awards. Establishing a career and becoming a leader in the field while raising a family is difficult, and Scott praises her husband. “I have a great spouse who also deserves a lot of credit,” she says. “Since he writes software for the oil and gas industry in his own business, he has a lot of flexibility and takes primary responsibility for our household and for our two wonderful daughters.” While juggling so many activities, Scott still occasionally finds time for scuba diving, but “not so much in Kansas,” she laments. In between various travels, she lives vicariously by reading her favorite genre—true survival stories of extreme adventures, such as climbing Mount Everest, fighting an Ebola outbreak . . . and of course, scuba diving. Passionate about science, family, and adventure, ISSX may be seeing a lot more of Dr. Emily Scott.
International September 29–October 3, 2013
Why You Should Attend the 10th International ISSX Meeting This meeting will bring together individuals who are actively working on drug/xenobiotic research in diverse fields including basic and clinical pharmacology and therapeutics, toxicology, oncology, endocrinology, physiology, biochemistry, medicinal chemistry, molecular and structural biology, and genetics. If you work in the fields of toxicology, pharmacy, or molecular biology or if you study xenobiotics, you can’t afford to miss the 10th International ISSX Meeting. • L earn the latest information in this dynamic and specialized field through our Short Course program, a variety of timely scientific symposia, and topical keynote and plenary sessions. •E xpand your knowledge of drug metabolism and disposition by learning from our outstanding faculty assembled from leading experts in the field worldwide. •G ain recognition and feedback on your research by submitting an abstract and presenting a poster. All accepted abstracts will be printed in a special supplemental issue of Drug Metabolism Reviews. Students and postdocs may enter the poster competition and compete for prizes and recognition.
Denis Grant (Meeting Chair), University of Toronto, Toronto, ON, Canada Stelvio Bandiera, University of British Columbia, Vancouver, BC, Canada Jack Bend, University of Western Ontario, London, ON, Canada Chantal Guillemette, Laval University, Quebec, QC, Canada Malle Jurima-Romet, Celerion, Montreal, QC, Canada David K.H. Lee, NoAb Biodiscoveries, Mississauga, ON, Canada Tom Massey, Queen’s University, Kingston, ON, Canada Eddie Morgan, Emory University, Atlanta, GA, USA Sandy Pang, University of Toronto, Toronto, ON, Canada Allan Rettie (SAC Member), University of Washington, Seattle, WA, USA David Riddick, University of Toronto, Toronto, ON, Canada Nathalie Rioux, Boehringer Ingelheim (Canada), Ltd., Laval, QC, Canada Rachel Tyndale, University of Toronto, Toronto, ON, Canada Peter Wells, University of Toronto, Toronto, ON, Canada A complete listing of the International Scientific Advisory Board (ISAB) is available online at www.issx.org/ international2013/isab
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•E njoy informal social interactions with fellow researchers, and also enjoy exploring Toronto—Canada’s largest city, its financial center, and the capital of the province of
Meeting Organizing Committee and International Scientific Advisory Board
Issue 1, 2013
•S cientific meetings organized by ISSX offer numerous outstanding scientific sessions and many opportunities for substantive conversations with scientists worldwide. Our exhibitors will be showcasing the products and services important to you in your research and development.
Ontario. In Toronto you will find a vibrant, safe and walkable downtown core, excellent transit access to many cozy neighborhoods, stunning traditional and modern architecture, world-class museums and galleries, an abundance of nightlife, and more than 7,000 restaurants of every price range and ethnic flavor imaginable!
Preliminary Schedule (Schedule is subject to change) Sunday, September 29, 2013
Parallel Symposia 1 and 2 | 13:30 – 15:30
Concurrent Morning Short Courses | 09:00 – 12:00
Parallel Session 1: Nuclear Receptors as Regulators of Drug Metabolism and as Therapeutic Targets Co-Chairs: Ulrich Zanger, IKP, Stuttgart, Germany; Hongbing Wang, University of Maryland, Baltimore, MD, USA
Short Course I: Metabolomic Profiling as a Tool for Identifying Novel Drug-Target Interactions Chair: David Wishart, University of Alberta, Edmonton, AB, Canada Short Course II: Model Systems and Methods for Assessing Uptake and Efflux of Small Molecules Chair: Reina Bendayan, University of Toronto, Toronto, ON, Canada
Parallel Session 2: Pharmacogenomics and Personalized Medicine: Progress in Clinical Implementation Chair: Rachel Tyndale, University of Toronto, Toronto, ON, Canada Poster Viewing | 15:30 – 16:00
Lunch for Short Course Attendees | 12:00 – 13:30
Parallel Symposia 3 and 4 | 16:00 – 18:00
Concurrent Afternoon Short Courses | 13:30 – 16:30
Parallel Session 3: Regulation of Drug Transporter Expression and Function Chair: Micheline Piquette-Miller, University of Toronto, Toronto, ON, Canada
Short Course III: Strategies and Techniques for Predicting Human Drug Metabolism and Drug-Drug Interactions Chairs: Uwe Fuhr, Uniklinik Koln, Koln, Germany; Olavi Pelkonen, University of Oulu, Oulu, Finland Short Course IV: Application of Mass Spectrometric Methods to Drug Metabolism and Pharmacokinetics Chair: Ragu Ramanathan, QPS, Newark, DE, USA
Parallel Session 4: Application of Structural Biology to the Prediction of Drug Response, Metabolism and Toxicity Chair: Jim Halpert, University of California, San Diego, CA, USA
Opening Welcome | 18:00 – 18:15
Young Investigators Reception | 18:00
Keynote Lecture | 18:15 – 19:00 Systems Pharmacology and Xenobiotic-Host Interactions Doug Lauffenburger, Massachusetts Institute of Technology, Cambridge, MA, USA
Tuesday, October 1, 2013
Monday, September 30, 2013
Utility of Genetic and Epigenetic Technologies in Drug Development and Safety Assessment Chair: Ann Daly, Newcastle University, New Castle Upon Tyne, UK
Plenary Session 1 | 09:00 – 10:30 Drug-Metabolizing Enzymes as Potential Therapeutic Targets Chair: Paul Hollenberg, University of Michigan, Ann Arbor, MI, USA Poster Viewing | 10:30 – 11:00
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ISSX Awards Presentation | 11:00 – 12:00 Nominations are now being accepted for the two awards which will be presented at the 10th International ISSX Meeting: • T he R.T. Williams Distinguished Scientific Achievement Award •The Frederick J. Di Carlo Distinguished Service Award Submit a nomination by Sunday, June 30, 2013 at www.issx.org/awards/nominations.
Plenary Session 2 | 09:00 – 10:30
Poster Viewing | 10:30 – 11:00 Parallel Symposia 5 and 6 | 11:00 – 13:00 Parallel Session 5: Metabolism, Pharmacokinetics and Interactions of Traditional Medicines and Natural Products Co-Chairs: Chuan Li, SIMM, Shanghai, China; Ge Lin, Chinese University of Hong Kong, Hong Kong, China Parallel Session 6: Cell Type Specific Mechanisms of Adverse Drug Reactions Chair: Yvonne Will, Pfizer, Groton, CT, USA Lunch, View Posters, and Visit Exhibitors 13:00 – 14:00 Free Afternoon in Toronto | 14:00
Lunch, View Posters, and Visit Exhibitors 12:00 - 13:30
Wednesday, October 2, 2013 Plenary Session 3 | 09:00 – 10:30 Identification and Use of Novel Biomarkers for XenobioticInduced Toxicity Chair: Malle Jurima-Romet, Celerion, Hudson, QC, Canada Poster Viewing | 10:30 – 11:00 Parallel Symposia 7 and 8 | 11:00 – 13:00 Parallel Session 7: Targeted Drug Delivery for Enhanced Therapy Chair: Christine Allen, University of Toronto, Toronto, ON, Canada Parallel Session 8: Use of PB-PK Modeling in Pharmaceutical Safety Assessment Chair: Aleksandra Galetin, University of Manchester, Manchester, UK Lunch, View Posters, and Visit Exhibitors 13:00 - 14:30 Parallel Symposia 9 and 10 | 14:30 – 16:30 Parallel Session 9: Regulatory Perspectives in Drug-Drug Interactions and Metabolites in Safety Testing Chair: Greg Slatter, Amgen, Seattle, WA, USA Parallel Session 10: Toxicogenomic and Metabolomic Profiling: Current Status and Future Utility in Assessing Drug Efficacy and Safety Chair: Tim Zacharewski, Michigan State University, East Lansing, MI, USA Poster Viewing | 16:30 – 17:00 Party at the Hockey Hall of Fame | 19:00 – 22:00 Enjoy a delicious buffet dinner, catch up with friends, and meet new acquaintances at the ISSX Hockey Hall of Fame Party! This is a ticketed event and a separate fee of $100 applies.
Plenary Session 4 | 09:00 – 10:30
Refreshment Break | 10:45 - 11:00 Parallel Symposia 11 and 12 | 11:00 – 13:00 Parallel Session 11: Tissue Imaging and Distribution Studies in Drug Development Chair: Yasuyoshi Watanabe, RIKEN Center, Kobe, Japan Parallel Session 12: Development and Uses of Hepatocyte-Derived and Hepatocyte-Like Cells for Predicting Human Drug Metabolism Chair: Martine Daujat-Chavanieu, INSERM, Montpellier, France Close of Meeting | 13:00
Abstract Submission
Submit an abstract at www.issx.org/international2013/ abstracts. Present a poster in the general abstract poster sessions. General abstract sessions will be held Monday, September 30–Wednesday, October 2 in the exhibit hall. Compete in the student poster awards competition. Open to the categories of predoctoral and postdoctoral students, six finalists from each category will be chosen to present their posters. The awards presentation will be held on Thursday, October 3. This meeting also features abstract-based sessions. Abstracts will be selected by the meeting organizers from the general abstract submissions. At least one abstract author must be a current ISSX member. The deadline for Abstract Poster Presentations submissions and for Predoctoral and Postdoctoral Poster Awards Competition submissions is Friday, May 31, 2013 at 11:59 p.m., Eastern Time (US).
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/ISSX Newsletter / 13
Genetically Modified Animal Models for Predicting Human Drug Disposition and Response Chair: Xinxin Ding, Wadsworth Center, Albany, NY, USA
Predoctoral and Postdoctoral students are invited to visit www.issx.org/international2013/abstracts to submit an abstract by Friday, May 31.
Issue 1, 2013
Thursday, October 3, 2013
Poster Awards Presentation | 10:30 - 10:45 Open to the categories of predoctoral and postdoctoral students, six finalists from each category will be chosen to present their posters. The finalists posters will be posted for the entire meeting and the top three posters from each category will be chosen and presented an award by the Poster Awards Review Committee.
Special Event: ISSX Hockey Hall of Fame Party Enjoy a delicious buffet dinner, catch up with friends, and meet new acquaintances at the ISSX Hockey Hall of Fame Party on Wednesday, October 2! Located in an architecturally ornate former bank building in downtown Toronto, the Hockey Hall of Fame is only three blocks from the Westin Harbour Castle Hotel. This spectacular museum is a highly unique venue that presents Canada’s national sport through the world’s largest collection of hockey artifacts and the fun of interactive games. Attendees can take shots at real-time goalies, stop the shots of Gretzky and Messier, call the play-by-play of some of hockey’s greatest goals, get up close and personal with the Stanley Cup in the museum’s vault, and explore the largest collection of hockey memorabilia in the world. A separate fee of $100 applies for this event ticket.
Nominations are now being accepted for the following awards to be presented at the 10th International ISSX Meeting in Toronto, Ontario, Canada. The two awards to be presented at our 2013 International Meeting are: •T he R.T. Williams Distinguished Scientific Achievement Award Sponsored by Charles Crespi and Family. Presented to an ISSX member from any region who has made substantial and seminal scientific contributions to the field over a sustained period. The focus of this award is the individual’s scientific accomplishments and it is intended to recognize the best in the field, internationally. •T he Frederick J. Di Carlo Distinguished Service Award Presented to an ISSX member from any region who has a record of important service to the Society and its goals. Nominations are due Sunday, June 30, 2013. Submit nominations at www.issx.org/awards/nominations.
/ISSX Newsletter / Issue 1, 2013
Hotel rooms have been reserved at the Westin Harbour Castle Hotel at a special rate of $215 CAD for ISSX attendees. Book online by Monday, September 3, 2013 to obtain the special rate. Located 28 km from Pearson International Airport (YYZ), the hotel is easily accessible by airport shuttle, public transportation, taxi, and rental car. Depending on the agreements between Canada and your country, a visa may be required. Please check with your local embassy/consulate or travel agent to obtain information regarding visa requirements. If you require a letter of invitation in order to obtain a visa please contact ISSX at information@issx.org. Visit www.issx.org/international2013/accommodations for more information.
Travel Grants
Awards
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Hotel, Travel, and Visa
Travel grants are available for students and postdocs as well as scientists from disadvantaged nations to attend the 10th International ISSX Meeting. ISSX recognizes the considerable benefit that scientists from disadvantaged nations, students, and others can gain from attending this important meeting and is proud to continue the travel grant program. Please visit www.issx.org/international2013/travelgrant. There, you will find an online grant submission form and information related to various deadlines associated with this funding program.
Exhibition Information
The 10th International Meeting will feature an exhibition showcasing the products and services that researchers need to advance their work. The exhibition begins with the welcome reception on Sunday evening and continues throughout the meeting. Meet with representatives from top suppliers and maximize the value of your attendance! Companies interested in exhibiting, sponsoring, or advertising should download the Exhibitor Prospectus at www.issx.org/international2013/exhibits.
ISSX Member Spotlight Read about ISSX Member, Emily Scott in this issue on page 2. Would you like to be featured in our next newsletter? Do you know someone who should be featured? E-mail us at information@issx.org! Or go online and fill out the form: www.issx.org/Membership/Spotlight.
Register Today for the 10th International ISSX Meeting Registration is now open! Visit www.issx.org/international2013/registration to take advantage of the early registration discount.
Short Courses will be held on Sunday, September 29 SHORT COURSE ATTENDEE CATEGORY
EARLY January 31 - June 28
Regular June 29 - September 27
On-Site September 29 - October 4
ISSX Member
$175
$225
$250
Student/Postdoc
$100
$125
$150
$225
$275
$325
Non-Member
The 10th International ISSX Meeting will officially begin on Sunday, September 29 at 18:00 with an Opening Welcome Address and Keynote followed by the Welcome Reception with the exhibitors. MEETING ATTENDEE CATEGORY
EARLY January 31 - June 28
REGULAR June 29 - September 27
ON-SITE September 29 - October 4
ISSX Member
$595
$695
$795
Student/Postdoc
$225
$250
$275
$745
$825
$945
Non-Member Guest*
$50
$50
$50
*Guest registration allows guest admittance to the Opening Welcome Reception on Sunday, September 29 and to refreshment breaks throughout the 10th International Meeting. Guest registrants are not permitted into the session rooms.
ISSX Membership Before registering for the meeting, join ISSX or renew your ISSX Membership to be eligible for steep registration discounts! Membership in ISSX grants reduced meeting registration fees and the opportunity to submit an abstract for poster presentation at the 10th International Meeting.
The Role of Drug Metabolism in Immune-Mediated Drug Toxicity: Molecular, Clinical and Mechanistic Aspects
Registration for the NEDMDG/ISSX Workshop is open! Visit www.issx.org/Workshop/Registration to register online today!
Renew with ISSX for the 2013 Membership term and renew journal subscriptions online today! www.issx.org/Membership.
/ISSX Newsletter / 15
ISSX 2013 Membership
Issue 1, 2013
April 17–19, 2013 | Cambridge, Massachusetts, USA
2013 Membership Renewal and ISSX Support Remain a member by renewing online today! Your membership with ISSX demonstrates your support of the Society and our program of activities. Annual membership dues remain affordable at only $100 USD for Full Regular Members and $25 USD Dollars for Postdoctoral Fellows and Students as well as members from disadvantaged nations.
To renew your ISSX membership today, log in to your ISSX member account at https://issx.site-ym.com/ members/manage_profile.asp to view and print your invoice or renew online. In your Member Profile, scroll to the bottom of the page and click on the “Membership” icon under “Account History.” Select the icon to view your renewal options, including instant payment by credit card or, if you require an invoice, you can select the “Bill Me” option, which will generate an invoice you can submit with your check or other payment.
ISSX is an international association of scientists that promotes the understanding of the interactions of medicines and chemicals with living systems. ISSX will host two exceptional events in 2013: a joint workshop with the New England Drug Metabolism Discussion Group (NEDMDG) at the Boston Marriott Cambridge Hotel in Cambridge, Massachusetts, USA April 17–19, 2013 and the 10th International ISSX Meeting at the Westin Harbour Castle Hotel in Toronto, Ontario, Canada September 29–October 3, 2013. Only ISSX Members receive registration discounts on the 10th International ISSX Meeting registration. Students and senior scientists alike are encouraged to submit abstracts and present work in the poster presentations during these scientific meetings. Whether you plan to join us at one of our scientific meetings planned for 2013 or if you are renewing to receive great discounts on scientific journals, your membership with ISSX will advance the science and promote the interaction of our researchers in the field. ISSX is the international society for the exchange of knowledge among individuals interested in the study of xenobiotics and other related disciplines. Additional member benefits include: •Q uarterly Newsletter: Members receive a quarterly newsletter that highlights Society news, upcoming meetings, late breaking scientific news, and much more. • Membership Directory: Members have access to a searchable online membership directory. •R educed Registration Fees: Members receive a significant reduction on registration fees for the 10th International ISSX Meeting.
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•S ociety Awards Program: Only ISSX members are eligible for the prestigious Scientific Achievement Awards presented at our regional meetings and the Distinguished Service Award which is presented at our International Meeting. •S pecial Journal Subscription Discounts: Members receive special subscription discounts to multiple scientific journals, including Drug Metabolism Reviews, Xenobiotica, Annual Review of Pharmacology and Toxicology, and many more. Log in and visit our online store for details. •S earchable Meeting Abstracts: Members may perform searches for and review abstracts presented at past ISSX meetings.
Your continued membership with ISSX will keep you informed of the latest scientific developments and enable you to network with scientific and industry leaders worldwide. When submitting your 2013 dues, please consider making a donation to one of our funds to support Society programs. ISSX is a charitable organization and your contribution may be tax deductible to you. Please consult your tax advisor. Our federal tax identification number is 22-2432063. To make a donation online, please visit www.issx. org/donations.
We look forward to serving you in 2013 and beyond!
ISSX Welcomes New 2013 Members! Christopher Aluise, Vanderbilt University School of Medicine, United States
Jie Ping, Wuhan University, China Chad Pope, University of Connecticut, United States
Thomas Arnhold, BI Pharma GmbH & Co. KG, Germany Giandomenico Brogin, Chiesi Farmaceutici S.P.A., Italy
William Proctor, National Institutes of Health, United States
Waranya Chatuphonprasert, Faculty of Medicine, Mahasarakham University, Thailand
Anuruddha Rajapakse, Vanderbilt University, United States
Yacine Chtourou, Faculty of Sciences Sfax, Tunisia
Madhav Sachar, University of Kansas Medical Center, United States
Upendra Dahal, Pfizer, United States Kurt Enslein, Enslein Research Inc., United States Panos Hatsis, Novartis Institutes for Biomedical Research, United States
Abdul Naveed Shaik, Massachusetts College of Pharmacy & Health Science, United States Manjunath Shet, Purdue Pharma, LP, United States Kenji Shinkai, Ajinomoto Pharmaceuticals Co.,Ltd., Japan
Makoto Hirasawa, DAIICHI SANKYO CO., LTD., Japan Ralph Stearns, Vertex Pharmaceuticals, United States Yukako Ito, Kyoto Pharmaceutical University, Japan Toshio Teramura, Astellas Pharma Inc., Japan Carine Jacques-Jamin, Pierre Fabre Dermo-Cosmetique, France
Kazunori Uenaka, Eli Lilly Japan K.K., Japan
Eun-Ha Joh, KAERI, Korea, South
Jian Wang, Hutchison Medipharma Ltd., China
Ganessan Kichenadasse, Flinders University, Australia
Noriko Watanabe, Nippon Kayaku Co., Ltd., Japan
Toshiki Nagasawa, Bayer Yakuhin, Ltd., Japan
Jittima Weerachayaphorn, Mahidol University, Thailand
Mathew Njoroge, University of Cape Town, South Africa
Tooru Yokoyama, Mochida Pharmaceutical Co., Ltd., Japan
Yoshinori Ochiai, EPS Corporation, Japan
Lei Zhang, FDA, CDER, Office of Clinical Pharmacology, United States
Damon Papac, United States
Issue 1, 2013
September 29–October 3, 2013. Visit www.issx.org/international2013/abstracts to submit an abstract. This meeting features the Pre-Doctoral and Postdoctoral Poster Awards Competition. Abstract submissions for the general poster presentations and the Poster Awards Competition are due by Friday, May 31.
/ISSX Newsletter / 17
Submit an abstract for the 10th International ISSX Meeting in Toronto, Ontario, Canada
Change of Address
ISSX Newsletter is published quarterly in the spring, summer, autumn, and winter. For information concerning advertising in this publication, including rates and specifications, please visit www.issx.org or contact information@issx.org.
If your mailing address, telephone, fax number, or e-mail has changed or will change, please let us know as soon as possible. You may update your contact information at any time using the online membership directory, which you can access in the Member Only section of the Web site. If you have forgotten your username and/or password, please contact information@issx.org.
Advertise with ISSX in the quarterly ISSX Newsletter. Rates and additional advertising opportunities are available at www.issx.org/advertising.
Deadline for the submission* of material to the ISSX Office: ISSUE
MATERIALS DEADLINE
RELEASE DATE
Issue 2, 2013
April 12, 2013
May 2013
Issue 3, 2013
July 12, 2013
August 2013
Issue 4, 2013
October 11, 2013
November 2013
*
Subject to change
Editor Dr. Allen Cato, III Cato Research, LTD 6480 Weathers Place, Suite 104 San Diego, California 92121 USA Telephone: +1-858-452-7271 Fax: +1-858-452-7784 E-mail: jcato@cato.com
Make Plans to Attend: NEDMDG/ISSX Workshop: The Role of Drug Metabolism in Immune-Mediated Drug Toxicity: Molecular, Clinical and Mechanistic Aspects Cambridge, MA, USA April 17–19, 2013
10th International ISSX Meeting Toronto, Ontario, Canada September 29–October 3, 2013
Visit www.issx.org for more information!