I N F O C U SI B P 2 0 1 2

I B P : O N W A R D A N D U P W A R D !

F A L L 2 0 1 2 V O L . 2 , N O . 3

Integrative Biology and Physiology

I N S I D E T H I S I S S U E

2 Kudos

3 Graduate program

5 Education updates

7 ZofiaZukowska:In Memoriam

8 IBP Photo Gallery

C O M I N G U P :

D E C E M B E R

IBP Winter Potluck Wednesday, December 13 6-135Jackson

M A Y 2 0 1 3

Visscher Symposium Wednesday, May 15, 2013

Jackson Hall 6-125 321 Church St. SE 612-625-5902 ibpdept@umn.edu

www.physiology.med.umn.edu

It’s shaping up to be another exciting year for IBP. Our graduate programrecruitedtwomorenewtoprankedPh.D.graduatestudentstocontinue our excellence in building an outstanding graduate program in integrative biology and physiology. We are seeing successes at all phases

ofourtripartitemission:knowledge,discovery,knowledgedisseminationandservicetoouruni-versity and community. This is a great time for our departmentaswecontinuetogrowandflourish.Nextsummermanyofuswilltransitionourlabstothe state-of-the-art Cardiovascular-Cancer Building thatwillserveasthegatewaytotheBiomedicalDiscovery District. I hope you enjoy reading our annual IBP In Focusnewsletterandlearnabout our recent achievements and highlights of the major events to come.

Joe Metzger, Ph.D.Professor & Head

4 T H A N N U A L V I S S C H E R S Y M P O S I U M T O F E A T U R E J O S E P H T A K A H A S H I

Dr. Joseph Takahashi, aworldleaderinthemolecularbasisofchronobiology,willdeliverthekeynoteaddressatthenextVisscherSymposiumscheduledforWednesday, May 13, 2013 at 4 p.m.inMCB3-120.TakahashiisChairoftheDepartmentofNeuroscienceandanInvestigatoroftheHowardHughesMedicalInstituteatUTSouthwestern.HecurrentlyholdstheLoydB.SandsDistinguishedChairinNeuroscience.BeforemovingtoUTSouthwestern,TakahashiwastheWalterandMaryElizabethGlassProfessorinLifeSciences

atNorthwesternUniversity.Duringhis26-yeartenureatNorthwestern,heheldappointmentsas professor in the Department of Neurobiology and Physiology on the Evanston campus and asprofessorintheDepartmentofNeurologyatNorthwesternUniversityMedicalSchool.Inaddition,hewasalsothedirectoroftheCenterforFunctionalGenomics.

2012 IBP faculty, staff and students

D E C A D E O F D I S C O V E R Y G R A N T T O A L E S S A N D R O B A R T O L O M U C C I

BecauseobesityisthegreatestriskfactorforType2diabetes,Universityof Minnesota Integrative Biology and Physiology faculty member Alessandro Bartolomucci, Ph.D. has focused his research on developing ananti-obesitydrug.Todosoheneededtodiscovernewmoleculartargetsforthedrugs.AprimedrugcandidateisthepeptideTLQP-21,whichwasrecentlyidentifiedinDr.Bartolomucci’slab.Ithasbeenshowntopreventobesityinmicebyincreasingfatdecompositionanddecreasingthesizeoffatcells.Forthenextyear,hisresearchteamwillbeuncoveringhowthepeptidefunctions,aswellasdeterminingitsreceptor,itsbiochemicalproperties,andchemicalstructure.Thatknowledgewillformthe

foundationofanewanti-obesitydrugprogram.Thegoalistocreatemedicationsthat,usedincombinationwithlifestylechanges,willlimitobesityandthuspreventType2diabetesand associated cardiovascular disease. Dr. Bartolomucci is also the recipient of a TR01 grant throughtheNIH.Granttitle:“Energetics,Disparities,&Lifespan:Aunifiedhypothesis”withPrincipalInvestigator,DavidAllison,UofAlabamaatBirmingham.

K U D O S

Congratulations to Michelle Asp,post-docintheMetzgerLab,forherrecentNIHF32awardtitled“Novelcalciumbufferforthetreatmentofdiastolicheartfailure.”MichellehasbeenwiththeMetzgerlabsince2010,afterreceivingherPh.D.fromtheOhioStateUniversityinColumbus, Ohio.

A S P C L A I M S A N N I HF 3 2 A W A R D

I B P M I S S I O N

Dedicated to an integrative systems biology approach to bio-medical discovery. Wepartnerwithcolleaguesacross disciplines to investigate questions ranging from the gene/molecule to the intact animal,whilestrivingfor excellence in research anddisseminationofnewknowledgewithlocal,national, and global impact.

Committed to mentoring and training graduate students. Weempowerstudentsto develop a deep understanding of the complexity of physiological systems to enable them to pursue unique career pathwaysspanningfromacademica to bio-industry.

Devoted to excellence, innovation and scholarship in education. We eduate students in the integration of structure and function of cells, organ systems, and living animals, providing a strong foundation for knowledgediscoveryinbasic sicence and human healthfields.

The Lifson/Johnson Memorial Awardrecognizedexcellenceinteachingbyundergraduateorgraduatestudents.IBPgavetwoawardsfor2011-2012,oneofwhichwenttoDalay Hirsch. Dalay is an IBP graduate studentwhoexcelledasaTAinourundergraduatephysiologylabcourse(PHSL3701).

http://physiology.med.umn.edu/kudosarchive

L I F S O N / J O H N S O N M E M O R I A L A W A R D

M E E T O U R N E WG R A D U A T E S T U D E N T S

F R O M T H E D G S

S N I D E R D E S I R IgraduatedfromKutztownUniversityinPennsylvaniawithaB.S.inbiologywheremyinterestforresearchwasdeveloped.While gaining further research experience atVirginiaTech,Idecidedtoseekouta program that placed an emphasis on integratingmultiplescientificdiscplinesin the study of human diseases. IBP at theUofMwasthatprogramforme.IamcurrentlyrotatinginDr.JoesphMetzger’slab,whereIamworkingoncardiacenterovirusprotease2A-cleaved dystrophin.

A N T H O N Y V E T T E R IgrewupintheTwinCitiesandgraduatedfrom the University of Minnesota in 2011 withaB.S.inbiochemistryandgenetics.I am interested in using biochemical and biophysical techniques to study the conformationaldynamicsofthinfilamentproteinswhichregulatecontractionofcardiac muscle. The long term goal of my research project is the development of a high-throughput drug screen capable of findingnovelsmallmoleculecardiacinotropes.

T I M O T H Y M A T S U U R AIwasbornandraisedinMinnesota.Aftergraduatingin2005withaBAinBiologyfrom Dartmouth College, I returned to Minnesotaandworkedinhealthcareand pre-clinical research. I transitioned from a medical device company into the laboratory of Dr. Yannopoulos, a University of Minnesota physician and investigator. His research focuses on identifyingnovelmethodstoimproveoutcomesfollowingcardiacarrest.LastyearIjoinedtheIBPprogramandgreatlyenjoyed returning to the classroom for a more rigorous understanding of a broad array of physiology topics. I remain very interested in resuscitation research, but I am also excited toexperiencenewresearchpursuitsandtechniques.Iamcurrently learning about dystrophin and its role in muscle organizationwhilerotatinginDr.Townsend’slaboratory.

John Osborn, Ph.D.Professor, Director of Graduate Studies

The Graduate Program in Integrative Biology andPhysiology(IBP)isinitsfourthyearandexpanding.Wenowhaveelevengraduatestudents.SecondyearstudentsDan Rossi (Mortarilab), Nathan Zaidman(O’Gradylab)

and Tim Matsuura(Townsendlabrotation)havesuccess-fullycompletedtheirfirstyearintheprogram.

Weareexcitedtowelcometwonewoutstandingstudentsintotheprogramthisfall:Snider Desir and Anthony Vetter. SniderandAnthonywereintroducedtotheIBPgraduatefacultyattheannualFallWelcomeheldattheCampusClubonSeptember6th.Seeprofiles(totheright)formoreinformationaboutSniderandAnthony.

Third year students Evelyne Houang(Metzgerlab),Cheryl Cero (Bartolomuccilab)andDalay Hirsch(Bernlohrlab)willbetakingtheirpreliminaryexamsinthenearfuture.Forum Kamdar,PhysicalScientistPh.D.candidate,passedherPOEAugust27th.Congratulations,Forum!Preceedingher in this achievement are IBP graduate students Jason Foss (Osbornlab)andDusty Moore(Tranquillolab).

I B P G R A D P R O G R A M

IBP Grad Students 2012 Back Row L-R: Snider Desir, Dan Rossi, Nathan Zaidman, Tim Matsuura, Jason Foss. Front Row L-R: Anthony Vetter, Dusty Moore, Cheryl Cero, Dalay Hirsch, Evelyne Houang.

G R A D U A T E P R O G R A M U P D A T E S

V I S S C H E R Y O U N G I N V E S T I G A T O R A W A R D W I N N E R S

Kristin Hellberg, Ph.D. Candidate

“Fatty Acids Induce Cysteinyl Leukotriene Synthesis in

Macrophages”

Antoinio Filareto, Post-Doc Associate

“An ex vivo Gene Therapy Approach to Treat Muscular Dystrophy Using iPS Cells”

G R A D U A T E P R O G R A M U P D A T E S

*EricK.Long,*KristinaHellberg,RocioFoncea,AnnV.Hertzel,JonathanS.Marchant,JillSuttlesandDavidA.Bernlohr

ABSTRACTObesity-inducedinsulinresistanceisassociatedwithchroniclow-gradeinflammationlinkedtomacrophageinfiltrationofadipose tissue. Macrophages produce a variety of eicosanoids linkedtothepropagationoftheinflammatorystateandassuch,weevaluatedtheroleoffattyacidsineicosanoidsynthesisusingavarietyofmacrophagecelllinesaswellasinhighfatfedC57Bl/6Jmicethatdevelopobesity-linkedinsulinresistance.TreatmentofeitherRAW264.7orprimarymacrophageswithsaturated,mono-unsaturated or polyunsaturated free fatty acids induced a sustained increaseinintracellularcalciumarisinglargelyfrominfluxfromtheextracellular medium. In RAW264.7 cells and primary peritoneal macrophages,fattyacidtreatmentledtosecretionofleukotrieneC4(LTC4)whereasinTHP-1monocytes,palmitatetreatmentledtosynthesisofLTC4 anditsmetabolismtoleukotrieneD4(LTD4).AdipocyteFattyacidbindingprotein(AFABP)knockoutmiceare protected against high fat diet-induced insulin resistance and inflammation.FABPsarecapableofstabilizingtheleukotrieneprecursor,leukotrieneA4 (LTA4).Interestingly,treatmentofprimaryperitonealmacrophageswithHTS01037,apan-specificFABPinhibitor,resultedinadrasticdecreaseinbothbasalandfattyacid-stimulatedLTC4 secretion. In high fat fed C57Bl/6J mice, LTC4 levels increased in the visceral depot but decreased in the subcutaneousdepotrelativetolean,chowfedcontrolmice.Theseresults indicate that fatty acids can stimulate macrophage productionofpro-inflammatoryleukotrienesthatmaycontributeto the insulin-resistant state.

*denotes co-first authors

AntonioFilareto,SarahParker,RadbodDarabi,LucieneBorges,IacovinoMichelina,TorySchaaf,TimothyMayerhofer, JeffreyS.Chamberlain,JamesM.Ervasti,R.ScottMcIvor,MichaelKybaand Rita C.R. Perlingeiro

ABSTRACTDuchennemusculardystrophy(DMD)isaprogressiveandfatalneuromuscular disease caused by genetic and biochemical defects ofthedystrophin-glycoproteincomplex(DGC).Thesealterationslead to cell membrane damage and apoptosis of muscle cells, resulting in chronic tissue degeneration and impaired muscle contractility. To date, there is no cure for DMD. Approaches to date involving cell transplantation and gene therapy have given suboptimal results. An alternative strategy that holds promise is thedirectreprogrammingofadultfibroblaststoapluripotentstate,generatingpatient-anddisease-specificstemcells,andcorrectingtheseinvitropriortotransplantation.Hereweshowtheregenera-tive potential of myogenic progenitors derived from corrected dystrophiciPScellsgeneratedfromfibroblastsofmicelackingbothdystrophinandutrophin(dKO).WecorrectedthephenotypeofthesedystrophiciPScellsusingaSleepingBeautytransposoncarryingthemicro-utrophin(µUTRN)gene,differentiatedthesecellsintoskeletalmuscleprogenitors,andassessedwhethertheirtransplantationbackintodystrophicmicewouldamelioratethemusclewastingphenotype.Transplantedmusclesdisplayedlargenumbersofμ-UTRN+myofibers,withbiochemicallyrestoredDGC,anddemonstratedsignificantlyimprovedcontractilestrength.Notably,weshowthatdonorcellsalsoseedthesatellitecellcompartment and respond to injury. Our results represent an importantadvancetowardthetreatmentofmusculardystrophiesusinggeneticallycorrectedautologousiPScells.

“…first of all, pay attention to your scientific creativity and productivity. But also remember that you live in a society…in which the ethic of truthfulness, which is at the heart of the

scientific method, may be infused into societal decisions.”~Maurice Visscher

M A K E A G I F T T O I B PThegenerosityofindividualswhorecognizetheimportanceofourdepartment’sworkisindispensibletooursuccess.Donateonline at www.mmf.umn.edu/give andselectMMFfund#6819.

E D U C A T I O N U P D A T EF R O M S T E V E K A T Z

L I S A A N D E R S O N R E C E I V E S N A T I O N A L T E A C H I N G A W A R D

U N D E R G R A D U A T E P H Y S I O L O G Y N E W S

IBP Assisant Professor, Dr. Lisa Carney Anderson, received the prestigious 2012 Didactic Instructor of the YearAwardfromtheAmerican Association of NurseAnesthetists(AANA)inaceremonyinSanFran-ciscoinAugust.TheawardrecognizedLisa’sexcellencein teaching in the UMNnursingprogramsince1997.

The IBP undergraduate physiology major serves approximately 200 junior and senior undergraduate physiologymajorsperyear.Ournewestproject is the planned formationofaB.S.degreeinPhysiologytoaccompanyourpre-existing BA degree.

IBP graduated forty-eight students this spring, including nine whograduatedwithdistinction(>3.75GPA)andthreewhograduated Summa Cum Laude.PatrickMcGarrah(seephotobelow)receivedanawardfromDr.Metzgerforaperfect4.0 GPA.

TheIBPUndergraduatePhysiologySociety(picturedbelow)isbeginningitsfourthyearwithanewleadershipteam.UPSstudents actively engage in departmental activities during the yearandhaveplansforseveralhealthandwellnessrelatedphilanthropy outreach events for the upcoming school year.

Pictured left to right are Dr. Vince Barnett, Advisor; Hannah Dotterman (Pres.); Jason Hass (Historian); Marriah Bollensson (VP/Treasurer); Elizabeth Marring (Public Relations); Brittany Osgood (Social/Philanthropy Chair)

The education mission of the department of Integrative Biology and Physiology (IBP)is

accomplished in part by both Anatomy and Physiology classes aimed at undergraduate, graduate, and professional students. We continue to see high demand for our classes and have responded by adding bothnewclasssectionsandnewclasses.Fortheyearending in June, 2012, the sum of all of our Physiology and Anatomy classes yielded total tuition revenue of approximately $5,000,000,

withmorethan3,000students enrolled in almost 50 IBP classes.

Twoassistantprofessorsarenownewcoursedirectors:Alessandro Bartolomucci is thenewcoursedirectorforournewStressPhysiologyclass, and DeWayne Townsendisthecoursedirector for our graduate student Critical Readings in Physiology course.

Finally,congratulationstoMarkCookwhoonceagainreceivedtheMMFDistinguished Teaching AwardduringtheMMFAwardCeremonyinApril.

E D U C A T I O N U P D A T E S

Congratulations to Patrick McGarrah, who graduated in May 2012 with a perfect GPA of 4.0.

C A R D I O P A L O O Z A F E A T U R E S R E S E A R C H

Tara Rasmussen (center), a post-doc in cardiology, receives the Investigator Award from Drs. Dan Garry (left) and Joe Metzger (right) at the 4th Annual Cardio Palooza research event held in the McNamara Alumni Center August 1, 2012.

E D U C A T I O N U P D A T E S

CongratulationstoourCardioPalooza(a.k.a.CVRetreat)researchawardwinners:Monica Knaack, summer scholar; Tara Rasmussen, post-doc; Forum Kamdar, clinicalfellow;andCheryl Cero, graduate student.

Toseeadditionalawardwinnersandeventphotos,visithttp://physiology.med.umn.edu

S H O R T C O U R S E S T O B E O F F E R E D I N J A N U A R Y 2 0 1 3

Register Online for January 2013 Advanced Cardiac Anatomy Pelvic Short Courses at

http://physiology.med.umn.edu/shortcourses

ThiscomingJanuary2013,IBPwillagainoffertwoshortcourses:Advanced Cardiac Physiology and Anatomy and Anatomy and Physiology of the Pelvis and Urinary System. The courses are attractive to the biomedical-industrialcommunity,aswellastograduateandundergraduate physiology majors. Our goal is to increase enrollment by 50% in both courses in January.

Forcoursecontentandphotosfrompastcourses,visithttp://physiology.med.umn.edu/shortcourses

I N M E M O R I A M

Esteemed colleague and friend, Professor Zofia Zukowska, M.D., Ph.D., passedawayatherhomeonApril25,2012.Wordscannotbegintoexpressoursorrowatherpassing.IknowthatIspeakonbehalfoftheentireUMNcommunity in extending our deepest sympathy and condolences to her family.

ZofiaobtainedbothherM.D.andPh.D.fromtheMedicalAcademyinWar-saw,Poland,andcametotheUSin1980totrainasaFellowandAssociatewithDr.IrvKopinintheLaboratoryofClinicalScience,NIHM.In1985shetookafacultypositionintheDepartmentofPhysiology&BiophysicsatGeorgetownUniversity,whereshewaspromotedtofullprofessorin1995,andwentontobecomedepartmentchairin2006.ZofiaalsofoundedtheStressPhysiologyCenteratGeorgetownin2006wheresheserved as its director until 2010.

Zofia’sworkcenteredonneuropeptideYfunctioninobesityandcardiovasculardiseaseandherstudieswerewellknownandhighlyregardedincontextoftheuniqueinsightsmadeinstressphysiology.Herworkwaspublishedinthemostrigorouspeer-reviewedjournalsandherdynamiclaboratorywasfundedbynumerousNIHandfoundationgrants,includingthe

prestigiousNIHMERITaward.ShereceivedmanynotableawardsforherworkincludingtheprestigiousCopernicusAwardforExcellenceinNeuropeptideResearch.ZofiawasahighlyvaluedmemberoftheAmericanPhysiologicalSociety.AschairofthephysiologydepartmentatGeorgetownshewasastrongandeffectiveadvocateforthephysiological-centricpursuitofnewknowledgeinbiomedicalresearch.

WewerethrilledtorecruitZofiatoournewIntegrativeBiologyandPhysiologydepartmentin2010.ShecametotheUniversityofMinnesotawithhervisiontodirectaworld-classcenterin“StressPhysiology.”Herpassionanddriveputherwellonthewaytowardplacingthisinitiativeonthemapasaleaderinthishighlycompetitiveand vibrant area of research.

Zofia’swarmsmileandgenerousspirit,togetherwithherlegacyofscholarshipanddiscovery,touchedallwhomether.Shewillbedeeplymissedbyallofus. May she rest in peace, Joe Metzger, Ph.D. Professor and Chair, Department of Integrative Biology and Physiology

Z O F I A Z U K O W S K A , M . D . , P H . D .July 16, 1948 - April 25, 2012

I B P P H O T O G A L L E R Y

Above top, left to right: Dan Garry, Russell Luepker, Bob Bache, and Mary Garry at the Visscher dinner reception

Above bottom: IBP Faculty 2012

Above, top:UPS members at Visscher receptionAbove, bottom:Dr. Kahn receives t-shirt fromDr. Metzger

Staff of Goldy’s Locker Room prepares for EKG readings at the State Fair with Lisa Anderson and grad student Tony Vetter

IBP faculty at the Grad Student Welcome at Coffman Union

Above, top:String trio at the Visscher receptionAbove, bottom:Anthony Filareto receives theYoung Investigator Award from John Osborn

DeWayne Townsend explains cardiac physiology

to State Fair fans

Bartolomucci, Mortari and Osborn gather on the terrace

IBP graduate students continue to build a strong program

IBP Grad Student Welcome Party

For more fun photos from the 2012 events, visit http://physiology.med.umn.edu, Recent Events in right column.

State Fair 2012

Visscher Symposium 2012