July 2010 ASBMB PreSidentiAl PriMer: Suzanne Pfeffer American Society for Biochemistry and Molecular Biology AAdjuvdjuvAAntnt IImmunothermmunotherAApypy ususIIngng KKrnrn70007000 KRN7000 (α-Galactosyl Ceramide) Avanti Number 867000 Supplier: Funakoshi Co. Ltd. Hepatic metastasis is a major clinical problem in cancer treatment. We examined antitumor ac- tivity of alpha-galactosylceramide (KRN7000) on mice with spontaneous liver metastases of re- ticulum cell sarcoma M5076 tumor cells (spontaneous metastasis model). In this model, all mice that were s.c. challenged with one million tumor cells developed a solid s.c. mass by day 7 and died of hepatic metastases. In the current study, we administered 100 microg/kg of KRN7000 to the model mice on days 7, 11, and 15. This treatment suppressed the growth of established liver metastases and resulted in the prolongation of survival time. Fluorescence-activated cell sorter analysis of phenotypes of spleen cells, hepatic lymphocytes, and regional lymph node cells around the s.c. tumor revealed that CD3+NK1.1+ (NKT) cells increased in hepatic lym- phocytes of the KRN7000-treated mice. Cytotoxic activity and IFN-gamma production of hepatic lymphocytes were augmented in comparison with those of spleen cells and regional LN cells. At the same time, interleukin (IL)-12 production of hepatic lymphocytes was markedly enhanced. Neutralization of IL-12 using a blocking monoclonal antibody diminished the prolonged survival time. These results showed that the in vivo antitumor effects of KRN7000 on spontaneous liver metastases were dependent on the endogenous IL-12 production, where NKT cells in the liver are suggested to be involved. Adjuvant immunotherapy using KRN7000 could be a promising modality for the prevention of postoperative liver metastases. Fuji, N., Y. Ueda, H. Fujiwara, T. Toh, T. Yoshimura, and H. Yamagishi. (2000). Antitumor effect of alpha-galactosylceramide (KRN7000) on spontaneous hepatic metastases requires endogenous interleukin 12 in the liver. Clin Cancer Res 6:3380-7. Visit our new E-commerce enabled web site for more details www.avantilipids.com or Email us at [email protected] from reseArch to cgmp productIon - AvAntI’s here for you contents July 2010 On the Cover: Learn more about ASBMB’s 82nd society news president. 2 Letters to the Editor 16 3 President’s Message 5 Washington Update 6 News from the Hill 9 ASBMB News A retrospective on Leon A. Heppel. 9 New Council and Committee Members 12 11 ASBMB Receives NSF Award 12 Retrospective: Leon A. Heppel (1912-2010) 14 Member Spotlight feature stories 16 ASBMB Presidential Primer: Suzanne Pfeffer in every issue 18 Meetings 18 The Three Rs Phosphoinositide Signaling: Getting 20 The Life of Proteins to the Root of the from Womb to Tomb Matter. 22 Structural and Mechanistic 36 Enzymology 24 Chromatin and Transcription: a Symbiotic Relationship 26 NIGMS Introduces New PSI:Biology Initiative 27 World Science 28 Education 28 False Choices 30 Uphill, Both Ways, in the Snow 32 BioBits 34 Career Insights asbmb today online 36 Lipid News Last month we ran a story on biochemistry rap artist Tom McFadden. Now, you can view a follow up videocast with McFadden at http://bit.ly/b6Spsl. July 2010 ASBMB Today 1 letters to the editor A monthly publication of The American Society for Basic versus given in defining basic research as Biochemistry and Molecular Biology something without evident trans- Officers lational components. This is the Suzanne R. Pfeffer President Translational Gregory A. Petsko Past-president base line required for translational Mark A. Lemmon Secretary Research Merle S. Olson Treasurer research. We need much more data Council Members Dear Greg, on the molecular mechanisms asso- Karen N. Allen Ruma V. Banerjee ciated with normal homeostasis in Dafna Bar-Sagi Benjamin F. Cravatt In your May President’s Message, human biology, as well as the change Michael A. Marletta Thomas E. Smith discussion continues on the apparent Ann M. Stock Jonathan S. Weissman involved in the disease process. In lack of support of “basic research” Ex-Officio Members this regard, our “basic research” has Peter J. Kennelly versus “translational research” by Chair, Education and Professional led to new models of the interactions Development Committee the National Institutes of Health. I’m of lectins with cell surface glycans Kuan-Teh Jeang concerned because this affects our Daniel M. Raben of pathogens in innate immunity (1) Co-chairs, Meetings Committee research into the molecular basis of John D. Scott and cellular homeostasis in meta- Chair, Membership Committee lectin-carbohydrate interactions in zoans (ground state for health) (2). Craig E. Cameron cellular recognition (glycobiology), Chair, Minority Affairs Committee These findings are a result of more Laurie S. Kaguni which, until recently, was supported 2011 Annual Meeting Program Coordinator than 30 years of basic research! William C. Merrick by the National Cancer Institute for Chair, Public Affairs Advisory Committee For future discussion, you may 30 years. Toni M. Antalis consider the effects on NIH funding Chair, Publications Committee So, let’s examine the linguistic Herbert Tabor of having predominantly one sector Editor, JBC claims that basic and translational Ralph A. Bradshaw of science define equilibrium and A. L. Burlingame research are separate efforts. In Co-editors, MCP nonequilibrium chemical interac- the present context, let’s define Edward A. Dennis tions in humans. Joseph L. Witztum “basic research” as studies of bio- Co-editors, JLR logical processes and the molecules Sincerely, ASBMB Today Editorial Advisory Board Fred Brewer Alex Toker (Chair) Greg P. Bertenshaw involved. “Translational research” Albert Einstein College Craig E. Cameron A. Stephen Dahms can be defined as studies that target of Medicine Irwin Fridovich Richard W. Hanson Elizabeth A. Komives Bettie Sue Masters the molecular basis of disease, with References Luke A. O’Neill Duanqing Pei 1. Tadano-Aritomi, K, Kubo, H., Ireland, P., Carol C. Shoulders Robert D. Wells the hopeful goal of a “cure.” How- Hikita, T., and Ishizuka, I. (2010) Isolation and Characterization of a Unique Sulfated Ganglioside, ASBMB Today ever, finding cures for diseases such Sulfated GM1a, from Rat Kidney. Glycobiology 20, 270 – 278. Nicole Kresge Editor as cancer requires understanding 2. Glycobiology, in press. [email protected] Nick Zagorski Science Writer the alteration of normal cellular [email protected] processes to the transformed state Nancy J. Rodnan Director of Publications [email protected] and then changing the latter to the The President’s Barbara Gordon Executive Director former. Thus, both the disease state [email protected] Farewell and normal state need molecular For information on advertising, contact Capitol Media Solutions at 800-517-0610 definition, which requires research Dear Editor, or [email protected] into both. In other words, you can’t Our outgoing (in both senses) fix something unless you understand president penned a lovely farewell in what the differences are. (Auto- the June issue of ASBMB Today. He www.asbmb.org mobile mechanics know this well.) was as engaged and creative as any Thus, both basic and translational ASBMB leader in recent years. I wish research need NIH support because to add my view that his monthly col- they are interlocked scientifically. It follows that care needs to be continued on page 7 2 ASBMB Today July 2010 president’smessage Your ASBMB BY SUZANNE PFEFFER t is a special honor and a privilege to begin my term Under the watchful eye of Merle Ias president of the American Society for Biochem- Olson, our finance committee has istry and Molecular Biology. Our outgoing president, done a wonderful job of shepherd- Greg Petsko, deserves an enormous thank you from ing the society’s reserve funds all of us— for guiding the society so ably and for that have now recovered to pre- making us feel that we really are a part of ASBMB by economic downturn levels. These funds support all of writing such engaging, thought-provoking and humor- our activities, including staffing and production of our ous columns. He has been a terrific role model, and journals, as well as enabling the Undergraduate Affili- his shoes will be impossible to fill. Luckily, for all of us, ate Network Committee, Minority Affairs and Education Greg will continue to serve as an officer of the society and Professional Development Committees (UANC led for an additional year, in the role of past-president. I by Neena Grover, MAC led by Craig Cameron and EPD am especially grateful that I will be able to rely on his by Ellis Bell followed by Peter Kennelly) to offer 316 wise counsel during my term. travel or child care fellowships for students, postdocs I hold a special place for ASBMB in my scientific and faculty to attend our 2010 annual meeting. Thanks heart. I had the privilege of starting my life as a bio- to all of the members of these committees for excellent chemist while still an undergraduate student, first dur- program contributions during the meeting in Anaheim. ing a brief summer stint with Don Lightfoot at Virginia The Public Affairs Advisory Committee, led by Bill Polytechnic Institute and State University and then Merrick, has dedicated itself to forging new relation- returning to my undergraduate University of California, ships with members of U.S. Congress, as well as with Berkeley, campus and the lab of Mike Chamberlin, representatives of all of the institutes at the National where I worked on Escherichia coli RNA polymerase Institutes of Health and with key program directors for two years. My project culminated in a first author at the National Science Foundation. The commit- paper in the Journal of Biological Chemistry. At the tee’s main focus this year has been to work to ensure time, several of the Berkeley faculty members were the continued prioritization of investigator-initiated JBC editorial board members, and I remember asking research.