UAN Announces 2009 Award Winners

An ASBMB History May 2009

American Society for Biochemistry and Molecular Biology

contents May 2009 On the Cover: ASBMB unveils its society news new history book. 12 3 President’s Message 6 Washington Update 7 Showcasing the National Science Foundation

12 The First Hundred Breast Cancer Years Are the Hardest Biomarkers 16 Premiering in May: 27 A New JLR Thematic Review Series on Proteomics

special interest 14 Power to the Postdocs

science focus 28 Benjamin Neel: Phosphatases and Disease

departments 2 Letters to the Editor 8 News from the Hill 10 Member Spotlight 17 Lipid News 18 Education and Training 22 Minority Affairs Benjamin Neel studies phosphatases and disease. 28 24 Career Insights 26 BioBits

resources podcast summary Scientific Tune into this month’s podcasts and hear Meeting interviews with the authors of the JBC thematic Calendar minireview series “Metals in Biology” and online only “The Biochemical Basis for Triplet Repeat Neurodegenerative Diseases.” You can listen to the podcasts at www.asbmb.org/Interactive.aspx

May 2009 ASBMB Today 1 letter to the editor A monthly publication of The American Society for tive yet informal and that the views Biochemistry and Molecular Biology Facts and expressed by the speakers are their Officers Gregory A. Petsko President own thoughts and perceptions Heidi E. Hamm Past President Fictions on matters of interest. In regard Mark A. Lemmon Secretary Dear ASBMB, Merle S. Olson Treasurer to the specifics of the question, I Rewriting history is an unsa- Council Members have carefully looked over Norum’s Dafna Bar-Sagi Alan Hall John D. Scott vory process that creates confusing questionnaire (Norum, K. R. (1978) Joan A. Steitz Ann M. Stock paradoxical views between those Kevin Struhl James A. Wells Adrian Whitty Nutr. Metab. 22, 1–7), and yes, the who believe and those who remem- Ex-Officio Members particular question highlighted in Ellis Bell ber. Your ASBMB interview with your letter was phrased differently Chair, Education and Professional Development Committee Daniel Steinberg illustrated some than as Dr. Steinberg stated. The Laurie S. Kaguni of the allusions and illusions (and Chair, Meetings Committee question reads: “Do you think there John D. Scott the “drift” in truth) that underlie is a connection between plasma Chair, Membership Committee “The Cholesterol Wars.” Of course, Craig E. Cameron cholesterol levels and the develop- Chair, Minority Affairs Committee you merely report what Steinberg ment of coronary heart disease?” Joan W. Conaway answered, and the task of verify- James H. Hurley However, it may not be entirely Co-chairs, 2009 Program Committee ing a story remains for some other accurate to label Dr. Steinberg’s Ralph A. Bradshaw venue. If you had the time to do so, Chair, Public Affairs Advisory Committee comments as a misrepresentation Toni M. Antalis you might have seen how the facts Chair, Publications Committee of the truth; rather, it is just his Herbert Tabor were misrepresented in your article. interpretation of an open-ended Editor, JBC Steinberg claimed that Norum’s Ralph A. Bradshaw question. For although Norum’s A. L. Burlingame questionnaire asked: “Do you think questions do not specifically address Co-editors, MCP that the evidence supports cho- Edward A. Dennis a “proof of cause,” they do not Joseph L. Witztum lesterol as a major contributor to discount it either, and as one of the Co-editors, JLR atherosclerosis and heart attacks?” 200+ scientists who took part in ASBMB Today Editorial Advisory Board and he also claimed that the Alex Toker the survey, Dr. Steinberg is simply Chair “experts” said “yes” to that question. relating his belief in what the ques- Greg P. Bertenshaw Craig E. Cameron They did not. This is how misunder- A. Stephen Dahms Irwin Fridovich tion means. It is possible that many Jonathan Gitlin Richard W. Hanson standings begin. of the other survey participants Elizabeth A. Komives Bettie Sue Masters The scientists in 1978 clearly saw Luke A. O’Neill Duanqing Pei believed the connection was causal Carol C. Shoulders Robert D. Wells an ASSOCIATION of food calories as well; we cannot be sure. However, ASBMB Today with elevated blood cholesterol. it is interesting to note that Norum Nicole Kresge Editor They did not elevate the association [email protected] himself pointed out that, because to a PROOF OF CAUSE—as Stein- Nick Zagorski Science Writer a few of the survey participants [email protected] berg implies. We still have concerns hesitated to call any dietary connec- Nancy J. Rodnan Director of Publications about the flow of information today. [email protected] tions “causal,” the answers to the key One vital principle is that major- Barbara Gordon Executive Director question, “Do you think that our [email protected] ity votes do not constitute a logical knowledge about diet and coronary Magazine design & production: Amy Phifer scientific proof. heart disease is sufficient to recom- For information on advertising contact mend a moderate change in the diet Capitol Media Solutions at 800-517-0610 Sincerely yours, or [email protected] William E. M. Lands for the population in an affluent society?” were of great interest. And RESPONSE in this area, 92 percent said “Yes,” Dear Dr. Lands, suggesting a belief that diet and www.asbmb.org cholesterol play a contributory role, Thank you for your input on as Steinberg said. this topic. First, we would like to state that our ASBMB Roundtable Nick Zagorski series is designed to be informa- ASBMB Science Writer

2 ASBMB Today May 2009 president’smessage Too Big to Succeed?* BY GREG PETSKO

e hear the phrase “too big to fail” a lot these they had always gone through Wdays. It means that a company is so vital to cycles of rising and falling for, the national economy that its demise would be cata- oh, the previous 5,000 years or strophic, so the government will go to extraordinary so, seems to have been lost on the lengths to keep it afloat. General Motors Corporation, self-styled geniuses who created the mess we’re in. the sinking U. S. car maker, is said to be too big to fail. The real problem, though, is that nobody knows if Lehman Brothers, the investment bank whose collapse that $11 trillion figure is right because nobody knows precipitated financial crises around the world, was what the toxic securities are really worth. They may be too big to fail—although George W. Bush’s Secretary worth anything from close to their nominal value to of the Treasury, Henry Paulson, didn’t realize that in zero, and that’s a heck of an error bar. So let’s look at time. And, as the world credit market tries to become Citibank. Yes, it has $2.3 trillion in assets, but it also unstuck before a global depression sets in, we hear the has big liabilities. How big? It’s unknown. There might same thing about two U. S. bank holding companies, be, say, $1 trillion in liabilities, in which case Citibank Bank of America and Citibank. is in great shape. But there could well be $3 trillion in But what exactly does it take to make a company too liabilities, in which case this enormous bank is actually big to fail? In the case of General Motors, it is the huge broke. And no one, not the chief executive of Citibank number of jobs that would be lost if it went under, but nor the head of the U. S. Treasury nor a gypsy reading that consideration doesn’t apply to a financial services tea leaves, can say which is the case. The banks had firm, at least not directly. In the case of banks, it’s the grown so large and had created such an elaborate web magnitude of the monetary loss that matters. Bank of of interdependent, chopped-up, over-leveraged securi- America has assets of approximately $2.7 trillion and ties that their own financial people had no real idea of Citibank has assets of around $2.3 trillion. The Gross how much debt they were taking on. Domestic Product (GDP) of the United States is $14 In other words, I think Bank of America and Citi­ trillion, so each of these banks has assets in excess of 14 bank (as well as Lehman Brothers and most of the other percent of the yearly output of the largest economy on companies at the heart of the global financial crisis) Earth. That’s too big to fail. have become too big to succeed because they are too But I would argue that, if you can be too big to fail, big to be managed. No one individual—or group of you also can be too big to succeed. Your very size can individuals—can assimilate the amount of informa- be your undoing, as it may have been for the huge, lum- tion needed to keep tabs on what goes on at a company bering dinosaurs who weren’t flexible enough to survive that size, so even if they themselves are not crooked or the global catastrophe that our small, furry, mammalian incompetent, they are fated to be hostages to crooked ancestors were able to weather. or incompetent people who work, undetected, at some Consider the two giant banks. Over $2 trillion in lower level of the Byzantine corporate structure. Yet, assets sounds great, right? Well, maybe, but there’s until recently, these companies were touted as the also the small matter of their liabilities. Both banking epitome of excellence, precisely because, through merg- companies hold enormous quantities of so-called “toxic ers and acquisitions, they had grown so enormous. securities,” which is a polite way of saying mortgage- Why do we mistake growth for success? When did backed debts. As many of the mortgages are effectively sheer size become equivalent to excellence? Because a worthless, these companies may have huge liabilities. monomaniacal insistence on being the biggest so often It’s estimated that there might be as much as $11 trillion derives entirely from the person at the top, it seems of such debt in the U. S. economy, because many large fair to ask if there isn’t some psychological explanation. banks essentially bet the farm on the incredibly naive Washington Post columnist Sally Jenkins had a marvel- idea that house prices would rise forever. The fact that ous article in the February 19, 2009 issue, titled “Arm-

May 2009 ASBMB Today 3 president’smessage continued chair Field Generals, Getting Sacked on Wall Street,” in public has realized something that the Bush Administra- which she notes that the hypercompetitive CEOs of large tion never did and that the Obama Administration may corporations were usually good sportsmen but never quite not have figured out yet: CEO compensation is not a side good enough to become great. “Maybe the real lesson,” issue; CEO compensation is the problem. If you offer out- she writes, “is to beware of the wannabe. Some of these rageous salaries to people who run your companies and people seem to fall into the dangerous category of ‘pretty give them even more outrageous bonuses if they increase good’ athletes… Experience plus some armchair Freudian share prices and revenues—not profit, revenues—then analysis tells us there are a fair number of overcompensated it stands to reason that you will probably attract greedy, jerks out there who almost made it in sports… There’s the aggressive people who are only interested in short-term sneaking suspicion that more than one shareholder is suf- results. That’s what created the Wall Street culture that has fering from these guys’ sublimated failures to reach the top gotten us into this fix. in the more primal competitions of their youth… The most And the reason you’re reading this in ASBMB Today, important quality of leadership,” she goes on to state, “is instead of in The Economist, is that I fear this culture not competitiveness, but judgment.” may now be spreading, like some virulent flu strain, to And as corporate boards, which appoint CEOs, are the pharmaceutical industry. Look at what has happened usually stocked with present or past CEOs of other cor- in the past 15 years. A wave of mergers is threatening to porations, it shouldn’t surprise us reduce the number of so-called when these win-at-all-cost short- “big pharma” companies to a sighters pick people like themselves There are no handful, and the results haven’t to head the companies they over- “ always been pretty. Pfizer almost see. And so the culture of “whoever data indicating that choked to death from swallow- has the most when he dies, wins” ing Pharmacia/Upjohn a few goes merrily on. increasing the size years ago and now is planning But where did that culture of a pharmaceutical to acquire Wyeth. Merck has come from, and why did it get so announced plans to merge with out of control? I think the answer company leads Schering-Plough. And analysts might be pretty simple, and if I’m (more about them later) are bus- right, it explains why I also think to increased ily proposing other fusions. the current debate about exces- ability to make I’m not sure this trend makes sive CEO compensation misses the much sense from the point of point. You will recall that, as part of pharmaceuticals. view of the primary purpose of the financial bailout, the govern- ” these companies, which is to dis- ment proposed to limit the bonuses and other payouts cover new drugs (although in the short term it may help to the CEOs of the corporations receiving federal funds, fill one of the companies’ empty pipelines). There are no which provoked an immediate outcry on the part of their data indicating that increasing the size of a pharmaceu- boards, the claim being that, without enormous compen- tical company leads to increased ability to make phar- sation, companies would not be able to hire or retain the maceuticals. In fact, there are worrying suggestions that best people. Don’t worry about this side issue, they said, it may often do the opposite. Innovation usually scales fix the real problems. inversely with bureaucratic complexity. If a merger or Well, never mind that “the best people” have just lost acquisition is proposed solely for the purpose of acquir- hundreds of billions of dollars and nearly wrecked the ing a drug that one company makes, longer term issues of economy of the world. (I could do that and would hap- research complementarity or synergy of talent might get pily accept a lot less in pay and bonuses than they keep secondary consideration, leading to internal culture wars demanding.) And never mind that I am unaware of a and strategic paralysis. single study that shows a correlation between the sal- Recent history may bear this out. Despite more than a ary and bonuses paid to executives and their talent (in decade of mergers and acquisitions, big pharma actu- fact, in many professions, like ours, money usually isn’t ally makes no more drugs per company today than it the motivating factor in a career at all). The uproar in did in 1995 (although one has to be careful to take into the United States over bonuses just paid to some of the account drug approval rates by regulatory agencies, which very employees of the insurance giant AIG, who caused also change with time). Larger companies also have a the mess that the company is now in, suggests that the tendency to be more conservative, so the worry is that

4 ASBMB Today May 2009 president’smessage continued innovation could suffer as firms merge. Biopharmaceu- I have to say I was not that impressed. It seems crazy that ticals, the newest trend in the industry and the source part of the financial health of companies whose output of about 50 percent of its profits last year, originated in is so important to human health should rest with people biotechnology companies, not pharmaceutical houses. The who are not scientists or business executives, who don’t notion that proteins such as antibodies could be profitable have the public welfare in mind, and whose track record is drugs was resisted for years by big pharma, which is now spotty, to say the least. scrambling furiously to catch up. I’m not trying to bash the pharmaceutical industry Of course, giant pharmaceutical companies can buy here. I have enormous respect for it and for the people innovation, new targets, and even lead compounds from who work in it; most of them are motivated by a sincere small biotech companies—and frequently do. That may desire to improve the health of mankind. It’s that respect well be the future: big pharma outsourcing target dis- that leads to my concern for the industry’s own health. covery and some other aspects of innovation to smaller, Some mergers and acquisitions are good ones, of course, independently-operating biotech arms, with the parent but I remain unconvinced that, overall, a few huge drug company focusing on chemistry, testing, and marketing. It companies will innovate better than a larger number of might not be a terrible model, but I still think we’d end up smaller ones, even with the help of biotech partners. with fewer drugs, since the large pharmaceutical compa- The notion that something can be too big to succeed nies actually used to discover the bulk of them, and there shouldn’t be that foreign because it even applies to people. are a lot of weak biotechnology companies out there. There’s a famous example of an individual who became so Industry analysts love to tout mergers and acquisitions big and lumbering that he was easily bested by a smaller, as tools to raise share prices, and if stockholders clamor more nimble adversary. You’ll find his story in Chapter 17 for their advice to be followed, it can seriously affect those of the First Book of Samuel. His name was Goliath. share prices. I’ve never understood why analysts seem to exert such influence on the market. I’ve known a few, and *adapted with permission from Genome Biol. (2009) 10, 103.

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Bills on Animal Research, Gender Equity Encouraging OMB to in Science, and International Science Reduce Regulatory Burden FASEB is watching two recently reintroduced bills and FASEB sent a letter to the Office of Management and one new bill in the House that could affect biomedi- Budget (OMB) in response to an OMB request for informa- cal researchers. The Great Ape Protection Act (H.R. tion intended to inform the development of a set of recom- 1326) would eliminate the use of chimpanzees and mendations for a new Executive Order on federal regulatory other great apes in research. In the previous Con- review. Responding to a directive from President Obama, gress, the bill had few sponsors and was referred to OMB’s recommendations are to offer suggestions related to three separate committees. The new version of the the disclosure and transparency of regulations, the role of bill has 44 co-sponsors and has been referred solely cost-benefit analysis in the development of regulations, public to the House Energy and Commerce Committee, participation in agency regulatory processes, and identifica- increasing its chance of passage. FASEB opposes tion of methods to ensure that regulatory review does not the measure because of the importance of chim- produce undue delay, among other issues. panzees in ongoing research. The legislation has the In its letter, FASEB expressed concern that the cumulative strong support of the Humane Society of the United burden of regulations is having a deleterious effect on scien- States. tific productivity. Citing research conducted by the Federal Another bill that has resurfaced in the 111th Demonstration Partnership, FASEB noted that scientists Congress is the Fulfilling the Potential of Women in devote 42 percent of the time they spend on federally funded Academic Science and Engineering Act (H.R.1144), research to administrative and regulatory activities. In addi- whose main sponsor is Rep. Eddie Bernice John- tion, federal agencies and institutions spend $85 million on son of Texas, and aims to promote gender parity in administrative tasks directly linked to those projects. STEM at the university faculty level. The legislation, FASEB encouraged OMB to make every effort to ensure which has been referred to the Science Committee, accountability and transparency in research while minimizing would direct federal agencies to: (1) hold workshops the administrative burden regulations place on the scientific with study section members and department chairs community. The Federation encouraged OMB to review on gender bias and (2) develop policies to extend proposed regulations to determine whether or not the costs research grant support and/or hire interim technical they impose are balanced by meaningful improvements to help during times of family leave. the current oversight system. Where new regulations are nec- Finally, the Science Committee is considering the essary, FASEB stated that they should be based on sound International Science and Technology Cooperation justification. In addition, they should be harmonized with Act (H.R. 1736), which would establish a new com- existing regulations in order to avoid unnecessary duplication, mittee under the National Science and Technology confusion, and inconsistency. Council. The mission of this committee would be to FASEB also encouraged OMB to solicit input from the sci- (1) coordinate interagency activities related to cooper- entific community when making regulatory decisions related to ative international research and training; (2) establish science. The full letter may be found at tinyurl.com/d8aezn. priorities to align international science activities with foreign policy goals; and (3) identify opportunities for Carrie D. Wolinetz is Director of Scientific Affairs and Public Relations new international science and technology cooperative for the Office of Public Affairs at FASEB and can be reached at research and training activities. None of the three bills [email protected]. Jennifer A. Hobin is a Senior Science Policy has yet been introduced in the Senate. Analyst for FASEB OPA. She can be reached at [email protected].

6 ASBMB Today May 2009 washington update Showcasing the NSF BY ALLEN DODSON

peaker of the House of Representatives Nancy SPelosi repeated her familiar refrain, “science, sci- ence, science, and science,” at the 15th annual Capitol Hill Exhibition held by the Coalition for National Science Funding (CNSF). The presence of such a prominent policymaker at the event was less familiar but was welcomed as a hopeful sign after years of flat budgets at the National Science Foundation (NSF). ASBMB was one of 31 professional societies, organizations, and institutions that participated in the The ASBMB delegation: (left to right) Julio Turrens, William th March 24 exhibition. As part of this effort, the Society Merrick, Lee Swem, Mike Harris (back), and Rasul Chaudhry. brought the following NSF awardees to Washington to meet with their Congressional delegations and to in chemistry, physics, the social sciences, and basic explain the importance of the NSF: biology. These projects ultimately produce the new • Rasul Chaudhry (Oakland University in Michigan) has a grant from the NSF’s Office of International Science technologies and methods that make advances in and Engineering to collaborate with researchers at biomedical research possible. In addition, NSF funds a the University of Rajshahi in Bangladesh. This work number of education programs, such as the one run by examines the effects of the pesticide carbofuran on Turrens, that play a significant role in preparing the next local crops. generation of researchers for careers in science. • Michael Harris (Case Western Reserve University’s Speaker Pelosi, who attended the exhibition, along School of Medicine) has an NSF award to study the with Reps. Rush Holt (D-NJ), Bart Gordon (D-TN, nucleophilic activation of water in enzyme catalysis Chair of the House Science Committee), and Vern using mass spectroscopy. Ehlers (R-MI), has received much of the credit for the • Lee Swem (an NSF-supported postdoctoral fellow recent attention to NSF in the fiscal year 2009 omnibus at Princeton University) presented the poster for ASBMB’s exhibit, describing his work on drugs appropriations bill and the economic stimulus package. that affect bacterial quorum sensing—cell to cell However, she was quick to credit the advocacy com- communication that helps the bacteria to react to their munity for providing the justification—showcased at the environment. exhibition—for continued support to the agency, which • Julio Turrens (Associate Dean at the University of she views as crucial to the nation’s economic recovery. South Alabama) heads the University’s Research ASBMB, in turn, could not advocate for this important Experiences for Undergraduates program. His NSF cause without the support of members such as the grant has supported dozens of undergraduates for 10-week research projects on the structure and CNSF delegation who flew to Washington and the hun- function of proteins. dreds of others who have answered email advocacy The group was able to visit 13 House and Senate alerts in support of NSF in the past. Together, we can offices, representing five states, to emphasize the value all work for “science, science, science,” and perhaps a of continued support for the NSF. little bit more science, in our future. Though the NSF is a smaller agency than the NIH—its budget in 2009 is $6.5 billion compared Allen Dodson is an ASBMB Science Policy Fellow. He can be to the NIH’s $30.3 billion—it bears a heavy burden. reached at [email protected]. ASBMB estimates that 15 percent of our members receive direct support from the NSF, but that number Email the author to join ASBMB’s Local Advocacy Network for the latest updates on ASBMB’s advocacy efforts. merely scratches the surface of the agency’s impact. Speaker Pelosi’s prepared remarks are available online at: www.speaker.gov/ NSF funding is a major source of support for research newsroom/speeches?id=0177.

May 2009 ASBMB Today 7 news from the hill House, Senate Pass Budget Resolutions; Obama Budget Priorities Largely Intact BY PETER FARNHAM

he first week of April saw action in both the House and of priorities—health care, education, and energy. House TSenate on the annual budget resolution, a spending Budget Committee Chairman John Spratt (D-SC) notes: blueprint that Congress is supposed to pass each year by “…the President’s budget launches initiatives to make our May 15. The House passed its version of the resolution on economy more productive and our people more competi- April 2 on a near party line vote (no republicans voted for tive: first, in education and in Pell Grants in particular; next, the resolution and only a few democrats voted “no”). The in health care for the millions uninsured; and finally, in alter- Senate followed suit that same afternoon, also adopting its native energies to reduce our dependence on foreign oil version of the resolution with no GOP votes. and the depletion of our environment. This mark upholds The budget resolution is not a binding document in those priorities.” large part. It sets broad spending goals by category (called In the Senate, Budget Chairman Kent Conrad (D-ND) “functions”). The two functions of most interest to biomedi- also “preserves the major priorities in President Obama’s cal research are Function 250, “science, space, and tech- budget.” The resolution provides an overall figure of $3.5 nology,” and Function 550, “health.” The amounts included trillion, including $525 million in non-defense discretionary in these functions are not binding. The only number in the spending. The Senate budget resolution also specifically resolution that is binding is the overall total for discretion- singles out the National Institutes of Health, noting that ary spending, which includes all funds the federal govern- the Senate “continues to support funding for NIH in 2010 ment spends (including funds for defense, which is about including support for cancer research.” Readers will recall half of discretionary spending) that are not mandated by from the last issue of ASBMB Today that the President’s law; that is, the amounts that cover spending on every- budget summary referred to $6 billion in cancer research thing in the federal government except Social Security and at NIH, although there were no details provided as to what other entitlements, and interest on the national debt. this figure meant at the time. The Senate budget resolution The non-defense discretionary total in the House sheds no light on the matter either. budget resolution is $533 billion for fiscal year 2010, which The differences between the House and Senate ver- begins on October 1 of this year. The overall House-approved budget is for $3.45 trillion. As can be seen, the amount of money that is avail- able to Congress to spend on non- defense discretionary items is less than 14 percent of the total budget. The House resolution also includes a statement that the “reso- lution builds on significant funding provided in the American Recovery and Reinvestment Act (the Presi- dent’s stimulus package) for scien- tific research.” The House budget resolution also largely protects the increases President Obama seeks for his trinity

8 ASBMB Today May 2009 news from the hill

sions must be ironed out, as with all legislation. The purpose is to reconcile existing law with the new spending Congress is in recess for the Easter and Passover holidays plan laid out in the budget. But it has been used by both for most of the first half of April, but the staff is ironing parties to pass large, difficult bills that are important to the out differences between the two resolutions, and once particular administration’s priorities (Presidents Reagan the Congress returns later in the month, an agreement is and Clinton both used it to advance their agendas during expected soon thereafter. their presidencies). The budget is expected to be approved by both There would be little the GOP could do to oppose this Houses handily once differences are ironed out. Although use of the reconciliation process. the GOP still has enough strength in the Senate to filibus- The budget resolution also does not require a presi- ter the resolution if it chooses to do so (assuming all GOP dent’s signature, and he cannot veto it. However, he senators remain opposed), the majority has indicated retains the right to veto any legislation put forth intended to its willingness to use the reconciliation process to pass advance the goals of the budget resolution. In a Congress the bill. Under reconciliation, only a simple majority of 51 solidly under the control of the President’s own party, how- senators is needed to pass the bill, rather than the 60 ever, this is an unlikely scenario. needed to pass a bill if a filibuster has been launched. The process was intended as a mere book-keeping process Peter Farnham is Director of Public Affairs at ASBMB. He can be when it was adopted as part of the Budget Act of 1974; its reached at [email protected].

ASBMB Members Visit the Hill: Second of Two Hill Days a Big Success

On March 25, ASBMB members came to Washington to lobby for work and mission. The only cautionary points made were related the budget of the National Institutes of Health, making it two “Hill to the difficult budgetary situation the nation faces, which con- Days” in a row (see Allen Dodson’s story on p. 7 about the NSF- strains the amount of resources available to the agency this year. focused hill day on March 24). The NIH hill day was organized by Furthermore, most Representatives and Senators were aware of the staff of the Coalition for the Life Sciences, of which ASBMB the impact of the $10 billion in stimulus money that NIH will be is a new member (the CLS was once known as the Joint Steering receiving in 2009 and 2010. However, no one raised this money Committee for Public Policy, and ASBMB renewed its member- as a reason not to fund NIH further in the regular appropriations ship last fall after a five-year hiatus). process, either this year or in future years. ASBMB members attending the hill day under ASBMB’s The luncheon briefing featured David Botstein, Princeton sponsorship were William Merrick, Case Western Reserve Uni- University, who presented a talk about his research under the versity Medical School (and deputy chairman of the Public Affairs aegis of the Congressional Biomedical Research Caucus. Rep. Advisory Committee); his colleague at Case Western, Michael Bart Gordon (D-TN), chairman of the House Science Committee, Harris; Bettie Sue Masters, University of Texas, San Antonio attended the caucus as well. Health Sciences Center; and Leslie Parise, University of North The Coalition for Life Sciences was organized in 1991, and Carolina. current members, in addition to ASBMB are the American Society Visits were arranged with the staff of 31 House and Sen- for Cell Biology, The American Society for Clinical Investigation, ate members, and ASBMB members met with more than half the Genetics Society of America, the Howard Hughes Medical the representatives involved during the course of the day. A Institute, the Society for Neuroscience, and the Society for Sci- high point of the day was a personal meeting with Rep. David ence and the Public. Price (D-NC) who dropped by unexpectedly at a meeting with a Hill visits are an excellent way to advocate for issues of con- member of his staff. He stayed and chatted for several minutes, cern to biomedical research. ASBMB will be participating in and making it very clear that he continued to support NIH and would organizing several more hill days this year. If you are interested in work on behalf of NIH, although progress would be difficult due coming to Washington to spend a day advocating for biomedical to budgetary constraints. research, please contact the ASBMB Office of Public Affairs at In fact, Price’s comments about NIH were very typical of the 301-634-7147, or email ASBMB’s Director of Public Affairs, Pete day; virtually no one had anything other than praise for NIH’s Farnham, at [email protected].

May 2009 ASBMB Today 9 asbmb member spotlight Barbas and Hruby Win Bond to Become Vice President- Cope Scholar Awards Elect for Science Policy Carlos F. Barbas III of The Scripps Research ASBMB Past-President Judith S. Bond, Institute and Victor J. Hruby of the University Professor and Chair of Biochemistry and of Arizona are the recipients of 2009 Arthur Molecular Biology at the Pennsylvania State C. Cope Scholar Awards. The awards, given University, was elected FASEB Vice by the American Chemical Society and President-Elect for Science Policy. Bond will sponsored by the Arthur C. Cope Fund, are begin her term on July 1, 2009, will serve as intended to recognize and encourage Vice President-Elect through June 30, 2010, excellence in organic chemistry. and will then take office as FASEB Vice Barbas was nominated “for exceptional President for Science Policy on July 1, 2010. Barbas creativity and pioneering studies in organic In these positions, Bond will serve as a spokesperson for FASEB on chemistry, particularly in the areas of organo- matters of science policy. catalysis and the application of organic The focus of research in Bond’s laboratory is the structure, func- chemistry to chemical biology.” In his research tion, and regulation of proteolytic enzymes. She is particularly inter- program, Barbas designs zinc finger protein- ested in the function, mechanism of action, regulation of biosynthesis, based transcription factors for the directed oligomeric assembly, and post-translational processing of secreted regulation of gene expression and gene and cell surface mammalian metalloproteases called meprins. Bond discovery; programs complex reaction mecha- was president of ASBMB from 2004 to 2006 and is currently an asso- nisms into antibodies and uses them to treat ciate editor of the Journal of Biological Chemistry. cancer; and develops new approaches to Hruby catalytic asymmetric synthesis with DNA, pro- teins, and small molecules (organocatalysis). DeBose-Boyd and Spies Named Hruby, who is a Regents Professor Emeritus of Chemistry at Early Career Scientists the University of Arizona, was honored for his groundbreaking Russell A. DeBose-Boyd, Associate contributions in organic chemistry related to design, synthesis, Professor of Biophysics and Molecular and evaluation of conformationally constrained amino acids and Genetics at the University of Texas their incorporation into biologically relevant peptides. His research Southwestern Medical Center, and Maria centers on biologically active peptides and peptide mimetics with Spies, Assistant Professor of Biochemistry an emphasis on hormones and neurotransmitters that affect human and Biophysics in the School of Molecular behavior. and Cellular Biology at the University of Illinois at Urbana-Champaign, were named Early Career Scientists by the Howard Hughes Carlson Receives 2009 Genetics Debose-Boyd Medical Institute. The pair is among 50 Society of America Medal scientists given six-year appointments to the Marian B. Carlson, Professor of Genetics & prestigious institute along with $1.5 million Development and Microbiology at the toward research. All of the researchers Columbia University Medical Center, selected for these appointments have only received the 2009 Genetics Society of been leading a lab for two to six years. America Medal. The medal recognizes Debose-Boyd studies the regulation outstanding contributions to genetics over of HGM-CoA reductase, an enzyme that the last 15 years and was given to Carlson in produces an intermediate in the synthesis of

recognition of her research on understanding u ffe r , UIU C Ne w s Bur ea p ho t o: L. Bri a n S ta cholesterol. The cholesterol-lowering statins metabolic and growth regulation by protein Spies block HGM-CoA reductase, but, para- kinases and critical aspects of eukaryotic gene expression. doxically, they also inhibit its degradation. As Carlson’s research focuses on the Snf1/AMP-activated protein more enzyme accumulates, more statins are needed. By studying kinase (AMPK) family. She is particularly interested in the regula- HGM-CoA reductase, Debose-Boyd hopes to improve the effects tion of the Snf1 pathway, with respect to both catalytic activity and of statins or find alternatives to the drug. subcellular localization of the kinase, and in the mechanisms by Spies’ lab studies DNA helicases and how they function in DNA which Snf1 kinase regulates transcription. Carlson has identified repair. Specifically, she focuses on how different helicases perform the first upstream kinases for the Snf1/AMPK family and is currently a diverse set of activities, how they utilize unique structural features investigating the roles of these kinases in responding to different incorporated into otherwise conserved motor cores, and how other stress signals. She has also identified the LKB1 tumor suppressor players in the genome maintenance pathways modulate activities of kinase, which is associated with a hereditary cancer syndrome, as selected helicases, adapting them to desired cellular tasks. an upstream kinase in the AMPK cascade.

10 ASBMB Today May 2009 asbmb member spotlight Please submit member-related news to [email protected] Conn Selected for Media Award Losick, Shapiro, and Mori P. Michael Conn, Associate Director and a senior scientist at the to Receive Gairdner Oregon National Primate Research Center, was selected to receive International Awards the American College of Neuropsychopharmacology (ACNP) Media Richard Losick, Lucy Shapiro, and Award for his book The Animal Research War. Kazutoshi Mori have been named as The award was established in 2002 to “honor a member of the recipients of the 2009 Gairdner Awards, print or electronic media who has made a major contribution to the Canada’s most prestigious international education of the public about mental illness and substance abuse award. Over the past 50 years, some 298 research, and the positive impact of research on treatment.” It is scientists have won Gairdner Awards; intended to reflect the appreciation that members of the ACNP feel among them, 73 scientists have gone on toward outstanding leaders in the media who inform and educate to win the Nobel Prize. the public about the brain and scientific research in this field. Both Richard Losick and Lucy Shapiro Conn, who is also Professor of Physiology and Pharmacology Losick won the award “for their discovery of and Cell Biology and Development at Oregon Health and Science mechanisms that define cell polarity and University, co-authored The Animal Research War with James V. asymmetric cell division, processes key in Parker. The book tells the story of the impact of animal extrem- cell differentiation, and in the generation of ism on scientific discovery and the changing view of the public cell diversity.” Losick is a Harvard College toward animals. It has received positive reviews in Science and Professor and the Maria Moors Cabot the Journal of Clinical Investigation and has been referenced on Professor of Biology at Harvard University. National Public Radio’s Science Friday/Talk of the Nation, and has Shapiro is the Director of the Beckman also been referenced in the LA Times, The Washington Post, The Center for Molecular and Genetic Medicine Scientist, and the American Scientist. at Stanford University and the D. K. Shapiro Ludwig Professor of Cancer Research Elgin Honored with at the Stanford University School of Education Award Medicine. Mori, of the Department of Biophysics, Sarah C. R. Elgin, the Viktor Hamburger Graduate School of Science at Kyoto Professor in Arts & Sciences at Washington University, received the award, along with University in St. Louis, was selected to Peter Walter of the University of California, receive the second Elizabeth W. Jones San Francisco, “for their dissection Award for Excellence in Education. The and elucidation of a key pathway in the award, given by the Genetics Society of unfolded protein response, which regu- America, recognizes individuals or groups Mori lates protein folding in the cell.” who have made a significant and sustained The awardees are selected by two impact on genetics education. According to separate judging panels made up of Canadian and international the Genetics Society, Elgin is “an indefatigable leader and medical researchers. A Gairdner Award comes with a cash innovator in science education for students of all levels.” prize of $100,000 CAD. Recipients also take part in academic Elgin has been an active proponent of science education at and public lectures and forums held across Canada before they the K-12 level. In the early 1990s, she initiated a science educa- receive their awards at a dinner in Toronto on October 29. tion partnership between Washington University and the public schools in her St. Louis community to implement a novel “hands- on” science curriculum for grades K-8 and to bring hands-on DNA science to the high school genetics curriculum. Elgin was also awarded a Howard Hughes Medical Institute Professorship in 2002, which she used to develop a course that couples the exper- tise of Washington University’s world-renowned Genome Center with the enthusiasm and interest of undergraduates for the field of genomics. Additionally, Elgin and her husband endowed the Elgin Fund for Summer Student Research at Pomona College, and she has served for three years as a founding co-Editor-in-Chief of Cell Biology Education (now CBE-Life Sciences Education).

May 2009 ASBMB Today 11 asbmbfirstsecond news words The First Hundred Years Are the Hardest BY RALPH A. BRADSHAW, CHARLES C. HANCOCK, AND NICOLE KRESGE

hey say that the first hundred years are the hardest, a chronological fashion Talthough most of us don’t get to take advantage of that details the Soci- the next hundred. But the ASBMB has—it first celebrated ety’s early growth and its 100th birthday at the ASBMB annual meeting in San partially reflects a previ- Francisco in April 2006, and then again on December 28, ously published history 2006 (the actual anniversary of its founding was Decem- of the first 25 years by th ber 26 ) in New York City and has moved into its second Russell Chittenden. It ASBMB Founder John J. Abel century with typical enthusiasm and gusto. However, contains copies of many the Society still has one more present to open: a book of the documents that were essential to the founding of entitled, “The ASBMB Centennial History: 100 Years of the Society, including a letter from ASBMB founder John the Chemistry of Life.” This project, which has been in the Jacob Abel proposing the formation of a new society, the works for several years, reached fruition at the Society’s Society’s first membership ledger, and the front and back annual meeting in New Orleans this past April when of the program from the first annual meet- the completed centennial commemorative volume was ing. This section also describes unveiled. The timing was not entirely inappropriate as the several events of the 2009 meeting was actually the Society’s 100th (the three- year discrepancy being due to a few years without meetings during World War II). The volume is divided into four parts: the founding and first 50 years (1906-1957), the second 50 years (1958-2006), the Society’s publications, and the Centennial. The first section is presented in

12 ASBMB Today May 2009 firstasbmbsecond news words

1950s, including the purchase of the Beaumont House The book includes a timeline that illustrates ASBMB (and grounds), which eventually became the Society’s member involvement in major scientific breakthroughs, headquarters, the establishment of an Executive Officer, photographs and biographies of ASBMB’s Presidents, and which greatly impacted how both the Society and the an appendix listing ASBMB’s Nobel Laureates along with Journal of Biological Chemistry were run, and the start of brief descriptions of their prize-winning research. the International Union of Biochemistry (now IUBMB) and This commemorative book was written and assembled the U. S. National Committee for Biochemistry. by Ralph A. Bradshaw, Society Historian; Charles C. Han- Part two of the book takes a look at the second half cock, Past-ASBMB Executive Officer; and Nicole Kresge, century through the Society’s activities, including its Editor of ASBMB Today. They gathered information from meetings, its awards, and the committees formed to many sources, including the Society’s archives at the address both social and scientific issues that did not exist University of Maryland, Baltimore County, to produce the in the earlier period. volume. Several chapters were also contributed by friends The third part of the book centers on the Society’s and members of the Society. publications—the Journal of Biological Chemistry, the The book celebrates one of the more remarkable Journal of Lipid Research, Molecular and Cellular Pro- stories in the pursuit of scientific wisdom. The ASBMB, teomics, and ASBMB Today—and also looks at its which began life as the American Society of Biological partnership with Cadmus Communications. Because Chemists, has had an admirable record of supporting both detailed histories covering the first 75 years of the JBC biochemistry and biochemists and thus being one of the are available, the JBC chapter places more emphasis on most accomplished learned societies in existence today. recent accomplishments such as the Journal’s pivotal The foresight of the 26 founders, led by John Jacob Abel, role in initiating electronic publishing. in breaking from the Physiological Society and striking out The final section of the book recounts the Society’s on their own, has certainly been rewarded. This 100-year centennial celebrations, including the 2006 annual meet- history of the ASBMB is dedicated to that spirit and to all ing and a commemorative ceremony and plaque dedica- the biochemists that the Society has served well in this tion in New York City. The book concludes with a look at period. We hope you will enjoy the stories and pictures the ASBMB of tomorrow and the Society’s coming that document this 100-year history. opportunities and challenges. If you would like to purchase a copy of this limited-edition book, visit: www.asbmb.org/historyorder.

May 2009 ASBMB Today 13 special interest Power to the Postdocs BY NICK ZAGORSKI

s Jonathan Wiest, Associate Director for Training hands the whole time, because they need to build their Aand Education at the Center for Cancer Research independence.” And allowing the fellows, specifically the (CCR) at the National Cancer Institute (NCI), addresses FYI Steering Committee (a body of fellows that acts as the sea of intent faces during his opening remarks at this an advocacy group and leadership liaison for their young year’s CCR Fellows & Young Investigators Colloquium, investigator peers), full control in planning, organizing, he takes a moment to emphasize that their eyes may be and moderating this colloquium provides a great example focused on the wrong person. “Look all around you,” he of that empowerment. says to the gathered audience of postdocs and research This year the fellows behind the colloquium, dur- fellows (with a smattering of post-baccalaureates as well). ing a 10-month brainstorming and organizing process “This is your future; these are the people who will be your that could best be described as a labor of love, delivered colleagues, your collaborators, and your connections for a sterling event that provided something for everyone. the next 30 years. This colloquium is not about me; it’s There were five keynote lectures on emerging areas of about you.” cancer research (cancer metabolism, small and micro It’s a point that’s plainly obvious once stated, but one RNAs, cancer stem cells, and T-cell homeostasis); six that’s often overlooked in a scientific world where the workshops on diverse topics such as effective publish- only future many can focus on is the immediate future. ing strategies, guides to transitioning to patient-oriented But although it’s definitely important for young investiga- research, careers in industry, non-benchwork career tors to reach out to established and senior scientists to options, and a virtual tour of some NCI core facilities help them take their next few steps, it’s equally as vital like the Cancer Biomedical Informatics Grid; and 40 oral to cultivate relationships with peers and gain valuable presentations and over 140 posters from some of NCI’s resources down the road—and perhaps more often than best and brightest. you think. As Wiest notes, “after all these years, it’s still “This year, in addition to events that appeal to all the surprising how small the scientific community is.” And in attendees, we wanted to include some sessions that really the backdrop of the city referred to as “the sweetest place impact first and second year fellows,” says Krista Zanetti, on Earth,” over 400 young NCI researchers have come to one of the six members of the colloquium planning com- do just that. mittee that devoted so much of their energy to bring this Specifically billed as an event “by the NCI fellows, for colloquium together. “We wanted to help them figure out the NCI fellows,” the Ninth Annual CCR-FYI Colloquium what they want to do and how to go about doing it early (held March 18-20 in Hershey, PA) brought these train- on, so they can get the most out of their five-year fellow- ees together in a “retreat”-style setting where they could ship and really excel at their chosen path.” network with their colleagues and invited guests to foster Undoubtedly, though, the most memorable segment employment contacts, research collaborations, or even of the event was the screening of the documentary “Dear just new friendships. Along the way they could listen to Talula: An Intimate Portrait of a Breast Cancer Survivor,” excellent scientific presentations, take in career-related a poignant film that chronicles both the major events and panel discussions, see some of their friends’ posters, everyday experiences of a young mother rising up to meet speak with some of the reps at the career fair, and maybe the challenges of her cancer diagnosis head on (www. even catch a few minutes of “March Madness” with some deartalula.com). “Many of these fellows have been doing of their newly made friends. basic research for years now and may have lost sight of Wiest notes that this colloquium illustrates the strong, the human aspect of cancer,” says Wiest. “This film was working relationship the NCI has with its fellows. “We a great reminder that cancer has, or will, touch all of us truly value our young investigators; they are our most directly.” precious resource, and the NCI does its best to empower Hopefully, adds Robert Wiltrout, director of CCR, this them,” he says. “But we know we can’t just hold their colloquium will also serve as an illustration that the NCI,

14 ASBMB Today May 2009 special interest

Recipients of the 2009 Travel Awards for excellence in scientific presentations at the NCI Colloquium. Left to Right: Tiffany Wallace, Luhua Zhang, Kimberly Shafer-Weaver, Sam Hong, Patricia Tsang, Tai Chi Cheuk.

and to a broader extent NIH as a whole (as other insti- Each of the four centers (Chromosome Biology, Immu- tutes have similar colloquia), is more than just a funding nology, AIDS & Cancer Virology, and Integrative Cancer agency. As he looks around during one of the mentored Biology) serves as a hub to promote interactions among lunches (the meals are structured to allow fellows to sit investigators across NIH and externally to help acceler- at tables with one of the keynote speakers or workshop ate discovery and delivery of therapies in these fields presenters and pick their brain) and reflects on another of research. Wiltrout notes these centers will help train successful colloquium—though there will inevitably be a young investigators to address their scientific pursuits few complaints about the food—Wiltrout says, “one of the through collaboration and multidisciplinary approaches; most exciting things for me is when I get comments from “it’s part of my hope that when our fellows talk about NCI invited guests who rave about this colloquium and say, ‘I mentors, it’s always in the plural.” wish our institute did something like this.’ And that rein- As with the colloquium though, the Steering Commit- forces the idea that NCI can and should set an example in tee, working with the Office of Training and Education, post-doctoral training and mentoring.” also contributes heavily throughout the year to support Although many people may comment on the slow their fellows’ training by organizing career fairs, network- pace of government, Wiltrout stresses that “the NCI is ing lunches with invited speakers, and grant-writing not afraid to evolve and change on the fly to adjust to workshops, among other initiatives. But they note more changing times, just like this colloquium has changed help is always welcome and needed and, much like CCR and grown every year.” And these times, as both Wiltrout empowered fellows with a large say in their NCI training and Wiest noted in their opening remarks, include a program, the FYI Steering Committee tries to empower post-doctoral workforce of which only one-third wish to their colleagues to help as well, by joining up with one of pursue a career in academia—and, of those, less than half the many groups and committees across NIH’s campus or will ultimately find success. To maximize these odds, NCI volunteering in some other capacity—such as, perhaps, is undergoing a “Renaissance in Training.” helping plan next year’s colloquium. For example, realizing that research should not be car- ried out in individual silos, CCR created four Centers of Nick Zagorski is a science writer for ASBMB. He can be Excellence, designed to bridge traditional lab boundaries. reached at [email protected].

May 2009 ASBMB Today 15 asbmb news Premiering in May: A New JLR Thematic Review Series on Proteomics BY MARY L. CHANG

he May issue of the Journal Vaisar will look specifically at Tof Lipid Research marks the the proteomics of two groups beginning of a new Thematic of lipid-protein complexes. Review Series on proteomics in Integral membrane proteins the study of lipids. The series (like transmembrane phospho- is being coordinated by Jay W. lipids) have been extensively Heinecke of the University of researched in the past, and Washington, an associate editor there are many well-validated of the journal. protocols for their analysis. In the introduction to the new However, less analysis has series, Heinecke will review two been done on plasma lipopro- mass spectrometry (MS) methods teins (such as HDL and LDL), that have greatly advanced the and, because of the unique study of proteins involved in lipid structure of these compounds, metabolism and biology. The first, investigators will have to matrix-assisted laser desorption be innovative in their analy- ionization (MALDI), is the chief sis. Vaisar’s review will also method used to examine solid- discuss the steps of isolation, state biomolecules. Matrix mate- solubilization, delipidation, rial that can absorb the frequency digestion, and MS analysis for of a rapidly pulsing laser is co-crystallized with a both types of lipid-protein complexes. protein product of interest so that when a laser strikes Eicosanoids are oxygenated essential fatty acids the compound, the matrix absorbs energy and causes that act as signaling molecules and play important the protein product to enter the gaseous phase. MALDI roles in inflammation and immunity. The June issue is extremely useful in that it is so sensitive it can detect of JLR will feature a review about “-omics” analysis subpicomolar quantities of an analyzed substance, and of eicosanoids by Matthew W. Buczynski, Darren S. when used with time-of-flight (TOF) MS, many samples Dumlao, and Edward A. Dennis of the University of Cal- can be analyzed in a short time if a high-throughput liq- ifornia, San Diego. They will look at how characteriza- uid chromatography system is employed. Furthermore, tion of eicosanoid biosynthetic pathways has allowed MALDI-TOF-MS can be used, via peptide mapping or for the unique integration of genomics, metabolomics, peptide mass fingerprinting, to identify unknown pro- and proteomics in studying the pathology of diseases teins. A second technique, tandem mass spectrometry associated with eicosanoids. This review will provide (MS/MS), can detect post-translational modifications a systematic overview of phospholipase A2, cyclooxy- of proteins. Heinecke will describe how MS/MS can genase metabolites (including prostaglandins), cyto- detect the oxygenation of thiol residues and how this chrome P450 metabolites, 5-lipoxygenase metabolites modification is related to the regulation of matrix metal- (including leukotrienes), and other lipoxygenases, as loproteinases by myeloperoxidase. well as products of eicosanoid catabolism. The May issue of JLR will also contain the first review Four more reviews are planned for this series and in the series. This review, by Tomas Vaisar of the Univer- will appear in JLR in the coming months. sity of Washington, will cover lipid-associated proteins and discuss the difficulties related to, and approaches Mary L. Chang is Managing Editor of the Journal of Lipid for, successful proteomic analysis of these complexes. Research. She can be reached at [email protected].

16 ASBMB Today May 2009 lipid news Getting Off of the Ground! BY DANIEL M. RABEN

ast month in the Lipid News col- Lipid Division Committees Lipid Corner Website Lumn, we announced the inaugu- Additionally, we have begun to orga- Finally, I encourage you to visit ration of the ASBMB Lipid Division. nize some important Lipid Division our website at www.asbmb.org/ This month, I thought I would outline committees: lipidcorner. I have started a thread some of our “works in progress.” • A steering committee is in place in the Forum titled “Issues for and and has been crucial to getting about the Lipid Division.” If there this division started. The Lipid News Column are any issues or concerns you The fundraising committee has First, I would like to discuss this • would like to raise, please post monthly column in ASBMB Today. been tasked with raising funds to support awards at our meetings. I them there. This will allow for an If anyone has a topic they would like am pleased to announce that Rob open discussion among mem- to see addressed, they can contact Stahelin (Indiana University School bers of the entire lipid community. me directly. Additionally, I am hoping of Medicine-South Bend) has Please also feel free to contact to engage our overseas colleagues agreed to chair this committee. me directly if you have an issue by encouraging them to contribute We are in the process of forming • you would like to discuss in a less to this column; the topics will vary, an Awards Committee, which will public venue. but they will all highlight the research be responsible for organizing Lipid Division awards. We are excited about the forma- and issues in different countries. tion of the ASBMB Lipid Division The ASBMB NIH Panels and have high hopes that it will Annual Meeting Many scientists have expressed bring recognition to the lipid com- The presentation of lipid research concern that the breadth and depth munity on a national and interna- has been a major component of of various lipid fields are not ade- tional level. ASBMB’s annual meetings. Starting quately represented on NIH study in 2010, the members of the Lipid panels. We are currently assess- Division will be intimately involved ing the lipid representation on the Daniel Raben is director of the ASBMB in selecting the organizers for the various study panels. Our data will Lipid Division and also a professor in the lipid theme. We hope that this will be available on the Lipid Corner Department of Biological Chemistry at serve as a mechanism for enhanc- website as soon as this assessment The Johns Hopkins University School ing the impact of the entire lipid is complete. We hope then to bring of Medicine. He can be reached at community. this data to the attention of NIH. [email protected].

Visit the ASBMB Lipid Division Website at www.asbmb.org/lipidcorner

May 2009 ASBMB Today 17 education and training

UAN Announces 2009 Award Winners BY WEIYI ZHAO

he ASBMB Undergraduate Affiliate Network (UAN) is service-learning opportunities. Each project pairs one grade Ta national organization comprised of university-based 7-12 school teacher and a grade 7-12 student with a UAN fac- chapters dedicated to the advancement of undergraduate ulty mentor and a UAN student. This Award is being piloted research, research-based undergraduate education, and in 2009. The following winning teams will work together for K-12 outreach in biochemistry and molecular biology. two years (two summers and one academic year): This year the UAN was able to offer several awards and Stan Richter—Detroit Lakes High School and —Minnesota State University Moorhead scholarships designed to support undergraduate and K-12 Joe Provost research and community engagement in the study of bio- Anne Mach & Miranda Sanchez— La Crosse Central High School and chemistry and molecular biology. Todd Weaver & Sarah Schreiner— Please join the ASBMB in congratulating the following University of Wisconsin La Crosse 2009 award winners. John Spengler—Pine Creek High School and Mike Taber & Neena Grover—Colorado College Undergraduate Research Rachel Gruner & Rachel Jones— Award Winners Robious Middle School, and Ellis Bell, Hugo Guterres, & Farren Billue— Undergraduate Research Awards in the amount of $1,000 are University of Richmond awarded to UAN student members conducting research under the direction of a faculty member who is an ASBMB 2009 Outstanding Regional member. The award is to be used for the purchase of research UAN Chapter Award supplies. Awardees are expected to present their findings at This Award aims to recognize UAN chapters that have dem- the next ASBMB annual meeting and/or a regional ASBMB onstrated leadership in their educational activities in the areas UAN meeting. This year’s awardees areChristopher Doucette of biochemistry and molecular biology, exhibited exceptional of Wesleyan University and Daniel Laurent of the University commitment to increasing public scientific awareness, dem- of Wisconsin, La Crosse. onstrated interaction with other campus activities and events, Outreach Support Award Winners participated in regional and national meetings, and showed sustained chapter activity. The three chapters receiving the The Outreach Support Award provides UAN Chapter win- award this year are Colorado College, Tennessee Technical ners with $250 to hold outreach events in K-12 schools in University, and the University of Delaware. their region to promote Science, Technology, Engineering, and Mathematics (STEM) education and careers in bio- 2009 UAN Travel Award Winners chemistry and molecular biology. The recipients of the 2009 Outreach Support Award are: College of the Holy Cross, Travel awards in the amount of $400 are used to support Tennessee Technological University, Seattle University, and UAN students and faculty members attending the ASBMB Western Illinois University. Annual Meeting. The following recipients attended this year’s Annual Meeting in New Orleans. All UAN Student Travel 7-12 Teacher Summer Award recipients also participated in the 13th Annual ASBMB Research Award Winners Undergraduate Student Poster Competition. —Montclair State University Totaling $12,000 per team, the purpose of this award is to Pablo Apablaza —Colorado College promote research-based educational activities by building Chloe Benson —Western Illinois University connections between teachers and students in secondary Kelsey Bohn —University of Michigan, Dearborn schools and colleges. A secondary purpose of this award is to Eric Brandt —Minnesota State University, Moorhead provide grades 7-12 students with role models and to present Jenny Canine —University of Richmond UAN faculty members and their students with meaningful Rachel Chikowski

18 ASBMB Today May 2009 education and training

Jennifer Chmielowski—Western Illinois University Matthew Richards—University of Delaware Cheerena Clay—Hampton University Alex Ritter—Concordia College Sarah Connor—Washington and Lee University James Ruble—Grand Valley State University Brad Falk—University of Richmond Kyle Schneider—Grand Valley State University Jarrett Failing—North Dakota State University Jessica Stevens—Marymount Manhattan College Andrew Haak—Minnesota State University, Moorhead Ryan Wilson—University of Delaware Jason Hocking—University of Wisconsin, La Crosse Meghan Woods—University of Delaware Casey McCormick—Tennessee Technical University Daniel York—College of the Holy Cross Derek Janssens—Grand Valley State University Robert Jones—University of Michigan, Dearborn Join the ASBMB UAN today and qualify for the 2010 Jessica Karr—Texas State University—San Marcos UAN Awards! Apply now and pay only $100 (a 50 percent Adam Kerrigan—College of the Holy Cross discount) in application fees. For more information and Craig Kutz—Minnesota State University, Moorhead to obtain an application, visit: www.asbmb.org or contact Brittany Lekies—Viterbo University Weiyi Zhao at [email protected]. David Nemer—University of Notre Dame Ka Yang—Adelphi University Weiyi Zhao is the ASBMB Manager of Education and Professional Daniel Osipovitch—University of New Haven Development.

How to Enhance Your Postdoctoral Experience BY FABIAN V. FILIPP

t the seventh annual National Postdoctoral Association ence, making it a very attenuated traineeship. Ironically, Ameeting in Houston, Texas this past March, plenary when my father obtained his Ph.D. in 1960, he had only speaker Peter S. Fiske spoke to a packed auditorium about one publication to his name but standing faculty offers career planning and the job hunting process. His talk, titled at Harvard, U.C. Santa Barbara, and the U. S. Geological “Putting Your Science to Work: Creating New Options and Survey. Back then, once you had an appointment as assis- Opportunities via the Postdoc,” attracted approximately 300 tant professor, you were supposed to learn how to publish postdoctoral fellows, eager to learn how to leverage their and how to get your first grant. Today the bar is set much degrees in a faltering economy. In the interview below, Fiske higher—a postdoc, today, is what an assistant professor talks about the postdoc experience and how to make the used to be. most of it. ASBMB: What kind of career training is required to make ASBMB: What makes postdoctoral training a special the postdoctoral fellowship an effective experience? period? PSF: You always have to actively work on your career, PSF: Postdoctoral appointments were always intended as even in research science. Obviously, the postdoctoral short periods of transition between graduate school and years are a marvelous experience. I had a great time dur- “academy” when they were first started at Johns Hop- ing my postdoc. It is a period after your Ph.D. giving you kins about a century ago. Today, mostly due to economic time to explore your own direction, but before you have forces, the postdoctoral years have evolved and expanded. lots of responsibilities that come with a faculty position In the life sciences, the postdoctoral experience can be like teaching. Postdoctoral fellows have also become a as long, or even longer, than the graduate school experi- flexible reservoir that accommodates the surge in Ph.D.

May 2009 ASBMB Today 19 educationand training continued

production and the dearth of Ph.D. jobs. After spending are very good mentors, just as most parents feel they years of talking to NIH and NSF on the subject of looking are very good parents. However, when you talk to the rationally at the level of Ph.D. production, I simply don’t children, the evaluations are much more mixed! [Men- think that these funders will ever regulate Ph.D. produc- toring] is a very personal relationship, and in a way, tion in any meaningful way. that can pose as many problems as benefits. It is very Of course you want to make every career choice full of difficult for a mentor not to see a bit of him/herself in purpose and with absolute clarity. The fact is that it is per- you. This transference is part of the bond. And when you fectly okay to do a postdoc as a means of exploring whether choose pathways and activities that your mentor might a research career makes sense for you. I did that myself. My not agree with, it can set you up for a lot of conflict or research advisor at the time was really put off by that! I just frustration. Choosing your own path is exactly what caution postdocs who find themselves in year three, four, you should be doing as a postdoc. The National Acad- or five of their appointment to question whether they really emy of Sciences came out with a book called Adviser, want to go on this path. The sooner you begin exploring Teacher, Role Model, Friend, a very small volume that options the better, especially while you are still a postdoc, was supposed to summarize the Academy’s view of what while there is some protection. A postdoc is a great oppor- advisors should do for their students and their postdocs. tunity also to move your career laterally. I went from geo- The problem I had with that approach is that, while chemistry to planetary science. Once you have an assistant you would like to be “advisor, teacher, role model, and professorship you don’t have the flexibility to move around friend,” as a PI you are also going to be “boss, jerk, and a intellectually that much anymore. guy who tells people to work harder!” It is just too much in a work relationship to try to pack all those personal expectations into mentoring. ASBMB: The requirements in the academic job market are Collaborations are the way that you will build your very different from those in the industrial or private sec- career: by branching out and working with other people. tor. Is it possible to prepare for the next step during your That brings in a second very important component, the postdoc? network. A lot of young scientists have an incomplete PSF: Anyone’s career options, whether for an academic view of networking. They view it as very shmoozy. And career, an industry career, or for a career in public policy, yet networking is a very important part of being a success- critically depend on the professional network they ful scientist. We do networking as young scientists all the develop. An important thing that should be on every time; we just don’t tend to call it that. When you go to a postdoc’s mind is how they develop their professional meeting and present a poster, it is not just scientific com- network, who they are getting to meet, who they are munication, it is networking! I try to unpack the whole getting to work with, and what opportunities are being term “networking” and frame it in terms of relationships. created as a result. The worst situation that postdocs can Networking is nothing more than making relationships; find themselves in is one in which they feel very much in particular, relationships with people who share your like graduate students: they are stuck in a research group, personal and professional interests. From time to time, they have no collaborations on the outside, and they lack you might talk to these people about career transitions interactions with people in other universities or industry. that you make. Practically speaking, anyone you know is If you find yourself caught in a very small environment, part of your network. However, within this set there is a you need to bust out! Strictly speaking, postdoc programs certain subset of people who will be extremely valuable to are supposed to be developmental assignments as well as you. Those are the people in the career field that already “regular jobs.” Sometimes postdocs find their PIs are very interests you, and who are willing to give you help. Let’s uncooperative in that regard and very inflexible about giv- say you are a graduate student in biochemistry; you are ing them time to explore or develop other collaborations. debating whether you want to do a postdoc, but you are But those outside collaborations are going to be absolutely also really interested in learning more about intellec- critical for the postdoc’s ability to transition to the next tual property and law in the biotech industry. You know step, whatever that may be. someone who works in marketing at Bayer ,who knows and works with the people in the intellectual property office. [This person] will be delighted to introduce you ASBMB: How can one enhance the mentoring experience? and arrange an informational interview with the people PSF: The term “mentor” is a very mythologized term in in the intellectual property office at Bayer. That is a great academia. Certainly most academic professors feel they example how networking works.

20 ASBMB Today May 2009 educationand training continued

setbacks can be very devastating. And yet ASBMB: At the seventh annual NPA that disappointment, that setback, is itself Meeting, the University of California Regular the seed for a new opportunity that you was often cited as a model system for seminar simply had not considered before. One postdoctoral training. What is the Uni- thing I am concerned about is that gradu- versity of California doing right in its series in ate students and postdocs are steeped postdoc programs? Where do you see into what can sometimes be a very opportunities to improve the training professional conservative intellectual culture, where experience of postdocs? development, risk-taking is considered dangerous and PSF: I love to see postdoctoral associa- frowned upon. And yet that risk-taking tions and societies. Regular seminar outside is exactly what we need for science and series in professional development, speakers, what people need for their own profes- outside speakers, and panel discus- sional development. The biggest oppor- sions with alumni are always valuable and panel tunities for me have come when I have and very informative for postdocs, found the courage (or foolishness) to take and they do not cost much money. discussions a risk. Frankly, grad students and post- Postdocs could organize these things docs are smart people; they know risk for themselves if their institutions are with alumni and they know the consequences—they willing to let them. What it takes is the are always are not deluded. The best thing that you institution creating a culture whereby can do is to offset those risks by creating postdocs are genuinely understood as valuable other options. As one very dear mentor of not just a flexible labor force but actu- mine said, the definition of mental health ally developing scientists. In my MBA and very is the feeling that you have options. One program, we had classes on negotiat- informative of the ways that you can create the most ing, leadership skills, extemporary options is by having a strong professional speech, and business etiquette. MBA for postdocs. network made up of people who know programs realized that their students you and think highly of your work and needed to be armed with those skills who are willing to help you when those in order to be successful professionals around the world. transitions are necessary. A strong network provides a Similarly, research institutions need to understand that level of safety and will keep you alive, even if you fall off a postdocs need to be armed with the exact same set of professional tightrope. skills. It is a convenient rationale for an institution or a PI In the course of doing my Ph.D., I did some “extracur- to simply say “the best students understand all this and do ricular research,” initially to the frustration of my advi- not need any help in this regard; the ones who don’t get sor, but eventually he got onto the idea. And that extra- it are beyond saving.” That kind of rationale conveniently curricular research actually led to my postdoc in the lightens the workload on their side. Nevertheless, we are Livermore lab: a wonderful three-year postdoc. At the talking about an academic institution: the university. The end of it, I was certain I was leaving science and never fundamental reason for its existence is the production of coming back. I went to Washington, D. C. for a year on a new minds and intellectual leaders. As difficult as it is to science policy program called the White House Fellow- run a research group today and balance a load of grant ship. About six weeks into my life in Washington, I real- applications and publications, postdocs still need to be ized that I did not want to spend the rest of my career considered by their PIs as special; and their institution there. So I made my way back to Lawrence Livermore needs to uphold that when conflicts arise between PIs and National Laboratory in the Bay area as a member of the postdocs. technical staff for four years. After that, I left to start my first company. That was probably my biggest professional risk. But I am glad I did it. ASBMB: You took some dramatic shifts in your personal career. What lessons did you learn from that? Fabian V. Filipp is a postdoctoral fellow at the University of PSF: Every career is going to come with some degree of California, San Diego and is also president of the University of setback. I have not had nearly as many as others. Often, California Council of Postdoctoral Scholars. He can be reached at when you become very invested in a certain pathway, [email protected].

May 2009 ASBMB Today 21 minorityaffairs Science in the Obama Administration: Are We Coming Out of the Dark? BY SQUIRE J. BOOKER

n 1991, Gloria Estefan released the single “Coming Out considerations. As a result, our once dominant position in Iof the Dark,” a future number one hit on the Billboard the scientific world has been shaken, and our prosperity Top 100. This single was in response to a near-fatal col- has been placed at risk. We have lost time critical for the lision between her tour bus and a truck, which almost development of new ways to provide energy, treat dis- ended the singer’s acclaimed career. In the chorus of the ease, reverse climate change, strengthen our security, and song, which is primarily a tribute to her husband’s sup- improve our economy.”1 port during a difficult period of physical and emotional rehabilitation, she celebrates, “…Coming out of the dark, I Learning from Problems finally see the light now, and it’s shining on me…” of the Past Administration Few will argue against the notion that science in the The problems of the past administration with respect to United States has endured a perilous, if not a near fatal, its relationship with science were many; however, one of period during the last eight years. After an era in which the gravest mistakes was the perception that the admin- the budget for NIH was nearly doubled between 1998 istration was distorting or misusing science for political and 2003, funding increases for science became stag- gain. A number of transgressions were outlined in a 2004 nant in many disciplines, whereas in others funding was statement entitled “Restoring Scientific Integrity to Federal decreased, especially after accounting for annual rates of Policy Making,” which was signed by more than 62 scien- inflation. More dishearteningly, many expressed concern tists, including several Nobel Laureates, leading medical that fundamental scientific values were under attack and experts, and university presidents.2 The statement claimed, that the opinions of internationally recognized scientific “When scientific knowledge has been found to be in con- experts were neglected, if not disrespected. Indeed, the flict with its political goals, the administration has often downturn in the perceived value of science and scientific manipulated the process through which science enters into expertise left many scientists demoralized and resentful. its decisions. This has been done by placing people who The magnitude of the state of affairs on the eve of an are professionally unqualified or who have clear conflicts upcoming presidential election warranted an open letter of interest in official posts and on scientific advisory com- to the American people in support of then Sen. Obama, mittees; by disbanding existing advisory committees; by which was eventually signed by more than 75 Nobel Prize- censoring and suppressing reports by the government’s winning scientists who are American citizens or perma- own scientists; and by simply not seeking independent nent residents. Although some past presidential candidates scientific advice.” Some of the findings were rebutted by have enjoyed similar backing by acclaimed scientists— the administration, and a revised, but still critical, version notably John Kerry in 2004 and Al Gore in 2000—their of the letter was eventually released.3 support of Barack Obama this past year was significantly In addition, notable scientists took issue with the augmented. The urgency of the situation was apparent in administration’s lack of support of condom use in protec- the opening statements of the letter, which claimed, “This tion from HIV/AIDS, its views on human involvement in year’s presidential election is among the most significant in climate change, and its ban on federal support for embry- our nation’s history. The country urgently needs a vision- onic stem cell research using stem cell lines created after ary leader who can ensure the future of our traditional 2001, despite the wide belief in the scientific community strengths in science and technology and who can harness that embryonic stem cells have the potential to impact those strengths to address many of our greatest problems: significantly on a number of diseases or conditions.4 energy, disease, climate change, security, and economic Many scientists warmly welcomed the words of President competitiveness.”1 It was further stated, “The government’s Obama’s inauguration speech on January 20, 2009, “We scientific advisory process has been distorted by political will restore science to its rightful place.”

22 ASBMB Today May 2009 minorityaffairs

President Obama’s Policy The executive summary of a 2006 report entitled for Science and Innovation Beyond Bias and Barriers: Fulfilling the Potential of Women So, what’s in store for science under the Obama adminis- in Academic Science and Engineering, by the Commit- tration? The major elements of the Obama-Biden science tee on Maximizing the Potential of Women in Academic policy are: Science and Engineering of the National Academies of 1. restoring integrity to U. S. science policy to ensure Sciences and Engineering and the Institute of Medicine, that decisions that can be informed by science are warned that the United States would have to pursue the made on the basis of the strongest possible evidence; innovative capacity of all sectors of society, regardless of 2. doubling the federal investment in basic research by sex, in order to compete and maintain scientific leader- key science agencies over a 10-year period, with a ship amid increasing economic and educational global- special emphasis on supporting young researchers at ization.8 the beginning of their careers, and backing high- The report further concluded that, although risk, high-return research; the percentage of women majoring in STEM (Science, Technology, Engineering, Mathematics) fields is increas- 3. making a national commitment to science education and training by recruiting some of America’s best ing, the percentage of women on science or engineering minds to teach K-12 math and science, by tripling faculties is relatively small and that they typically receive the number of the National Science Foundation’s fewer resources than their male counterparts. It was Graduate Research Fellowships; further stated that the small proportion was not due to a 4. encouraging American innovation to flourish by lack of talent but was instead due to unintentional biases making the R&D tax credit permanent, streamlining and outmoded institutional structures that hindered the our patent system, eliminating the capital gains tax access and advancement of women. on start-ups and small businesses, and promoting the deployment of next-generation broadband Obama and Biden agreed with the report’s conclu- networks; and sions and with the premise that the leadership of the 5. addressing the “grand challenges” of the 21st century United States in innovation is the key to its prosperity and through accelerating the transition to a low- national security. They argued that the workforce in STEM carbon, oil-free economy, enabling all Americans will need to be increased significantly, engaging “not just to live longer and healthier lives, and protecting women and minorities but also persons with disabilities, our country from emerging threats to our national English language learners, and students from low income security.5 families.”9 All indications suggest that the administration has gotten off to a solid start, which is undoubtedly fueled Squire J. Booker is an associate professor of chemistry and an by President Obama’s strong scientific advisory board. associate professor of biochemistry and molecular biology at President Obama expeditiously chose John Holdren, a The Pennsylvania State University. He is also Deputy Chair of physicist and expert in energy, as his Science Advisor and the ASBMB Minority Affairs Committee. He can be reached at Director of the White House Office of Science and Tech- [email protected]. nology Policy, as well as Steven Chu, Nobel Prize winner in physics as the Energy Secretary.6 He has reversed the executive ban on some of the limitations on using federal References 1. obama.3cdn.net/6667d14fd1301d9e8e_dbg0mvxzz.pdf taxpayer dollars for embryonic stem cell research and has 2. Union of Concerned Scientists, www.ucsusa.org/scientific_integrity/abuses_ of_science/ ushered through Congress a massive economic stimu- 3. Malakoff, D. (2004) White House Rebuts Charges It Has Politicized Science. lus bill, which includes over $21 billion for research and Science 304, 184-185. 4. Baltimore, D. (2004) Science and the Bush Administration. Science 305, development projects over the next two years. Excitingly, 1873. Nancy Pelosi, the Speaker of the House, recently stated 5. www.barackobama.com/pdf/issues/FactSheetScience.pdf 6. Kintisch, E. and Mervis, J. (2009) Holdren Named Science Adviser, Varmus, to a group of academic leaders, “if you want to know our Lander to Co-chair PCAST. Science 323, 22-23. 7. Bohaty, R. (2009) Science in the Domestic Agenda. Chemical and domestic agenda, it is science, science, science, and sci- Engineering News 87, 7. e n c e .” 7 With this seemingly renewed focus on science and 8. Committee on Maximizing the Potential of Women in Academic Science and Engineering (2007) Beyond Bias and Barriers: Fulfilling the Potential technology, a developing challenge will be to ensure that of Women in Academic Science and Engineering. National Academies of Sciences and Engineering and the Institute of Medicine. National Academy of Americans are suitably equipped to take full advantage of Sciences Press, Washington, D. C. emerging and/or expanding resources in this area. 9. www.sciencedebate2008.com/www/AWSSWEObamaMcCainResponses.pdf

May 2009 ASBMB Today 23 careerinsights Mastering Microscopes BY BRET L. JUDSON

never imagined that I would one cally challenging because the alga was I day find myself running an imaging calcified. This challenge honed my facility for an Ivy League university. In research and troubleshooting skills, high school, I had envisioned a career both of which would serve me well in in law enforcement and was intent on the future, especially when dealing with going to college for that. Shortly after technically complex microscopes. I also high school, however, I enlisted in the realized that I really enjoyed teach- army and spent a few years at Fort ing, and between undergraduate and Knox and Fort Campbell. I realized Masters work I spent a total of nine that a career in the military was not semesters teaching. for me, but it was a time for me to do I decided to take a break from many things that I would not have the graduate work after spending a Judson chance to do again, like jumping out semester in the Ph.D. program at Bret Judson attended the State of airplanes and driving track vehi- SUNY-Binghamton. To my very good University of New York at Bing- cles. After the army, I spent one year fortune, an opportunity presented hamton, where he earned his at a local community college before itself at the Upstate Medical Center in bachelor’s and master’s degrees. transferring to the State University Syracuse, NY. The position involved a He then worked on an American of New York at Binghamton, where I study investigating the role of inhaled Lung Association-funded study at started my biological studies. particulate matter in the death of the Upstate Medical University in I entered college, as many biology Londoners who expired during the Syracuse, NY for two years, after undergraduates, with an idea of being Great Smog event of December 1952. which he took a position at Cornell “pre-med.” I envisioned myself finish- This was a very exciting project, and University, where he was the ing undergraduate work, going on to I spent the next two years doing pri- laboratory manager for a research medical school and so on. I quickly marily x-ray microanalysis using the lab and also the manager of the realized that this was not the path for SEM on lung tissue from archival tis- departmental transmission electron me. I ended up taking a course load sue specimens. This position made me microscope facility. After more than that favored botany, and I also served realize that I could use the research four years at Cornell, Bret accepted as an undergraduate teaching assis- skills I’d learned through undergradu- a position as the manager of the tant for a few semesters. During my ate and graduate work with something W. M. Keck Bioimaging Labora- senior year, I took a lecture/labora- I really liked, i.e. microscopy, to earn a tory at Arizona State University. In tory course in phycology that utilized living. This particular project ended in the spring of 2008, Bret returned microscopy for a large portion of the a key publication on inhaled particu- to Cornell University, where he is class. If I had to pinpoint a time when late matter and an invited poster at a currently the Director of Imaging for my interest was piqued, that would conference in London, England. the newly founded Weill Institute for be it. I realized that I really enjoyed Shortly before my grant-funded Cell and Molecular Biology. working on and with microscopes. position in Syracuse ended, a position I ended up enrolling in the biology working in the laboratory of William department for my Masters degree with Brown at Cornell University became electron microscopy facility. This was my phycology professor as my thesis available. The position was two-fold: a very exciting position for me as I advisor. I spent the next two years half of my time would be spent as the could continue doing research but doing primarily ultrastructural (TEM lab manager for Bill, and the other could also train users and collaborate and SEM) studies on Jania, a coralline half would be devoted to maintain- with others using TEM. Shortly after alga. My Masters project was techni- ing the departmental transmission I started in this position, Bill Brown

24 ASBMB Today May 2009 careerinsights

and Tony Bretscher jointly purchased co-worker David Lowry, the electron 330-plus days of Arizona sunshine a confocal microscope for their labs, microscopy facility manager, was just would be sorely missed. I had many and I was placed in charge of this as down the hall. fruitful discussions with Scott and well. Light microscopy began to excite Shortly before I left Cornell Uni- Tony, and after a visit back to Cor- me as much as electron microscopy. versity, ground had been broken for a nell in the fall of 2007, we decided to I ended up as a co-author on several new building just adjacent to my old make the trip back to Ithaca. The new publications from Bill’s lab position would be Director and taught countless peo- of Imaging for the recently ple confocal and transmis- endowed Joan and Sanford sion electron microscopy. There are I. Weill Institute for Cell and After over four years in Molecular Biology housed in Bill’s lab, an exciting oppor- the newly opened Weill Hall. tunity opened up at Ari- “ many exciting This exceptional position zona State University. The would combine both light and position was for a man- electron microscopy. ager for the W. M. Keck opportunities in the I returned to Cornell Uni- Bioimaging Laboratory in versity in early 2008, and the the School of Life Sciences. world of research, future looks very promising. This position would involve I have gone back to teaching light microscopy only but and training both light and would also have a teach- and I encourage electron microscopy and have ing component, a graduate already had many interesting level lab course in micros- collaborations. I was also able copy. I decided to accept everyone to pursue to pick up on some projects the position, and my wife where I had left off. The pos- and I moved to Arizona in sibilities of collaborative and the summer of 2006. Was that which they independent studies are what it hot? Yes, but at least it interest me most about my was a dry heat. I certainly current position. Addition- enjoyed my surround- truly enjoy. ally, I enjoy the troubleshoot- ings, especially learning ing and maintenance aspects about unfamiliar plants and animals laboratory. This new building was to of my position. and hiking a variety of landscapes be one of the cornerstones of” Cornell’s As a new undergraduate in biologi- that were quickly accessible. The new life sciences initiatives. Housed cal sciences, I did not envision myself school was a newly founded multi- in this building would be an institute one day running an imaging facility; departmental endeavor with many founded primarily for cell biology. I in fact, I am not sure it even occurred new faculty members. The lab’s user was approached about the possibility to me. I do remember one of my first base was very cosmopolitan, coming of coming back to Cornell University days on campus walking outside of from all over campus and off-campus a short time after having moved to the biological sciences building and as well. I had many exciting times in Arizona. Cornell had hired a direc- seeing a sign for the electron micros- the lab, and teaching the lab course tor for the new institute, Scott Emr, copy facility, and maybe it was then was certainly a highlight of my time and Tony Bretscher, my next-door that a spark was ignited. My position there. The only unfortunate part for lab PI from my previous position at today involves everything I enjoyed in me was that the electron microscopy Cornell, was named the associate school, teaching, and research. There component, which I really enjoyed, director. I was very excited at first, but are many exciting opportunities in the was missing. But I was still able to the thought of moving back across world of research, and I encourage have many stimulating conversations the country so soon after relocation everyone to pursue that which they about electron microscopy as my was difficult to imagine. Also, the truly enjoy.

May 2009 ASBMB Today 25 biobits asbmb journal science

Two Hemes Are Getting under Better than One BH’s Skin Psi factors are fatty acid-derived molecules, generated The natural ability of by enzymes known as psi factor producing oxygenas- our skin to remain es (Ppos), which regulate the balance between sexual hydrated is due to and asexual life cycles in many fungi. Of the three Ppos the presence of nu- in Aspergillus nidulans, PpoA is intriguing because it’s merous hygroscopic predicted to contain two distinct heme domains: an amino acids known N-terminal peroxidase domain and a C-terminal P450 as natural moisturiz- heme thiolate domain. In this article, A. nidulans PpoA ing factors or NMFs. was cloned and expressed in Escherichia coli to better Concentrated in the characterize its biochemical properties. Biochemical epidermal upper Immunofluorescence staining and site-directed mutagenesis studies revealed that layer, these NMFs of human skin tissue shows the PpoA uses both domains to catalyze two separate arise from an insol- co-localization of bleomycin hydrolase (red) and filaggrin (green) in the upper uble protein known reaction steps; the peroxidase domain first oxidizes layer of the epidermis. linoleic acid to (8R)-hydroperoxy-octadecadienoic acid as profilaggrin, (8-HPODE), and then the C-terminal thiolate domain which during the course of epidermal progression is isomerizes 8-HPODE to 5,8-dihydroxy-octadecadieno- first broken down into smaller filaggrin filaments, that ic acid (5,8-DiHODE). This mechanism is quite different are subsequently deiminated (creating citrulline side than that of a related fatty acid dioxygenase in Gaeu- chains), and then further broken down to peptides mannomyces graminis, which has only one predicted and finally individual amino acids. The proteases re- heme domain and converts the 8-HPODE intermediate sponsible for most of these processing steps remain to (7S,8S)-DiHODE. PpoA is similar to other enzymatic unknown, but in this study, the researchers employed partnerships in which separately expressed fatty acid some elegant biochemical analyses to identify bleo- dioxygenases and cytochrome P450s form bioactive mycin hydrolase (BH) as an essential component of products; in PpoA, the final step that generates the free amino acids. though, the roles Immunohistochemical analysis also revealed that of fatty acid perox- BH and filaggrin co-localized in the granular layer of ide production and the epidermis, which, together with some previous its isomerization genetic studies, confirms the role of BH as an NMF are combined in a protease. This study provides valuable insight on single fusion protein, a protein that has been well-known for its ability to making this enzyme detoxify bleomycin-based cancer drugs, but whose Hypothetical catalytic mechanism of A. nidulans PpoA. unique. normal function has remained somewhat elusive.

Identification of PSI Factor Producing Neutral Cysteine Protease Bleomycin Hydrolase Oxygenase A (PpoA) from Aspergillus nidulans Is Essential for the Breakdown of Deiminated as a Fusion Protein of a Fatty Acid Heme Filaggrin into Amino Acids Dioxygenase/Peroxidase and a Yayoi Kamata, Aya Taniguchi, Cytochrome P450 Mami Yamamoto, Junko Nomura, Florian Brodhun, Cornelia Göbel, Kazuhiko Ishihara, Hidenari Takahara, Ellen Hornung, and Ivo Feussner Toshihiko Hibino, and Atsushi Takeda J. Biol. Chem. 2009, published online J. Biol. Chem. 2009, published online March 13 March 13

26 ASBMB Today May 2009 biobits asbmb journal science For more ASBMB journal highlights go to www.asbmb.org/Interactive.aspx

The Conundrum of Breast Cancer Cholesterol Transport Biomarkers The cells in our body continually replace, or “turn Tamoxifen is an anti- over,” the cholesterol present in cell membranes, estrogenic agent that has shuttling the cholesterol to the liver where it can achieved great success be converted to bile acids and excreted from the in the treatment of breast body. For a while, it had been envisioned that the cancer; however, in about ATP-binding cassette transporter A1 (ABCA1) was 50 percent of cases of a key component enabling this reverse cholesterol recurrent disease, tamox- transport, but recent data suggest otherwise. In ifen provides no benefit this study, the researchers use mouse models due to intrinsic resistance, to definitively quantify that functional ABCA1 is and many of the patients not required for cholesterol turnover in peripheral who do respond will even- Hierarchical clustering of organs or in cholesterol excretion. The sterol pool tually develop progressive objective response (OR) and progressive disease (PD) breast in the peripheral organs of both control and abca- disease due to acquired tumor samples. mice was consistently around 2200 mg/kg, and tamoxifen resistance. though there was a marked reduction in the rate Therefore, identifying proteins that associate with ta- of cholesteryl ester movement through HDL to the moxifen resistance would be a vital step toward bet- liver in abca- mice (3.9 mg/day/kg versus normal ter response prediction. In this study, the researchers rate of 44.8 mg/day/kg), neither the total centripetal undertook a comparative proteome analysis of over efflux of cholesterol nor the rate of fecal sterol ex- 5,000 pooled tumor cells obtained through laser cretion was reduced in these animals. So, although capture microdissection (LCM) that contained both ABCA1 still has critical cellular functions such as tamoxifen-sensitive and tamoxifen-resistant tumors. removing cholesterol from macrophages, it appears They identified 100 differentially abundant proteins to play no role in controlling reverse cholesterol between the two tumor types and verified 47 of transport. those through targeted nanoLC-MS/MS. One of the most promising candidates was EMMPRIN, which was more prevalent in therapy-resistant tumors and significantly associated with an earlier tumor progres- sion following first-line tamoxifen treatment. EMM- PRIN and the other differentially expressed proteins may hold potential as biomarkers to identify tamox- ifen resistance in recurrent breast cancer. Flow chart comparing centripetal cholesterol transport in normal and ABCA1-deficient mice (abca- numbers in parentheses). Identification of a Putative Protein Profile Associating with Tamoxifen Therapy Resistance in Breast Cancer ABCA1 Plays No Role in the Arzu Umar, Hyuk Kang, Annemieke M. Timmermans, Centripetal Movement of Cholesterol Maxime P. Look, Marion E. Meijer-van Gelder, from Peripheral Tissues to the Liver Michael A. den Bakker, Navdeep Jaitly, and Intestine in the Mouse John W. M. Martens, Theo M. Luider, Chonglun Xie, Stephen D. Turley, John A. Foekens, and Ljiljana Pasa-Tolic and John M. Dietschy Mol. Cell. Prot. 2009, published online March 27 J. Lipid Res. 2009, published online March 12

May 2009 ASBMB Today 27 sciencefocus Benjamin Neel: Phosphatases and Disease BY NICK ZAGORSKI

very once in a while, Ben Neel could still become Elikes to joke that he peaked too cancerous after a few early. As a vivid example, he recalls months, indicating an incident from 1983. Neel, then some mechanism of conducting the medical portion of his activation. MD/PhD degree at Cornell Medical So what was the School in New York (having just com- activating factor? Neel pleted his PhD at nearby Rockefeller notes that Hayward University), had traveled to Boston proposed the idea that to visit his future wife, who was a ALV was integrating graduate student in the computer near cellular genes, science department at MIT. One day, inducing an overstim- as they were leaving her departmen- ulation of expression tal building, which just happened to and transforming the be located directly across from the cells, which was an newly formed Whitehead Institute, unusual theory back a postdoc in Robert Weinberg’s lab in the 1970s. “Science (the pioneering researcher who first had not yet clearly isolated the ras oncogene and Rb shown that bona fide tumor suppressor gene) approached tumors could arise him and asked, “Hey, didn’t you used solely from activated cellular onco- the remaining viral src with cellu- to be Ben Neel?” genes,” Neel says. “Researchers were lar src to create a fusion gene. Soon The basis for that playful ribbing intent on uncovering how the cellular thereafter, George Vande Woude at stemmed from Neel’s recent ground- genes could get into viruses and help the National Cancer Institute showed breaking graduate studies at Rock- inform the molecular basis for viral that simply attaching the long termi- efeller under William S. Hayward oncogenesis; they hadn’t yet demon- nal repeats (LTRs) that flank retro- on slowly transforming RNA tumor strated that the cellular genes them- viral genes onto a normal cellular viruses. Unlike rapidly transform- selves were a rich source of cancer in gene could be sufficient to promote ing viruses, such as the noted Rous their own right.” transformation. sarcoma virus (RSV), which helped But there were some recent studies So when Neel heard Hayward’s spur two different Nobel prizes to support the idea of cellular trans- idea, it seemed intuitively correct. in medicine, and which drive an formation. For example, Hidesaburo “When I started in the lab, Bill actu- efficient transformation of normal Hanafusa, the head of Rockefeller’s ally gave me two projects,” Neel notes. cells into cancerous ones, avian viral oncology lab where Neel and “One was the work with slow virus leukosis virus (ALV) and other slowly Hayward worked, had demonstrated activation, and the other involved transforming viruses don’t have any that RSV particles missing part of identifying the numerous small RNAs specific “transforming genes,” like their src gene, and thus supposedly that were packaged into retrovi- src in RSV, that can induce rapid cell defective, could still induce cancer in ral particles. But when Bill started growth. However, ALV-infected cells chickens by means of recombining explaining his model, I focused my

28 ASBMB Today May 2009 sciencefocus

energies into those studies because I joined their group. “I actually hadn’t, than succeeded—that may have realized the tremendous implications but it seemed as good a lab as any, reinforced his belief that his best days if we could prove it.” so I decided to pick it.”) Now, just a were behind him. But since beginning In examining numerous ALV- few short years later, Neel stood on his own lab at Harvard in 1988, Neel infected cells, Neel, Hawyard, and the campus of MIT wondering if he has become recognized as a leader collaborator Sue Astrin at Fox-Chase really was washed up before 30. in the field of signal transduction, soon found a connection: the cells “There you have it,” he says wryly, particularly in regard to protein- that eventually became cancerous all “My first two papers were my best, tyrosine phosphatases (the enzymes had similar sites of viral integration. and it’s been all downhill since.” that remove the phosphate modifica- “These slow viruses were inserting tions attached by kinases). “Coming themselves next to a normal gene, A Plethora of PTPs from a background of identifying and thus placing it under control of the Despite his assertions, however, it is analyzing oncogenes, it was a natural highly active viral promoter and an injustice to consider Neel, cur- progression for me to begin look- ratcheting up its expression, which in rently the Director of the Ontario ing into the functional aspects of the turn caused transformation,” proteins encoded by these he says. “What’s more, in all oncogenes,” Neel says. of the tumors, the gene in Researchers were For example, Neel has question was c-myc, which contributed much to our happened to be very simi- “intent on uncovering knowledge of Protein lar to a viral ‘transforming tyrosine phosphatase-1B gene.’” As Neel notes, the how the cellular genes (PTP1B), such as his group’s other shoe had now dropped. could get into viruses findings that this phosphatase This discovery helped localizes on the endoplas- change scientific thinking on and help inform the mic reticulum and is a these cellular “oncogenes” molecular basis for major mechanism by which and the origins of cancer. receptor tyrosine kinases are “In fact, I realized that this viral oncogenesis; inactivated (following their model of ‘promoter inser- endocytosis). In addition, tion’ could be generalized for they hadn’t yet along with Barbara Kahn at other events, like cancer aris- demonstrated that Beth Israel Deaconess Medi- ing because genes switched cal Center, he’s been elucidat- promoters via a chromo- the cellular genes ing PTP1B’s importance in somal translocation,” Neel themselves were a rich regulating glucose homeo- says. “I actually wrote that stasis and its association theory into the first draft of source of cancer in with diabetes and obesity; our paper, but Bill made me and Neel and his postdoc take it out because it was too their own right. Mohamed Bentires-Alj also speculative.” recently demonstrated that Still, it was certainly an ” PTP1B was involved in impressive way to begin a research Cancer Institute as well as a Profes- Her-2/Neu-induced breast cancer. career, especially considering that it sor of Medical Biophysics at the Another significant part of Neel’s really began by accident. (When he University of Toronto, solely for work has been studying src homol- arrived at Rockefeller, Neel didn’t his work done as a graduate stu- ogy domain-containing phosphatase have any specific labs in mind and dent. Admittedly, after finishing his 2 (SHP2), a ubiquitous phosphatase interviewed with several investiga- residency and beginning a postdoc that activates the Ras/Erk signaling tors; then one day several students with Raymond Erikson in 1985, Neel pathway and is a vital component of from Hanafusa’s lab came up to experienced some difficulties—more many developmental processes. As him and said they had heard he had of his postdoctoral projects failed such SHP2 is connected with several

May 2009 ASBMB Today 29 sciencefocus continued human diseases, including Noonan were in fact brought on by different own lab has usually produced studies syndrome and the clinically related biochemical mechanisms: Noonan that didn’t seem important at the time LEOPARD syndrome, inherited syndrome arises from SHP2-hyperac- but have ended up being some of his disorders that result in numerous tivating mutations; whereas in LEOP- most relevant work. growth defects (Noonan syndrome ARD, the mutations create an inactive “In retrospect, one of our most is one of the leading contributors to form of SHP2, revealing that Noonan important studies was carried out by congenital heart disease). Following and LEOPARD are distinct disorders Alana O’Reilly in 2000 on Shp2 acti- up on the work of Bruce Gelb and that manifest in a similar manner. vating mutants,” he says. Initially, that Marco Tartaglia, which identified As he reflects back on his academic project started out simply as an effort that dominant SHP2 mutants were career, though, Neel notes that unlike to test some predictions about SHP2 responsible for these disorders, Neel his PhD project, which he knew would activity that were suggested by the helped show that these conditions be significant, the work done in his crystal structure recently solved by

The domain structure of Shp2 featuring mutations associated with Noonan syndrome (top) and leukemia (bottom); mutants found in both diseases are shown in red. Featured below is a superimposition of the Shp2 crystal structure with the peptide-bound tandem SH2 domain structure, revealing the locations of the various mutations. Neel has focused a good portion of his research into understanding the complex relationship between Shp2 mutations, altered intracellular signaling, and disease pathology.

30 ASBMB Today May 2009 sciencefocus continued Harvard colleagues Scott Pluskey and Steven Shoelson. They created two Out of Focus: Immortality Denied “active” SHP2 mutants and examined While phosphate-removing enzymes have been Neel’s primary focus, their effect on Xenopus frog devel- one of his first major contributions to the signaling arena involved identify- opment; these active phosphatases ing a novel protein kinase that could be induced by serum (he and fellow could induce elongation in embryo postdoc Dan Simmons carried out this work during his time with Erikson). cells similar to what would happen Naturally, Simmons and Neel named this protein serum-inducible kinase if fibroblast growth factor (FGF) had or SNK. “Of course, it didn’t escape our attention that SNK could also been added. stand for ‘Simmons-Neel kinase,’ giving us a permanent fixture in the “Little did we realize that this scientific literature.” Unfortunately, their immortality would be short-lived; it paper would anticipate and explain was subsequently discovered that SNK was just one member of a larger how the SHP2 gain of function Polo-like family of kinases, and a few years after its discovery, SNK was mutants that cause Noonan syndrome renamed PLK2 so that all the Polo-like kinases would have consistent operated,” he says, referring to one nomenclature. of his newest discoveries in which he uncovered the mechanism explain- ing the cardiac defects brought on by Noonan syndrome: an excess of decided to head in a new direction in research in Boston is so staggering SHP2 activity in the endocardium order to bring back some of that per- that it’s not even the case that there’s (the inner layer of the heart) causes sonal side of science. “Having gradu- someone in every area of study; excessive valvular mesenchyme ated as an MD/PhD, I felt I had a there’s probably four or five people production, resulting in defective duty to undertake more translational in every area of study,” he says. “And heart valves (similar disruptions in research,” he says. “I also wanted an it reaches a point where intellectual the developing neural crest cause the opportunity to have a bigger impact space can get pretty crowded.” And he facial abnormalities). than just running my own lab.” also adds that Toronto, which features The very first paper from his group, That impact would be found researchers like Tak Mak and recent in which they demonstrated that the as Director of the Ontario Cancer Kyoto Prize winner Anthony Pawson, expression of the retinoid receptor Institute (OCI), Canada’s largest is no slouch when it comes to hosting RAR-beta was frequently defective in cancer center—thus making his move smart and intellectual people. lung tumors, is another fine example. quite significant at both the personal And with the numerous well- “Later work showed that RAR-beta and professional levels. And it has run hospitals and clinics in the city, induction in response to retinoids was required a bit of adjustment. “From Toronto also provides a large patient a good marker to test whether patients the visits I took before moving here, I and sample population that Neel sees would respond to retinoid chemo- had the impression that Toronto was as a tremendous resource. “One of my prevention therapy,” Neel says. “So basically New York with a little less main long-term goals as director is to our work had an important clinical crime and pollution,” he says. “But create a platform that brings our basic impact, but it’s something we don’t get in my first year, I have noticed that researchers and clinicians together, credit for because our lab has been so there is definitely a different culture so we can better utilize our clinical strongly associated with the phos- here.” One major difference Neel population and speed up the transla- phatase field.” highlights is that, despite its status as tion of our exciting work in cancer a metropolis, Toronto has a far less genetics to the patients,” he says, cit- North by Northwest stressed atmosphere than major cities ing the work Massachusetts General As in many cases, Neel’s interest in in the Northeastern United States Hospital has begun in genotyping cancer biology has a personal side; (and having lived most of his life in tumors to test for genes that may one of his major motivations for Philadelphia, New York, or Boston, correlate with clinical outcome as choosing medicine was experienc- Neel doesn’t mind this change). an example. To help with this effort, ing many family members succumb And although Neel will miss the Neel is refocusing and recharging the to this disease, especially his grand- extremely high concentration of “sci- OCI to make it more interactive, a mother Ida whom he was close to entific dynamism” present in Boston, task that includes hiring several new growing up. So in 2007, after a distin- he points out this can be both good faculty members. guished tenure in basic research, Neel and bad. “The depth and breadth of On the research side of things,

May 2009 ASBMB Today 31 sciencefocus continued Neel has continued his studies into working at the Division of Stem Cell References Araki, T., Chan, G., Newbigging, S., Morikawa, L., phosphatases, and in addition to and Developmental Biology, he too Bronson, R. T., and Neel, B. G. (2009) Noonan using the great clinical resources frequently heard the question: “Oh, Syndrome Cardiac Defects Are Caused by PTPN11 Acting in Endocardium to Enhance available, he is taking advantage of are you moving to Canada because Endocardial-Mesenchymal Transformation. Proc. Natl. Acad. Sci. U. S.A. 106, 4736– a local strength in proteomics to of Bush and the restrictions on 4741. get a broader view of phosphatase stem cells?” Much like the ques- Xue, B., Kim, Y. B., Lee, A., Toschi, E., Bonner- Weir, S., Kahn, C. R., Neel, B. G., and Kahn, substrates and binding partners tion posed by Weinberg’s postdoc B. B. (2007) Protein-Tyrosine Phosphatase 1B in order to answer questions such Deficiency Reduces Insulin Resistance and many years ago, this one took him the Diabetic Phenotype in Mice with Polygenic as why the opposite SHP2 defects slightly aback; while not getting Insulin Resistance. J. Biol. Chem. 282, 23829–23840. underlying Noonan and Leopard overly political, Neel thinks that Kontaridis, M. I., Swanson, K. D., David, F. S., syndromes produce such similar some people, including scientists, Barford, D., Neel, B. G. (2006) PTPN11 (Shp2) Mutations in LEOPARD Syndrome have phenotypes. Neel has also decided have been overly dramatic about the Dominant Negative, Not Activating, Effects. J. Biol. Chem. 281, 6785–6792. to use his move to Toronto and the stem cell controversy. Fortunately, O’Reilly, A. M., Pluskey, S., Shoelson, S. E., and associated clinical population to Neel didn’t have to worry about Neel, B. G. (2000) Activated Mutants of SHP-2 Preferentially Induce Elongation of Xenopus initiate a study into cancer stem any political discussions because he Animal Caps. Mol. Cell. Biol. 20, 299–311. cells, particularly in identifying and could always reply, “No, it was just Gebert, J. F., Moghal, N., Frangioni, J. V., Sugarbaker, D. J., and Neel, B. G. (1991) characterizing the native stem cell a matter of finding a great opportu- High Frequency of Retinoic Acid Receptor populations in solid tumors such as Beta Abnormalities in Human Lung Cancer. nity in a great location.” Oncogene 6, 1859–1868. ovarian and lung cancers, as well as Neel, B. G., Hayward, W. S., Robinson, H. L., in leukemia. Fang, J., and Astrin, S. M. (1981) Avian Nick Zagorski is a science writer Leukosis Virus-induced Tumors Have Of course, he notes that when at ASBMB. He can be reached at Common Proviral Integration Sites and Synthesize Discrete New RNAs: Oncogenesis he mentioned that he would be [email protected]. by Promoter Insertion. Cell 23, 323–334. Your KEY to Success in ASBMB Biochemistry and Molecular Biology

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