StepUp! 2025 Booklet

Page 1


Ice Cream Social

Ella Harshyne

Faculty Mentor: Rajanikanth Vadigepalli, PhD

AIDeepLearningAidsinExaminationofProstateTumorArchitectural DifferencesbetweenAfricanAmericansandCaucasians EllaHarshyne,AnkitaSrivastava,RajanikanthVadigepalli DepartmentofPathologyandGenomicMedicineStepUp!toCancerResearchProgram SidneyKimmelComprehensiveCancerCenter

Introduction

ProstateCancerisaleadingdeathamongmen AfricanAmericanmenarediagnosedmorefrequentlyandhavehgher mortaityratescomparedtoCaucasianmen

- 176xhigherlkelhoodofdiagnosis

-214xhighermortaltyrate

-Understudiedarchtecturaldifferencesinthetumortssuesmaybea contributingfactortotheracia dispartesobservedinprostatecancer outcomes butremainunderexploredinresearch

TheuseofAIalowsforaquickanddetaledanayss,comparedtohumans, ofmorphologicalfeaturesfromhistoogyimages Woudtakeahuman30min–1hourcomparedtoAIonlytakng5-15minper core

Hypothesis

-Therewillbemorphologicaldifferencesintheprostatetumortissues

Results ofAfricanAmericanversusCaucasiansandbetweentumorgrades withinthoseracesprostatetumors:3+3,3+4,4+3 -Attheglandular,luminal,andnuclearlevelbetweenracesdisparitiesinprostatetumorlikeaggressiveness,treatment responseandsurvivalrates Thesedifferencesmaycontributetotheexplanationofknown

MaterialsandMethods

-We usedanAIbasedimageanalysstoo caledVisiopharmtoanalyze tumormorphologyinH&EstainedTumorMicroArray(TMA)prostate cancersamples RegionofInterests(ROIs)

-

-ManuallyannotatedonanH&EstainedTMAimageandeachannotated areamarkedadifferenttumorsection Apps -Orderallowedfordatalinkage

-Glanddetectionapp:GlandDETECT Modified -HighlightsglandsinbluetocreatenewROIs

-Providesinformationusefultoevaluatingstructuraldifferences -Providesinformationlikeglandcount,glandarea,largerandsmaller diameters,majorandminors,andperimeter -Lumenidentficationapp:Lumen ID NewModified - Isranineachseparateglandcreatedinthepreviousstep -Provides nformationlikelumencount,lumenperimeter,minorand major,andareainwhichweusetolookatratiosandlookfor abnormalities

-Nucleidetectionapp:NucleiDetection parameter

-Informationlikenucleicount,largestandsmallestdiameter,perimeter, nuceieccentricity cellsoldarityisextracted RStudio - packagesfordatacleaningandcreatingvisuals

--dplyr:filterng&groupingdata ggplot2:creatingplots purrr:loopingoverlistsofdata readr:reading csvfiles stringr:cleaningandextractingstrings

Discussion

-SignificantdifferencesinRacewereobservedinglandareatotalnumberofglands

lumen andnuclei andnucleieccentricity Blackpatientsexhibitedlargerglands hgher nucle counts,andmoreirregulartyinnucleishape Thesestructuraldifferenceswerestill presentinseparateracesevenwhentheGeasonscoreswerethesame Gleason3+3

-AfrcanAmericanmenshowlessarchitectura disruptionbutearlysignsofnuclear atypia,whieWhitemenshowmoretumorcel density

Gleason3+4

-AfrcanAmercanmenstumorbeginlosngstructure,earierthanwhitemen,andshow greaternuclear rregularitywhchcanreflectearlyprogressiontowardsaggressive behavor

Gleason4+3

Conclusions

Acknowledgements I

-BothshowaggressivefeaturesbutAfricanAmericanmenshowmoreseverestructural breakdownandvariabiitywhichcanbeasignofmoreaggressvetumorbehavor

@ResearchAtJeff

Gabrielle McFarlane Faculty

Mentor: Elena Blanco-Suárez, PhD

Astrocyte-SecretedChordin-Like1andItsRoleinStrokeRecovery

GabrielleMcFarlane,,GabrielaDaszewska-Smith,ElenaBlano-Suarez

Background

Intheearlystagesofbraindevelopment immaturesynapsesfeaturecalciumpermeable AMPA glutamate receptors AMPA receptors play a crucial role in neuronal plasticity, learning, and memory As synapses stabilize and mature, the calcium-permeable AMPA receptors are replaced with calciumimpermeableGluA2AMPAreceptors

Chordin-like1(Chrdl1),aproteinsecretedbyastrocytes,hasbeenfoundto haveanegativeeffectonneuronalplasticitybyregulatingsynapticmaturation oftheAMPAreceptors

Chrdl1expressionisconcentratedincertainareasofthemousebrain,and whenischemicstrokes orstrokesresultingincelldamageanddeath occurin thoseareasthenChrdl1isupregulated,potentiallyhinderingcellrecovery

• IthasbeenpreviouslyfoundthatwhenChrdl1isknockedoutinmicepriorto birth,theyrecoverfromcelldamageandmotorcontrolfasterthanwildtype mice

Researchquestion

CanknockingoutChordin-like1expressioninadultmice leadtofasterischemicstrokerecovery?

Figure1.(A)BargraphcomparisonoftimespentinthecenterofopenfieldtestingareabetweenCre (-)andCkomice,beforeand1dayafterstrokesurgery Eachbarrepresentsthemean±SEMofthe specifiedgroupatagiventimepoint.(B)Bargraphcomparisonofthetotaldistancetraveledwithin theopenfieldtestingareabetweenCre(-)andCkomice,beforeand1dayafterstrokesurgery. Statisticaldifferencesbetweengroupsortimepoints,whereapplicable,areindicatedbyasterisks(*p< 0.05,**p<0.01).(C)Bargraphcomparisonoftimespentintheperipheryoftheopenfieldtesting areabetweenCre(-)andCkomice,beforeand1dayafterstrokesurgery.(D)Bargraphcomparisonof themeanspeedwhilstintheopenfieldtestingareabetweenCre(-)andCkomice,beforeand1day afterstro@keRessue

Figure 2. (A-B) Representative MRI images showcasing the lesioned brain area ofChrdl1 Ckoand Cre(-)mice at1daypost-stroke and 7days post-stroke. (C) Bar graph comparison of stroke volume between Cre (-) andCkomice,1dayand7dayspoststroke.Statisticaldifferencesbetween groups or time points, where applicable, are indicated by asterisks (*p< 0.05, **p<0.01). (D) Line graph comparison of stroke area percentage betweenCre(-)andCkomice,1dayand7dayspoststroke.

ComparedtoCre(-)mice,Chrdl1Ckomicerecovermotorfunctionata slowerrate.ThiscouldsuggestthattheChrdl1proteinisimportantfor motorfunctionandrecovery.

Sincethesynapsesarealreadymaturatedinadults,theAMPAreceptors couldalreadyhavelessplasticitycomparedtoyoungerages,which wouldhaveadverseeffectsonneuronalcellrecovery.

ApossiblefuturedirectioncouldbetoseeifandhowtheAMPA receptorsareaffectedinadultsonceChrdl1hasbeenknockedout.

Partofamuchlargerstudy,soconsequently,moredatacouldshowa moredefinitivepicture.

IamgratefultohavebeenabletoparticipateintheStepUp!ToCancer Researchprogramoverthissummer!Throughthisprogram Ihave beenabletohearaboutmanydifferentstories,trajectories,andcareer paths,whichhaveallhelpedtoimpactmydecisionsaboutmyfuture Beforeenteringthisprogram IhadarockyvisionofwhatIwantedmy futuretolooklike,whatstepsIhadtotaketogetthere,andhowI wouldmanagemyselfasIpursuedevenhighereducationandentered theworkingfield Now Ihavemoreexperiences connections and knowledgetodrawbackasIcontinuetothinkaboutwhatmyown careerpathmaylooklike

Acknowledgment

IwouldliketoacknowledgetheworkandeffortsofDr.AnaMariaLopez,Dr.ElenaBlanco-Suarez,andGabriela Daszewska-Smithfortheirhelpinthecollection,analysis,and presentationofthisdata.Iwouldalsoliketothanktherestof theStepUp!ToCancerResearchcohortfortheircontinued support.

fisticaldifferencesbetweengroupsortimepoints,whereapplicable,are indicatedbyasterisks(*p<0.05,**p<0.01).

Cre(-) Chrdl1Cko
Cre(-)
Chrdl1Cko

Umme Orthy

Faculty Mentor: Ana Maria López, MD, MPH

Background

Mindfulness-BasedStressReduction(MBSR)hasbeenshownto reducestress,anxiety,anddepressioninindividualsdiagnosed withbreastcancer.Researchhasshownthatmindfulnesscanhelp withemotionalwell-being,supportcopingandcognitivefunction, decreaseinflammation,andsupportsurvivorship.

-Mindfulnessinvolvesintentionallyfocusingonthepresent momentwithopennessandacceptance,usingtechniqueslike meditation,breathingexercises,andmindfulawarenessof thoughts,emotions,anddailyexperiences.

-Dr.Lopez’steamhasjustcompletedamindfulnessinterventionfor personswithbreastcancerwhoareundergoingchemotherapy.

-Iamexploringwhethermindfulnessinterventionscanprovide meaningfulbenefitsforindividualswithmetastaticbreastcancer.

Methods

Ofimportantnote:

-"Anothertask"–Mindfulnessfeltlikeanaddedburdenduringan alreadyoverwhelmingtime.

-"Goodteacherisamust"–Askilled,compassionateinstructorwas seenasessentialforengagement.

-"Mindisallovertheplace"–Difficultyfocusingwascommon, highlightingbothachallengeandapotentialbenefitofmindfulness.

-“Helpsmecalmandlessstressful”–Participantsnotedthat mindfulnesspracticeshelpedreducestressandpromoteasenseof calm.

Mindfulnessisflexible:Participantspracticeditindifferent ways,oftenwithoutusingtheterm“mindfulness.”Clear, relatableframingisimportant.

-Stronginterestacrosstheboard:Eventhosenewto mindfulnessshowedopennesstolearningandparticipating.

-Barriersexist:Fatigue,techaccess,andgroupdiscomfort suggestaneedforflexible,low-effortformats(e.g.,Zoom, phone).

-Groupvs.Individual:Somevaluedgroupsupport;others preferred1-on-1.Choicematters.

-Timingiskey:Earlyintroduction—atdiagnosisortreatment changes—mayincreaseimpact.

-Mindfulnesshelpedparticipantsmanagestress,buildresilience, andregainasenseofcontrolduringtreatment.

-Eventhoseunfamiliarwithmindfulnesswereopenandcurious onceintroduced.

-Listeningtopatients’storieswasapowerfulreminderoftheneed forpatient-centered,flexiblecare.

-Asapre-medstudent,thisexperiencedeepenedmy understandingoftheemotionalandpsychologicalneedsof patients,andtheimportanceofcompassionate,holistic approachesinmedicine.

FutureDirection

-Expandthemindfulnessprogramtoincludepatientswith metastaticbreastcancer,apopulationthatoftenexperiences heightenedpsychologicaldistress.

-Integratedigitaltools(e.g.,mobileappsoronlineplatforms) toincreaseaccessibility,engagement,andadherencetothe program.

-Broadenthestudytoincludediversepatientpopulationsand exploredifferentdeliverymodalities(e.g.,one-on-one, group,virtual).

-Investigatepotentialbiologicalcorrelatestobetter understandthemechanismsthroughwhichmindfulness mayimpacthealthoutcomes.

Acknowledgement

IwouldliketothankDr LopezandLe'Annfortheirmentorshipand leadershipthroughoutthisproject IamalsogratefultoJuliaforher invaluablecontributionstothedevelopmentandimplementationof thestudy SpecialthankstotheAmericanCancerSocietyfor supportingthisresearch

Adriana Pagan Faculty

Mentor: Mauricio Reginato, PhD

Background

Breastcanceristhemostcommonlydiagnosedcancerinwomen,where 20%-30%ofpatientsexperiencebreastcancerbrainmetastasis.

SLC7A11isaproteinthatservesasanaminoacidtransporterinvolvedin glutamateandcystineexchange;promotingcancercellsurvivalthrough oxidativestress

ProteomicanalysisofSLC7A11overexpressingcellsshowedincreasedin extracellularmatrix(ECM)proteins

Figure3.FAKinhibitionshrinks

preformedBCBMtumorsexvivo

Figure4. SLC7A11 overexpressing cellshas increasedFAK activityandtotal levels

TheoverexpressionofSLC7A11increasestheactivation,or phosphorylation,ofFAKinbreastcancerbrainmetastaticcelllines. TargetingFAKwithsmallmoleculeinhibitorsshrinksBCBMtumorsex vivo

ThesefindingssuggestapotentialroleforSLC7A11inregulatingFAK signalinginBCBM.Ongoingworkwillclarifywhethertargetingthis pathwaycouldbeaneffectivestrategytoinhibitbrainmetastaticgrowth.

Objectives

DoesSLC7A11regulateECMsignalingandFAKphosphorylation inBCBMcells?

●ProjectAims

○DetermineifSLC7A11regulatesactincytoskeletonandFAKsignaling inBCBMcells

○EvaluateiftargetingFAKblocksBCBMgrowthexvivo

Immunofluorescence-usedtovisualizeproteinlocalizationand expressionincells WesternBlot-performedtodetectandquantifyproteinlevels Exvivoassay-braintissuesliceswereusedtoassesstheeffectsofFAK inhibitionontumorgrowth

Figure1.BCBMcellsandSLC7A11overexpressing

Figure2.SLC7A11knockdownBCBMcellshas

TotestiftargetingFAKreducesSLC7A11-mediatedgrowthinBCBM cellsinvivo

TotestiftargetingFAKinBCBMinducescelldeath

TounderstandthemechanismbywhichSLC7A11regulatesFAKand ECMsignaling

Acknowledgements

@ResearchAtJeff

I have great faith in a seed. Convince me that you have a seed there, and I am prepared to expect wonders.
Henry David Thoreau

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