an interview with the 2007 milstein award winner, dr...

August, 2007

ISICR OfficersPresidentOtto Haller

President-ElectEleanor FishSecretaryTom Hamilton TreasurerBob Friedman

Executive DirectorJohn Lord

Future ISICR Meetings

Sept. 15, 2007(History of the Interferons)

Sept. 16-19, 2007Oxford, UK

2008 MeetingJoint ISICR/ICS

Montreal, CanadaOct. 12-16

www.cytokines2008.org

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Seng-Lai (Thomas) [email protected]

INTERNATIONAL SOCIETY FORINTERFERON AND CYTOKINE RESEARCH

August 2007Volume 14, No. 2

An Interview with the 2007 MilsteinAward Winner, Dr. Shizuo AkiraThomas Tan

Dr. Shizuo Akira is a Professor at theResearch Institute for MicrobialDiseases at Osaka University, Japan(since 1999), and also a project directorof AKIRA Innate Immunity, ERATO(Exploratory Research for AdvancedTechnology) of Japan Science andTechnology Corporation (JST) (since2002). He received his M.D. in 1977,and Ph.D. in 1984 from OsakaUniversity. After two years of postdoc-toral working in Department of

Immunology, University of California at Berkeley, he started toinvestigate IL-6 gene regulation and signaling in the Institute forMolecular and Cellular Biology, Osaka University, and cloned thetranscription factors, NF-IL6 and STAT3. He was a Professor inDepartment of Biochemistry, Hyogo College of Medicine from 1996to 1999, where he became involved in Toll-like receptor (TLR)research. His current research interests are molecular mechanisms ofhost defense and innate immunity, and as part of these studies, he hasgenerated many important knockout mice. In 2006 and 2007 he wasrecognized as the hottest scientist who had published the greatestnumber of 'Hot Papers' (11 papers) over the preceding two years. Heis the recipient of several international awards, including the RobertKoch Prize and the William B. Coley Award.

ISICR: Congratulations on receiving the Milstein Award. Wherewere you when you first learned that you have been selected byISICR to receive the prestigious Award?

SA: In my office. Professor Paula Pitha-Rowe called to inform methat I have been selected as the winner of the Milstein Award 2007.

(Continued on Page 2)

(Dr. Shizuo Akira, cont. from page 1)

ISICR: What does the Award mean to you?

SA: Interferon research was and now is very strongin Japan. Indeed, we already have famous Japaneseresearchers as Milstein Awardees. I am very honoredto be included in such prominent list, and proud ofthe internationally high standard of interferonresearch in Japan.

ISICR: What do you feel are your most importantcontribution to the field of cytokine research?

SA: Identification of TLR9 as CpG DNA receptor.

ISICR: And if you have to pick one TLR member orpathway, which one would you target for therapy?

SA: Of course, TLR9. I have high hopes for TLR9stimulating molecules in vaccine development, aller-gy treatment, and cancer immunotherapy.

ISICR: You also made seminal discoveries on IL-6and STAT3. Which disease indications do you thinkwould best benefit from therapies targeting IL-6 andSTAT3 pathways?

SA: IL-6 is now found to be an essential cytokinewhich drives Th17 response. Blockade of IL-6 actionor STAT3 signaling will be useful for treatment ofchronic inflammatory diseases and autoimmune dis-eases.

ISICR: What ignited the fire in you to become a sci-entist? Who was your mentor or role model in yourscientific career?

SA: I was initially trained as a medical doctor, andpracticed two years in a municipal hospital aftergraduation. I wanted to do research, and decided topursue graduate studies at Osaka University, MedicalSchool. My mentor was Professor TadamitsuKishimoto, who was studying B cell differentiationand discovered IL-6. In order to learn moleculartechnology, I was sent to the lab of Professor TasukuHonjo, who was a professor in the Department ofGenetics at Osaka University. The encounter with

2 International Society for Interferon and Cytokine Research

both superb scientists determined my fate to becomea scientist.

ISICR: Thinking back, how has the trajectory ofyour Ph.D. pursuit influenced your career choicesand present position?

SA: I think two things during my PhD course influ-enced my career choices and present position. One isthat I could publish my experimental results in Celland EMBO journal as the first author and Nature asthe second author. The other is I met two distin-guished immunologists, Professors Kishimoto andHonjo, and I was much influenced by their personal-ities and their achievements.

ISICR: You were a postdoctoral fellow at theUniversity of California-Berkeley. Was this yourfirst trip to the US? Any cultural shock?

SA: That was my first trip to the US. I had not expe-rienced cultural shock much because Japan wasalready immersed with American culture. But I haddifficulty in communicating in English.

ISICR: You have authored and co-authored over 500papers, and you're one of the most cited immunolo-gists. How did you do it?

SA: For one, the generation of various knockoutmice increased the number of papers because themice are utilized in other laboratories in a collabora-tive manner. And I always searched the next targetfrom the results obtained by knockout mice. Forinstance, we found by chance that MyD88 knockoutmice are unresponsive to LPS. This got me involvedin innate immunity research. Then, we started toknock out all receptors which might use MyD88 asadaptor, including IL-1 receptors family and Toll-like receptors. Once it was shown that TLR4 is anLPS receptor, the next question became what wasthe role of other TLRs. We searched for manyimmunostimulants which activate immune cells toproduce cytokines. Step by step we identified theligand recognized by individual TLRs. We thennoticed that LPS still activates NF-κB in the absenceof MyD88. We searched for the genes which areinduced in response to LPS in MyD88 knockout

(Dr. Shizuo Akira, cont. from page 2)

mice and found interferon-inducible genes. We alsoexpected the presence of MyD88-related molecules,and mined for such molecules in database, and foundseveral genes, and started knocking them out as wellin mice, and uncovered their role. Our main strategyis to find out the next research target from the pheno-type of knockout mice before embarking on the invitro experiments.

ISICR: If you weren't a scientist, what would you be?

SA: Medical doctor. Perhaps a novelist, but I know Iwill not become a good writer.

ISICR: What's your idea of relaxation?

SA: I like to read novels.

ISICR: Can you describe the research environment atOsaka University?

SA: The building is old, and the space of my lab issmall. The University is constructing a new building,which is scheduled to be completed by April, 2009,and my lab will move to the new building.

ISICR: What are your current priorities?

SA: To continue the high quality of our publications,but it does not mean to simply publish papers inhigh-impact journals.

ISICR: What are you most looking forward to at thisyear's ISICR Annual Meeting in Oxford?

SA: New findings regarding the DNA sensors.

ISICR: And that's why you're a highly cited immu-nologist--always working and always on the lookoutfor the next target! Thank you for your time, Dr.Akira.

SA: My pleasure.

August, 2007 3

ISICR AwardsThe Seymour and Vivian Milstein YoungInvestigator Awards The Milstein Young Investigator Awards are present-ed to ISICR members who have made notable contri-butions to either basic or clinical research within 8years after receiving their Ph.D or M.D.. This awardis provided by a generous gift of the Milstein Family.

2007 Young Investigator Awards

Luis Martinez-SobridoMount Sinai School of Medicine

Vladimir Hurgin,Weizmann Institute of Science

Andrea K. EricksonUniversity of Texas Southwestern Med Ctr - Dallas

Jesper B. AndersenNational Institutes of Health, USA

Brenda L. FredericksenUniversity of Maryland

The Christina Fleischmann Memorial Award toYoung Women Investigators Eligibility: The rulesfor this ISICR award are the same as for theSeymour and Vivian Milstein Young InvestigatorAward (see above) except for gender and that candi-dates within 10 years after receiving a PhD or M.D.degree. Every year the Christina FleischmannMemorial Award is presented to a young womanISICR member who has made notable contributionsto either basic, translational or clinical research.This award is made possible through the generosityof the Fleischmann Foundation and is dedicated tothe memory of ISICR member and outstanding inter-feron research scientist Christina Fleischmann.

2007 Christina Fleischmann Awardee

Nancy JewellColumbus Children’s Research Institute


Distinguished Scientist and runs a busy laboratory inthe Lerner Research Institute. Dr. Stark was electedto the National Academy of Sciences (USA) in 1987and became a Fellow of the Royal Society (London)in 1990. In October 2002, he was elected to theInstitute of Medicine of the National Academy ofSciences. Dr. Stark is also a winner of the ISICRMilstein Award.

Major objects of research conducted by Dr. Starkinclude the interferons, pathways that activate orrepress the transcription factor NFκB and stress-induced pathways that activate the tumor suppressorprotein p53 and pathways that respond to activatedp53.

2007 ISICR Honorary Members

Dr. Ian KerrDr. Ian Kerr has had a long andvery distinguished career study-ing the mechanism of action ofthe interferons. Obtaining hisPhD in 1963, he did postdoctor-al work at Stanford and MIT,and was a group leader at the

MRC National Institute of Medical Research formany years before moving to Lincoln's Inn Fields in1980. Dr. Kerr has made numerous ground breakingcontributions to our understanding of how interfer-ons alter cellular behaviour. These include the dis-covery of 2-5A, the 2'-5' oligoadenylates which acti-vate RNA degrading enzymes as part of the interfer-on response; the identification and characterizationof interferon-responsive genes; and the application ofsomatic cell genetic approaches to elucidate signaltransduction pathways controlling interferon-inducedgenes. Dr. Kerr was made a Fellow of the RoyalSociety in 1985, and amongst other awards has twicereceived the ISICR Milstein Award. Dr. Kerr retiredin 2005 as a senior group leader at Lincoln's InnFields, London Research Institute. (Info copied fromthe 2005 London Research Institute Annual Report).

Dr. George StarkDr. George Stark graduated inChemistry from ColumbiaUniversity and became a post-doctoral fellow at theRockefeller University. He thenwent to Stanford University andeventually became a Professor of

Biochemistry. In 1983 he moved to the ImperialCancer Research Fund in London as AssociateDirector of Research. Dr. Stark joined The ClevelandClinic Foundation in 1992, as Chairman of theLerner Research Institute, a position he held untilAugust 2002. He currently holds the title of

THE ISICR SLIDE REPOSITORY

Ever see a slide in a talk that you wish youcould use for your own presentation? Wellnow this may be possible through the ISICRSlide Repository. Members can now go inand post slides that they have developed ordownload slides that others have provided tothe membership. OVER 280 SLIDES ARENOW AVAILABLE!!!!!! For this memberonly feature, you need to have your membernumber so if you are not sure what that is,please contact the membership office. We urge members to upload general slides thatother members can use for lectures, classes,seminars, etc. Slides are not to be changedwithout permission from the donor and allcopyright permissions must be obtained. Therepository now has a useful search capabilitythat allows you to find slides on a particulartopic. If you have trouble uploading or down-loading slides, please contact Howard Youngat [email protected].

PLEASE CONSIDER CONTRIBUTINGYOUR SLIDES. The success of this initia-tive depends upon you, the membership!!!!

NEW ISICR MEMBERS

August, 2007 5

We welcome these members to the ISICR and welook forward to their participation in the annualmeeting and ISICR committees and activities.

Joined March 2007 thru July 2007

Jessica Kaplan AltmanNorthwestern Univ, USA

Gila Arad Hebrew Univ of Jerusalem, Israel

Glen N. BarberUniv of Miami, USA

Sonja Marie Best Natl Inst of Allergy & Infect Dis, NIH, USA

Danielle BrabantLaurentian Univ, Canada

Daniel BurkeUniv of Toronto, Canada

Krisztina Kormondine Buzas NIH/NCI-Frederick, USA

Mei Po Chan Univ of Hong Kong-LKS, China

Ridong Chen HumanZyme Inc, USA

Maria Vincenza ChiantoreIstituto Superiore di Sanita, Italy

Sharon Sue Wen ChowPOWH & UNSW Rsch Labs, Australia

Ricardo Roque CibottiMedImmune Inc, USA

Troy ClineOhio State Univ, USA

Alfred CoreyHuman Genome Sciences, Inc, USA

Blossom DamaniaUniv. North Carolina-Chapel Hill, USA

Valentina D'EscamardNew York Univ Sch of Med, USA

Nicole Anne De WeerdMonash Inst of Med Rsch, Australia

Mark Stephen Diamond Washington Univ Sch of Med, USA

Lasse Dissing-OlesenUniv of Southern Denmark

Linda DixonInst for Animal Hlth Pirbright Lab, UK

Raymond Peter DonnellyFDA CDER, USA

Jamila El BougriniCNRS, France

Andrea Kaup Erickson Univ of Texas Southwestern Med Ctr-Dallas, USA

(New Members, cont. from page 5)

Felix Ivanovich ErshovGamaleya Inst for Epid & Microbiol, Russia

Joyce EskdaleHumigen, USA

Michele FiscellaHuman Genome Sciences, Inc, USA

Eugene FriedmanNew York Univ Sch of Med, USA

Dirk R. GewertBioLauncher Ltd, UK

Gael GibbsMurdoch Univ, Australia

Leorid GratovskiyNew York Univ Sch of Med, USA

Seda S. GrigorianGamaleya Inst for Epid & Microbiol, Russia

Diego A. JaitinWeizmann Inst of Sci, Israel

Danlin JiaUniv of Toronto, Canada

Cecilia Johansson Imperial College London, UK

Susan JohnKings Col London, UK

Adam Joseph KarpalaAustralian Animal Hlth Lab

Surinder KaurNorthwestern Univ, USA

HeeSun Kim Yeungnam Univ Col of Med, Korea

Hyon-Suk KimYonsei Univ Col of Med, Korea

Yeon Hyang KimHallym Univ, Korea

Barbara KroczynskaNorthwestern Univ, USA

Thomas Kuri Inst for Med Microbiol & Hygiene, Germany

Guy Lemay Univ de Montreal, Canada

Xikui LiuMD Anderson Cancer Ctr, USA

Stephen LocarniniVIDRL, Australia

Rhiannon May Lowe Imperial College/GSK, UK

Dorthe LundsgaardNovo Nordisk A/s, Denmark

Uwe MarxProBioGen Ag, Germany

Jacqueline M. McBrideGenentech, USA

Jia MengNew York Univ Sch of Med, USA

Frederique MichelInst Pasteur, France

Jehangir S. MistryMillipore Corp, USA


Anthony SadlerMIMR, Australia

Sandra Marie SchaalUniv. of Miami Miller Sch of Med, USA

Federico SeranaLaboratorio di Biotecnologie-Spedali Civili Med, Italy

Veronika SexlUniv Vienna, Austria

George Mariane SoaresFiocruz, Brazil

Phillip StumblesMurdoch Univ, Australia

Tomohiko SuzukiToray Industries Inc., Japan

Manuel VegaNautilus Biotech, France

Eugenia N. VyhlovaGamaleya Inst of Epidemiol & Microbio, Russia

Dakang XuMonash Inst of Med Rsch, Australia

Jae-Kwang YooUniv of Toronto, Canada

Chia-Yi YuAcademia Sinica, China

Zhenghong YuanFudan Univ-Shanghai Med Col, China

Fuquan ZhangInst for Animal Hlth Pirbright Lab, UK


Takashi MoriguchiKyoto Univ Grad Sch of Pharm Sci, Japan

Bei MorrisonCleveland Clinic Fnd, USA

Bindukumar B. NairSUNY Buffalo, USA

Yu NakashimaKyoto Univ Grad Sch Parm Sci, Japan

Shreeram Chakravarthy NallarUniv of Maryland Sch of Med, USA

Anatoliy Davidovich NamgaladzeFarmaclon Ltd, Russia

Roza I. NurievaMD Anderson Cancer Ctr, USA

Atsushi OkumuraUniv of Pennsylvania, USA

Manjing PanUMDNJ-Robert Wood Johnson Med Sch, USA

Inger Lund PedersenNovo Nordisk, Denmark

Yann PercherancierC.N.R.S., France

Penny PowellUniv of East Anglia, UK

Katrin RamsauerMed Univ of Vienna, Austria

Amanda J. RedigNorthwestern Univ, USA

August, 2007 7


Antonia Percario ZulemaUniv Degli Studi Roma Tre, Italy

Claudia ZylberbergAkron Biotech, USA

Linda Dixon, Ph.D.Head, African swine fever virus group, Institute forAnimal Health, Pitbright, UK

Dr Linda Dixon studied for her PhD in the Dept ofMolecular Biology, University of Edinburgh,Scotland. She carried out postdoctoral research atthe University of Edinburgh and the FriedrichMiescher Institute, Basel Switzerland before joiningthe staff at the Institute for Animal Health,Pirbright, UK to establish a group working onAfrican swine fever virus. Her research hasinvolved characterising the genomes of ASFV iso-lates of different pathogenesis and functional analy-sis of the encoded proteins. The main focus hasbeen on virus encoded proteins involved in evasionof host defences. This large DNA virus replicates inmacrophages and encodes a number of proteinswhich interfere with signalling pathways. One pro-tein studied by her lab, A238L, acts to inhibit bothNF-kB dependent gene transcription and calcineurinphosphatase activity. A second protein, CD2v, is atransmembrane protein with an extracellulat domainthat resembles the host CD2 but differs in the cyto-plamsic domains. Her lab has worked on interac-

tions of the cytoplasmic domain of CD2v with hostproteins. Recently several ASFV proteins whichinhibit type I interferon induction have been identifiedand ongoing work is involved in defining their mech-anism of action. Another area of research is in the useof porcine microarrays to study macrophage respons-es following infection and to evaluate the role of indi-vidual virus proteins in modulating host gene expres-sion. The knowledge gained from studies on genesinvolved in immune evasion and virulence is beingapplied to the rational development of candidateattenuated virus vaccines by sequential gene deletion.

Reason for joining ISICR“Being a member of ISICR will provide an opportuni-ty for me to learn from and interact with scientistsworking both on the basic mechanisms involved ininterferon and cytokine signalling as well as thoseinterested in how viruses manipulate these responses.”

New Member Minibios Gilla Kaplan, Ph.D.Head, Laboratory ofMycobacterial Immunity andPathogenesis Public Health Research Institute225 Warren Street, Newark, NewJersey 07103-3535Telephone: [email protected]

Dr. Gilla Kaplan earned a PhD degree from theUniversity of Tromso, Norway. Postdoctoral trainingwas undertaken as a Fogarty International Fellow inthe Laboratory of Cellular Physiology andImmunology at the Rockefeller University where shesubsequently held the positions of Assistant andAssociate Professor.

Dr. Kaplan is currently head of the Laboratory ofMycobacterial Immunity and Pathogenesis, at thePublic Health Research Institute (PHRI), in Newark.She was appointed full Member at PHRI in 2002. Dr.Kaplan also holds the positions of Professor ofMedicine at UMDNJ and honorary Professor ofMedicine, at the University of Cape Town, SouthAfrica. She serves as Advisor to The HeiserProgram for Leprosy and Tuberculosis and The


(New Members minibios, cont. from page 8)

Institute of Infectious Diseases and MolecularMedicine, Cape Town, South Africa..

Internationally recognized for her many contribu-tions to the field of infectious disease immunology,Dr. Kaplan, a member of the American Academy ofMicrobiology, is also a member of many scientificadvisory committees and editorial boards. She hasbeen an invited speaker at international scientificcolloquia focusing on infectious diseases, innateimmunology, cytokines, HIV and vaccine develop-ment.

Dr. Kaplan's laboratory has been at the forefront ofdissecting the cellular and molecular mechanismsgoverning immune responses to pathogenic micro-organisms, such as Mycobacterium tuberculosis. Dr.Kaplan is the author of over 150 publications inpeer-reviewed scientific journals, as well as numer-ous monographs, book chapters and review articles.

join the ISICR when we celebrate the 50th anniver-sary of the discovery of interferons."

Daniela Verthelyi, M.D. Ph.D.Principal InvestigatorLaboratory of Immunology,Division of Therapeutic Proteins,Center for Drug Evaluation andResearch, Food and DrugAdministration, 8800 RockvillePike, Bethesda, MD 20892

Dr. Verthelyi received her M.D. degree from theUniversity of Buenos Aires, Argentina, in 1988, andher Ph.D. degree in Immunology from the Virginia-Maryland Regional College of Veterinary Medicineat Virginia Tech in 1996. During this phase of hercareer, her research focused on understanding theeffects of sex hormones on B cell homeostasis. Shewas the first to show that chronic exposure of non-autoimmune mice to estrogen leads to B cell hyper-activity and increased expression of auto-antibodiesthat are associated with systemic lupus and anti-car-diolipin syndrome. Following completion of her doc-toral research, Dr. Verthelyi joined the laboratory ofDr. Dennis Klinman, where she described, a newclass of immunostimulatory DNA, called CpG ODNtype D, which selectively induce the production ofIFN-a by human plasmacytoid dendritic cells and thematuration of monocytes into dendritic cells. Usingthese, she developed the first model of CpG ODNmediated immunoprotection in primates and estab-lished their effectiveness in immunocompromisedhuman and non-human primates. In 2002, shebecame a research/reviewer and a principal investi-gator in at the FDA, where she continues to work onthe identification and characterization of modulatorsof the innate immune response as they relate topotential therapies for infection with agents ofbioterrorism and emerging pathogens. Her group hasrecently developed novel pro-drug forms of CpGODN that resolve issues of product aggregation insequences containing poly G strands and can be usedto prolong the immunoprotective effect of these oli-gos. She is currently interested in the impact ofinnate immune modifiers on inflammatory processesin the CNS. Dr Verthelyi lives in Maryland with her husband and 2 daughters.

Xiaoyu Hu, M.D., Ph.D.InstructorHospital for Special Surgery, New York, NY

Dr. Xiaoyu Hu received her M.D.degree from Beijing MedicalUniversity in 1997 and Ph.D.degree from Weill Graduate School of MedicalSciences of Cornell University in 2004. Dr. Hujoined the Research Division of Hospital for SpecialSurgery in 2004 as a postdoctoral fellow and waspromoted to instructor in 2005. Her research interestsinclude many aspects of macrophage biology, partic-ularly signaling crosstalk between interferons andother macrophage activating factors. Currently she isinvolved in projects studying the crosstalk betweeninterferons and toll-like receptor (TLR) signalingpathways and the effect of interferons on TLR-induced inflammatory responses. Dr. Hu is the recip-ient of Arthritis Foundation Young Scholar Awardfrom New York Chapter.

Reason for joining ISICR: "My research has alwaysfocused on the biology and signaling mechanisms ofinterferons. I thought that this is the perfect time to

August, 2007 9

ISICR Members in the News

Eleanor Fish, incoming ISICR President Canada Research Chair in Women's Health andImmunobiology

The Canada Research Chair in Women's Health andImmunobiology is a partnership between theWomen's College Research Institute, the UniversityHealth Network (UHN) and the Department ofImmunology at the University of Toronto. This Chairconducts and inspires research focused on sex differ-ences in the immune system.

“Do men and women's bodies work differently at themost basic level? Why are women more likely tohave lupus? MS? Arthritis? Should treatment ofthese conditions be different for women and men?”

These are questions we don't have the answers to yet,says WCRI Senior Research Scientist GillianEinstein.

"Why should autoimmune disease be more com-monin women than in men? Is it due to hormones,genes or both?"

The answers to these questions lie in basic scienceresearch, laboratory-based studies that examine thebody's workings at the cellular and molecular level."The University of Toronto has an incredibly talentedpool of basic science researchers," says Einstein."That is a real opportunity for women's health,because there is also an enthusiasm here to collabo-rate."

Almost three years ago, Einstein developed a propos-al for a Canada Research Chair in the basic scienceof women's health; many of the Faculty ofMedicine's basic science programs as well as hospi-tal research institutes were ultimately involved. Inthe spring of 2007, the dream became a reality withthe announcement of Dr. Eleanor Fish as CanadaResearch Chair in Women's Health andImmunobiology. The new chair is a partnershipbetween the Women's College Research Institute, the

University Health Network and the Department ofImmunology.

Dr. Fish leads the Arthritis & AutoimmunityResearch Centre (AARC) at the University HealthNetwork, Canada'slargest and mostcomprehensiveresearch centre ded-icated to autoim-mune disease. Sheis a well-known sci-entist, who studiesthe molecularmechanisms under-lying the actions of the immune system.

"I am thrilled that Eleanor allowed herself to be putforward for this the new chair," says Einstein. "Sheis a widely-respected researcher, with an internation-al reputation as an immunologist and with collabora-tions in the developing as well as the developedworld. She has a strong commitment to turning herwork toward understanding sex differences. Her lab-oratory and research team at the University HealthNetwork are well poised to take on this project. Weanticipate that a group of people will form aroundherwho want to understand why carrying two X chro-mosomes correlates with other gene expressions sothat women's immune systems responded differently- including the over-exuberant response that leads toautoimmune disease."

Fish will expand her own studies of the immune sys-tem to document sex-based differences in how werespond to infection, but she agrees that it's thebuilding of a research collaborative that is reallyimportant.

"One of the things I have committed to as theCanada Research Chair is to recruit a faculty mem-ber to UHN who will really begin to look at the sexdifferences in autoimmune disease." Like herself,she hopes her new recruit will have an appreciation

Dr. Eleanor Fish and Dr. Gillian Einstein


Mouse Interferon αα Gene Family

This picture represents a comparison of the mouseInterferon alpha gene sequences as analyzed by aprogram developed by Dr. Tom Schneider, NCI-Frederick. The height of the letters reflects thesequence conservation of the nucleotide (tallest arethe most conserved). For more information on thistype of analysis, see Schneider TD and StephensRM. Sequence Logos: A New Way to DisplayConsensus Sequences, Nucleic Acids Res. 18:6097-6100, 1990.

POST DOCTORAL OPENINGPosition description:The successful candidate will conduct independent basic molecular and cellular pharmacology research in thearea of anti-cancer therapy. He/she will be responsible for designing and conducting experiments to under-stand the mechanism of action, intracellular metabolism and localization, and resistance development forGilead's small molecule anti-cancer lead inhibitors including compounds in early stage clinical development.The candidate will also closely interact with a multidisciplinary discovery team focusing on the identificationof novel selective small-molecule anticancer inhibitors. The candidate is expected to present and publishresults of his/her research.

Requirements:PhD degree in life sciences, preferentially in cellular or molecular biology, immunology, or molecular pharma-cology with 3 to 5 years of laboratory experience. Solid theoretical understanding and excellent technicalskills in molecular and cellular biology together with well developed communication skills and computer liter-acy are essential. Background in molecular oncology, drug metabolism, bioinformatics, and/or enzymologywill be a plus.

Contact: Dr. Tomas Cihlar at [email protected]

(Members in the News, cont. from page 10)

for the broad scope of women's health research.

"I'm part of a basic science department[Immunology] at the University, says Fish, "but I amhospital-based, so I've always had an interest intranslational research -work that can apply what welearn about the underlying mechanisms to the treat-ment of disease." She says that Gillian Einstein hasfurther inspired her with her passion for buildingbridges between disciplines to create a more inte-grated body of women's health knowledge. "It'sinfectious and she is right. Building an integratedcommunity that shares knowledge across disciplinesis the essential function of this Chair."

Reprinted with permission from the Women'sCollege Research Institute, Toronto, Ontario, Canada

August, 2007 11

Interferon & the Comics

The first mention of interferon appeared in a FlashGordon comic strip as shown below (circa early1960s).

While there are no other examples of the mention ofinterferon in the comics (readers are welcome tosubmit other examples if they are aware of such),PBL Biomedical, a long time Corporate Sponsor ofthe ISICR, has just released the first of what is to bea series of comic books about Interferon.

The purpose of this publi-cation is to teach youngerscientists and laypeopleabout interferons andtheir role in immunity,although there has been agreat response from sen-ior scientists as well.PBL wants people toappreciate that whileinterferons have beenstudied for over 50 years,they are still an activeand vibrant area of

research. The comic is freely available to anyonewho signs up to receive the comic at the PBL web-site (www.interferonsource.com), but also to anyprofessors who teach immunology and/or virology.In future issues, PBL will profile each of the type Iand II interferons, and once a year, highlight themajor role that interferons play in disease (lupus,MS, cancer, etc), starting, in the first issue, withinfluenza.

The Interferon Foundation

One of the interesting stories in the early history ofthe science and politics surrounding the discoveryof interferon is that of the "Interferon Foundation".The early promise of interferon as a therapy forcancer reached all the way to the halls of the USCongress as individuals such as Dr. Mathilde Krimwere instrumental in getting the Congress to consid-er an appropriation earmarked for the production ofwhat was being hyped as a wonder drug. As inter-feron was so difficult and labor intensive to purify,the cost for a full treatment was >$30,000 (relative-ly modest by today's standards but very high in1980). Furthermore, as was stated in the March 31,1980 issue of Time Magazine, almost no one gotinterferon. The promise of this new drug to combatcancer led Texas oilmen Leon Davis and RoyHuffington to try and do something to help patientsthat might benefit from interferon treatment.Encouraged by Dr. Jordan Gutterman, one of theearly pioneers in the clinical use of interferon andthe 1992 recipient of the ISICR Milstein Award,Davis and Huffington formed the InterferonFoundation with the goal of raising money to payfor interferon for cancer patients. Leon Davis wasthe Chairman of the Interferon Foundation and hisfundraising approach was a bit different from mostcharitable foundations in that he went directly tocorporate executives in the oil industry and privatefoundations, bypassing the more commonly usedmethod of specific fundraising events. Davis and


Graphical matrix data viewing tools Shaded alignment figures Translation-based nucleic acid alignment ABI trace viewing, editing and printing Customizable ...

CRISPhttp://crisp.cit.nih.gov/

CRISP (Computer Retrieval of Information onScientific Projects) is a searchable database of feder-ally funded biomedical research projects conductedat universities, hospitals, and other research institu-tions. The database, maintained by the Office ofExtramural Research at the National Institutes ofHealth, includes projects funded by the NationalInstitutes of Health (NIH), Substance Abuse andMental Health Services (SAMHSA), HealthResources and Services Administration (HRSA),Food and Drug Administration (FDA), Centers forDisease Control and Prevention (CDCP), Agency forHealth Care Research and Quality (AHRQ), andOffice of Assistant Secretary of Health (OASH).Users, including the public, can use the CRISP inter-face to search for scientific concepts, emergingtrends and techniques, or identify specific projectsand/or investigators. Below you will be able toaccess additional general information about theCRISP database, as well as obtain answers to ques-tions frequently asked about CRISP. In addition, thishome page serves as the gateway to interactivesearching of Award Information.

fRNAdb: Functional RNA Databasehttp://www.ncrna.org/frnadb

Functional RNA Database (fRNAdb) is a databaseservice that hosts a large collection of non-codingtranscripts including annotated/un-annotatedsequences from H-inv database, NONCODE, andRNAdb. A set of computational sequence analysesare performed over these registered sequences. Theanalyses include RNA secondary structure motif dis-covery, EST support, finding cis-regulatory ele-ments, sequence homology search, etc. The fRNAdbprovides an efficient interface to help users filter outparticular transcripts that match their own criteria tosort out functional RNA candidates.

(Interferon Foundation continued from page 12)

Huffington proved very successful as up to $20 mil-lion was raised through their efforts. All of thismoney went to the purchase of clinical grade inter-feron as no funds were used for foundation expens-es. The majority of the funding went to M.D.Anderson but other institutions performing clinicaltrials with interferon also benefited. It is believedthat this is the largest amount of money that wasever privately raised for clinical trials of a singledrug.

While no longer in existence, the InterferonFoundation set a distinct example as a charitywhose sole purpose was to obtain sufficient quanti-ties of a new experimental drug for the treatment ofcancer. Thus the efforts of Leon Davis and RoyHuffington are an important and unique chapter inthe history of Interferon.

WWWBioEdithttp://www.mbio.ncsu.edu/BioEdit/bioedit.html

BioEdit is a biological sequence alignment editorwritten for Windows 95/98/NT/2000/XP. An intu-itive multiple document interface with convenientfeatures makes alignment and manipulation ofsequences relatively easy on your desktop computer.Several sequence manipulation and analysis optionsand links to external anaylsis programs facilitate aworking environment which allows you to view andmanipulate sequences with simple point-and-clickoperations.

New version is WinXP compatibleBioEdit's features include:

Several modes of hand alignment Automated ClustalW alignment Automated Blast searches (local and WWW) Plasmid drawing and annotation Accessory application configuration Restriction mappingRNA comparative analysis tools

August, 2007 13

HubMedwww.hubmed.org

An alternative interface to the PubMed medical liter-ature databaseIncludes:1. Daily updates of search results via web feeds.2. Quick access to searches with a Firefox searchplugin or a HubMed bookmarklet (drag to yourbrowser's bookmarks toolbar).3. Export citations in RIS, BibTeX, RDF and MODSformats, or directly to RefWorks.4. Unzip HubMed's import filter into Endnote'sFilters folder for direct import into Endnote, orinstall the RIS Export plugin for direct import intoProCite, RefMan and older versions of Endnote.5. Use the Citation Finder to convert reference listsfrom PDFs into search results.6. Create lists of closely related papers using RankRelations, then visualise and browse clusters of relat-ed papers using TouchGraph (requires Java).7. Graph occurrences of keywords in publishedpapers over time.8. Tag and store annotated metadata for articles ofinterest.Recommended by Kevin Ahearn in GeneticEngineering News

MedHelp: Section on interferonhttp://www.medhelp.org/HealthTopics/Interferon.html

Questions and answers about interferon from theDoctor's Forum.

Mouse Phenome Databasehttp://phenome.jax.org/pub-cgi/phenome/mpdcgi?rtn=docs/home

MPD is a database of mouse strain characterizations.Phenotype and genotype data presented on this website are voluntarily contributed by researchers from avariety of institutions and settings, or in some casesretrieved by us from open public sources. MPD goalsinclude: to assist investigators in selecting mouse strains forexperiments

to provide a standardized platform for discoveringgenotype/phenotype relationships to provide a stan-dardized collection of reference data on the laborato-ry mouse

AffiliationMPD is headquartered at The Jackson Laboratory, anorganization that uses the laboratory mouse to betterunderstand human health (http://www.jax.org). MPDis a grant-supported research effort with 3 fulltimestaff members.

Phenotype dataNumber of publicly-available contributed phenotypeprojects: 54 Number of publicly-available measurements: 837 Average number of strains tested per measurement:18 Data for females and males are always segregated.

Genotype data (SNPs)Number of SNP locations: ~10 million 16 strains have been assayed at more than 8 millionlocations. Lesser amounts of data are available for125 inbred strains and strains in 7 RI panels. Number of available SNP data sets: 23

Mouse strainsTotal number of strains having any phenotype orgenotype data in MPD: 570

NIAID RESEARCH RESOURCES FORINTERFERON RESEARCHhttp://www.beiresources.org/registration/register.cfm

A. Background and PurposeThe need for well-characterized reference reagents asan adjunct to research has long been recognized bythe National Institute of Allergy and InfectiousDiseases (NIAID). In 1969, NIAID accepted theresponsibility for the preparation and evaluation of apanel of Interferon International Reference Reagents.These reference reagents, produced under NIAIDcontracts with industry, universities, and nonprofitresearch organizations, were selected in consultationwith acknowledged authorities in the field. The

WWW (continued)


potency of the reagents is based on the results ofrepetitive testing in a number of different laboratorieshaving expertise in interferon assay procedures.Complete details concerning production and testingare provided with each ampoule shipped. The inter-feron standard preparations designated by the WorldHealth Organization (WHO) as InternationalStandards or International Reference Preparations arethe sole reagents for the international standardizationof interferons used for both clinical therapy andexperimental research. Reference standards forhuman and murine interferons as well as antibodiesto the interferons are distributed by the Repository.These materials are not intended for either diagnosticor therapeutic use.

B. Availability and Distribution of ReagentsNIAID interferon reagents are intended for use aslaboratory reference standards only. One ampoule ofa reagent is provided to an investigator per year.They are not intended for either diagnostic or thera-peutic use. Each of the reagents has been defined ascontaining a certain amount of interferon perampoule based on specific assay methods. If youhave questions about a particular reagent, please con-tact the Repository at the number below. Interferonreagent catalogs and order forms are available fordownloading at the NIAID Repository website,ww.bratonbiotech.com. If you are unable to accessthe Internet, you may request the latest copy of theinterferon catalog and order form by directly contact-ing the Repository using the fax or telephone num-bers listed below. Reagent request forms must becompleted by hand, they are not available for on-linecompletion or submission. Prior to submitting yourcompleted and signed request form, please make acopy for your files. Then forward all completed andsigned original documents to the Repository addresslisted below. To help expedite your order theRepository does accept the completed and signedforms by fax. Failure to submit all completed andsigned original documents to the Repository will pre-vent us from considering any future reagent requeststhat are submitted by you or your organization.

Please forward all correspondence to:BEI ResourcesP.O. Box 4137Manassas, VA 20108-4137Tel #: 1-800-359-7370Email: [email protected]

NIH Videocasthttp://videocast.nih.gov/PastEvents.asp

This site contains a collection of events, includingseminars, lectures and some symposia, that wereheld on the NIH campus. Included are the NIHImmunology Interest Group weekly seminar seriesand the NIH Director's Wednesday Afternoon semi-nar series.

Oncolink: the Web's first cancer resourcehttp://oncolink.upenn.edu/index.cfm

OncoLink was founded in 1994 by Penn cancer spe-cialists with a mission to help cancer patients, fami-lies, health care professionals and the general publicget accurate cancer-related information at no charge.Recent changes have been made to OncoLink toupdate the look and feel of our site. OncoLink isdesigned to make it easy for the general public tonavigate through the pages to obtain the informationthat they want. The home page has buttons andhypertext links. If you click on the buttons or theunderlined text with your mouse, you will go direct-ly to your area of interest.

Through OncoLink you can get comprehensiveinformation about specific types of cancer, updateson cancer treatments and news about researchadvances. We update the information everyday andprovide information at various levels, from introduc-tory to in-depth. If you are interested in learningabout cancer, you will benefit from visitingOncoLink.

WWW (continued)

August, 2007 15

WWW (continued)Understanding Cancerhttp://www.cancer.gov/cancertopics/understanding-cancer/

This Web site contains graphic-rich tutorials for edu-cational use by life science teachers, medical profes-sionals, and the interested public. Each tutorial isalso available in PDF and PowerPoint formats thatmay be downloaded from the Web. Simply click onany title listed below and when the tutorial opens,click within the Page Options box located in the leftmargin. The art presented here is copyrighted and dis-tributed free of charge for educational purposes. ANational Cancer Institute citation must appear on allcopies.

Brainteaser

See if you can figure out what these words have incommon?

BananaDresser

GrammarPotatoReviveUnevenAssess

Are you peeking or have you already given up? Giveit another try.... You'll kick yourself when you discover the answer.Go back and look at them again, think hard.

OK.. Here you go... Hopeyou didn't cheat. This Is Cool.

Answer: In all of the words listed, if you take the first letter,place it at the end of the word, and then spell theword backwards, it will be the same word. Did youfigure it out? I did not!


Obtained from http://xkcd.com/242/

Clips from the Daily Drug NewsHannah Nguyen

[July 19, 2007] RANKL: Target To Watch for devel-opment of therapeutics for treatment of osteolyticbone disorders

RANKL (receptor activator of NFkappaB ligand): isa member of the tumor necrosis factor (TNF) familyof cytokines that is produced by cells of osteoblasticlineage and is a crucial modulator of bone remodel-ing and required for the development and activationof osteoclasts. It is a target for the treatment of oste-olytic bone disorders such as osteoporosis, rheuma-toid arthritis and cancer-related bone disease like fol-licular lymphoma with bone involvement whereaberrant expression of RANKL has been observed inmalignant cells. There are a few products targetingRANKL for the treatment of these indications: TheRANKL vaccine, RANKL AutoVac from Pharmexaand the human monoclonal anti-RANKL antibodydenosumab from Amgen are currently under activepreclinical and phase III clinical development,respectively, for the treatment of osteoporosis,rheumatoid arthritis, multiple myeloma and/or can-cer-related bone disease (Prous Science Integrity[R]).

[July 17, 2007] NatureMed has patented the use of aseries of sinomenine derivatives with cytokine pro-duction inhibitory properties for treating inflam-matory disorders such as rheumatoid arthritis andosteoarthritis. The therapeutic potential of such com-pounds is attributed in particular to their ability tocurb tumor necrosis factor-alpha, interleukins IL-1,IL-6 and IL-8 biosynthesis. Additional indicationsinclude Alzheimer's disease and Parkinson's disease,among other neurodegenerative disorders, asthma,arrhythmia and inflammatory pain (WO2007070703).

WO 2007071952

WO 2007070703

[June 19, 2007] Merck and Merck Frosst have joint-ly disclosed a novel series of tricyclic compoundsthat act as inhibitors of protein kinases, notablyIKK-beta kinase (IKK-2), JAK1, JAK2, JAK3 andTYK2 and, as such, are considered to have potentialfor use in treating myeloproliferative disorders andcancer, as well as asthma, chronic obstructive pul-monary disease, rheumatoid arthritis, osteoarthritis,inflammatory bowel disease, dermatitis, psoriasis,atherosclerosis, hypertension, myocardial infarction,heart failure, diabetes, osteoporosis, stroke,Alzheimer's disease, multiple sclerosis, neuropathicpain and rhinitis (WO 2007061764).

WO 2007061764

[June 11, 2007] Kemia scientists have disclosed anovel series of bisamide compounds that act ascytokine (TNF-alpha) release inhibitors and arethus expected to be useful for treating inflammatorydisorders such as arthritis. Their potential for use asanalgesic and anticancer agents is additionallydescribed (WO 2007056016).

WO 2007056016

Biotech News

August, 2007 17

(Biotech News, cont. from page 17)

[July 30, 2007] ChemoCentryx earns milestonepayment from GlaxoSmithKline ChemoCentryxhas earned a milestone payment fromGlaxoSmithKline for progress in its small-moleculeCCR1 product discovery and development pro-gram. The milestone payment was triggered by theacceptance of ChemoCentryx' orally bioavailablesmall molecule, CCX-354, as a candidate for fulldevelopment. CCX-354 selectively inhibits thechemokine receptor known as CCR1, a validated tar-get for the treatment of certain autoimmune diseasessuch as rheumatoid arthritis (RA), as well as otherinflammatory diseases. Unlike existing injectable orinfusible treatments for RA, CCX-354 is designed asan oral medicine which is highly potent and selectivefor the CCR1 target. This approach provides advan-tages such as the potential to treat the devastatingeffects of RA without the safety consequences some-times seen by globally suppressing the immune sys-tem, as happens with such current therapies such asthe anti-TNF biologics available today. In preclinicalstudies, CCX-354 has been shown to block the activ-ity of all known naturally occurring proinflammatoryproteins that drive CCR1-mediated inflammation.The compound exhibits encouraging pharmacokinet-ic properties and is highly potent. Notably, CCX-354appears to block only the activity of the CCR1chemokine receptor without binding to any otherreceptors, which may minimize off-target side effects(ChemoCentryx News Release).

[June 15, 2007] Coley acquires 3M's therapeuticToll-like receptor R&D programs ColeyPharmaceutical Group today announced that it hasentered into an agreement with 3M to acquire themajority of its therapeutic Toll-like receptor (TLR)cancer programs. The acquisition includes apipeline of clinical and preclinical small-moleculecandidates targeting TLR7 and TLR8, as well asmore than 200 issued and several hundred pendingpatents and a library of approximately 10,000 small-molecule activators of TLR7 and TLR8. In additionto their role in cancer treatment, these compoundshave other possible indications in the treatment ofasthma, allergic disorders, viral diseases and certaindermatological diseases. Coley anticipates initiatingphase I/II clinical trials in a cancer indication in 2008

with one of the newly acquired TLR small mole-cules. The lead molecule in this portfolio was studiedby 3M in several phase I/II monotherapy clinical tri-als in cancer. It has demonstrated pharmacologicalactivity and has been administered safely at clinical-ly relevant doses to more than 100 subjects (ColeyPharmaceutical Group News Release).

[August 01, 2007] Anadys and Novartis discontin-ue development of ANA-975 for HCV AnadysPharmaceuticals and Novartis have decided to dis-continue the development of ANA-975, a phase Ibcompound for the treatment of hepatitis C virus(HCV) infection. The parties have determined thatthe results received to date from the ongoing 13-week toxicology study together with the resultsobserved in the previous 13-week toxicology studydo not support further clinical evaluation of chronicdaily dosing of ANA-975 in hepatitis C patients.Anadys continues its development of ANA-773,another Toll-like receptor 7 (TLR7) agonist prodrugdistinct from ANA-975, and expects to file an INDby the end of 2007. Anadys plans to evaluate ANA-773 in phase I clinical trials for the treatment ofadvanced cancer. The program is independent of theNovartis collaboration and is not affected by thedecision to discontinue development of ANA-975.TLR7 is a pattern-recognition receptor that activatesthe innate immune response. Stimulation of TLR7induces the release of interferon alfa and other type Iinterferons from immune cells, the release of variousproinflammatory cytokines, the upregulation of cos-timulatory molecules and the development of anadaptive immune response. Small-molecule TLR7agonists have been shown to have broad antiviral andanticancer effects in preclinical models and in someclinical settings (Anadys Pharmaceuticals NewsRelease)

[July 13, 2007] OT-551 holds promise for oncolo-gy and inflammatory conditions. Activation of pro-coagulant mechanisms as a result of cancer orinflammation can lead to venous thromboembolism.Scientists from Albany College of Pharmacy andOthera Pharmaceuticals evaluated the antithromboticpotential of OT-304 analogues in human monocytesand endothelial cells. Microarray and thrombelastog-raphy experiments revealed that OT-304 analogues,which target NF-kappaB and oxidative stress path-


(Biotech News, cont. from page 18)

ways, downregulated various proinflammatorycytokines and chemokines such as TNF-alpha, IL-1beta and IL-6 and procoagulant mediators such astissue factor (Mousa, S. A. et al. 21st Congr Int SocThromb Haemost (ISTH) (July 6-12, Geneva) 2007,Abst O-M-004). OT-551, the lead compound in theseries of OT-304 analogues, is currently in a phase IIprogram at Othera Pharmaceuticals as a potentialdrug to inhibit the progression or prevent cataracts inpatients who have undergone vitrectomy surgery. Inaddition to the newly discovered inhibitory activityat the level of NF-kappaB, the compound also pos-sesses potent antioxidant and antiangiogenic activi-ties. OT-551 holds therapeutic promise for such dis-eases as age-related macular degeneration, cataracts,dry eye, resistance to cancer chemotherapy, cancer-related thrombosis and rheumatoid arthritis (OtheraPharmaceuticals News Release).

NCT00449345. At the Community TuberculosisService, Rehovot, Israel. Principal Investigator:David Shitrit, MD, Maccabi Health Services. StudyID Numbers: 2006055.

Safety and Efficacy of Intravenous ACZ885 (a fullyhuman anti-interleukin-1 monoclonal antibody)and Oral Methotrexate Therapy in Patients WithEarly Rheumatoid Arthritis. In many US States,Belgium, Germany, Italy, Netherlands, Spain.Principal Investigator: Novartis, Investigative StudyID Numbers: CACZ885A2204

Inflammation, Proteolysis and IL-1 Beta ReceptorInhibition in Chronic Hemodialysis Patients.ClinicalTrials.gov identifier NCT00420290. AtVanderbilt University Medical Center, Nashville,Tennessee, 37232, Cindy Booker [email protected]. PrincipalInvestigator: Adriana Hung, MD, VanderbiltUniversity. Study ID Numbers: 060661

Interleukin-2 With Sorafenib (BAY 43-9006) forUnresectable or Metastatic Clear Cell RenalCarcinoma. ClinicalTrials.gov identifierNCT00418496. At Ohio State University,Columbus, Ohio, 43210, Ohio State UniversityCancer Clinical Trial Matching Service, 866-627-7616, [email protected]. PrincipalInvestigator: J. Paul Monk, M.D., Ohio StateUniversity. Study ID Numbers: OSU-06006; SR05-890; CPRL002AUS07

Safety and Efficacy Study of ALT-801 (a recombi-nant fusion protein with an interleukin-2 compo-nent) to Treat Progressive Metastatic Malignancies.ClinicalTrials.gov identifier NCT00496860 UnitedStates, Florida H. Lee Moffitt Cancer Center &Research Institute, Tampa, Florida, 33612, UnitedStates; Recruiting Study ID Numbers: CA-ALT-801-01-06

Interleukin 11, Thrombocytopenia, CML, Imatinibin CML Patients. ClinicalTrials.gov identifierNCT00493181. At U.T.M.D. Anderson CancerCenter, Houston, Texas, 77030. PrincipalInvestigator: Jorge E. Cortes, MD [email protected]. Study ID Numbers:2004-0113

More information on this list can be obtained athttp://clinicaltrials.gov [CT], http://www.center-watch.com/search.asp [CW], or http://clinicalstud-ies.info.nih.gov [CCNIH].

Gefitinib and PEG-Interferon Alfa-2b in TreatingPatients With Unresectable or Metastatic KidneyCancer. ClinicalTrials.gov identifier. In California.Study Chair: Primo N. Lara, MD, University ofCalifornia, Davis. Study ID Numbers:CDR0000540598; CCC-PHII-40; ZENECA-AZ1839US/0227; UCD-200412338-4; UCD-ZD1839

Study to Evaluate the Safety and Efficacy of Adeno-IFN Gamma in Cutaneous B-Cell Lymphoma.ClinicalTrials.gov identifier NCT00394693. InCalifornia Illinois & Texas, USA, France,Switzerland. Study ID Numbers: 12928

Screening for Latent Tuberculosis in HealthcareWorkers With Quantiferon-Gold Assay: A Cost-Effectiveness Analysis. ClinicalTrials.gov identifier

Clinical TrialsHannah Nguyen

August, 2007 19

(Clinical Trials, cont. from page 19)

Safety and Efficacy of EGEN-001 (contains thehuman gene for interleukin-12) Combined WithCarboplatin and Docetaxel in Recurrent, Platinum-Sensitive, Ovarian Cancer. ClinicalTrials.gov identi-fier NCT00473954. At the University of Alabama atBirmingham, Birmingham, Alabama, 35233.Principal Investigator: Ronald D. Alvarez, MD,Division of Gynecologic Oncology at University ofAlabama at Birmingham. Study ID Numbers:EGEN-001-201.

MS-275 and GM-CSF in Treating Patients WithMyelodysplastic Syndrome and/or Relapsed orRefractory Acute Myeloid Leukemia.ClinicalTrials.gov identifier NCT00462605. At theSidney Kimmel Comprehensive Cancer Center atJohns Hopkins, Baltimore, Maryland, 21231-2410,Clinical Trials Office - Sidney KimmelComprehensive Cancer Center, 410-955-8804, [email protected]. Study ID Numbers:CDR0000540608; JHOC-NA_00006989

Alterations of Immunologic Mediators DuringSevere Sepsis (LAVISS_01). ClinicalTrials.gov iden-tifier NCT00484146. At Klinikum St. GeorggGmbH, Interdisciplinary Intensive Care Unit,Leipzig, Sachsen, 04129, Germany, Armin RSablotzki, MD, 0049-341-909-2570, [email protected]. Study ID Numbers:ISRCTN34508816

Pilot Study of Allergy Immunotherapy andPrevention of Viral Respiratory Infections.ClinicalTrials.gov identifier NCT00405899. AtAllegheny General Hospital, Pittsburgh,Pennsylvania, 15212, Jennifer Koehrsen, MS 412-359-6988, [email protected]. PrincipalInvestigator: Deborah Gentile, MD. Study IDNumbers: RC - 4064

In a recent issue of the JBC

Samuel CE. Interferons, Interferon Receptors, SignalTransducer and Transcriptional Activators, andInterferon Regulatory Factors. J. Biol. Chem.282:20045-20046, 2007

Pestka S. The Interferons: 50 Years after TheirDiscovery, There Is Much More to Learn. J. Biol.Chem. 282:20047-20051, 2007

de Weerd NA, Samarajiwa SA, Hertzog PJ. Type IInterferon Receptors: Biochemistry and BiologicalFunctions. J. Biol. Chem. 282:20053-20057, 2007

Ozato K, Tailor P, Kubota T. The InterferonRegulatory Factor Family in Host Defense:Mechanism of Action. J. Biol. Chem. 282:20065-20069, 2007

Other reviews

Baccala R, Hoebe K, Kono DH, Beutler B,Theofilopoulos, AN. TLR-dependent and TLR-inde-pendent pathways of type I interferon induction insystemic autoimmunity. Nature Medicine 13: 543-551, 2007

Boyman O, Purton JF, Surh CD, Sprent J. Cytokinesand T-cell homeostasis Curr. Op. Immunol. 19: 320-326, 2007

Brandt K, Singh PB, Bulfone-Paus S, Rückert R.Interleukin-21: A new modulator of immunity, infec-tion, and cancer. Cytokine & Growth Factor Rev. 18:223-232, 2007

Kanzler H, Barrat FJ, Hessel EM, Coffman RL.Therapeutic targeting of innate immunity with Toll-like receptor agonists and antagonists. NatureMedicine 13:552-559, 2007

Khabar KS, Young HA. Post-transcriptional controlof the interferon system. Biochimie. 89:761-769,2007

Reviews of Interest


100 YearsTHE YEAR 1907 (mostly US info)

One hundred years ago.What a difference a century makes!

Here are some of the US Statistics for the Year 1907:

************************************

The average life expectancy in the US was 47 years.

Only 14 percent of the homes in the US had a bath-tub. Most women only washedtheir hair once a month, andused Borax or egg yolks forshampoo.

Only 8 percent of the homes had a telephone. Athree-minute call from Denver to New York City cost$11 USD.

There were only 8,000 cars in theU.S. and only 144 miles of pavedroads.

The maximum speed limit in most cities was 10 mph.

Alabama, Mississippi, Iowa, and Tennessee wereeach more heavily populated than California. With amere 1.4 million people, California was only the 21stmost populous state in the US.

The population of Las Vegas, Nevada was only 30.

The tallest structure in the world was theEiffel Tower!

The average wage in the U.S. was 22 cents per hour(0.16 euros at todays' rate) and the average US work-er made between $200 and $400 per year.

A competent accountant could expect to earn $2000per year, a dentist made $2,500 per year, a veterinari-an $1,500 per year, and a mechanical engineer about$5,000 per year.

(Reviews of Interest, cont. from page 20)

Nagy G, Clark JM, Buzás EI, Gorman CL, Cope AP.Nitric oxide, chronic inflammation and autoimmuni-ty. Immunol. Lett. 111:1-5, 2007

O J. Review: Commercial interferon-gamma releaseassays have high specificity but suboptimal sensitivi-ty for detecting latent TB. ACP J Club. 2007 147:21,2007

Menzies D, Pai M, Comstock G. Meta-analysis: newtests for the diagnosis of latent tuberculosis infection:areas of uncertainty and recommendations forresearch. Ann. Intern. Med. 146:340-354, 2007

O'Doherty C, Villoslada P, Vandenbroeck K.Pharmacogenomics of Type I interferon therapy: Asurvey of response-modifying genes. Cytokine &Growth Factor Rev. 18: 211-222, 2007

Stockinger B, Veldhoen M. Differentiation and func-tion of Th17 T cells. Curr. Op. Immunol. 19: 281-286, 2007

Yoneyama M, Fujita Y. Function of RIG-I-likeReceptors in Antiviral Innate Immunity. J. Biol.Chem. 282:15315-15318, 2007

August, 2007 21

(100 Years, cont. from page 21)

More than 95 percent of all births in the US tookplace at HOME.

Two out of every 10 U.S. adults couldn't read orwrite and only 6 percent of all Americans had gradu-ated from high school.

Ninety percent of all U.S. Doctors had NO COL-LEGE EDUCATION! Instead, they attended so-called medical schools, many of which were con-demned in the press AND the government as "sub-standard."

Sugar cost four cents a pound.

Eggs were fourteen cents a dozen.

Coffee was fifteen cents a pound.

Canada passed a law that prohibited poor peoplefrom entering into their country for any reason.

Five leading causes of death in the US were:1. Pneumonia and influenza2. Tuberculosis3. Diarrhea4. Heart disease5. Stroke

Crossword puzzles, canned beer, andice tea hadn't been invented yet.

There was no Mother's Day or Father's Day.

Marijuana, heroin, and morphine were all availableover the counter at the local corner drugstores. Backthen pharmacists Said, "Heroin clears the complex-ion, gives buoyancy to the mind, regulates the stom-ach and bowels, and is, in fact, a perfect guardian ofhealth."

There were about 230 reported murders in theENTIRE U.S.A.!

During the years 1971-73 I was privileged to work inIan Kerr's laboratory in the Biochemistry Departmentat Mill Hill in London. It was a wonderful time bothscientifically and socially. Although I made manyfriends, I was told repeatedly that I would never real-ly understand the British unless I became familiarwith cricket. So, when the rain temporarily stopped,and the cricket season came around, I signed up toplay for the Biochemistry team.

There was some hesitancy about allowing me toplay, as I had only vague notions of the rules of thegame, but the team was short-handed, so I was per-mitted to participate in the first match of the season,which was a truncated version of a real match. Iwould explain that last statement fully, but it wouldtake too long, suffice to say that in the Mill Hillintramural league the matches took place over oneafternoon rather than five days, each side batted onlyonce, and the team with more runs was declared thewinner. If you wish to determine how this differsfrom real cricket, consult Google.

At any rate, because of my unfamiliarity with thegame, while the other team batted, I was put in thefurthest reaches of the cricket pitch, where it wasjudged unlikely I would be much involved with theproceedings. Little did we realize how the matchwould develop, for after a few batsmen had been dis-missed, a ball was hit on the ground directly at me. Ipicked it up, wondering what to do with it. The othermembers of my team gesticulated, trying to conveysomething to me, but it wasn't getting through. The

How I Got to Understand the BritishBob Friedman


(Understand the British, cont. from page 22)

most significant directions seemed to be comingfrom our wicket-keeper (roughly equivalent to acatcher in baseball), so I threw the ball in his direc-tion. I have a good throwing arm, being left-handed,

and accustomed to playingthe outfield in baseball,and the ball went directlyat him on a single bounce.Too late I realized he wasstanding behind severalpoles stuck in the ground

(which I later discovered to be called stumps) withsomething suspended across them (bails), whichafter a bounce my throw hit, and knocked apart,whereupon the members of my team went wild. Iwas totally perplexed about what they were on aboutuntil it was explained that I had dismissed the strikerout by knocking down the stumps while he was run-ning between the two wickets. Had I known the sig-nificance knocking down the wicket, and aimed forit, I'm sure I wouldn't have hit it in a thousand years.

After everyone had quieted down, the match wenton. The best batsmen on the other side took a turn,and proceeded to slaughter us, hitting the ball allover the pitch, and sometimes out of it. After about10 minutes of this, one of them hit a high drive rightto me. I took a step back, and caught the ball in thesame manner I would have, had I been playing base-ball, in the palm of my right hand with my left handcradling the ball. It was a perfect catch, but therewas one thing missing - a glove, which would havebeen present in a baseball game, but not in a cricketmatch, except for the wicket-keeper. Ouch! It reallyhurt, but it dismissed the batsman.

Soon, the other side was all out, so it was ourinning. The members of my team complimented meon my catching the ball, but explained that no Britwould have tried to do what I had done, but wouldhave taken a few steps back, and picked up the ballafter it hit the ground. And I could well understandwhy this was so, for as I waited to take my turn as

batsman, I noticed my righthand was beginning to becomequite sore and swollen. When Iactually did bat, every time Istruck the ball, I experiencedexcruciating pain in my righthand. When I had been dis-missed, I commented on the

pain I had experienced, and was told it was unusual.Another look at my right hand convinced me that Ihad probably broken a bone in it at the time I hadcaught the ball. My teammates volunteered to bringme to the local hospital to have my hand examinedafter the match ended. This occurred rather soonerthan anyone had expected, when two American visi-tors on the other team, who also wanted to betterunderstand the British, collided head to head chasinga ball that had been hit high in the air. Indeed, onewas knocked momentarily unconscious, and theother, badly shaken up.

The three of us were loaded into a car, and broughtto Edgeware General Hospital. I was triaged toorthopedic (excuse me, orthopaedic) surgery to havemy hand examined; the other two injured Americans,to neurology from which they were soon discharged.The x-ray of my hand indicated a clean brake in thethird metacarpal of my right hand, and to this day, Ilack one knuckle on that hand as a result of the frac-ture. The attending radiologist, with a laugh, com-mented that I ought not to engage in such dangerousactivities as cricket, and to stick to American foot-ball. I replied that I had thought that the only injuryone could suffer in a cricket match was to die ofboredom.

He frowned.

August, 2007 23


All right? - This is used a lot around London and thesouth to mean, "Hello, how are you"? You wouldsay it to a complete stranger or someone you knew.The normal response would be for them to say "Allright"? back to you. It is said as a question.Sometimes it might get expanded to "all right mate"?Mostly used by blue collar workers but also commonamong younger people.

Bladdered - This rather ugly expression is anotherway of saying you are drunk. The link is fairlyapparent I feel!

Cock up - A cock up means you have made a mis-take. It has nothing to do with parts of the malebody!

Fagged - If you are too lazy or tired to do somethingyou could say "I can't be fagged". It means you can'tbe Bothered.

Fruity - If someone is feeling fruity then they arefeeling frisky. Watch out!

Give us a bell - This simply means call me. Youoften hear people use the word "us" to mean "me".

Her Majesty's pleasure - When visiting England,try to avoid being detained at Her Majesty's pleasure.This means being put in prison with no release date!

Hiya - Short for hi there, this is a friendly way ofsaying hello.

I'm easy - This expression means I don't care or it'sall the same to me.

Keep your pecker up - This is one way of sayingkeep your chin up. Use with caution.

Khazi - Another word for the toilet. Our version ofyour bathroom.

Spend a penny - To spend a penny is to go to thebathroom. It is a very old fashioned expression thatstill exists today. It comes from the fact that in ladiesloos you used to operate the door by inserting an oldpenny.

Taking the piss - One of the things Americans findhardest about the Brits is our sense of humour. It isobviously different and is mainly based on irony,sarcasm and an in-built desire to "take the piss". Thishas nothing to do with urine, but simply meansmaking fun of someone.

TTFN - Short for "ta ta for now". Which in turnmeans goodbye! Said by older folks and one RadioTwo DJ in particular.

Wacky backy - This is the stuff in a joint, otherwiseknown as pot or marijuana!

Yonks - "Blimey, I haven't heard from you foryonks". If you heard someone say that it wouldmean that they had not seen you for ages!

Zonked - If someone is zonked or "zonked out" itmeans they are totally knackered or you might sayexhausted. When a baby has drunk so much milk,his eyes roll into the back of his head, it would befair to say he was zonked!

British Slang that may come in handy while you're in Oxfordhttp://www.effingpot.com/index.shtml

Cytokines 2008Oct. 12-16, 2008

7th Joint Conference:International Society for Interferon and Cytokine Research & the

International Cytokine Society

Translating Science into Health:Cytokines in Cancer and Infectious Diseases

Montreal Quebec CANADAFairmont Queen Elizabeth Hotel

August, 2007 25


Cytokines 2008The organizers cordially invite you to participate inthe 7th Joint Meeting of the International Society forInterferon and Cytokine Research and theInternational Cytokine Society "Cytokines 2008" tobe held October 12 to 16, 2008 in Montreal, Quebec,Canada. Our Conference will harness the biomedicalexpertise and energies of these major societies to pro-vide a comprehensive update of recent insights intobasic and clinical aspects of Cytokines in Cancer,Inflammation, and Infectious Diseases. The overalltheme of this Conference is Translating Scienceinto Health, and is chosen to emphasize the integra-tion of basic, pre-clinical, pharmaceutical and clinicalresearch in the areas of cancer, immune modulation,inflammation and infectious diseases. Topics to becovered will include cytokine/interferon structure andfunction, gene regulation, signal transduction, regula-tion of cell survival, microenvironment, newcytokines, as well as the multiple roles of cytokines inimmunology, inflammation, angiogenesis, hostdefense and tumor biology. A significant part of theconference will be devoted to cytokine-based thera-pies in malignancy and other disorders as well asemerging therapies targeting cytokines in autoim-mune, inflammatory and malignant diseases. Seniorscientists, young investigators, physicians, postdoc-toral fellows, graduate students and representatives ofthe pharmaceutical industry all stand to profit fromthe interactions available at this venue. We believethat this Conference - set in the beautiful cosmopoli-tan city of Montreal during the stunning fall displayof colors - will reflect the best of current cytokineresearch and will provide a vital impulse for furtherdevelopment.

Canadian Organizing CommitteeJohn Hiscott - McGill UniversityMarc Servant - Universite de MontrealEleanor Fish - University of TorontoKaren Mossman - McMaster UniversityMichele Barry - University of AlbertaJohn Schader - University of British Columbia

International Advisory Committee

Christine Czarniecki (USA)Jean Michel Dayer (Switzerland)Scott Durum (USA) Takashi Fujita (Japan)Otto Haller (Germany) Raymond Kaempfer (Israel)Santo Landolfo (Italy)Warren Leonard (USA)Alberto Mantovani (Italy)Eliane Meurs (France)Joost Oppenheim (USA)Luke O'Neill (Ireland)Sidney Pestka (USA) Michael Tovey (France) Jan Vilcek (USA)Carl Ware (USA)Bryan Williams (Australia)Howard Young (USA)

Important Addresses & Information

CONFERENCE SECRETARIATGabriella Di PancrazioLady Davis Institute for Medical ResearchSir Mortimer B. Davis - Jewish General Hospital3755 chemin de la Côte Ste-CatherineMontréal, Québec H3T 1E2Tel: (514) 340-8308 Fax: (514) 340-7502E-mail: [email protected]: http://www.cytokines2008.org

SCIENTIFIC SECRETARIATProf. Dr. John HiscottLady Davis Institute for Medical ResearchJewish General HospitalE-mail: [email protected]

EXHIBITION MANAGEMENTClarkson Conway - exhibitsChristine Lalonde - printingMary Lou Coupal - Hotel liasonCongress Home Pagehttp://www.cytokineresearch.com/2008

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an interview with the 2007 milstein award winner, dr...

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