19TH ANNUAL MEETINGNovember 14 - 18, 2012 Hilton San Diego BayfrontSan Diego, CA USA

IN THIS ISSUE

President's Message...............2

Next FRS Webinar.................3

Research Forum.....................3

Foundation Supports Young Investigators..........................4

Call for Nominations: Lifetime Achievement Award...............8

Literature Review....................9

SFRBM at SOT.....................10

SFRBM HEADQUARTERS

8365 Keystone Crossing Suite 107Indianapolis, IN 46240 317/205-9482 fax: 317/205-9481info@sfrbm.orgwww.sfrbm.org

UPCOMING EVENTS

THE RADICAL VIEW Barry Halliwell, B.A., D.Phil., D.Sc.

FREE RADICAL SCHOOL WEBINARMitochondrial Redox ProcessesMay 24, 2012

continued on page 7

SPRING 2012 • VOL. 4 • ISSUE 2

SFRBM dot ˙DOT: Tell us a little about your background and current passions in your professional life.

Halliwell: I was born in a small town in the North of England, called Preston. A small textile town, it had a good football team (Preston North End) and a large railway station, but not much else special. Luckily for me, the local school system was excellent and I did well in both Humanities and Science. The Sciences won, and I obtained an exhibition (scholarship) to St. Catherine’s College−Oxford University, to study Biochemistry. The course, unlike many Biochemistry courses today, had a deep grounding in Chemistry, which I have found enor-mously useful in the free radical field. Some knowledge of Chemistry helps one to challenge the alleged miraculous properties of certain “an-tioxidants” by showing that they have no chemical basis.

In my final year at Oxford, I did a research project on plant science which inspired me so much that I stayed on to do a D. Phil (Ph.D) in the Botany School, on plant metabolism during photosynthesis, supported by St. Cross College. I mainly worked on photorespiration, the path-way that plants use to recycle 2-carbon compounds accidentally sent into the wrong metabolic process when O2 instead of CO2 reacts with the first enzyme in the Calvin Cycle. It turned out that H2O2 plays an important role in photorespiration, and I learned that plant organelles read-ily make H2O2. After a period, I was then offered a junior academic position (lectureship) in a medical school (Kings College London) and switched my research largely to the role of free radicals and antioxidants in human disease. However, I still have a soft spot for plants: they are our source of life-giving yet poisonous O2 and of most diet-derived antioxidants. London and its environs was an excellent place to develop an interest in redox biology with such pioneers as Eric Wills, Tony Diplock and Trevor Slater being close at hand. My long-time colleague, John Gut-teridge, and I worked closely together to understand the in vivo role of hydroxyl radicals, and of transition metal ions (especially iron) as catalysts of oxidative damage and how this contributes to human diseases as diverse as atherosclerosis, dementia and cancer. We had little competition in this novel area: most researchers were focussing on superoxide as a directly-toxic species.

During my academic career at King's College London, I was lucky enough to go on sabbatical to University of California−Davis, with considerable interaction with the Bruce Ames group at University of California, Berkeley. Working with Carroll Cross and his team at Davis, I was able to extend my research interests into how air pollutants interact with humans and other animals to cause oxidative damage, an especially fruitful line of enquiry. This productive interaction con-tinued for many years even though it was only supposed to be a one-year sabbatical.

Returning to King's, I received a Lister Institute Research Fellowship which freed me from teaching to focus purely on research, again involving the role of free radicals and disease and in particular the development of new methods to detect oxidative damage in vivo, particularly to DNA. The Lister scheme was completely non-targeted, they picked scientists based on their

Barry Halliwell

2 SOCIETY FOR FREE RADICAL BIOLOGY AND MEDICINE

SPRING 2012

I trust that this message finds all members well as we are a quarter of the way through the New

Year. SFRBM’s leadership and committees have been active on a number of projects, several of which I will briefly report on here.

We are in the final stages of planning our next Annual Meeting, which will be held this November in sunny San Diego. Special thanks goes to our Program Committee, who evaluated innovative plenary session proposals submitted by members. Featured symposia will include:

• Redox Regulation of Cancer Metabolism • Cellular Redox Sensors • Redox Lunchbox: What Your Gut is Telling You • The Free Radical Theory of Aging • Enabling Technologies in Free Radical and Redox Research

Stay tuned for future details on invited speakers and prompts to submit your latest research for oral or poster presentation at the meeting.

SFRBM is continuing fundraising efforts for our Foundation, with the express intent to support Travel and Young Investigator Awards as well as the association’s Mini-Fellowship program. Please consider a donation to ensure valuable training opportunities for our future redox biology and antioxidant researchers.

Don’t forget about recognizing the contributions and achievements of our senior investigators as well. The nominations deadline for SFRBM’s Lifetime Achievement Award is May 7. We encourage members to submit candidates for the Senior Award Committee’s consideration (see page 8 for more information).

There are also new developments with our Journal, Free Radical Biology and Medicine. Many of you were aware of the charges of widespread scientific fraud that were leveled by the University of Connecticut against Dr. Dipak Das. The FRBM Ethics Committee, chaired by Dr. Giovanni Mann, reviewed the allegations and, after following the proper protocols, has confirmed the findings of scientific fraud and misconduct for 2 articles published in FRBM. They forwarded their findings to the FRBM Editor-in-Chief Dr. Kelvin Davies who has informed our publisher (Elsevier) to formally retract these two articles. I appreciate the efforts of the Ethics Committee for handling this most unfortunate case.

On a more positive note, I wanted to thank Anthony Newman and Elsevier for sponsoring awards recognizing the most prolific FRBM reviewers in 2011. Congratulations and many thanks to Drs. Dale Dickinson, Al Girotti, Neil Hogg, Chris Kevil and Jacek Zielonka for their efforts and support to FRBM. We have also restructured the terms for FRBM’s Associate Editors that will allow increased member opportunity to serve in these important positions.

PresidentHarry Ischiropoulos, Ph.D. Children's Hospital of Philadelphia Research InstituteUniversity of Pennslyvania

Vice President of Research & Scientific Development (President-Elect)Henry Forman, Ph.D. University of California - Merced

Vice President of FinanceMargaret Briehl, Ph.D.University of Arizona

Vice President of Education & Professional DevelopmentPaul Brookes, Ph.D.University of Rochester

Vice President of MembershipSally Nelson, Ph.D.SomaLogic, Inc.

Vice President of CommunicationsChris Kevil, Ph.D.LSU Health Sciences Center

Past PresidentVictor-Darley-Usmar, Ph.D.University of Alabama - Birmingham

Executive DirectorKent Lindeman, CMP

Council Members Marcie Cole, Ph.D.Brian Day, Ph.D.Rick Domann, Ph.D.Neil Hogg, Ph.D. Eric Kelley, Ph.D. Alicia Kowaltowski, Ph.D.Aimee Landar, Ph.D.Francisco Laurindo, MDLee Ann MacMillan-Crow, Ph.D.Lin Mantell, MD, Ph.D. Andre Melendez, Ph.D. Bulent Mutus, Ph.D. Tim Oury, MD, Ph.D.Homero Rubbo, Ph.D.Sruti Shiva, Ph.D.Daret St. Clair, Ph.D. Albert van der Vliet, Ph.D.

SFRBM COUNCIL PRESIDENT'S MESSAGE Harry Ischiropoulos, Ph.D.

Harry Ischiropoulos

Internal Marketing Committee Dot Editor: Lee Ann MacMillian-Crow, Ph.D.Tak Yee Aw, Ph.D.Ines Batinic-Haberle, Ph.D.Christian Schöneich, Ph.D.Matthew Zimmerman, Ph.D.

continued on page 3

WWW.SFRBM.ORG 3

SPRING 2012

FREE RADICAL SCHOOL VIRTUAL SEMINAR SERIES

LATEST ARCHIVED WEBINARHemoglobin Mediated NO SignalingSpeaker: Daniel Kim-Shapiro, Ph.D. Wake Forest UniversityOriginally presented February 16, 2012

Visit the Members Only area at www.sfrbm.org.

SFRBM offers virtual programming on a quarterly basis, providing valuable education on a wide range of topics. The sessions are open to SFRBM members only and are offered at no charge.

Mitochondrial Redox ProcessesWednesday, May 30, 20121:00 pm Eastern (17:00 GMT/UTC)Speaker: Alicia Kowaltowski, Ph.D. University of São PauloCost: FREE for SFRBM members

PROGRAM OVERVIEWMitochondria are a quantitatively relevant source of reactive oxygen species (ROS) in the majority of cell types. We will review the sources and metabolism of ROS in this organelle, including the conditions that regulate the production of these species, antioxidant pathways, regulation of mitochondrial content and coupling. We will discuss substrate-, tissue-, and organism-specific characteristics of mitochondrial oxidant generation. Several aspects of the physiological and pathological roles of mitochondrial ROS production will also be addressed.

ABOUT THE SPEAKERDr. Alicia J. Kowaltowski joined the Department of Biochemistry, University of São Paulo, Brazil in 2000, and is currently a full professor and coordinator of the Graduate Program in Biochemistry. Her work focuses on the interrelationship between mitochondrial energy metabolism, ion transport and redox state.

COST There is no cost for SFRBM members to participate. The webinar is open to SFRBM members only.

LATEST POSTS IN RESEARCH FORUM

In an effort to help in the exchange of information in our field, SFRBM has rolled out a new Research Forum as a way to increase interaction and discussion among members. Members can post comments about methods, techniques or general questions for which they are looking for input from colleagues.

Here are the latest posts and discussions that can be found on the Research Forum:

Aging & Disease• Molecular mechanisms of epicatechin in the vasculature• Oxygen tension and Nox activity

Antioxidants and Novel Therapeutics• Antioxidants and Antioxidant Treatment of Disease

Generation, Action & Metabolism of Reactive Species• A way to oxidize cell surface thiols• Changes in mt DNA and mitochondrial biogenesis

Cell and Systems Biology• Cocoa and enhanced mitochondrial function• Palmitate on various cells and lipotoxicity

To stay up-to-date, sign up for the SFRBM Research Fo-rum Digest which summaries daily posts and replies within a single email. SFRBM members can access the Research Forum by logging in to the Members Only section of the SFRBM website and clicking on SFRBM Research Forum.

Finally, make sure to visit our website to view the latest posts to our Scientific Forum, watch an archived webinar (the latest is Dr. Dany Kim-Shapiro’s session on “Hemoglobin Mediated NO Signaling”) or update your Member/Research Directory profile.

As always, please contact me with your suggestions, ideas and concerns. Thanks for your continued participation in SFRBM.

President's Message, continued from page 2

SAVE THE DATE: SFRBM 2012See page 6 for featured sessions and more information.

4 SOCIETY FOR FREE RADICAL BIOLOGY AND MEDICINE

SPRING 2012

SFRBM FOUNDATION SUPPORTS YOUNG INVESTIGATORS

Interview by Jianhua Zhang, Ph.D.

The SFRBM Foundation is the charitable arm of SFRBM and supports our educational and training programs. The donations from our membership are absolutely critical and go towards fund-ing our Young Investigator Awards. Below we highlight the ex-perience of one our recent awardees and encourage you to help support this outstanding program!!

We interviewed one 2011 awardee, Brian Sansbury and his men-tor, Dr. Bradford Hill, for their perspective of the SFRBM confer-ence and what the Travel Award meant to them in their careers and pursuit of science.

Dr. Bradford Hill is an Assistant Professor in the Department of Cardiovascular Medicine at the University of Louisville. Brad won a SFRBM YIA as a postdoc in 2008. During a brief 2 year postdoctoral training, he published 9 manuscripts with his men-tor. Since becoming independent in 2009, he has kept up with his dynamite research rigor, creativity and productivity. He is also an inspiring mentor as attested by one of his mentees; Brian Sansbury has published 2 papers under Dr. Hill’s supervision and has obtained very exciting data on diabetes using mouse genetic models.

DOT: How important is the conference to you and your trainees?

Hill: Attending the SFRBM conference is a unique experience. Compared with other national meetings, I find it to be more stimulating, interactive, and educational. It is the only conference that I have found to consistently and effectively balance educa-tional and training experiences with cutting-edge science presented from leaders in the field. Personally, I have found the interface that occurs between attendees at poster sessions to be extraordinarily helpful, and I want all of my trainees to experience this as well. For example, just this year, I presented data from a project that had stalled. We were so stiflingly close to the project that we couldn’t distinguish a solution, i.e., we could not “see the forest for the trees.” The poster session gave me the opportunity to let the project “breathe” a bit, and I received suggestions and comments that have revived the work. For that, I am very thank-ful. I have also found the workshops to be extremely helpful. For example, Paul Brookes gave an overview of “How to Write the Training Plan of a Fellowship Application” this past year, which was of enormous help to me in developing Brian’s training plan for a predoctoral fellowship application. In my opinion, these qualities of the SFRBM meeting make it the “working model” for scientific conferences.

Sansbury: The SFRBM conference was an absolutely fantastic experience for me. I was given the opportunity to present our work and was really thrilled by the numerous responses, feedback and encouragement I received. The entire conference has a very cohesive feel and I immediately felt welcomed into the group. The meeting’s attendees seem to have a genuine interest in helping each other and want to become engaged with you and your work. This overwhelming sense of inclusion makes it easy to exchange ideas with each other and for a student or young investigator to meet established investigators to get valuable input or to discuss future opportunities. For example, on the final night of the conference, another student and I ran into Dr. Harry Is-chiropoulos, SFRBM President, outside the hospitality room. A simple “hello” wasn’t sufficient for him as he introduced himself and wanted to know all about our projects, our institutions and mentors, our experience at the conference and, of course, if we played soccer and what teams we followed. That type of genuine interest in one another, personally and professionally, regardless of career status, certainly made an impression on me and made me feel like I was welcome, that I belonged and that I was just as important as anyone else at the meeting. I think that is an extremely unique quality of the SFRBM conference as opposed to other national meetings.

Dr. Bradford Hill (left) and graduate student trainee Brian Sansbury (right). Brian's abstract on "Nitric Oxide Prevents Diet−Induced

Obesity by Regulating Adipose Tissue Phenotype" was selected for presentation during the Opening Session at SFRBM 2011.

continued on page 5

WWW.SFRBM.ORG 5

SPRING 2012

Foundation Supports Young Investigators, continued from page 4

DOT: From your perspective, how important are the SFRBM Travel awards to our junior scientists? What impact have you seen these awards make on the training experience of the awardee(s) you mentored?

Hill: Brian is my first student, and, I, being a junior investiga-tor, do not have much travel money to work with. Fortunately, his hard work over the past year was awarded with an SFRBM Travel Award, which allowed him to attend the meeting and present his research. I think Brian found the meeting to be re-freshing and motivating. It gave him the opportunity to pres-ent his work in front of a relatively large audience and to have in-depth discussions with other researchers working in or near the subject area. These types of experiences and interactions have been critical components to his training.

In addition, I think that the Sunrise Free Radical School ses-sions, a distinct characteristic of the SFRBM meetings, pro-vided Brian with a unique opportunity to become more versed in free radical biology. These sessions are especially useful if a trainee’s major is not related to biochemistry. Brian, for ex-ample, is a student in the physiology program, and he has had little formal, structured learning in the area of free radical biol-ogy. Hence, these sessions have helped him “bridge the gap” between his knowledge of physiology and biochemistry, which has been useful in his ongoing dissertation project.

The SFRBM conference should certainly be on the radar for anyone working in the free radical field. It is especially worth donating to the cause; in the end, it benefits everyone.

Sansbury: I was very honored to receive a SFRBM Travel award and am unsure if I would have been able to attend the conference without it. Aside from the financial benefit of the award, I also had the privilege to present our work during the opening session of the conference. In my experience, present-ing as often as possible is extremely beneficial. I can get so absorbed in the details of the project that taking a step back to put a story together in presentation (or poster) form helps me to reevaluate the progress we’ve made and what the next steps should be. It helps me to gather my thoughts and rein-force the direction of the study. This presentation opportu-nity, specifically, was also of great benefit as I was able speak in front a crowd that was much larger than any other I have previously addressed. Getting this experience at an early stage of my development and becoming comfortable presenting data and answering questions is very important as I hope to have the opportunity to present to many more large audiences in the future.

DOT: Do you have any advice for SFRBM junior faculties and junior student/postdoc members who are preparing to compete for the 2012 Travel/YIA awards?

Hill: Yes. Spend time writing the abstract. Make sure it is the best it can be. This is especially important for the Travel Award because the abstract is the primary source from which the work is judged. Also, if chosen for an oral presentation, it is impor-tant to give a clear talk. If you do not deliver a clear presenta-tion, the chances of receiving a YIA will be nil. Short presenta-tions typically take a longer time than expected to prepare; so start early and practice often! SFRBM usually offers workshops on effective communication, and, commonly, the lecturers on such topics will happily provide materials to assist in prepar-ing for presentations. For example, last year a workshop on “How to Give an Effective Short Presentation” was available to attendees. In short, if the research is communicated well, it will typically be received well and will have a better chance of receiving an award.

Sansbury: Don’t be afraid to go for it. Even if the study has holes or gaps or is incomplete, if there is an interesting finding and you are excited about the project, other people will find it interesting as well. Put an abstract together and make the story as complete and possible, then see how it is received. Don’t be overly dismissive of a project. If you believe in the study, sub-mit it and don’t be too afraid to give it a chance.

If your abstract gets accepted, there is no substitute for prepara-tion. Practice your talk repeatedly; know exactly the message you want to send with each piece of data. It is impossible to an-ticipate everything that may happen during a presentation, the only thing you have complete control over is your preparation. Being sufficiently (or overly) prepared will make you more re-laxed and will make your message clearer to the audience.

Sunrise Free Radical School Webinars

Visit the Members Only section at www.sfrbm.org to view the latest archived Sunrise Free Radical School Presentations

from SFRBM's 18th Annual Meeting.

6 SOCIETY FOR FREE RADICAL BIOLOGY AND MEDICINE

SPRING 2012

For further details regarding SFRBM 2012, please visit www.sfrbm.org and click on the SFRBM 2012 meeting logo. Questions about SFRBM 2012 can be directed to SFRBM via phone (317) 205-9482,

fax (317)205-9481 or e-mail at info@sfrbm.org.

19TH ANNUAL MEETING OF THE SOCIETY FOR FREE RADICAL BIOLOGY AND MEDICINE

FEATURED SESSIONS Redox Regulation of Cancer Metabolism

Cellular Redox Sensors

Redox Lunchbox: What Your Gut is Telling You

The Free Radical Theory of Aging (A Special Joint Symposium with the Gerontological Society of America)

Enabling Technologies in Free Radical Research

Team Science: Integrating Multiple Perspectives

Adaptative ResponsesBiological Formation of Reactive SpeciesBiological Regulation by Reactive Oxygen SpeciesCancer, Cell Proliferation and DeathCardiovascular Redox Biology and PathologyChemotherapyDNA Damage and its ConsequencesFree Radical Chemistry and BiochemistryHydrogen Sulfide Chemistry and BiologyInflammatory Oxidative Signaling and InjuryLipids In Redox BiologyMacromolecule Modification Mitochondria and Cell ProliferationNitric Oxide Chemistry, Biology and PhysiologyNovel TherapeuticsProtective EnzymesRedox ImagingRedox SignalingRedox Reaction Mechanisms Signal Transduction and Gene ExpressionSuperoxide and Superoxide DismutasesTargeted AntioxidantsUV Effects and Atmospheric Pollutants

ORAL PRESENTATIONS & POSTER SYMPOSIA

SFRBMHILTON SAN DIEGO BAYFRONT / SAN DIEGO, CA

NOVEMBER 14-18, 2012

Plan to join us during SFRBM’s Annual Meeting to be held November 14-18 in San Diego, CA, USA

WWW.SFRBM.ORG 7

SPRING 2012

The Radical View, continued from page 1

project and irrespective of its likely applicability. Nevertheless, the royalties made by Lister Fellows on patentable discoveries (es-pecially Alec Jeffreys’ DNA fingerprinting) were substantial, yet another demonstration of the value of investigator-led research. I must mention here my valuable collaboration with Miral Dizdaroglu, using the chemical techniques he pioneered to measure DNA oxidation products and applying them to biological samples to show the relevance of oxidative DNA damage to human disease.

In June 1998, I went on another sabbatical, to the National University of Singapore (NUS). This time, I never went back to London and am still in Singapore but contemplating yet another sabbatical (perhaps a dangerous thing to do!). Singapore is a remarkable place, dedicated to investment in education and research, which has helped transform this small country with no natural resources into an economic powerhouse. My own research there flourished, and I had the privilege of working alongside two excellent University Presidents in helping to steer NUS from being a well-regarded but rather staid teaching University into a serious player in the world research leagues, over a wide range of disciplinary and inter-disciplinary areas. I have been Deputy President, in charge of research and technology, for almost five years now. Hard work, but its exhilarating to see research quality and quantity getting rapidly better, and in some areas already among the best in the world.

My current passions are to find novel and interesting research areas related to preventing dementia and understanding ageing, as well as to help develop NUS from a top 40 to a top 20 University.

DOT: What made you decide to be a scientist and what are the important factors that shaped your career?

Halliwell: I came from a “working class” background but was lucky in my parents – they had an enormous belief in education as an avenue of social mobility, and I was lucky to be able to attend Preston Grammar School – a state school that had teaching staff equivalent in quality to that of many leading private schools (the British call them “public schools”). This passion for quality education has drained away somewhat in the UK (sadly) but is still strongly evident in Asia (and in Asians, wherever they may be) today. The curriculum was broad-based and I enjoyed many subjects, eventually picking the sciences to study at University. I toyed with the idea of doing Medicine and in retrospect I probably should have since the opportunities for clinician-scientists are enormous now, but this was not a recognized career pathway then in the UK.

DOT: What was your most exciting discovery in research?

Halliwell: I still feel a sense of excitement when a set of previously-incomprehensible data suddenly begins to make sense, and an experiment at last gives the result that you predicted. My first Ph.D. student, Christine Foyer, and I elucidated the ascorbate-glutathione cycle (Halliwell-Foyer-Asada cycle), a novel pathway used by chloroplasts to remove H2O2. Work by Groden, Beck and Asada helped us to firm up the details. The pathway has now taken on a new importance because genetic manipulation of its activity can help crops resist environmental changes.

I am also proud of our work on the role of iron in free radical reactions, our unequivocal demonstration of the formation of hydroxyl radicals in vivo, and our developing methods to detect free radicals and oxidative damage in human material. It was apparent to me early on that while many researchers in the field were speculating on a role for oxygen radicals and other reactive oxygen species (ROS) in human disease and assuming that high doses of nutritional antioxidants would scavenge these radicals and delay disease onset, the methods required to measure ROS and (probably more importantly) the biological damage that they cause in vivo were inadequate. We applied a number of methods, from aromatic hydroxylation to urate degradation and ‘finger-printing’ of oxidative DNA damage (with Miral), which have become widely used. The question of whether free radicals really do play an important role in human disease pathology is still an open one for most diseases, although I am convinced that they are important in neurodegeneration, and cancer, and the former is one focus of my current work. Most recently, we are studying the free radical theory of ageing using C.elegans as a model: the results are weird and wonderful. This simple nematode seems to be a useful model for frailty in humans, and a good testbed for strategies to help delay age-related disability.

In a “negative” sense, our work showing how artefacts in cell culture can seriously mislead researchers in the antioxidant/poly-phenol field is a simple example of how failure to consider the basic chemistry of cell culture media (rapidly fluctuating O2 levels – often hyperoxic, abnormal chemical environment, strong pressure for rapid adaptation to the cell culture environment causing genetic changes) can lead scientists astray. The work is simple (largely conducted by Lee Hua Long, a very able laboratory tech-nologist under my direct supervision), yet the implications are profound. continued on page 8

8 SOCIETY FOR FREE RADICAL BIOLOGY AND MEDICINE

SPRING 2012

DOT: How has science/research changed during your life as a scientist?

Halliwell: Almost every method I learned in my BA and D.Phil. studies is now obsolete, as is most of the informa-tion (although not the fundamental chemistry) I learned from my lectures and tutorials. Perhaps the most useful skill I obtained at University, through the Oxford tutorial sys-tem, was that of good communication, both verbally and in writing (write a short essay, write it again until the tutor is satisfied), together with the ability to dig out and marshall facts from the literature (pre-Google, pre-Yahoo, and pre-PubMed!). One thing that worries me now is that people rely too much on kits and published “protocols”, without enquiring how these things actually work and can they really do what they promise. Often methods are relegated to “sup-plementary material” in papers, as if they mattered little. There is too much “kitology research” in the redox biology field already, and it seems to be growing.

Nonetheless, methodological advance has been enormous and is beginning to reveal the true complexity behind such vague terms as “oxidative damage” – what is damaged, where, and how much – and what is the biological impact at the molecular level? The omics have helped enormously, al-though proteomics, genomics and lipidomics are still prone to methodological artefacts that need careful consideration.

DOT: What advice would you give to young researchers entering the field?

Halliwell: First, pick the right lab for your Ph.D. and post-doctoral research. The PI could be new and upcoming or older and established, but make sure they are at the cut-ting edge of whatever field you are interested in. If older and established, do they actually spend time with students? Choose an important project that will get you excellent papers if it works, plus a couple of sub-projects related to ongoing work that are more likely to deliver good results. Learn by attending seminars (even if outside your field), discussion groups, conferences and lab meetings. Take op-portunities to showcase your work at major international meetings and learn from the suggestions/criticisms made by the international research community. It’s not only the supervisor who matters, find out how well the post-docs, graduate students and technicians in the research group and Department interact – you may learn far more from them. Make friends with graduate students from other labs and institutions. During my D. Phil. at Oxford, it was expected that everyone in the Department attended afternoon tea several days a week. Originally, I thought this was an irrita-tion as I had to plan experiments around it. I soon learned its value – you chatted purely by accident to people (other

students, post-docs, academics etc) who had the same research problems as you, and sometimes a solution! It felt good as my research developed to be sometimes able to offer help to others working on entirely different projects.

Such advice is particularly important for Singapore – it has been too easy in Asia to repeat and extend what has been done in the west. My great pleasure at the moment at NUS is to watch the rise of science; in some areas NUS is now in a leading position globally and forging its own path.

The Radical View, continued from page 7

CALL FOR NOMINATIONS 2012 Lifetime Achievement Award

Deadline: May 7, 2012

SFRBM is now calling for nomina-tions from members for the 2012 Lifetime Achievement Award. This award recognizes an aggregate body of work important to the field of free radical chemistry, redox biology and antioxidants over a scientist's career.

This award will include a featured lecture at SFRBM's 19th Annual Meeting in San Diego, CA USA as well as:

• $2,500 cash award

• Paid travel expenses to SFRBM 2012

• A bronze medal with stand

• Invited to publish a review article for Free Radical Biology & Medicine, SFRBM’s journal, celebrating their scientific contributions and the presentation of the award

• Have a one page bio and picture prominently displayed in the SFRBM 2012 Abstract/Program book.

Nominations for the Lifetime Achievement Award will be taken through May 7, 2012. For more information regarding nominations please visit:http://sfrbm.org/sections/senior-awards.php

WWW.SFRBM.ORG 9

SPRING 2012

LITERATURE REVIEWMetabolomics implicates altered sphingolipids in chronic pain of neuropathic origin. Patti GJ, Yanes O, Shriver LP, Courade J-P, Tautenhahn R, Manchester M, Siuzdak G, Nature Chemical Biology (2012), doi:10.1038/nchembio.767.

Neuropathic pain is a debilitating condition for which the development of effective treatments has been limited by an incomplete understanding of its chemical basis, although inflammation and oxidative stress have been implicated in its development. To investigate the chemical basis of neuropathic pain, the authors performed MS-based metabolomics on Sprague-Dawley rats suf-fering from tibial nerve transection (TNT), a well-established model of neuropathic pain that induces allodynia, a condition in which normally innocuous stimuli elicit a pain response. Specifically, their investigation was focused on the metabolic alterations in the spinal cord during the later stages of neuropathic pain, showing that N,N-dimethylsphingosine (DMS), a endogenous ceramide metabolite that has not been previously implicated in nociception, induces pathological responses in the dorsal spinal cord that are associated with the development of pain behaviors and that the mechanism by which DMS mediates mechanical allodynia may occur via production of inflammatory mediators such as interleukin-1β (IL-1β) or monocyte chemoattractant protein-1 (MCP-1) in the CNS. Authors further suggest that inhibition of endogenous DMS production, with a methyltrans-ferase or ceramidase inhibitor, for example, may be an attractive therapeutic candidate to treat this debilitating condition. It may also be worthwhile noting that ceramide is a sphingolipid with powerful proapoptotic and proinflammatory properties and has been previously implicated in oxidative/nitrosative stress. Ceramide is generated by enzymatic hydrolysis of sphingomyelin by sphingomyelinases (the so-called sphingomyelin pathway) and is well established as a major proapoptotic mediator following ra-diation, chemotherapeutics, or exposure to proinflammatory cytokines, including TNF-α, IL-1β, IL-6, and oxidative/nitrosative stressors, whereby NF-κB and AP-1 pathways are involved. The increased formation of ceramide promotes oxidative/nitrosative stress and enzymatic inactivation of MnSOD, thereby triggering apoptosis. Therefore, the mediation of redox-based pathways may also be a valid approach to alleviate chronic neuropathic pain. Prepared by Tin Weitner and Ines Batinic-Haberle, Duke University Medical Center.

Antioxidant and Oncogene Rescue of Metabolic Defects Caused by Loss of Matrix Attachment. Zachary T. Schafer, Alex-andra R. Grassian, Loling Song, Zhenyang Jiang, Zachary Gerhart-Hines, Hanna Y. Irie, Sizhen Gao, Pere Puigserver, and Joan S. Brugge. Nature 461, 109-113, 2009.

Normal epithelial cells are dependent on interactions with specific extracellular matrix (ECM) components for survival, prolif-eration and differentiation functions. The ability of tumor cells to survive outside their natural ECM niches is dependent on the acquisition of anchorage independence. Apoptosis is the most rapid mechanism for eliminating cells lacking appropriate ECM attachment. In the paper the authors have demonstrated that detachment of mammary epithelial cells from ECM causes an ATP deficiency due to the loss of glucose transport. Overexpression of ErbB2 rescues the ATP deficiency by restoring glucose uptake through stabilization of EGFR and PI(3)K activation and this rescue is dependent on glucose-stimulated flux through the antioxidant-generating pentose phosphate pathway. They have found that the ATP deficiency could be rescued by antioxi-dant treatment without rescue of glucose uptake. This rescue was found to be dependent on stimulation of fatty acid oxidation, which is inhibited by detachment-induced reactive oxygen species (ROS). The significance of these findings was supported by the evidence of an elevation in ROS levels in matrix-deprived cells in the luminal space of mammary acini, and by the fact that antioxidants facilitate the survival of these cells and enhance anchorage-independent colony formation. These results reveal both the importance of matrix attachment in regulating metabolic activity and an unanticipated mechanism for cell survival in altered matrix environments through antioxidant restoration of ATP generation. Intriguingly, these data demonstrate that anti-oxidants promote the survival of cells that lack attachment to the ECM and raise the question whether antioxidants may have dichotomous activities with respect to tumorigenesis(1) suppressing tumorigenesis by preventing oxidative damage to DNA; and (2) promoting tumorigenesis by allowing survival of cells that are metabolically impaired (e.g. in altered matrix environments). Prepared by Artak Tovmasyan and Ines Batinic-Haberle, Duke University Medical Center.

continued on page 10

10 SOCIETY FOR FREE RADICAL BIOLOGY AND MEDICINE

SPRING 2012

Literature Review, continued from page 9

Autophagy proteins LC3B, ATG5 and ATG12 participate in quality control after mitochondrial damage and influence life span. Sören Mai, Britta Muster, Jürgen Bereiter-Hahn and Marina Jendrach. Autophagy 8:1, 47–62; January 2012; G 2012 Landes Bioscience.

Mitochondrial quality control is essential for cellular function and survival. Mitochondrial-targeted phototoxicity by irradiation of HUVEC cells led to transient fragmentation of mitochondria followed by mitophagy, with associated upregulation of LC3B, ATG5, ATG12, and PGC1α. Increased expression of LC3B, ATG5 and ATG12, but neither LAMP-1 nor ATG1, enhanced replicative life span up to 150%. So what are the mechanisms underlying the life span enhancement? First, the enhancements of life span by these autophagy proteins were associated with an improved mitochondrial membrane potential and enhanced ATP production, suggesting mitochondrial quality is associated with life span. Second, LC3B overexpressing cells also exhibit de-creased mtDNA damage. However, ROS levels (as measured by DHE) remained unchanged and the amount of oxidized proteins was slightly but not significantly increased. Although further studies are in need, the authors attributed the lack of global effect of increasing autophagy proteins on ROS or oxidized proteins to a redistribution of ROS and oxidized proteins. Third, although overexpressing LAMP-1 does not enhance replicative life span, it does protect cells against hydrogen peroxide-induced apoptosis, a phenomenon shared by overexpression of LC3B, ATG5, or ATG12 in HUVEC cells. This evidence suggested that increased autophagy may enhance life span by a mechanism independent of protection against apoptosis. Fourth, in already senescent cells, enhanced expression of autophagy proteins did not affect mitochondrial membrane potential, or ROS, suggesting that senescence is irreversible by autophagy proteins. Whether enhanced expression of autophagy proteins can further life span in senescent cells have not been measured in this study. This study supports a role of specific autophagy proteins in enhancing life span, via mecha-nisms that may involve improved mitochondrial membrane potential, enhanced ATP production, and decreased mtDNA damage. Prepared by Jianhua Zhang, University of Alabama at Birmingham.

A vesicular transport pathway shuttles cargo from mitochondria to lysosomes. Soubannier V, McLelland GL, Zunino R, Bra-schi E, Rippstein P, Fon EA, McBride HM. Curr Biol. 2012 Jan 24;22(2):135-41. Epub 2012 Jan 5.

Mitochondrial quality control is essential for cell function and survival. Mitochondrial quality has been shown to be high-ly regulated both by the fission/fusion machinery and by the autophagy of mitochondria (mitophagy) pathway that turn-over dysfunctional or damaged mitochondria. Up till recently, it was unclear whether any other pathways exist that may be able to exert similar functions. McBride and colleagues recently identified mitochondria-derived vesicles (MDVs) that con-tain an outer-membrane mitochondria-anchored protein ligase (MAPL), but not DRP1 or TOM20. In this article, the au-thors observed that treating cells with several reactive oxygen species generating agents, including glucose oxidase to HeLa cells, xanthine oxidase/xanthine to COS cells grown in galactose, or antimycin A, increased mitochondria-derived vesicles (MDV). N-acetyl-cysteine (NAC) decreased the MDV accumulation. Delivery of MDVs to the lysosomes does not require mitochondrial depolarization, and is independent of autophagy proteins, ATG5 and LC3, and does not require fission pro-tein DRP1. Comparing to mitophagy, the generation of MDVs occurs directly from the lateral segregation of cargo into budding vesicles that appear along the tubule of a respiring, functional mitochondrion. What are the signaling pathway to differentiate which parts of the mitochondria are to form the MDVs have not been determined. It was hypothesized to in-volve protein or lipid oxidation. This is an interesting work pointing to novel mechanisms of mitochondrial quality control. Prepared by Jianhua Zhang, University of Alabama at Birmingham.

SFRBM Exhibits at the Society of Toxicology (SOT)San Francisco, CA March 12 - 14, 2012

A primary Membership Recruitment committee goal is to reach out to other societies where there exists considerable overlap in scientific pur-suits in order to expose/advertise SFRBM and recruit new members. Accomplishment of this goal will serve to augment exposure of SFRBM to colleagues from related fields as well as enhance membership and maximize the potential for mutually beneficial professional networking. To assist with obtaining this goal, SFRBM was a first-time exhibitor at the Society for Toxicology (SOT) Annual Meeting in San Francisco, CA, March 12 - 14, 2012. We spoke to over 100 SOT attendees, and as a result, signed up over 35 new SFRBM members. SFRBM members, Drs. Marcelo Bonini (left) and Maria Kadiiska (right) at the SFRBM Exhibit Booth.