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Spring 2014 | The Medical I.B.I.S.

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From our Dean

CAMPUS

I

am proud to present the second issue of The Medical I.B.I.S., the Miller School of Medicine’s student-produced research publication, which showcases the innovative research conducted by our extraordinary students.

Research is the lifeblood of academic medicine. Discoveries in our laboratories advance prevention, GLDJQRVLVWUHDWPHQWVDQGFXUHVIRUWKHGLVHDVHVDQGFRQGLWLRQVWKDWDIà LFWKXPDQNLQG7KH\DOVR DGYDQFHZKDWLVWDXJKWLQRXUFODVVURRPVEHFDXVHPHGLFDOVWXGHQWV²MXVWOLNHSUDFWLFLQJSK\VLFLDQV ²PXVWKDYHDFFHVVWRWKHODWHVWNQRZOHGJH8QGHUWKHJXLGDQFHDQGPHQWRULQJRI RXUIDFXOW\RXU VWXGHQWVWDNHWKHLUÀUVWLPSRUWDQWVWHSVLQWKHFDUHHUWRZKLFKWKH\KDYHEHHQFDOOHG 7KHEUHDNWKURXJKUHVHDUFKSUHVHQWHGLQWKLVLVVXHLVWUXO\LPSUHVVLYH,WVSDQVDZLGHUDQJHRI LQWHUHVWVLQFOXGLQJVWHPFHOOWUHDWPHQWVVSLQDOFRUGLQMXULHVUHWLQDOGLVHDVHVJHQHWLFPDUNHUVDQGPXFK PRUH2XUVWXGHQWVDUHMXVWHQWHULQJWKHÀHOGRI PHGLFLQH\HWWKH\DUHDOUHDG\PDNLQJVLJQLÀFDQW FRQWULEXWLRQVWRPHGLFDONQRZOHGJH:HNQRZWKHUHZLOOEHPRUHJUHDWZRUNWRFRPH

Pascal J. Goldschmidt, M.D. Senior Vice President for Medical Affairs and Dean 8QLYHUVLW\RI 0LDPL0LOOHU6FKRRORI 0HGLFLQH &(28QLYHUVLW\RI 0LDPL+HDOWK6\VWHP 2

The Medical I.B.I.S. | Spring 2014

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From our Editors

:

e are pleased to present the second issue of The Medical I.B.I.S., a publication authored, SURGXFHGUHYLHZHGDQGHGLWHGHQWLUHO\E\PHGLFDOVWXGHQWV7KLVPDJD]LQHLVGHGLFDWHG WRZDUGVSURPRWLQJWKHVFLHQWLÀFDFKLHYHPHQWVRI 8QLYHUVLW\RI 0LDPL0LOOHU6FKRRORI  Medicine medical students, featuring research projects in both basic medical science and clinical studies. 7KHVHVWXGHQWVDWWKH0LOOHU6FKRROKDYHWDNHQDQDFWLYHUROHLQLQQRYDWLYHUHVHDUFKDQGZLOOFHUWDLQO\ VKDSHWKHIXWXUHRI PHGLFLQHDVWKH\HPEDUNRQWKHLUSURIHVVLRQVDVSK\VLFLDQV Selected through an internal peer review process, these research projects are just seventeen of the many admirable accomplishments that our students have achieved both on our Miller campus and DWRWKHULQVWLWXWLRQVDFURVVWKHFRXQWU\:HNQRZWKDWWKHVHVWXGHQWV¡FRPPLWPHQWVWRUHVHDUFKFDQ lead to novel medical advancements and we encourage them to continue pushing the boundaries of PHGLFDONQRZOHGJH

Angela Chang Editor-In-Chief

sg.mededu.miami.edu/medicalibis

5LFKD7DQHMD Managing Editor

Melissa Stone Senior Editor

Spring 2014 | The Medical I.B.I.S.

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CAMPUS

VOL. 2

ISSUE 1 SPRING 2014

EDITOR-IN-CHIEF Angela Chang MANAGING EDITOR Richa Taneja SENIOR EDITOR Melissa Stone

The Medical I.B.I.S. Staff 2014

SELECTION COMMITTEE CHAIR Matthew Phillips SECTION EDITORS Laura Huang Devon Cohen Amir Tarsha Caroline Chen Kevin Moore WRITERS Laura Bloom Le Zhong Jeffrey Smith Houda Boucekkine Sapir Karli Gabriel Nemzow-Weingrod Andrew Richardson

Selection Committee

Section Editors

SELECTION COMMITTEE Matthew Field Michael Durante Jeanna Harvey PUBLISHING EDITOR Nahim Dewan PRODUCTION EDITOR James Greenwood PHOTOGRAPHERS Nikesh Doshi Jonathan Parker COVER Wei Yang

Writers

INTERIM FACULTY ADVISOR Alex J. Mechaber, M.D. ADVISORY BOARD Pascal Goldschmidt, M.D. Alex J. Mechaber, M.D. The Medical I.B.I.S. LVSXEOLVKHGE\WKH8QLYHUVLW\ of Miami Miller School of Medicine Student *RYHUQPHQW:HUHVHUYHWKHULJKWWRHGLWDQ\ submissions, solicited or unsolicted, for publication. 7KLVPDJD]LQHLVWKHZRUNRI8QLYHUVLW\RI0LDPL PHGLFDOVWXGHQWVDQGWKH8QLYHUVLW\RI0LDPLLVQRW responsible for its contents. Perspectives expressed E\DXWKRUVGRQRWQHFHVVDULO\UHĂ HFWWKHRSLQLRQVRI WKH8QLYHUVLW\RI0LDPL:HUHWDLQWKHULJKWWRUHSULQW contributions, both text and graphics, in future issues as well as a non-exlcusive right to reproduce these LQHOHFWURQLFIRUP7KH0HGLFDO,%,6ZHOFRPHV FRPPHQWVDQGIHHGEDFN3OHDVHVHQGTXHVWLRQVDQG comments to medical.ibis@gmail.com.

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The Medical I.B.I.S. | Spring 2014

Photographers Jonathan Parker (left) and Nikesh Doshi (right) Not pictured: Michael Durante, James Greenwood, Sapir Karli, Melissa Stone, and Amir Tarsha. sg.mededu.miami.edu/medicalibis


UNIVERSITY OF MIAMI’S MEDICAL STUDENT RESEARCH PUBLICATION

MICHAEL KRITZER 6 Anchored p90 Ribosomal S6 Kinase 3 is Required for Cardiac Myocyte Hypertrophy KAITLIN YOUNG8 Characterization of Fragile X Syndrome Caused by FMR1 Deletions DARRYL CANNADY II10 Surrogate Fitness Measures Association with Functional Independence in Spinal Cord Injuries JOSHUA PARKER 11 Evidence of Acceleration Aging in Individuals with Spinal Cord Injury INNA GRANOVSKY 12 S7D Clinic Patients· Awareness of Non-AIDS Complications KATYAYINI ARIBINDI 13 Cholesterol and Glycosphingolipids Profiles of Human Trabecular Meshwork and Aqueous Humor JARED GANS 14 Plasmacytoid Dendritic Cells Induce Regulatory T-cells that can Prolong Cardiac Allograft Survival LUCAS CAVALLIN 16 The Quest to Cure Kaposi Sarcoma

MICHAEL SCHOOR 19 Bioluminescence Energy Capture by Quantum Dot ARASH SAYARI 20 Photograph-Based Goniometry: A Comparison of Techniques SPENCER SUMMERS22 Neuropathic Pain-Induced Depression and TNF LINSEY LINDLEY24 LBH Role in Normal and Neoplastic Mammary Stem Cell Control ZACHARY GERSEY 25 Curcumin Treatment Promotes Glioblastoma Stem Cell Death JAMIE DIAMOND 26 Insurance Implications for Choice of Stent Type AUDREY COX 28 Stem Cell Particles Promote Development of New Blood Vessels in the Healing of Chronic Wounds SHARON WOLFSON 30 Effect of Colon Transection on Spontaneous HighAmplitude Propagating Contractions

NIKESH SHAH18 Effect of AMPK Activator in the Treatment of Retinal Tumors sg.mededu.miami.edu/medicalibis

Spring 2014 | The Medical I.B.I.S.

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CAMPUS p90 Ribosomal S6 Anchored Kinase 3 is Required for Cardiac Myocyte Hypertrophy

BY MELISSA STONE

Michael working at his lab bench.

:

KHQ MLFKDHO .ULW]HU PKD ZDV D VHFRQG year medical student at the Miller School of Medicine searching for the perfect laboratory to complete his graduate thesis for the M.D./Ph.D. program, he sought a basic science project with translational implications. Michael .DSLORII MD PKD DLUHFWRU RI WKH CDUGLDF SLJQDOLQJ TUDQVGXFWLRQ DQG CHOOXODU BLRORJ\ LDERUDWRU\ DQG PURIHVVRU RI Cardiology at the Interdisciplinary Stem Cell Institute (ISCI), KDG D SURMHFW IRU MLFKDHO WKDW H[HPSOLÀHG EHQFK WR EHGVLGH identifying signal transduction pathways involved in cardiac P\RF\WH K\SHUWURSK\ ² D PDMRU ULVN IDFWRU IRU KHDUW IDLOXUH Desiring to apply a strong foundation in basic science towards the development of a therapeutic agent, Michael used in vitro and in vivo models to identify cardiac hypertrophic signaling. SLJQDO WUDQVGXFWLRQ SDWKZD\V DUH D FRPSOLFDWHG PHVKZRUN RI proteins that bind and modify each other to activate or inhibit WKHLU GRZQVWUHDP VLJQDOLQJ DU .DSLORII ’V ODE VSHFLDOL]HV LQ understanding how the scaffold protein mAKAP (muscle 6

The Medical I.B.I.S. | Spring 2014

A-Kinase Anchoring Protein) facilitates pro-hypertrophic VLJQDOLQJ TKH RS. IDPLO\ RI SURWHLQV LV LQYROYHG LQ FHOOXODU growth and Dr. Kapiloff had previously published that “RSKâ€? ZDV DVVRFLDWHG ZLWK PA.AP TR GHWHUPLQH WKH RS. LVRIRUP involved in mAKAP-based myocyte growth, Michael performed recombinant expression of different binding proteins with various mutations. Michael sought to determine which protein ELQGLQJ GRPDLQV ZHUH HVVHQWLDO IRU WKLV VLJQDOLQJ QRGH HH GLVcovered that the binding of RSK3 to mAKAP was an essential step in myocyte hypertrophic signaling. For his in vitro ZRUN MLFKDHO SDUWQHUHG ZLWK RHVHDUFK AVVLVWDQW PURIHVVRU -LQOLDQJ LL PKD ZKR FXOWXUHG QHRQDWDO UDW FDUdiac myocytes and exposed them to various agents that stimulate JURZWK TKLV ZDV GRQH LQ WKH SUHVHQFH RI VPDOO LQWHUIHULQJ RNA ² VPDOO PROHFXOHV VSHFLĂ€FDOO\ GHVLJQHG WR VLOHQFH FHUWDLQ RNA molecules – as well as various chemical inhibitors to identify SURWHLQV LQYROYHG LQ FHOO JURZWK TKH\ PDLQO\ HPSOR\HG WZR GLIIHUHQW DVVD\V FHOO VXUIDFH DUHD DQG DWULDO QDWULXUHWLF IDFWRU ANF PHDVXUHPHQWV CHOO VXUIDFH DUHD SURYLGHG D FOHDU SK\VLFDO sg.mededu.miami.edu/medicalibis


PHDVXUHPHQW RI P\RF\WH JURZWK ZKLOH WKH ANF OHYHOV ZHUH D SK\VLRORJLF FRUUHODWH MLFKDHO XVHG WKLV IUDPHZRUN WR WHVW D QXPEHU RI GLIIHUHQW FRQGLWLRQV LQ RUGHU WR LGHQWLI\ WKH NH\ RSK3 domains involved in the signal transduction of through PA.AP :KHQ WKH\ RYHUH[SUHVVHG WKH RS.ELQGLQJ GRPDLQ of mAKAP, it competed with the interaction between RSK3 and mAKAP, successfully inhibiting myocyte hypertrophy in vitro. TKH QH[W VWHS IRU MLFKDHO ZDV WR GHWHUPLQH UHOHYDQFH in vivo. UVLQJ NQRFNRXW PLFH KH HPSOR\HG WKUHH PHWKRGV WR LQGXFH hypertrophy and elucidate the roles of RSK3 and mAKAP in FDUGLDF K\SHUWURSK\ WUDQVDRUWLF FRQVWULFWLRQ FKURQLF LVRSURWHUHQRO LQIXVLRQ DQG VZLPPLQJ TUDQVDRUWLF FRQVWULFWLRQ LV a surgical procedure that models aortic stenosis and chronic pressure overload. Chronic isoproterenol infusion models the high catecholamine state of heart failure by increasing cardiac RXWSXW LDVWO\ KDYLQJ WKH PLFH VZLP VHUYHG WR SK\VLRORJLFDOO\ stress the heart. Once the mouse becomes stressed, the mouse’s organs were measured and the heart tissue was stained to assess JURZWK DQG PLFURVFRSLF PHDVXUHPHQWV RI P\RF\WH VL]H MHVVHQJHU RNA OHYHOV DQG SURWHLQ OHYHOV DQG PRGLÀFDWLRQ ZHUH DOVR DQDO\]HG MLFKDHO’V UHVXOWV FRQÀUP WKDW ERWK RS. DQG PA.AP DUH UHTXLUHG IRU FDUGLDF P\RF\WH K\SHUWURSK\

“Under standing how cel l biology changes from

physio l ogy to pathophysiology is the key to reversing those changes.� Michael plans to pursue a career in academic medicine, aspiring to run a lab for basic science research while also seeing patients and performing translational clinical research. In particular, he believes, “My future career in academic medicine will be largely IRUPHG RQ DQ LPSRUWDQW FRQFHSW I OHDUQHG GXULQJ P\ PKD collaboration.� Michael was eating lunch one day in the Stem Cell Institute’s ORXQJH FDVXDOO\ GLVFXVVLQJ KLV UHVHDUFK ZLWK -RQDWKDQ HHUW] D PKD VWXGHQW DQDO\]LQJ WKH UHWLQD DQG JODXFRPD LQ WKH ODE of Jeffrey Goldberg, M.D., Ph.D., associate professor of ophWKDOPRORJ\ MLFKDHO KDG D UHYHODWLRQ ZKDW LI WKH\ DSSOLHG KLV sg.mededu.miami.edu/medicalibis

Michael Kritzer, Ph.D. DHJUHH PURJUDP M.D./Ph.D. M D /Ph D E[SHFWHG *UDGXDWLRQ 2015 MHQWRU Michael Kapiloff, M.D., Ph.D. HRQRUV PUHVHQWHG DW WKH APHULFDQ HHDUW AVVRFLDWLRQ  SFLHQWLĂ€F SHVVLRQV PXEOLVKHG LQ CLUFXODWLRQ RHVHDUFK (PMID 22997248), Journal of Molecular and Cellular Cardiology (PMID 21600214), American Journal of PhysiolRJ\ HHDUW DQG CLUFXODWRU\ PK\VLRORJ\ PMID   FXQGHG E\ APHULFDQ HHDUW AVVRFLDWLRQ PUHDRFWRUDO FHOORZVKLS AZDUGHG BHVW OUDO PUHVHQWDWLRQ DW WKH MD Ph.D. Annual Research Symposium 2013 AFWLYLWLHV EWKLFV HXPDQLWLHV PDWKZD\ MDPKD SFLHQWLĂ€F DQG PURIHVVLRQDO DHYHORSPHQWDO CRPPLWWHH ESRF Judging Committee, Music Ensembles for the Enrichment of Medicine FXWXUH *RDOV Academic Medicine UHVHDUFK WR WKH ZRUN EHLQJ GRQH LQ WKH *ROGEHUJ ODE" IQ WKH heart, cell growth is harmful but in the eye, cellular growth of retinal ganglion cell axons could save someone’s vision. Michael and Jonathan approached their mentors and after promising preliminary results from experiments over the next several days, WKH WZR ODEV MRLQWO\ DSSOLHG DQG ODWHU UHFHLYHG D R NIH JUDQW MLFKDHO FUHGLWV KLV UHYHODWLRQ WR ISCI DLUHFWRU -RVKXD HDUH M.D., who designed the layout of the building to foster such dynamic collaboration. MLFKDHO’V ZRUN FXOPLQDWHG ZLWK KLV PKD WKHVLV DQG SDUW of this project was published in Circulation Research in 2013. MLFKDHO UHFHLYHG DQ APHULFDQ HHDUW AVVRFLDWLRQ AHA SUH GRFWRUDO IHOORZVKLS DV IXQGLQJ IRU KLV ZRUN DQG SUHVHQWHG WKH SUHOLPLQDU\ GDWD DW WKH AHA  SFLHQWLĂ€F SHVVLRQ HH ZDV DOVR DZDUGHG BHVW OUDO PUHVHQWDWLRQ DW WKH  MDPKD Annual Research Symposium and his mentor, Dr. Kapiloff, UHFHLYHG WKH UQLYHUVLW\ RI MLDPL MLFDK BDWFKHORU AZDUG EDVHG RQ WKH UHVHDUFK LQYROYHG LQ WKLV SURMHFW TKH .DSLORII ODE DOVR Ă€OHG D SDWHQW IRU WKH XVH RI WKH RS.ELQGLQJ GRPDLQ DV D SKDUmaceutical intervention for the inhibition of hypertrophy and prevention of heart failure. TKRXJK MLFKDHO KDV PRYHG RQ WR KLV FOLQLFDO \HDUV DV D SDUW of the M.D. program, he continues to collaborate with members of his lab, who are furthering his research to see if his in vitro UHVXOWV WKDW XWLOL]HG WKH RYHUH[SUHVVLRQ RI RS.ELQGLQJ domain can be replicated in vivo to inhibit mouse cardiac hypertrophy. Michael believes that his research has the potential to JUHDWO\ LQĂ XHQFH WKH PDQDJHPHQW RI K\SHUWURSK\ ² HLWKHU LQ hypertrophic cardiomyopathy, a leading cause of sudden death in young athletes, or in heart failure, a leading cause of death in the adult population. Future implications of Michael’s research could save countless lives. Spring 2014 | The Medical I.B.I.S.

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CAMPUS Characterization of Fragile X Syndrome Caused by FMR1 Deletions

BY HOUDA BOUCEKKINE

8

The Medical I.B.I.S. | Spring 2014

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My heart is with the patients and I knew I wanted to do research directly with them.�

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F

ragile X is the most commonly inherited form of intellectual disability in males as well as the PRVW FRPPRQ VLQJOH JHQH PXWDWLRQ NQRZQ WR FDXVH DXWLVP TKH VSHFLÀF JHQH UHVSRQVLEOH LV the FMR1 gene, which is typically silenced by the expansion of CGG trinucleotide repeats seen in Fragile ; TKLV FDXVHV D GHÀFLHQF\ LQ WKH FUDJLOH ; MHQWDO RHWDUGDtion Protein (FMRP), leading to the physical, intellectual, and EHKDYLRUDO PDQLIHVWDWLRQV RI WKLV GLVHDVH HRZHYHU WKHUH KDYH been cases of patients with the typical Fragile X phenotype who ODFN WKH C** H[SDQVLRQ WKHVH LQGLYLGXDOV ZHUH IRXQG WR KDYH PLFURGHOHWLRQV RI WKH FXOSULW JHQH UHVXOWLQJ LQ WKH VDPH ODFN of FMRP seen with the CGG expansion. In her case study, Kaitlin Young describes three such cases. TKH FDVH VWXG\ FRQVLVWHG RI D FROODERUDWLRQ LQYROYLQJ WKUHH patients treated at specialty Fragile X clinics. Physicians at these FHQWHUV LQFOXGLQJ .DLWOLQ’V PHQWRU DHERUDK BDUERXWK MD have been collecting information regarding these three children. Initially, they all presented with the Fragile X phenotype, but tested negative when the diagnostic tools for Fragile X—southHUQ EORW DQG PCR DPSOLÀFDWLRQ³ZHUH DGPLQLVWHUHG OQFH D chromosomal microarray was performed, the microdeletions were detected as the underlying cause. UQGHU WKH GLUHFWLRQ RI DU BDUERXWK DQG JHQHWLF FRXQVHORU AELJDLO RXSFKRFN DHSSHQ MS C*C .DLWOLQ RUJDQL]HG WKH data for these patients and helped write the case study, in which VKH FKDUDFWHUL]HG WKH SDWLHQWV’ V\PSWRPV GHYHORSPHQWDO GHOD\V through childhood, and physical features. Kaitlin described all of the testing that the children went through, placing emphasis on the detection of chromosomal deletions via microarray. Kaitlin explains that these cases illustrate the importance of incorporating chromosomal microarray into genetic testing, particularly for situations in which the etiology is not detected E\ RWKHU WRROV TKHVH FDVHV SURYLGH IXUWKHU VXSSRUW IRU WKH XVH of the microarray becoming the gold standard to determine genetic abnormalities underlying intellectual disability, autism, and other disorders without an apparent cause. Kaitlin further notes that early diagnosis of Fragile X is critical in order to SURYLGH DGHTXDWH LQWHUYHQWLRQV DQG PHGLFDO WUHDWPHQW .DLWOLQ EHJDQ ZRUNLQJ RQ WKLV SURMHFW LQ -XQH  GXULQJ WKH VWDUW RI KHU WKLUG \HDU DW MLOOHU DQG SUHVHQWHG KHU ZRUN DW ESRF WKLV SDVW FHEUXDU\ HHU LQYROYHPHQW ZLWK EDVLF VFLHQFH UHVHDUFK LQ WKH ÀHOG RI DXWLVP EHJDQ EHIRUH DWWHQGLQJ PHGLFDO sg.mededu.miami.edu/medicalibis

school. Once she was accepted to the Genetics Pathway of EPSKDVLV GXULQJ KHU ÀUVW \HDU VKH FRQWDFWHG DU BDUERXWK and became involved in a clinical drug trial for Fragile X SDWLHQWV DW TKH SRXWK FORULGD FUDJLOH ; COLQLF TKURXJK WKLV experience, Kaitlin met many Fragile X families and awareness groups around South Florida, and she has continued her LQYROYHPHQW ZLWK WKH FOLQLF LQFOXGLQJ IUHTXHQW VKDGRZLQJ Kaitlin presented the South Florida Fragile X Clinic poster at the International Fragile X Conference in Miami last summer and has participated in other volunteer activities involving FUDJLOH ; DQG DXWLVP TKURXJK KHU HQGHDYRUV VKH KDV VHHQ the abilities of dedicated individuals to come together to raise awareness and support for a common cause—something that VKH ÀQGV JHQXLQHO\ KHDUWZDUPLQJ As for future plans, one of Kaitlin’s main goals is to stay LQYROYHG ZLWK WKH FUDJLOH ; COLQLF DQG ZRUN FORVHO\ ZLWK WKH ´VZHHW DQG DPD]LQJ¾ FKLOGUHQ DV VKH GHVFULEHV WKHP .DLWOLQ DQG KHU PHQWRUV DUH DOVR LQ WKH SURFHVV RI ORRNLQJ IRU PRUH patients with Fragile X in other clinics across the country to expand the case study. She plans to spread awareness about genetic testing once she becomes a physician, in the hopes that PRUH SDWLHQWV ZLOO EHQHÀW IQ WHUPV RI KHU FDUHHU VKH LV FXUUHQWO\ considering pediatric neurology, but she plans to incorporate genetics into her practice regardless of her specialty. As for QRZ VKH HQMR\V ZRUNLQJ FORVHO\ ZLWK NLGV DW WKH FOLQLF ZKHQHYHU her busy school life permits.

Kaitlin Young DHJUHH PURJUDP M.D. E[SHFWHG *UDGXDWLRQ 2015 MHQWRU AELJDLO DHSSHQ MS C*C DHERUDK BDUERuth, M.D. HRQRUV Poster at the International Fragile X Conference  PRVWHU SUHVHQWDWLRQ DW ESRF  AFWLYLWHV Genetics Pathway of Emphasis, South Florida Fragile X Clinic Volunteer, DOCS Project Manager, CDULQJ HHDUWV PHGLDWULF IQWHUHVW *URXS *HQHWLFV SWXGHQW IQWHUHVW *URXS AFDGHPLF SRFLHWLHV TUDLQHU FXWXUH *RDOV PHGLDWULFV NHXURORJ\ RU *HQHWLFV Spring 2014 | The Medical I.B.I.S.

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CAMPUS Surrogate Fitness Measures Association with Functional Independence in Spinal Cord Injuries

BY ANDREW RICHARDSON

:

ith an undergraduate degree in exercise physiology and his eye on a residency in orthopedic surgery, Darryl Cannady II hoped to focus his research on patients with spinal cord injuries SCIV  DDUU\O IRXQG ZKDW KH ZDV ORRNLQJ IRU LQ WKH ODE RI MDUN NDVK PKD SDUW RI WKH MLOHU SFKRRO’V MLDPL PURMHFW WR CXUH PDUDO\VLV UQGHU WKH PHQWRUVKLS RI -RFKHQ .UHVVOHU’V PKD KH EHJDQ ZRUNLQJ RQ VXUURJDWH ÀWQHVV PHDVXUHV RI DHURELF FDSDFLW\ and anaerobic power. AHURELF FDSDFLW\ DQG DQDHURELF SRZHU DUH WZR NH\ PHDVXUHV RI ÀWQHVV ZKLFK DUH W\SLFDOO\ DVVHVVHG YLD SHDN R[\JHQ FRQVXPSWLRQ VOSHDN DQG WKH :LQJDWH SURWRFRO UHVSHFWLYHO\ IQ patients suffering from chronic SCIs, research has demonstrated WKDW ÀWQHVV LV UHODWHG WR LQFUHDVHG IXQFWLRQDO LQGHSHQGHQFH Functional independence can be thought of as a person’s ability WR SHUIRUP DFWLYLWLHV RI GDLO\ OLYLQJ ADLV  :KDW PRVW FRQVLGHU PXQGDQH ADLV OLNH VKRZHULQJ JRLQJ WR WKH EDWKURRP or moving from room to room, are often enormous challenges for someone suffering from a SCI. LRRNLQJ WR ÀQG D OHVV H[SHQVLYH DOWHUQDWLYH WR WKH VOSHDN DQG :LQJDWH H[DPV MDUN’V ODERUDWRU\ LQLWLDWHG D SURMHFW WR create their own measures to predict functional independence. TKH\ GHYHORSHG WKH PLQXWH PPT DQG VHFRQG VPT

push tests to assess aerobic capacity and anaerobic power, UHVSHFWLYHO\ TKH GHVLJQ RI WKHVH WHVWV LV LQWHQWLRQDOO\ VLPSOLVWLF TR UXQ WKHP \RX QHHG D  PHWHU KDOOZD\  FRQHV DQG D VWRSZDWFK IQ WKHVH WHVWV WKH ZKHHOFKDLUERXQG SDWLHQW LV DVNHG WR

Darryl Cannady II DHJUHH PURJUDP M.D. E[SHFWHG *UDGXDWLRQ 2016 MHQWRU Jochen Kressler, Ph.D. HRQRUV Presented at ESRF 2014, American College of Sports Medicine Conference 2014 AFWLYLWLHV PUHVLGHQW RI SWXGHQW NDWLRQDO MHGLFDO AVVRFLDtion, DOCS FXWXUH *RDOV Orthopedic Surgery, Sports Medicine 10

The Medical I.B.I.S. | Spring 2014

Darryl with his lab group at the Lois Pope Life Center. push her/himself as far as possible in either 6 minutes or 30 VHFRQGV TKH WRWDO GLVWDQFH WUDYHOHG E\ WKH SDWLHQW GHWHUPLQHV WKHLU VXUURJDWH ÀWQHVV VFRUHV AIWHU DQDO\]LQJ WKH GDWD DDUU\O IRXQG WKDW WKH PPT DQG VPT VFRUHV VKRZHG D GLVWLQFW UHODWLRQVKLS ZLWK WKH VSLQDO FRUG LQGHSHQGHQFH PHDVXUH SCIM  TKH UHVXOWV VXJJHVWHG WKDW their surrogate measures could provide predictive power for functional independence in patients who depend on wheelchairs as their primary mode of ambulation. Darryl pointed out that WKH ODE PLJKW XVH WKH PPT DQG VPT WR REVHUYH WKH HIÀFDF\ RI SCI WUHDWPHQWV RYHU WLPH TKH KRSH LV WKDW WKH SDWLHQW’V VXUURJDWH ÀWQHVV VFRUHV ZLOO FRQWLQXH WR ULVH DQG WKDW WKLV WUHQG will correlate with improved SCIM scores. DDUU\O EHOLHYHV WKDW KLV ZRUN KDV SURYLGHG KLP ZLWK ERWK a deeper understanding for the care of SCI patients, and the JUDWLÀFDWLRQ WKDW FRPHV DORQJ ZLWK PHGLFDO UHVHDUFK ´:DWFKLQJ the community support each other is inspiring, they can see the research progress and how it improves lives.� sg.mededu.miami.edu/medicalibis


Evidence of Accelerated Aging in Individuals with Spinal Cord Injury BY LE ZHONG

Joshua with Dr. Rachel Cowan in Lois Pope Life Center.

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V D ÀUVW \HDU VWXGHQW DW WKH MLOOHU SFKRRO -RVKXD PDUNHU ZDQWHG WR FRPELQH KLV LQWHUHVW LQ JHQHWics and his career aspiration in orthopedic spine VXUJHU\ LQWR D UHVHDUFK SURMHFW HH MRLQHG WKH ODE of Rachel Cowan, P.h.D. at the Miami Project to Cure Paralysis where he began researching the possibility of DNA ELRPDUNHUV IRU DFFHOHUDWHG DJLQJ LQ LQGLYLGXDOV ZLWK VSLQDO cord injury (SCI). Current research suggests that individuals with SCI tend to DJH DW D IDVWHU UDWH WKDQ WKH JHQHUDO SRSXODWLRQ :KLOH SUHYLRXV studies have shown correlations such as increased prevalence of chronic diseases, higher mortality rates, and reduced lifespans IRU LQGLYLGXDOV ZLWK SCI WKHUH LV D ODFN RI PROHFXODU HYLGHQFH WR FRUURERUDWH WKHVH ÀQGLQJV Dr. Cowan and her team postulate that mean telomere length sg.mededu.miami.edu/medicalibis

LV QHJDWLYHO\ FRUUHODWHG ZLWK SCI THORPHUHV DUH UHSHDWHG DNA VHTXHQFHV DW WKH HQGV RI FKURPRVRPHV WKDW FDQQRW EH IXOO\ FRSLHG ZKHQ D FHOO UHSOLFDWHV LWV DNA SULRU WR GLYLGLQJ AV D result, telomeres shorten after each round of cell division and eventually prohibit the cell from dividing further, ultimately leading to cell death. Joshua’s project aimed to see if telomere length was shortened in SCI individuals. Joshua hit the phones in the hopes of enrolling volunteers IRU WKH QHZ VWXG\ FRU HDFK SDUWLFLSDQW D EORRG VDPSOH FKHHN VZDE DQG D IHZ OLIHVW\OH VXUYH\V ZHUH WDNHQ DNA ZDV DQDO\]HG WR GHWHUPLQH WKH WHORPHUH IRU LWV VLQJOH FRS\ JHQH UDWLR TS  a measurement of the telomere length relative to the entire FKURPRVRPH SR IDU WKH VWXG\ KDV FROOHFWHG WKH TS UDWLR IRU eight SCI individuals and eight normal controls matched for DJH JHQGHU UDFH DQG VPRNLQJ VWDWXV TKH GDWD VKRZ WKDW ZKLOH WKH DYHUDJH TS UDWLR ZDV VPDOOHU LQ SCI individuals than in the controls, the results were statistically LQVLJQLÀFDQW -RVKXD FLWHV ORJLVWLFDO OLPLWDWLRQV RI WKH VWXG\ VXFK DV D UHODWLYHO\ VPDOO VDPSOH VL]H DQG WKH DELOLW\ WR RQO\ ORRN DW RQH ELRPDUNHU DV SRWHQWLDO UHDVRQV IRU WKH VWDWLVWLFDO LQVLJQLÀFDQFH -RVKXD’V UHVHDUFK WR LGHQWLI\ ELRPDUNHUV IRU LQFUHDVHG DJLQJ in SCI individuals will hopefully improve the lives of individuals with SCI through more effective, preventative screening in the future. Joshua’s favorite part of the project has been the ´RSSRUWXQLW\ WR ZRUN ÀUVWKDQG ZLWK SDUDO\]HG LQGLYLGXDOV DQG seeing how determined they are to live a normal life despite WKH REVWDFOHV¾ -RVKXD EHOLHYHV WKDW KLV DQG KLV ODE’V ZRUN ZLOO someday allow individuals with SCI to achieve the same goals as the rest of the non-disabled population with fewer obstacles than they face in their day-to-day lives now.

Joshua Parker DHJUHH PURJUDP M.D. E[SHFWHG *UDGXDWLRQ 2016 MHQWRU Rachel Cowan, Ph.D. HRQRUV Presented at ESRF 2014 AFWLYLWLHV Genetics Pathway of Emphasis, Genetics Interest Group, Orthopedics Interest Group, Deans Cup, Flag Football FXWXUH *RDOV Orthopedic Spine Surgery

Spring 2014 | The Medical I.B.I.S.

11


CAMPUSPatients¡ Awareness of STD Clinic Non-AIDS Complications

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BY SAPIR KARLI

XPDQ LPPXQRGHÀFLHQF\ YLUXV HIV LQIHFWV many types of cells, including the immune V\VWHP TKH QDWXUDO KLVWRU\ RI WKLV LQIHFWLRQ OHDGV WR VHYHUH LPPXQRGHÀFLHQF\ AIDS WKDW is almost always fatal. Although current theraSLHV DQWLUHWURYLUDO WKHUDS\ RU ART KDYH VLJQLÀ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she conducted a research project that aimed to create a better XQGHUVWDQGLQJ RI WKH PDJQLWXGH RI ZKDW LW PHDQV WR DFTXLUH DQ HIV LQIHFWLRQ DV D KLJKULVN LQGLYLGXDO SKH DOVR ZRUNHG WR promote the continuation of preventative methods by educating members of the community about complications unrelated to AIDS WKDW HIVLQIHFWHG LQGLYLGXDOV RIWHQ IDFH TKH SXUSRVH RI WKH VWXG\ ZDV WR REWDLQ SLORW GDWD DERXW DZDUHQHVV RI QRQAIDS FRPSOLFDWLRQV DQG VHOISHUFHLYHG HIV ULVN LQ STD SDWLHQWV LQ SRXWK FORULGD IQQD SHUIRUPHG D FURVV VHFWLRQDO VXUYH\ HYDOXDWLQJ SDWLHQWV’ NQRZOHGJH RI QRQHIV AIDS associated conditions such as cognitive implications,

Inna Granovsky DHJUHH PURJUDP M.D. E[SHFWHG *UDGXDWLRQ 2016 MHQWRU Jose G. Castro, M.D. HRQRUV Infectious Diseases Society of America ERF Medical SFKRODUV PURJUDP ID :HHN  ASSURYHG IRU SXEOLFDWLRQ LQ the Journal of Therapy and Management in HIV Infection AFWLYLWLHV DOCS AQDWRP\ RRVH CHUHPRQ\ HHDOWK LDZ PDWKway of Emphasis, Adler-Everitt Community Service Project Coordinator FXWXUH *RDOV UQGHFLGHG

12

The Medical I.B.I.S. | Spring 2014

FDUGLRYDVFXODU GLVHDVH DQG SUHPDWXUH DJLQJ TKH TXHVWLRQQDLUH DGGLWLRQDOO\ DVVHVVHG KRZ LPSRUWDQW LW LV IRU VXEMHFWV WR XWLOL]H HIV SUHYHQWDWLYH PHWKRGV It was found that only a third of patients viewed themselves DV EHLQJ DW ULVN RI DFTXLULQJ HIV HYHQ WKRXJK PRUH WKDQ KDOI of the participants had a sexually transmitted disease in the past. MRVW SDWLHQWV ZHUH XQGHU WKH SHUFHSWLRQ WKDW HIV FDQ EH IXOO\ WUHDWHG ZLWK ART DQG ZHUH QRW DZDUH RI HIVDVVRFLDWHG FRQGLWLRQV WKDW FXUUHQW PHGLFDWLRQV FDQQRW HDVLO\ WUHDW HRZHYHU DIWHU educating these patients on the prevalence and importance of QRQHIV FRPSOLFDWLRQV D YDVW PDMRULW\ GHPRQVWUDWHG DSSUHKHQVLRQ UHJDUGLQJ HIV DFTXLVLWLRQ TKH VWXG\ VKRZHG WKDW D EULHI LQIRUPDWLRQDO VHVVLRQ FRXOG increase patient willingness and dedication to using new biomedLFDO VWUDWHJLHV WR SUHYHQW HIV LQIHFWLRQ B\ VSUHDGLQJ DZDUHQHVV WKH QHZ SHUFHSWLRQ WKDW HIV LV D IXOO\ WUHDWDEOH GLVHDVH ZLWK IHZ DVVRFLDWHG ULVNV PD\ EH PRGLĂ€HG IQQD KRSHV WR XVH WKH GDWD gathered from this study in a preventative manner to spread DZDUHQHVV UHJDUGLQJ H[LVWLQJ FRPSOLFDWLRQV RI HIV LQIHFWLRQ HYHQ ZLWK FXUUHQW DQWLUHWURYLUDO WKHUDSLHV B\ VKDULQJ WKLV NQRZOedge with the community, she hopes to shift the focus from relying on life-prolonging therapies towards more preventative care. Inna hopes to combine her research experience and clinical career to become the best doctor and researcher she can be. sg.mededu.miami.edu/medicalibis


Cholesterol and Glycosphingolipids ProÀles of Human Trabecular Meshwork and Aqueous Humor BY SAPIR KARLI

Katya working with the mass spectrometer.

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laucoma is the second leading cause of EOLQGQHVV ZRUOGZLGH TKH GLVHDVH UHIHUV WR a group of ocular pathologies that lead to increased intraocular pressure and associated optic neuropathy secondary to optic nerve damage. Vision loss starts at the periphery and slowly SURJUHVVHV WR FHQWUDOO\ TKHUHIRUH V\PSWRPV RFFXU ZKHQ WKH GLVHDVH LV XQIRUWXQDWHO\ DOUHDG\ TXLWH DGYDQFHG TKRXJK XQGHUVWDQGLQJ WKH VSHFLÀF SDWKRORJLF SURFHVV XQGHUO\LQJ JODXFRPD can contribute to the creation of novel treatments, the physiological and mechanical changes that occur have not yet been previously explored. Katyayini Aribindi is hoping to contribute WR WKH ÀHOG E\ FRQGXFWLQJ UHVHDUFK DW WKH BDVFRP PDOPHU E\H IQVWLWXWH UQGHU WKH PHQWRUVKLS RI SDQMR\ BKDWWDFKDU\D MS M THFK PKD VKH H[SORUHG WKH OLSLG FRQWHQW LQ JODXFRPDWRXV and non-glaucomatous eyes as part of an ongoing collaboration EHWZHHQ DU BKDWWDFKDU\D DQG RLFKDUG LHH MD PKD Katyayini’s interest in conducting research in ophthalmology began in high school when she shadowed a glaucoma specialist. AV DQ XQGHUJUDGXDWH DW UM KHU DGYLVRU LQWURGXFHG KHU WR DU BKDWWDFKDU\D ZKR SURYLGHG KHU ZLWK WKH RSSRUWXQLW\ WR EH D SDUW of his research lab. Katyayini views her role in the laboratory not only as an opportunity to aspire to achieve her goals, but sg.mededu.miami.edu/medicalibis

also as a chance to use her capabilities to contribute to medicine. TKH SXUSRVH RI .DW\D\LQL’V UHVHDUFK SURMHFW ZDV WR GHWHUPLQH WKH GLIIHUHQWLDO SURĂ€OHV RI FKROHVWHURO DQG JO\FRVSKLQJROLSLG VSHFLHV DV ZHOO DV WKHLU TXDQWLWDWLYH GLIIHUHQFHV EHWZHHQ FRQWURO DQG JODXFRPDWRXV DTXHRXV KXPRU A4H DQG WKH WUDEHFXODU PHVKZRUN TM VDPSOHV GHULYHG IURP KXPDQ GRQRUV .DW\D\LQL TXDQWLĂ€HG FKROHVWHUROV DQG JO\FRVSKLQJROLSLGV LQ WKH VDPSOHV XVLQJ D PDVV VSHFWURPHWHU DQG WKHQ DQDO\]HG WKHLU VSHFWUD XVLQJ M=PLQH  DQG LQ KRXVH PDFURV HHU IDYRULWH SDUW RI FRQGXFWing this project was using the mass spectrometer, which she views as “a beautiful collaboration between computer science, physics, biology, organic chemistry, and biochemistry.â€? Katyayini found that control and primary open angle glaucoma (POAG) samples had a high percentage of cholesterol and JO\FRVSKLQJROLSLG VSHFLHV LQ FRPPRQ ZLWK ERWK A4H DQG TM VDPSOHV HRZHYHU WKHUH ZHUH VHYHUDO VSHFLHV WKDW ZHUH VSHFLĂ€F WR HLWKHU WKH POA* RU WR WKH FRQWUROV TKH UHVXOWV VXJJHVW WKDW the progression of glaucoma correlates with an accumulation RI D XQLTXH FKROHVWHURO LQ A4H ² WKH PHFKDQLVP RI ZKLFK remains to be further elucidated. Katyayini hopes that her research will set the stage for future SURMHFWV WR FRQWLQXH FKDUDFWHUL]LQJ WKH VSHFLĂ€F FKDQJHV WKDW occur in the cholesterol and glycosphingolipid species of glauFRPD SDWLHQWV TKLV ZLOO KRSHIXOO\ IXUWKHU DLG LQ WKH GLVFRYHU\ of novel treatment methods. :KLOH VKH HQMR\V RSKWKDOPRORJ\ .DW\D\LQL LV NHHSLQJ DQ RSHQ PLQG DERXW ZKLFK VSHFLDOW\ VKH ZRXOG XOWLPDWHO\ OLNH WR SUDFWLFH RHJDUGOHVV RI ZKLFK Ă€HOG VKH ZLOO HQWHU VKH SODQV RQ FRQWLQXLQJ WR SDUWLFLSDWH LQ UHVHDUFK LQ KRSHV RI LPSURYLQJ WKH TXDOLW\ RI life of affected people through discoveries in medicinal science.

Katyayini Aribindi DHJUHH PURJUDP M.D. E[SHFWHG *UDGXDWLRQ 2017 MHQWRU SDQMR\ BKDWWDFKDU\D MS M THFK PKD HRQRUV PUHVHQWHG DW ARVO  PMID 

AFWLYLWHV MHGLFDO HXPDQLWLHV COXE FXWXUH *RDOV UQGHFLGHG Spring 2014 | The Medical I.B.I.S.

13


CAMPUS Dendritic Cells Induce Plasmacytoid Regulatory T-cells that can Prolong Cardiac Allograft Survival

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BY ANDREW RICHARDSON

elected as a prestigious Sarnoff Cardiovascular Research Fellow, Jared Glans, Class of 2015, decided to dedicate a year to research after his third year at the Miller School. Aiming to explore his dual interest in surgery and immunology, Jared sought out a laboratory that would not only allow him to test hypotheses at the bench, but also gain exposure to surgery and translational medicine. After interviewing at several hospitals across the country, the lab of Joren Madsen, M.D., D.Phil., Director of WKH MDVVDFKXVHWWV *HQHUDO HRVSLWDO TUDQVSODQW CHQWHU VWRRG RXW IURP WKH UHVW -DUHG EHJDQ KLV RQH\HDU IHOORZVKLS LQ BRVWRQ in July of 2013. Jared explained that “the biggest problem of current organ WUDQVSODQWV LQ KXPDQV LV WKDW LW LV H[WUHPHO\ GLIĂ€FXOW WR SUHYHQW

organ rejection and even when we can prevent it, there is great morbidity and mortality from the immunosuppressive medications.� Successfully inducing tolerance in human transplants LV WKH ´KRO\ JUDLO¾ RI WUDQVSODQWDWLRQ UHVHDUFK TROHUDQFH LV GHÀQHG DV WKH DEVHQFH RI D GHVWUXFWLYH LPPXQH UHVSRQVH WR D transplanted tissue without ongoing immunosuppression. Jared’s project focuses on developing a method to achieve just that in heart transplants. -DUHG LV ZRUNLQJ WR IXUWKHU FKDUDFWHUL]H KRZ FHUWDLQ LPPXQH FHOOV VSHFLÀFDOO\ UHJXODWRU\ T FHOOV DQG SODVPDF\WRLG GHQGULWLF cells (pDCs), affect immune tolerance and long-term organ DFFHSWDQFH LQ PLFH HLV FRPHQWRU AOHVVDQGUR AOHVVDQGULQL PKD VKRZHG WKDW UHJXODWRU\ T FHOOV DQG SDCV SOD\ D SLYRWDO UROH LQ EXLOGLQJ WROHUDQFH WR WKH WUDQVSODQWHG PRXVH NLGQH\V -DUHG’V

Jared Gans working at the FACS machine at the Massachusetts General Hospital Transplant Laboratory.

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The Medical I.B.I.S. | Spring 2014

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GHYRWH P\ WLPH VROHO\ WR UHVHDUFK KDV JUHDWO\H[SDQGHGP\VFLHQWL�FDFXPHQDQG ZLOOSURYHLQYDOXDEOHWRP\IXWXUHFDUHHUರ project applies that same mechanism to mouse heart transplants. HH KDV K\SRWKHVL]HG WKDW SDCV DUH DQ LPSRUWDQW SOD\HU LQ WKH LQGXFWLRQ RI UHJXODWRU\ TFHOOV TR WHVW WKLV K\SRWKHVLV -DUHG ÀUVW WRRN SDCV DQG H[SRVHG WKHP WR QDwYH TFHOOV DQG YDULRXV F\WRNLQHV LQ FXOWXUH TKH SDCV LQGXFHG WKH TFHOOV WR FUHDWH FR[S D PDUNHU RI UHJXODWRU\ TFHOOV TFHOOV HH WKHQ WRRN WKH FR[S TFHOOV DQG WHVWHG WKHP IRU VXSSUHVVLYH DFWLYLW\ UVLQJ à RZ F\WRPHWU\ WR WUDFN SUROLIHUDWLRQ RI T HIIHFWRU FHOOV -DUHG discovered that his in vitroLQGXFHG FR[S TFHOOV SUHYHQWHG WKH SUROLIHUDWLRQ RI RWKHU TFHOOV TKHVH UHVXOWV FRQÀUPHG -DUHG’V RULJLQDO K\SRWKHVLV DQG KH LV FXUUHQWO\ ZRUNLQJ RQ UHSOLFDWLQJ the data in cultured non-human primate cells. Jared’s in vitro data correlates with his in vivo studies as well. FRU WKLV FRPSRQHQW RI KLV UHVHDUFK -DUHG WRRN KLV FXOWXUHG FR[S TFHOOV DQG LQMHFWHG WKHP LQWR PLFH SULRU WR KHWHURWRSLF KHDUW WUDQVSODQWDWLRQ TKH UHVXOWV VKRZHG D VWDWLVWLFDOO\ VLJQLÀFDQW SURORQJDWLRQ RI WKH DOORJUDIW KHDUW VXUYLYDO LQ WKH experimental mice. Concurrently, Jared is involved with Dr. Madsen’s non-human SULPDWH VWXGLHV RQ WKRUDFLF RUJDQ WUDQVSODQWV UWLOL]LQJ FR WUDQVSODQWDWLRQ RI D NLGQH\ RU WK\PXV ZLWK ERQH PDUURZ WUDQVplantation, Jared has attempted to induce tolerance to cardiac DQG OXQJ WUDQVSODQWV LQ OOG :RUOG F\QRPROJXV PRQNH\V FRU WKH ÀUVW WLPH WKHVH FRPSOH[ UHJLPHQV KDYH SURYHQ VXFFHVVIXO LQ SULPDWHV HH VSHQGV PXFK RI KLV WLPH KHOSLQJ ZLWK WKH FDUH RI WKH PRQNH\V SODQQLQJ SULPDWH VWXGLHV DQG DVVLVWLQJ VXUJLFDO RSHUDWLRQV TKH JRDO IRU ERWK SULPDWH VWXGLHV DQG -DUHG’V PRXVH UHVHDUFK LV WR ÀQG D FOLQLFDOO\ WUDQVODWDEOH PRGHO IRU FDUGLDF allograft acceptance in humans. -DUHG KDV VXEPLWWHG DQ DEVWUDFW WR WKH :RUOG TUDQVSODQW CRQJUHVV DQG SUHVHQWHG DW WKLV \HDU’V ESRF TKH SDUQRII RHVHDUFK Fellowship, a program in which twelve medical students are selected each year to pursue a project of their choice, funds -DUHG’V UHVHDUFK TKH SURJUDP KDV EHHQ HVWDEOLVKHG IRU RYHU thirty years and is dedicated to life-long mentorship of its memEHUV -DUHG LV WKH ÀUVW PHGLFDO VWXGHQW IURP WKH MLOOHU SFKRRO WR sg.mededu.miami.edu/medicalibis

be selected for the fellowship. Dean Pascal Goldschmidt, M.D., NDQHWWH BLVKRSULF MD DQG -RVKXD HDUH MD DUH WKH RQO\ other members of the Sarnoff Foundation at the Miller School. :LWK D SODQ WR SXUVXH D FDUHHU LQ DFDGHPLF PHGLFLQH -DUHG believes that his research year will provide him with a strong IRXQGDWLRQ LQ EDVLF VFLHQFH DQG WUDQVODWLRQDO UHVHDUFK HLV QXDQFHG VFLHQWLÀF XQGHUVWDQGLQJ RI LPPXQRORJLFDO WROHUDQFH LV DSSOLFDEOH WR PDQ\ ÀHOGV RI PHGLFLQH LQFOXGLQJ WKH RQH WKDW -DUHG LV PRVW LQWHUHVWHG LQ RWRODU\QJRORJ\ HH EHOLHYHV WKDW insights into immunological processes are crucial to new discoveries in otolaryngology – including facial transplants, allergic UKLQLWLV DQG KHDGQHFN FDQFHU LRQJWHUP LPPXQRORJLFDO WROHUDQFH UHPDLQV DQ XQPHW JRDO RI modern medicine, but Jared’s research has elucidated some of the underlying mechanisms that bring the profession one step FORVHU HLV SURMHFW FRQWLQXHV WR ZRUN WRZDUGV D FOLQLFDOO\ WUDQVlatable model for heart transplantation acceptance in humans.

Jared Gans DHJUHH PURJUDP M.D. E[SHFWHG *UDGXDWLRQ 2015 MHQWRU -RUHQ MDGVHQ MD DPKLO AOHVVDQGUR AOHVsandrini, Ph.D. HRQRUV Sarnoff Cardiovascular Research Fellow 2013 OUDO SUHVHQWDWLRQ DW WKH ESRF  SXEPLWWHG WR :RUOG TUDQVSODQW CRQJUHVV  SXEPLWWHG WR HDUYDUG Surgery Research Day Symposium 2014 AFWLYLWHV Alpha Omega Alpha, President of American MHGLFDO SWXGHQW AVVRFLDWLRQ CRFRRUGLQDWRU MDMPH JURVV DQDWRP\ SURJUDP AVVLVWDQW LRJLVWLFV DLUHFWRU IRU DOCS, Secretary CaneShare, Academics Coordinator for LDHQQHF FXWXUH *RDOV Otolaryngology Spring 2014 | The Medical I.B.I.S.

15


CAMPUS The Quest to Cure Kaposi Sarcoma

BY GABE WEINGROD-NEMZOW

“

I truly love translational research and I’m going to do my best to help patients by combining my medical and VFLHQWLÀF EDFNJURXQGV¾ VD\V LXFDV CDYDOOLQ PKD FXUUHQWO\ LQ KLV VHFRQG \HDU DW WKH MLOOHU SFKRRO LXFDV LV UHVHDUFKing Kaposi Sarcoma (KS), a cancer that is caused by Kaposi SDUFRPD HHUSHV VLUXV .SHV DOVR NQRZQ DV HXPDQ HHUSHV VLUXV   HLV JRDO LV WR XQGHUVWDQG WKH DOWHUHG VXUYLYDO SDWKZD\V LQ WKH .SHV LQIHFWHG FHOOV DQG H[SORLW WKLV SDWKZD\ WR SURGXFH D VSHFLÀF DQWLFDQFHU WKHUDS\ KS is a cancer of the cells that line the circulatory system HQGRWKHOLDO FHOOV DQG IRUPV EOXHSXUSOH SDWFKHV DQG SODTXHV LQ WKH VNLQ PRXWK LQWHVWLQHV DQG OXQJV ´.S KDV WKH FRORU RI D EUXLVH¾ VD\V LXFDV ´EHFDXVH RI WKH DQJLRJHQHVLV >EORRG YHVVHO formation] caused by the blood vessel tumor.� KS is particularly SUHYDOHQW LQ AIDS SDWLHQWV TUHDWPHQW RI .S LQYROYHV WKH XVH RI GUXJV WKDW GR QRW VSHFLÀFDOO\ WDUJHW .S VXFK DV DQWLUHWURYLUDO therapy and highly toxic cancer drugs. LXFDV IRXQG D VXUYLYDO SDWKZD\ WKDW FDQ EH GLVUXSWHG WR NLOO .S WXPRU FHOOV LQ D OHVV WR[LF PDQQHU ´NRUPDOO\ FDQFHU FHOOV are addicted to a few pathways that promote cell proliferation and survival, so by targeting these pathways we can disrupt the RQFRJHQLF SURFHVV :H ZDQW WR LGHQWLI\ D VXUYLYDO SDWKZD\ IRU .SHV VR ZH FDQ GHYHORS VSHFLÀF WKHUDSLHV ZKLFK ZLOO EH OHVV WR[LF WKDQ RXU FXUUHQW QRQVSHFLÀF GUXJV¾ LXFDV DQG KLV FROOHDJXHV LQ WKH ODE RI EQULTXH MHVUL PKD at the Sylvester Cancer Center and the Miami Center for AIDS Research, along with Pascal J. Goldschmidt M.D., Senior Vice President for Medical Affairs and Dean of the Miller School of Medicine, created a mouse model of KS as part of his doctoral thesis at the Microbiology and Immunology Graduate PURJUDP RI UM EHIRUH VWDUWLQJ PHGLFDO VFKRRO TKH\ LQIHFWHG

Lucas Cavallin, Ph.D. D DHJUHH PURJUDP M.D. P MD E[SHFWHG *UDGXDWLRQ 2016 MHQWRU EQULTXH MHVUL PKD PDVFDO *ROGVFKPLGW MD HRQRUV Sylvester Cancer Center Research Poster CompeWLWLRQ :LQQHU  FORULGD MHGLFDO AVVRFLDWLRQ’V AQQXDO PRVWHU S\PSRVLXP  AOYLQJ AZDUG :LQQHU ESRF  AFWLYLWLHV DOCS Public Relations Manager FXWXUH *RDOV Academic Medicine

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The Medical I.B.I.S. | Spring 2014

.SHV LQ HQGRWKHOLDO OLQHDJH SURJHQLWRU VWHP FHOOV ZKLFK ZHUH K\SRWKHVL]HG WR GHYHORS LQWR WKH QDWXUDO WDUJHW FHOOV IRU .SHV LQ KXPDQV LXFDV WKHQ LQMHFWHG WKHVH FHOOV LQWR DGXOW LPPXQRFRPSURPLVHG PLFH DQG SURGXFHG .SHV VDUFRPDV UVLQJ WKLV PRGHO LXFDV KDV QRZ LGHQWLĂ€HG D VSHFLĂ€F RQFRJHQLF pathway for KS. UVLQJ GDWD IURP PRXVH DQG KXPDQ .S WLVVXHV LXFDV SHUformed microarray analysis to sample thousands of messenger RNAV DW RQFH HH IRXQG WKDW ERWK KXPDQ DQG PRXVH .S H[SUHVVHG KLJK OHYHOV RI WKH W\URVLQH NLQDVH UHFHSWRU RT.

platelet derived growth factor receptor-Ď (PDGFRĎ) and the proteins that activate it. Although these cells have two PDGFR subtypes (Ď and ȕ  LXFDV KDG HYLGHQFH WKDW RQO\ WKH Ď VXEW\SH ZDV LPSOLFDWHG LQ .S TR GHWHUPLQH LI WKLV FHOOXODU UHFHSWRU GURYH WKH FDQFHU LXFDV SHUIRUPHG GLUHFWHG SKRVSKRSURWHRPLFV D VFUHHQLQJ WHFKQLTXH WKDW GHWHFWV DFWLYDWHG RT.V IW ZDV IRXQG WKDW WKH RQO\ RT. WKDW ZDV VLJQLÀFDQWO\ overexpressed in the mouse model of KS was PDGFRĎ TR YHULI\ WKH SKRVSKRSURWHRPLF VWXG\ LQ KXPDQV LXFDV XVHG LPPXQRKLVWRFKHPLVWU\ D WHFKQLTXH XVHG WR ODEHO SURWHLQV with histological sections supplied by Dr. Paolo Romanelli, a dermatopathologist at the Miller School and found active PDGFRĎ LXFDV K\SRWKHVL]HG WKDW WKLV UHFHSWRU ZDV WKH GULYing mutation for KS and that possible anti-cancer treatments could be tailored using this altered survival pathway. LXFDV’V QH[W JRDO ZDV WR XQGHUVWDQG KRZ WKH YLUXV DFWLYDWHV WKH UHFHSWRU .SHV LV D FRPSOH[ YLUXV ZLWK  JHQHV  RI these genes were pirated from humans, and all 14 are associated ZLWK RQFRJHQHVLV DQG DQJLRJHQHVLV LXFDV GHFLGHG WR IRFXV RQ the viral G-protein coupled receptor (vGPCR) because his lab showed that it is essential in KS oncogenesis and angiogenesis. HH IRXQG WKDW Y*PCR DFWLYDWHV R[LGDWLYH VLJQDOLQJ SDWKZD\V that lead to the production of the ligands for PDGFRĎ. FROORZLQJ WKLV GLVFRYHU\ LXFDV DWWHPSWHG WR VXSSUHVV WKH PDGFRĎ SDWKZD\ XVLQJ WZR GLIIHUHQW VWUDWHJLHV TKH ÀUVW VWUDWegy was to prevent PDGFRĎ oncogenesis (which is activated by R[LGDWLYH SDWKZD\V E\ XVLQJ NDFHW\OF\VWHLQH NAC  NAC LV D safe anti-oxidant most commonly used in acetaminophen overGRVHV WR GHWR[LI\ WKH OLYHU TKH RWKHU VWUDWHJ\ ZDV WR VXSSUHVV all of the PDGFR pathways with a drug called Imatinib, which EORFNV LQWUDFHOOXODU VLJQDOLQJ WKURXJK RT.V OLNH PD*FRĎ, by preventing its activation. It is already used for treating chronic P\HORJHQRXV OHXNHPLD JDVWURLQWHVWLQDO VWURPDO WXPRUV DQG VHYHUDO RWKHU UDUH WXPRUV LXFDV SHUIRUPHG in vitro and in vivo VWXGLHV RI WKH .S PRXVH PRGHO XVLQJ ERWK NAC DQG IPDWLQLE sg.mededu.miami.edu/medicalibis


Lucas (left) with Sachin Gupta Ph.D., M.B.A. (right), and Santas Rosario checking endothelium-derived KSHV-infected cells under the microscope.

“I’m going to do my best to help patients by combining my medical and scientif ic backgrounds.â€? to suppress the PDGFRÄŽ signaling, and found that there was a VLJQLĂ€FDQW UHGXFWLRQ LQ WXPRU JURZWK ZLWK NAC DQG IPDWLQLE TKH RQO\ FDYHDW WR WKH IPDWLQLE H[SHULPHQW LV WKDW IPDWLQLE DIIHFWV DOO WKH PD*FR VXEW\SHV TR SURYH WKDW IPDWLQLE LQKLEsg.mededu.miami.edu/medicalibis

ited oncogenesis only through the PDGFRĎ SDWKZD\ LXFDV SHUIRUPHG WDUJHW YDOLGDWLRQ KH KDUYHVWHG WKH WXPRUV DQG SHUIRUPHG :HVWHUQ EORWV WR GHWHUPLQH WKH SURWHLQ OHYHOV RI activated PDGFRĎ TKH GDWD VKRZHG D UHGXFWLRQ LQ PD*FRĎ, indicating that the PDGFRĎ needs to be activated in KS. LXFDV ZDV VWLOO XQVDWLVÀHG ZLWK MXVW SURYLQJ WKH LQYROYHment of PDGFRĎ E\ XVLQJ D GUXJ WULDO TR FRQFOXVLYHO\ YHULI\ the driving pathway was PDGFRĎ LXFDV GHYLVHG D JHQHWLF H[SHULPHQW LXFDV DQG KLV DVVRFLDWHV JHQHWLFDOO\ FUHDWHG .SHV infected cells that expressed a non-functional PDGFRĎ, called a dominant negative PDGFR Ď PXWDQW TKLV PXWDWLRQ ZRXOG NQRFNRXW RQO\ RQH VWHS LQ WKH LQWUDFHOOXODU VLJQDOLQJ FDVFDGH PDNLQJ LW D PRUH VSHFLÀF H[SHULPHQW WKDQ WKH IPDWLQLE DQG NAC WHVWLQJ LXFDV IRXQG WKDW WKH GRPLQDQW QHJDWLYH PD*FRĎ mutant failed to produce tumors. B\ DIIHFWLQJ RQO\ RQH JHQH LQ WKH KRVW LXFDV KDG QHDUO\ completely inhibited oncogenesis, which supports the hypothesis that PDGFRĎ SDWKZD\ LV RQFRJHQLF LQ .S BHFDXVH RI KLV ZRUN PDQNLQG QRZ KDV D VSHFLÀF SKDUPDFRORJLF WDUJHW LQ WKH ÀJKW DJDLQVW .S LXFDV KRSHV WR ORRN IRU PRUH SRWHQW VPDOO PROHFXOH GUXJV WKDW ZLOO EH PRUH HIIHFWLYH LQ EORFNLQJ the PDGFRĎ SDWKZD\ DQG WKXV KHOS WR GHYHORS VSHFLÀF DQG more effective anti-KS drugs. Spring 2014 | The Medical I.B.I.S.

17


EffectCAMPUS of AMPK Activator in the Treatment of Retinal Tumors BY JEFFREY SMITH

Nikesh in front of the Bascom Palmer Eye Institute.

R

etinoblastoma is a cancer that develops from WKH UHWLQDO FHOOV DW WKH EDFN RI WKH H\H IW IRUPV from the immature retinal cells in the eyes of children as a result of underexpression of the WXPRU VXSSUHVVRU JHQH RB DQG FDQ UDSLGO\ lead to blindness if it is not treated. Although retinoblastoma has one of the best cure rates of childhood cancers, there is room for improvement in treatment since the current treatment procedures of chemotherapy and radiation can lead to VLJQLÀFDQW PRUELGLW\ II WKH WXPRUV SURJUHVV WKH\ FDQ EHFRPH FKHPRUHVLVWDQW OHDGLQJ WR KLJK IDLOXUH UDWHV LQ WUHDWPHQW TKHVH tumors often have regions of hypoxia, which causes these cells to become dependent upon anaerobic glycolysis for energy producWLRQ BLRFKHPLFDO FKDQJHV JHQHUDWHG LQ WKHVH K\SR[LF FHOOV FRXOG EH XWLOL]HG DV D WDUJHW IRU WKHUDSHXWLF UHWLQREODVWRPD WUHDWPHQW :KHQ NLNHVK SKDK D VHFRQG\HDU VWXGHQW DW WKH MLOOHU SFKRRO VWDUWHG KLV VHDUFK IRU D UHVHDUFK SURMHFW KH NQHZ KH ZDQWHG WR ZRUN LQ HLWKHU DQ RSKWKDOPRORJLF RU RQFRORJLF ÀHOG Fortunately for him, he found a project under the supervision RI TLPRWK\ MXUUD\ MD MBA FACS IRUPHUO\ PURIHVVRU of Ophthalmology and Ocular Oncology at the Miller School, 18

The Medical I.B.I.S. | Spring 2014

DW WKH BDVFRP PDOPHU E\H IQVWLWXWH ZKLFK FRPELQHG KLV LQWHUHVWV NLNHVK ZDV IXUWKHU PRWLYDWHG E\ LQWHUDFWLQJ ZLWK FKLOGUHQ GLDJQRVHG ZLWK UHWLQREODVWRPD NQRZLQJ WKDW KLV UHVHDUFK FRXOG potentially change their treatment and improve their lives. TKH IRFXV RI KLV SURMHFW ZDV FHQWHUHG RQ D SRWHQWLDO WKHUDSHXWLF DJHQW IRU UHWLQREODVWRPD APLQRLPLGD]ROHFDUER[DPLGH ribonucleotide (AICAR), which has been used in treatment of other medical issues, primarily cardiac ischemic injury, but never in retinoblastoma. AICAR functions as an analog of AMP that LV FDSDEOH RI VWLPXODWLQJ AMP .LQDVH AMP.  WKHUHE\ LQà XHQFLQJ FHOO SUROLIHUDWLRQ TKH\ ZLVKHG WR WHVW WKLV LQ WUDQVJHQLF mouse models of retinoblastoma since these closely resemble KXPDQ UHWLQREODVWRPD HH IRXQG WKDW AICAR VLJQLÀFDQWO\ reduced tumor burden in mice and reduced hypoxic regions, which could indicate its use in conjunction with other treatPHQWV WKDW WDUJHW WKH UDSLGO\GLYLGLQJ WXPRU FHOOV HH ZDV DEOH to present the data from his project at ESRF 2013, where he won the Alving award, and at the Association for Research in Vision and Ophthalmology 2012 meeting. TKDQNV WR KLV H[SHULHQFHV LQ WKLV ÀHOG RI UHVHDUFK NLNHVK has decided to follow a career with an oncological component. HH LV FXUUHQWO\ ZRUNLQJ RQ UHVHDUFK LQ UDGLDWLRQ RQFRORJ\ DQG ORRNV IRUZDUG WR D FDUHHU WKDW KDV D PL[WXUH RI RQFRORJ\ research and a strong clinical component so he can continue to VHH WKH SDWLHQWV KLV UHVHDUFK LV ZRUNLQJ WR KHOS HH LV KRSHIXO WKDW KLV ZRUN ZLOO EH FRQWLQXHG ZLWK UHVHDUFK RI AICAR WUHDWPHQW DORQJVLGH FKHPRWKHUDS\ WR WHVW IRU UHGXFHG PRUELGLW\ HLV H[SHULHQFHV LQ WKLV ÀHOG RI UHVHDUFK KDYH FRQÀUPHG WR KLP WKDW KH ZRXOG OLNH WR SXUVXH D FDUHHU ZLWK D FRPSRQHQW RI UHVHDUFK DQG KDV VWUHQJWKHQHG KLV GHVLUH WR JR LQWR D ÀHOG ZKHUH KH FDQ focus on oncology.

Nikesh Shah D DHJUHH PURJUDP M.D. P MD E[SHFWHG *UDGXDWLRQ 2016 MHQWRU TLPRWK\ MXUUD\ MD MBA FACS HRQRUV Presented at ESRF 2013 AFWLYLWLHV DOCS HLDOHDK AVVLVWDQW PURMHFW MDQDJHU ESRF Judging Chair FXWXUH *RDOV Oncology

sg.mededu.miami.edu/medicalibis


Bioluminescence Energy Capture by Quantum Dots BY LE ZHONG

S

ince middle school, Michael Schoor has been fascinated by methods in biomedical technology applied to helping the environment. As a student at the Miller School, Michael wanted to explore interdisciplinary research combining biomedicine with biochemical methods. Michael joined the lab of Sapna Deo, PKD DQG S\OYLD DDXQHUW PKD WR ZRUN RQ D SURMHFW DLPHG WR FDSWXUH HQHUJ\ IURP ELROXPLQHVFHQW SURWHLQV XVLQJ TXDQWXP GRWV 4DV  FU\VWDOV PDGH RI VHPLFRQGXFWRU PDWHULDO WKDW GLVSOD\ TXDQWXP PHFKDQLFDO SURSHUWLHV GXH WR WKHLU PLFURVFRSLF VL]H 4XDQWXP GRWV DUH FRPPRQO\ XVHG DV D WHFKQLTXH WR GHWHFW VSHFLĂ€F QXFOHLF DFLGV LQ FHOOXODU LPDJLQJ EXW MLFKDHO DQG KLV FROleagues wanted to apply the principle to create a highly sensitive DQG VSHFLĂ€F PHDQV WR GHWHFW DNA DQG RNA MLFKDHO FXOWXUHG E. coli bacteria with Renilla luciferase protein expression and WKHQ KDUYHVWHG WKH SURWHLQ WR XVH IRU DNA GHWHFWLRQ Michael was able to show that the protein bioluminescence FRXOG FDXVH 4DV WR HPLW D QHZ VSHFWUXP LI D DNA OLQNHU IRXQG LWV WDUJHW VHTXHQFH RHVRQDQFH HQHUJ\ WUDQVIHU RFFXUUHG E\ REVHUYLQJ D QHZ SHDN RI YLVLEOH OLJKW HPLVVLRQ DW  QP D

“This is a very exciting step forward for the rapid and sensitive

detection of cancer

Michael with Dr. Sylvia Daunert, Dr. Sapna Deo and his lab group. YDULRXV FRPSOHPHQWDU\ DNA VHTXHQFHV WR VHH LI PXOWLSOH JHQHV FDQ EH LGHQWLĂ€HG DW RQFH MLFKDHO LV YHU\ H[FLWHG DERXW WKLV VWHS forward, hoping that it will allow for the rapid and sensitive detection of cancer, cells, infectious bacteria, and gene expression in the human body. AV IRU WKH UHVHDUFK H[SHULHQFH MLFKDHO KDV HQMR\HG ZRUNLQJ ZLWK D FORVHNQLW JURXS RI FROOHDJXHV LQ KLV ODE MLFKDHO ZRXOG OLNH WR SD\ WULEXWH WR LHWLFLD .RYDOVNL D JUDGXDWH VWXGHQW LQ KLV ODE ZKR UHFHQWO\ SDVVHG DZD\ HH LV JUDWHIXO IRU WKH RSSRUWXQLW\ WR ZRUN ZLWK VXFK DPD]LQJ PLQGV DW WKH LQWHUVHFWLRQ RI ELRHQJLQHHULQJ DQG VFLHQFH MLFKDHO VSHDNV KLJKO\ RI WKH PHQWRUVKLS from Dr. Daunert, Dr. Manoj Kumar, Dr. Daohong Zang, David BUR\OHV DQG EULF HXQW

cells, infectious bacteria, and gene expression in various parts of the human Michael Schoor DHJUHH PURJUDP M.D. body.� E[SHFWHG *UDGXDWLRQ 2014 decrease in Rluc light emission at 485 nm. In other words, the FKDQJHV LQ OLJKW HPLVVLRQ IURP ERWK WKH 4D DQG WKH ROXF ZHUH XVHG DV D PHDQV WR SURYH WKDW DNA WDUJHW VHTXHQFH FRXOG EH measured. In the future, Michael and his colleagues plan to develop and RSWLPL]H WKH V\VWHP DV D UDSLG GHWHFWLRQ WRRO IRU DOO W\SHV RI JHQHWLF PDWHULDO LRRNLQJ IRUZDUG WKH\ SODQ WR DWWDFK 4DV WR sg.mededu.miami.edu/medicalibis

MHQWRU Sapna Deo, Ph.D. HRQRUV Presented at ESRF 2014 AFWLYLWLHV Jewish Student Medical Association, Student *RYHUQPHQW *URVV AQDWRP\ TA NLFDUDJXD MHGLFDO Mission, Molecular Medicine Pathway FXWXUH *RDOV Orthopedic Surgery Spring 2014 | The Medical I.B.I.S.

19


CAMPUS

Arash demonstrating a goniometer on a model.

Arash J. Sayari DHJUHH PURJUDP M.D. MD E[SHFWHG *UDGXDWLRQ 2015 MHQWRU Robert Gray, M.D. HRQRUV Presented at ESRF 2014 AFWLYLWLHV DLUHFWRU RI CRXUYRLVLHU AFDGHPLF SRFLHW\ DOCS PURMHFW VROFDQR MLDPL SWXGHQWV :LWKRXW BRUGHUV FXWXUH *RDOV Orthopedic Surgery 20

The Medical I.B.I.S. | Spring 2014

sg.mededu.miami.edu/medicalibis


Photograph-Based Goniometry: A Comparison of Techniques

A

BY MELISSA STONE

V D ÀUVW\HDU PHGLFDO VWXGHQW AUDVK SD\DUL VSHQW KLV ZLQWHU EUHDN VKDGRZLQJ DQ RUWKRSHGLF VXUJHRQ QHDU KLV KRPH DW UCLA AUDVK EHFDPH fascinated by orthopedics as a specialty and the ability of surgeons to recover a patient’s abilLW\ WR ZDON GHVSLWH SUHYLRXVO\ OLPSLQJ LQ SDLQ ZLWKLQ D PHUH IHZ KRXUV DHVLULQJ JUHDWHU H[SRVXUH WR WKH ÀHOG KH FRQWDFWHG RR\ CDUGRVR MD DQ RUWKRSHGLVW DW WKH UQLYHUVLW\ RI MLDPL HRVSLWDO IRU VKDGRZLQJ RSSRUWXQLWLHV :KHQ AUDVK ZHQW WR DU CDUGRVR’V RIÀFH KH KDSSHQHG WR EH FKDWWLQJ ZLWK D FROOHDJXH Robert Gray, M.D. Overhearing Arash and Dr. Cardoso’s con-

“My research is one example of how we can use new technology to step forward in making medicine more efficient.â€? versation about Arash’s interest in orthopedics and past experiences, Dr. Gray offered him a research opportunity on the spot. Arash became highly engaged in Dr. Gray’s research study IURP WKH VWDUW HH VRRQ EHJDQ DVVHVVLQJ WKH GLIIHUHQW PHDVXUHPHQW WHFKQLTXHV IRU XSSHU H[WUHPLW\ MRLQW PRYHPHQWV VSHFLĂ€FDOO\ Ă H[LRQ DQG H[WHQVLRQ RI WKH HOERZ DQG ZULVW DQG ulnar and radial deviation of the wrist. Orthopedists routinely PHDVXUH DQJOHV RI Ă H[LRQ DQG H[WHQVLRQ RI MRLQW PRYHPHQWV to access the severity of the patient’s impediment and the SDWLHQW’V VXEVHTXHQW GHWHULRUDWLRQ RU LPSURYHPHQW TKH FXUUHQW gold standard for these measurements is manual goniometry, XVLQJ D PRGLĂ€HG SURWUDFWRU WR PHDVXUH WKH DQJOH AUDVK’V VWXG\ compared manual goniometry, photograph-based goniometry, and visual approximations in measuring joint angles for seventy SDWLHQWV ZKR YLVLWHG WKH OUWKRSHGLF HDQG SXUJHU\ COLQLF DW WKH BDVFRP PDOPHU E\H IQVWLWXWH AUDVK SHUIRUPHG PDQ\ RI the manual goniometry and photograph-based goniometry measurements while one orthopedic surgeon performed the visual approximations. IQ FRPSDULQJ WKH WHFKQLTXHV AUDVK IRXQG WKDW RQ DYHUDJH PDQXDO JRQLRPHWU\ WRRN HLJKW PLQXWHV WR SHUIRUP ZKLOH YLVXDO sg.mededu.miami.edu/medicalibis

DSSUR[LPDWLRQ DQG SKRWRJUDSKEDVHG JRQLRPHWU\ WRRN WZR DQG WKUHH PLQXWHV UHVSHFWLYHO\ TKH DFFXUDFLHV RI WKH WKUHH WHFKQLTXHV ZHUH GHWHUPLQHG WR EH FOLQLFDOO\ YDOLG AGGLWLRQDOO\ the inter-rater reliability for photograph-based goniometry was DVVHVVHG DQG GHWHUPLQHG WR EH FOLQLFDOO\ YDOLG TKLV ZDV LPSRUtant to assess because many health care providers are often involved with treating an orthopedic injury. Arash believes, “In 2014, inter-rater reliability is more important to assess than ever EHIRUH :LWK RXU FKDQJLQJ KHDOWK FDUH V\VWHP RUWKRSHGLVWV DUH PRUH OLNHO\ WR UHO\ RQ RWKHU PHGLFDO SHUVRQQHO WR SHUIRUP WKHVH measurements.â€? Arash envisions that the future of orthopedics PLJKW HQWDLO DQRWKHU PHGLFDO SHUVRQQHO WDNLQJ MRLQW PHDVXUHments as part of routine division of labor before the orthopedist HYHQ VHHV WKH SDWLHQW TKHQ WKH RUWKRSHGLVW FDQ VSHQG PRUH WLPH H[DPLQLQJ DQG WDONLQJ WR WKH SDWLHQW UDWKHU WKDQ UHFRUGLQJ measurements. IQ  ZH DUH DOVR PRUH OLNHO\ WR XVH WHFKQLTXHV WKDW HDVLO\ allow us to record measurements in the electronic medical UHFRUG EMR DQG ZRUN ZLWK H[LVWLQJ WHFKQRORJLHV SPDUWphones could act as the photograph-based goniometer, and the photographs can be easily stored in the EMR, easily accessed by various orthopedists for continued evaluation and assessment of improvement or deterioration. Arash is currently a third-year medical student and plans on DSSO\LQJ IRU UHVLGHQF\ LQ RUWKRSHGLFV QH[W \HDU UQGHU WKH GLUHFtion of Dr. Gray, Arash is currently in the process of writing the manuscript for the research study and will soon submit it IRU SXEOLFDWLRQ HH LV KRSLQJ WKDW JUHDWHU DZDUHQHVV ZLWKLQ WKH RUWKRSHGLF FRPPXQLW\ IRU WKH HIĂ€FLHQF\ YDOLGLW\ DQG KLJK LQWHU rater reliability for photography-based goniometry will inspire PRUH RUWKRSHGLVWV WR URXWLQHO\ XVH WKLV WHFKQLTXH WR LPSURYH HIĂ€FLHQF\ DQG DFFXUDF\ LQ WKH ULJKW FOLQLFDO VHWWLQJ AUDVK KRSHV that in the coming years his study will be further validated by expanding the study population to other institutions with difIHUHQW RUWKRSHGLVWV HH ZRXOG DOVR OLNH WR VHH WKLV DQDO\]HG LQ other joints, as his study was focused on the upper extremities. AUDVK LV YHU\ WKDQNIXO WKDW DU *UD\ KDSSHQHG WR EH LQ DU CDUGRVR’V RIĂ€FH RQ WKDW IDWHIXO GD\ DQG VWURQJO\ EHOLHYHV WKDW this experience in clinical research will enable him to be a better physician. Arash states, “Research pushes us to learn more, read PRUH DQG NHHS WKLQNLQJ DERXW KRZ ZH FDQ LPSURYH PHGLFLQH and better help our patients.â€? Arash’s research certainly is a step towards helping his future patients. Spring 2014 | The Medical I.B.I.S.

21


CAMPUS Neuropathic Pain-Induced Depression and TNF

BY HOUDA BOUCEKKINE

M

Spencer analyzing a slide at his lab bench. 22

The Medical I.B.I.S. | Spring 2014

ood disorders such as anxiety and depression are common comorbidities of chronic QHXURSDWKLF SDLQ HRZHYHU WKH PHFKDQLVP underlying this association has yet to be FODULÀHG CXUUHQW HYLGHQFH LQGLFDWHV WKDW OHYHOV RI SURLQà DPPDWRU\ F\WRNLQHV VXFK DV TNF DUH HOHYDWHG LQ VWDWHV RI GHSUHVVLRQ DQG PRUH VSHFLÀFDOO\ WKH VLJQDOLQJ RI WKH VROXEOH IRUP RI TNF VTNF WKURXJK LWV UHFHSWRU³ TNFR³FDQ LPSDLU P\HOLQ SURGXFWLRQ DQG QHXURJHQHVLV LQ WKH hippocampus—one of the main mood-regulating centers of the EUDLQ DHOODUROH HW DO  GDWD QRW SXEOLVKHG \HW  :LWK WKLV LQIRUPDWLRQ LQ KDQG SSHQFHU SXPPHUV MRLQHG D WHDP DW TKH MLDPL PURMHFW WR CXUH PDUDO\VLV WKDW KDV EHHQ VHHNLQJ WR HOXFLGDWH WKH UROH RI TNF DQG LWV UHFHSWRUV WKH SURLQà DPPDWRU\ TNFR DQG WKH QHXURSURWHFWLYH TNFR LQ QHXURSDWKLF SDLQ associated depression, which may provide evidence for more targeted treatment options. Spencer has always had an interest in immunology and neurology, having had performed neuroscience research as an underJUDGXDWH DW VDQGHUELOW UQLYHUVLW\ TKXV ZKHQ WKH RSSRUWXQLW\ to join the Immunologic Medicine Pathway of Emphasis presented itself, he searched for a project that would combine both ÀHOGV UQGHU WKH PHQWRUVKLS RI AQQD DHOODUROH PKD DQG -RKQ BHWKHD PKD SSHQFHU ZRUNHG DV SDUW RI D WHDP FRQGXFWLQJ EDVLF VFLHQFH UHVHDUFK ZLWK TNFR NQRFNRXW PLFH WR GHWHUPLQH the immunological mechanism underlying neuropathic pain and associated depression. Pain was induced by constriction of the VFLDWLF QHUYH DQG ZDV PHDVXUHG DW VXEVHTXHQW ZHHNV YLD WKHUPDO and mechanical sensitivity tests. Depression was assessed by the DPRXQW RI VXJDU ZDWHU WKDW WKH PLFH GUDQN ZLWK OHVV VXJJHVWLQJ D GHSUHVVLYH RU DQKHGRQLF VWDWH TKH PLFH ZHUH VDFULÀFHG DW GLIIHUHQW SHULRGV WR GHWHUPLQH WKH OHYHOV RI TNF TNFR DQG TNFR H[SUHVVLRQ DV ZHOO DV WKH DPRXQW RI P\HOLQDWLRQ in the hippocampus. TKH UHVXOWV VKRZHG WKDW WKH FRQWURO ZLOG W\SH PLFH SUHVHQWHG with increased signs of pain and depression with elevated levels RI KLSSRFDPSDO TNF IQWHUHVWLQJO\ WKH\ ZHUH DOVR IRXQG WR KDYH less neurogenesis and synaptic proteins within the hippocampus. AOWHUQDWLYHO\ WKH NQRFNRXW PLFH ODFNLQJ H[SUHVVLRQ RI TNFR did not present with neuropathic pain or depression. Furthermore, they did not exhibit any alterations in the hippocampus. TKLV GLIIHUHQFH VXJJHVWV WKDW TNFTNFR SOD\ DQ LPSRUWDQW UROH LQ WKH GHYHORSPHQW RI GHSUHVVLRQ AV IRU TNFR H[SUHVsg.mededu.miami.edu/medicalibis


“Performing research at the

Miami Project is inspiring; it’s a daily reminder of how much medicine has yet

to

discover.� sion was reduced in the wild type mice, but remained unchanged LQ WKH TNFR NQRFNRXW PLFH WKHUHE\ LQGLFDWLQJ WKDW TNFR may be a factor in preventing neuropathic pain and depression. TKLV LV WKH ÀUVW VWXG\ FRQÀUPLQJ D UROH RI TNFR LQ WKH mediation of neuropathic pain-induced depression. Spencer HPSKDVL]HG WKH SURPLVLQJ SRWHQWLDO RI WKHVH UHVXOWV IRU WDUJHWLQJ TNFR DV D VSHFLÀF PHWKRG IRU WUHDWLQJ SDLQ DQG WKH DVVRFLDWHG PRRG GLVRUGHUV A PRUH VSHFLÀF WUHDWPHQW WKDQ WKRVH currently available may provide alleviation of pain symptoms, as well as relief of the socially and psychologically crippling effects of depression that over half of those with neuropathic

pain suffer from. DU BHWKHD’V ODE LV FXUUHQWO\ ZRUNLQJ WR LGHQWLI\ WKH FHOOV SULPDULO\ UHVSRQVLEOH IRU VHFUHWLQJ TNF LQ WKH CNS DQG WR GHOYH GHHSHU LQWR WKH UROH RI TNFR DV D QHXURSURWHFWLYH IDFWRU Spencer continues to be involved in these experiments, conVWDQWO\ DPD]HG E\ KRZ VHHPLQJO\ VLPSOH FRQFHSWV SUHVHQWHG LQ OHFWXUH DUH WUDQVIRUPHG LQWR LQWULFDWH UHDOLWLHV LQ WKH ODE HH ÀQGV LW YHU\ UHZDUGLQJ WR EH SDUW RI QHZ GLVFRYHULHV WKDW PD\ have greater implications down the road. As such, Spencer hopes to continue his involvement in research throughout his career, potentially as a physician-scientist.

Spencer Summers DHJUHH PURJUDP M.D. E[SHFWHG *UDGXDWLRQ 2016 MHQWRU -RKQ BHWKHD PKD AQQD DHOODUROH PKD HRQRUV Poster presentation at the Florida Medical Association Annual Meeting 2013 AFWLYLWLHV EWKLFV RHSUHVHQWDWLYH DOCS SRXWK DDGH HHDOWK FDLU PURMHFW MDQDJHU *URVV AQDWRP\ TA DHUPDWRORJ\ IQWHUest Group, Immunologic Medicine/Infectious Diseases Pathway of Emphasis FXWXUH *RDOV NHXURVXUJHU\ OUWKRSHGLF SXUJHU\ RU AOOHUJ\IPPXQRORJ\

sg.mededu.miami.edu/medicalibis

Spring 2014 | The Medical I.B.I.S.

23


CAMPUS LBH Role in Normal and Neoplastic Mammary Stem Cell Control

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BY JEFFREY SMITH

QOLNH PRVW RI KHU SHHUV LLQVH\ LLQGOH\ D ÀUVW year student at the Miller School, was already a doctor upon entering medical school. She successfully defended her thesis and graduated with her Ph.D. from the Department RI BLRFKHPLVWU\ DQG MROHFXODU BLRORJ\ DW WKH MLOOHU SFKRRO XQGHU WKH VXSHUYLVLRQ RI .DUROLQH BULHJHO PKD LLQVH\’V UHVHDUFK IRFXVHG RQ WKH :NT VLJQDOLQJ SDWKZD\ DQG LWV UROH LQ breast cancer, which she became interested in due to the multiGLVFLSOLQDU\ QDWXUH RI WKH SURMHFW SKH UHFDOOV ´TKLV SURMHFW ZDV YHU\ H[FLWLQJ LQ WKDW DOO RI WKHVH ÀHOGV RI VWXG\ ZHUH PHOGHG WR IRUP D SURMHFW WKDW DLPHG WR WHDVH DSDUW WKH LQQHU ZRUNLQJV RI a completely novel potential therapeutic target for a particularly OHWKDO W\SH RI EUHDVW FDQFHU EDVDOVXEW\SH WULSOH QHJDWLYH EUHDVW FDQFHU TNBC µ BUHDVW FDQFHU LV WKH VHFRQG OHDGLQJ FDXVH RI FDQFHUUHODWHG deaths in women, with aggressive basal-subtype breast cancers disproportionally contributing to the number of deaths, SULPDULO\ GXH WR WKH ODFN RI WDUJHWHG PROHFXODU WKHUDSLHV DYDLODEOH TKLV EUHDVW FDQFHU VXEW\SH GLVSOD\V K\SHUDFWLYDWLRQ RI WKH :NT SDWKZD\ DQG LV FKDUDFWHUL]HG E\ DQ XQGLIIHUHQWLDWHG WXPRU SKHQRW\SH HQULFKHG LQ FDQFHU VWHP FHOOV LLPEBXG DQG HHDUW LBH LV D QRYHO WUDQVFULSWLRQDO UHJXODWRU\ SURWHLQ LQ WKH :NT SDWKZD\ ZLWK XQNQRZQ SK\VLRORJLFDO IXQFWLRQ ZKLFK ZDV RULJLQDOO\ GLVFRYHUHG E\ DU BULHJHO’V ODERUDWRU\ IQWHUHVWLQJO\ LBH LV H[SUHVVHG LQ EUHDVW VWHP FHOOV ZKLFK DUH ORFDWHG LQ WKH basal epithelial cell layer of the mammary gland, but is also overexpressed in basal-subtype breast cancers and may repreVHQW D PROHFXODU WDUJHW IRU TNBC WUHDWPHQW TR GHWHUPLQH WKH

Linsey Lindley, Ph.D. DHJUHH PURJUDP M.D. E[SHFWHG *UDGXDWLRQ 2017 MHQWRU .DUROLQH BULHJHO PKD HRQRUV Published in Genesis (PMID 23495064), PLoS ONE (PMID 22844464), Biochemical & Biophysical Research Communications (PMID 23495064), poster or oral presentations at 10 different conferences AFWLYLWLHV DOCS FXWXUH *RDOV Academic Medicine 24

The Medical I.B.I.S. | Spring 2014

PHFKDQLVWLF IXQFWLRQ RI LBH LQ QRUPDO VWHP FHOO ELRORJ\ DQG FDQFHU LLQVH\’V ODERUDWRU\ GHYHORSHG D XQLTXH LBH NQRFNRXW mouse model. It was demonstrated that upon inactivation of LBH IXQFWLRQ WKH PLFH H[KLELWHG D GHOD\ LQ SXEHUWDO PDPPDU\ JODQG GHYHORSPHQW DQG D VNHZHG GLVWULEXWLRQ RI HSLWKHOLDO FHOO GHYHORSPHQW TKLV FRXOG EH WUDFHG WR D GHÀFLHQF\ LQ WKH VHOI UHQHZDO DELOLW\ DQG QXPEHU RI PDPPDU\ VWHP FHOOV TKH\ DOVR PRGXODWHG WKH H[SUHVVLRQ RI LBH LQ KXPDQ EUHDVW FDQFHU FHOO OLQHV WR GHWHUPLQH WKH UROH RI LBH LQ FDQFHU VWHP FHOO GHYHOopment. TKH GDWD IURP WKHVH H[SHULPHQWV VKRZHG WKDW LBH LV UHTXLUHG for cancer stem cell formation by promoting a basal stem cell VWDWH DQG UHSUHVVLQJ H[SUHVVLRQ RI OXPLQDO OLQHDJHVSHFLÀF JHQHV VSHFLÀFDOO\ WKH JRRG SURJQRVWLF PDUNHU EVWURJHQ RHFHSWRU ER  TKH\ DOVR LGHQWLÀHG D LBH PROHFXODU WDUJHW SURWHLQ WKH NH\ HSLWKHOLDO VWHP FHOO WUDQVFULSWLRQ IDFWRU ¨NS ZKLFK LQ JUHDW SDUW PD\ H[SODLQ WKH VWHPFHOO SURPRWLQJ HIIHFWV RI LBH TKH\ FRQFOXGHG WKDW LBH SOD\V DQ HVVHQWLDO UROH LQ SURPRWLQJ mammary stem cell function in both normal and cancerous VHWWLQJV IPSRUWDQWO\ WKHLU ÀQGLQJV VXJJHVW LQKLELWLRQ RI LBH FRXOG EH XVHG WR UHVHQVLWL]H WXPRU FHOOV WR NQRZQ HQGRFULQH WKHUDSLHV WDUJHWHG DJDLQVW ER LLQVH\ EHOLHYHV IXWXUH VWXGLHV ZLOO IRFXV RQ FODULI\LQJ WKH QDWXUH RI LQWHUDFWLRQ EHWZHHQ LBH DQG ¨NS DQG KRZ WKLV UHSUHVVHV H[SUHVVLRQ RI ER LLQVH\ HQMR\HG WKH FKDOOHQJHV WKDW FDPH ZLWK VWXG\LQJ D QRYHO SURWHLQ DW D YHU\ EDVLF OHYHO DQG XVLQJ WKHVH ÀQGLQJV WR H[SORUH the pathological context of breast cancer. She believes this research will help her achieve her future goals, which include ZRUNLQJ LQ DQ DFDGHPLF PHGLFLQH VHWWLQJ WKDW ZRXOG DOORZ KHU to interact directly with patients and continue to pursue research focused on novel molecular treatments. sg.mededu.miami.edu/medicalibis


Curcumin Treatment Promotes Glioblastoma Stem Cell Death BY LAURA BLOOM

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achary Gersey came to the Miller School in 2012 NQRZLQJ KH ZDQWHG WR ZRUN RQ FDQFHU HDYLQJ VSHQW WZR \HDUV RQ NLGQH\ DQG SURVWDWH UHVHDUFK DW WKH UQLYHUVLW\ RI FORULGD =DFK ZDV TXLFN WR VKDGRZ LQ WKH RQFRORJ\ GHSDUWPHQW :LWK D GXDO interest in neurosurgery, it wasn’t long before a neuro-oncologist in the wards introduced Zach to Ricardo Komotar, M.D. and Regina Graham, Ph.D. Dr. Komotar conducts numerous UHVHDUFK SURMHFWV DW WKH UMBTI ² WKH BUDLQ TXPRU IQLWLDWLYH ZKLFK KH KRSHV VRPHGD\ ZLOO EHFRPH WKH BUDLQ TXPRU IQVWLWXWH TKLV SDVW -XO\ =DFK EHJDQ FRQGXFWLQJ UHVHDUFK ZLWK DU .RPRWDU DQG DU *UDKDP RQ *OLREODVWRPD MXOWLIRUPH *BM

– the most common and most lethal form of brain tumor in DGXOWV CXUUHQW WUHDWPHQW IRU *BM LV D FRPELQDWLRQ RI VXUJLFDO UHVHFWLRQ RI WKH WXPRU UDGLDWLRQ DQG WHPR]RORPLGH DQ RUDO FKHPRWKHUDS\ GUXJ  =DFK GHVFULEHV WKLV DV œLQYDVLYH SDOOLDWLYH

Zachary pipetting at the tissue culture bench. sg.mededu.miami.edu/medicalibis

Zachary Gersey DHJUHH PURJUDP M.D. E[SHFWHG *UDGXDWLRQ 2016 MHQWRU Regina Graham, Ph.D. HRQRUV PUHVHQWHG DW MLDPL :LQWHU S\PSRVLXP TKH MROHFXODU BDVLV RI BUDLQ DLVRUGHUV  AFWLYLWLHV VLFH PUHVLGHQW RI HHPDWRORJ\OQFRORJ\ SWXdent Interest Group, Academic societies training aid FXWXUH *RDOV NHXURVXUJHU\ RQFRORJ\ ccare,’ because patients are still only expected to survive 12-14 months due to tumor recurrence. m TKH VWHP FHOO WKHRU\ RI FDQFHU SURSRVHV WKDW DPRQJ FDQFHUous cells, a few act as stem cells that produce and sustain the o cancer, thereby leading to recurrence despite resection of many of the mature cancer cells. Previous research suggests a conQHFWLRQ EHWZHHQ *BM DQG WKH œQRWFK SDWKZD\’ DV ZHOO DV WKH anti-cancer properties of curcumin (the principle ingredient in WXUPHULF  ZKLFK LQVSLUHG WKLV UHVHDUFK SURMHFW *BM WXPRU FHOOV were collected from six consenting patients, and then cultured WR HQULFK IRU WXPRU VWHP FHOOV TKHVH FHOOV ZHUH WKHQ WUHDWHG ZLWK WKH VWDQGDUG WHPR]RORPLGH DV ZHOO DV FXUFXPLQ IQFUHGLEO\ HQRXJK WKH *BM WXPRU VWHP FHOOV EHJDQ WR GLH LQGLFDWLQJ great success. AV RIWHQ KDSSHQV LQ UHVHDUFK WKLV GLVFRYHU\ OHG WR PRUH TXHVWLRQV IQ IDFW RQO\ FXUFXPLQ ² QRW WHPR]RORPLGH ² DIIHFWHG WKH *BM VWHP FHOOV AOVR FXUFXPLQ ZDV QRW LQà XHQFLQJ WKH œQRWFK SDWKZD\’ DIWHU DOO EXW UDWKHU OHYHOV RI WKH SURWHLQ œVXUYLYLQ’ Survivin inhibits cell death, is overexpressed in many malignanFLHV DQG FRUUHODWHV ZLWK SRRU SURJQRVLV LQ *BM =DFK’V GDWD VXJJHVWV WKDW FXUFXPLQ LQGXFHV *BM VWHP FHOO GHDWK DW OHDVW in part by down regulation of survivin. Curcumin may target additional neoplastic pathways and thus has positive therapeutic LPSOLFDWLRQV IRU *BM DV ZHOO DV RWKHU FDQFHUV =DFK LV H[FLWHG IRU WKH IXWXUH RI WKLV UHVHDUFK HH SUHVHQWHG WKLV SURMHFW LQ -DQXDU\ DW WKH MLDPL  :LQWHU S\PSRVLXP TKH MROHFXODU BDVLV RI BUDLQ DLVRUGHUV TKHUH LV VWLOO PXFK ZRUN WR GR EXW =DFK KRSHV WKDW WKLV ZLOO HYHQWXDOO\ HQWHU FOLQLFDO WULDOV AIWHU DOO WKH XOWLPDWH JRDO LV WR ÀQG D FXUH WKDW FDQ someday help real people. Spring 2014 | The Medical I.B.I.S.

25


CAMPUS Insurance Implications for Choice of Stent Type

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BY HOUDA BOUCEKKINE

ealth care insurance is a topic that everyone LV VSHDNLQJ RI QRZDGD\V ZLWK DOO WKH UHFHQW changes that have occurred. A driving subject behind these changes has been the issue of healthcare disparities within our society in WHUPV RI DFFHVV WR DQG TXDOLW\ RI KHDOWKFDUH UHFHLYHG :LWK DQ interest in this topic, Jamie Diamond came up with a research SURMHFW ZLWK KHU PHQWRU LHRQDUGR TDPDUL] MD ZKLFK ZRXOG exemplify the extent to which healthcare disparities and stereotypes are present within the medical setting. -DPLH GHFLGHG WR ORRN LQWR WKH XVH RI GUXJHOXWLQJ VWHQWV DES YHUVXV EDUHPHWDO VWHQWV BMS WR UHGXFH UHVWHQRVLV LQ

angioplasty or percutaneous coronary intervention patients. It is well established in the literature that DES have clear clinical DGYDQWDJHV DQG DUH PRUH HIIHFWLYH WKDQ BMS LQ GHFUHDVLQJ WKH prevalence of restenosis in percutaneous coronary intervention SDWLHQWV TKH LVVXH LV WKDW DES DUH D PRUH H[SHQVLYH RSWLRQ FXUWKHUPRUH WKH\ UHTXLUH PRUH VHOIFDUH LQ UHJDUGV WR WKH SDWLHQW ZLWK DES GXDO DQWLSODWHOHW WKHUDS\ DAPT  VXFK DV Plavix and aspirin, must be implemented by the patient for a ORQJHU SHULRG RI WLPH WKDQ ZLWK BMS TKHVH IDFWV DQG SK\VLFLDQ opinions about compliance often drive physicians’ decisions WR XWLOL]H D DES RU BMS IRU SDWLHQWV -DPLH GHFLGHG WR GHOYH IXUWKHU LQWR WKLV WRSLF E\ GHWHUPLQLQJ LI WKH LQVXUDQFH RU ODFN

Jamie analyzing articles for meta-analysis.

26

The Medical I.B.I.S. | Spring 2014

sg.mededu.miami.edu/medicalibis


thereof) carried by the patient may play a factor in a physician’s GHFLVLRQ WR XVH D DES RU BMS TKH UHVHDUFK LQYROYHG D PHWDDQDO\VLV RI SXEOLVKHG DUWLFOHV WKDW QRWHG ZKHQ D SDWLHQW ZDV JLYHQ D DES RU BMS DQG ZKDW insurance the patient had. In order to do this analysis, Jamie SHUIRUPHG D V\VWHPDWLF VHDUFK RI PXEPHG ZLWK NH\ZRUGV VXFK DV ´LQVXUDQFHÂľ ´VWHQWÂľ ´UQLWHG SWDWHVÂľ DQG ´PHUFXWDQHRXV CRURQDU\ IQWHUYHQWLRQÂľ TKH VHDUFK UHVXOWHG LQ  SXEOLFDWLRQV DQG -DPLH VLIWHG WKURXJK DOO WKHVH DUWLFOHV WR SLFN RXW WKRVH LQ ZKLFK WKH UHVHDUFK ZDV SHUIRUPHG LQ WKH UQLWHG SWDWHV DQG ZKLFK FRPSDUHG DES YV BMS XVH DPRQJ JRYHUQPHQW LQVXUDQFH VXEW\SHV MHGLFDUH DQG MHGLFDLG HMO LQVXUDQFH DQG XQLQsured populations, with commercial insurance as the reference. She was able to reduce the analysis to 13 publications, on which she used two statistical random-effects models to calculate the UHODWLYH ULVN RI VWHQW XVH EDVHG RQ LQVXUDQFH TKH UHVXOWV RI WKH PHWDDQDO\VLV UHYHDOHG WKDW EDUHPHWDO VWHQWV ZHUH PRUH OLNHO\ WR EH XWLOL]HG LQ SDWLHQWV ZLWK JRYHUQment insurance or no insurance than in patients carrying commercial insurance. Similarly, Medicare and Medicaid patients ZHUH DOVR PRUH OLNHO\ WR UHFHLYH BMS UDWKHU WKDQ DES ZKHQ FRPSDUHG WR WKHLU FRPPHUFLDOO\LQVXUHG FRXQWHUSDUWV TKLV analysis in itself shows that care differs between patients who KDYH GLIIHUHQW NLQGV RI LQVXUDQFH VSHFLĂ€FDOO\ LW OHDQV WRZDUGV WKH LGHD WKDW WKRVH ZLWK OHVV FRYHUDJH UHFHLYH OHVV TXDOLW\ FDUH IW LV WKRXJKW WKDW DOO SDWLHQWV ZKR FDQ FRPSO\ ZLWK WKH DAPT regimen should receive the DES considering the greater effectiveness of these stents, but statistics indicate otherwise. Given the fact that physicians are the ones who decide whether the SDWLHQW UHFHLYHV D BMS RU DES WKH UHVXOWV VXJJHVW WKDW SK\VLFLDQV PD\ EH LQFOXGLQJ D SHUVRQ’V FRYHUDJH RU H[SHFWHG DAPT FRPSOLDQFH LQ WKHLU GHFLVLRQ YHUVXV PDNLQJ D SXUHO\ PHGLFDO decision. Jamie mentions hearing a physician admit that choice of stent placement is typically made by the physician based on physical appearance and expected medication compliance rather WKDQ VKDUHG GHFLVLRQPDNLQJ ZLWK WKH SDWLHQW OI FRXUVH WKLV ORJLF DQG SURĂ€OLQJ LV FRQMHFWXUH EXW UHJDUGOHVV WKH UHVXOWV RI the meta-analysis show that those with less coverage are less

“This is a good message to remind people not to judge their patients, and that they deserve high quality care no matter what type of insurance.� OLNHO\ WR UHFHLYH WKH KLJKHVW TXDOLW\ FDUH LQ WHUPV RI VWHQWV As Jamie puts it, the main message received from this research project is that people with different types of insurance receive different care. It is another example of health disparities that exist in our society. Jamie hopes that the results of this research ZLOO PDNH SHRSOH aware of a form of healthcare disparity that PDQ\ PD\ QRW NQRZ RI DQG VKH KRSHV LW ZLOO HQFRXUDJH PHGLFDO SHUVRQQHO WR QRW MXGJH WKHLU SDWLHQWV TKLV YLVLRQ LV LQ OLQH with her passion for public health and her future goal of being involved with healthcare policy and legislation. As such, this research project allowed her to not only experience a new type of research (i.e. a meta-analysis involving statistical methods), but it also enabled her to delve into the realm of public health, thus experiencing a real-life application of the lectures she receives as SDUW RI WKH MDMPH SURJUDP SKH HQYLVLRQV D IXWXUH FDUHHU that combines her interest in cardiology and her desire to help with the issue of discordant healthcare provision.

Jamie Diamond DHJUHH PURJUDP MDMPH E[SHFWHG *UDGXDWLRQ 2016 MHQWRU LHRQDUGR TDPDUL] MD MPH HRQRUV *OREDO HHDOWK SFKRODUV AZDUG IURP WKH UQLYHUVLW\ RI MLDPL DHSDUWPHQW RI PXEOLF HHDOWK SFLHQFHV PUHVHQWHG DW WKH APHULFDQ CROOHJH RI CDUGLRORJ\ UG AQQXDO SFLHQWLÀF SHVVLRQ   DQG  PUHVHQWHG DW ACC  DQG  AFWLYLWLHV AMSA ´:KDWV US DRF¾ CRRUGLQDWRU DOCS LLEHUW\ CLW\ HHDOWK FDLU PXEOLF RHODWLRQV CRRUGLQDWRU MDMPH RHSUHVHQWDWLYH RI WKH UMMSM PXEOLF HHDOWK SWXGHQW AVVRFLDWLRQ FXWXUH *RDOV CDUGLRORJ\ PXEOLF HHDOWK HHDOWKFDUH PROLF\ sg.mededu.miami.edu/medicalibis

Spring 2014 | The Medical I.B.I.S.

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StemCAMPUS Cell Particles Promote Development of New Blood Vessels in the Healing of Chronic Wounds BY LAURA BLOOM

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udrey Cox is devoting the year between her third and fourth years of medical school at the Miller School to full-time dermatologic research. In -XO\ VKH VWDUWHG ZRUNLQJ RQ DQ H[FLWLQJ SURMHFW exploring the relationship between stem cell particles and chronic wound healing. AXGUH\ FRPSOHWHG KHU XQGHUJUDGXDWH HGXFDWLRQ DW WKH UQLversity of Florida, where she majored in Zoology and minored LQ AUW HLVWRU\ SKH ZDV LQYROYHG LQ HVRSKDJHDO FDQFHU DQG PHODnoma research. Audrey has maintained her love for art by paintLQJ IRU WKH ACC FOLQLFV KHUH DW -DFNVRQ SKH LV D PHPEHU RI WKH EWKLFV HXPDQLWLHV SDWKZD\ DQG ZDV LQGXFWHG LQWR WKH AOSKD OPHJD AOSKD HRQRU MHGLFDO SRFLHW\ GXULQJ KHU MXQLRU \HDU Audrey plans to pursue a residency in Dermatology and intends to continue her involvement in research throughout KHU SURIHVVLRQDO FDUHHU :KLOH AXGUH\’V FXUUHQW UHVHDUFK KDV D dermatologic focus, the problems surrounding chronic wound KHDOLQJ H[WHQG WKURXJKRXW WKH ÀHOG RI PHGLFLQH ² QRWDEO\ LQ WKH complications associated with diabetes. Audrey was drawn to this particular research project because of the cutting-edge stem FHOO FRPSRQHQW TKH SURMHFW’V SULQFLSOH LQYHVWLJDWRU EYDQJHORV BDGLDYDV MD PKD FRPSOHWHG KLV IHOORZVKLS LQ GHUPDWRORpathology, and has a clinic and research lab at the Miller School. Stem cell therapy was previously thought to enhance wound KHDOLQJ E\ UHSODFLQJ LQMXUHG WLVVXH HRZHYHU LW WXUQV RXW WKDW YHU\ IHZ VWHP FHOOV DUH DFWXDOO\ IRXQG DW WKH VLWH RI LQMXU\ LQVWHDG they induce healing through communication with other cells in the wound bed. One of Audrey’s research partners, Dr. Arsalan

Audrey Cox DHJUHH PURJUDP M.D. E[SHFWHG *UDGXDWLRQ 2015 MHQWRU EYDQJHORV BDGLDYDV MD PKD HRQRUV AOSKD OPHJD AOSKD HRQRU MHGLFDO SRFLHW\ AFWLYLWLHV EWKLFV HXPDQLWLHV PDWKZD\ PDLQWLQJ IRU Ambulatory Care Center FXWXUH *RDOV Dermatology 28

The Medical I.B.I.S. | Spring 2014

our hope that

“It is

exosomes will

one day make

stem

cell therapy accessible t o

t h e

general population.� sg.mededu.miami.edu/medicalibis


SKDEELU DQ MDPKD DQG Ă€UVW \HDU DHUPDWRORJ\ UHVLGHQW EHJDQ H[SORULQJ VWHP FHOO SDUWLFOHV FDOOHG ÂśH[RVRPHV’ AXGUH\’V current research continues this exploration. Exosomes are YHVLFOHV WKDW FRQWDLQ RNA DNA DQG SURWHLQ IW LV VSHFXODWHG that exosomes carry signals from bone marrow derived mesHQFK\PDO VWHP FHOOV BMMSC WKDW UHVXOW LQ ZRXQG KHDOLQJ TR WHVW WKLV K\SRWKHVLV BMMSC H[RVRPHV ZHUH LVRODWHG ZLWK D FHQWULIXJH LGHQWLĂ€HG E\ HOHFWURQ PLFURVFRS\ DQG ODEHOHG ZLWK G\H TKHVH H[RVRPHV ZHUH IRXQG WR EH WDNHQ XS E\ KXPDQ XPELOLFDO YHLQ HQGRWKHOLDO FHOOV HUVEC  ZKHUH WKH\ VLJQLĂ€cantly increased capillary tube formation, indicating that these particles enhance angiogenesis (formation of new blood vessels from existing ones). TKH PDMRU Ă€QGLQJ RI WKLV SURMHFW LV WKDW BMMSC GHULYHG exosomes may act as “communication vehiclesâ€? through which

BMMSC LQGXFH ZRXQG KHDOLQJ TKHUH LV DQ LQFUHDVH LQ ERWK angiogenesis and migration, which can improve in vitro wound healing. It appears that exosomes are able to induce wound healing without the stem cells being present. TKH LGHDO FOLQLFDO DSSOLFDWLRQ RI WKLV UHVHDUFK ZRXOG EH WR JURZ BMMSC’V VWHULOHO\ LQ D ODE DQG WKHQ LQMHFW WKH H[RVRPHV LQWR WKH ZRXQG EHG TKH XVH RI H[RVRPHV UDWKHU WKDQ ZKROH VWHP cells, would hopefully avoid immune reactions and infections, be less invasive, easier, and provide better results. Audrey presented this project in March at ESRF 2014. Audrey hopes to see this become a treatment for patients suffering from chronic wounds.

Audrey at the tissue culture bench.

sg.mededu.miami.edu/medicalibis

Spring 2014 | The Medical I.B.I.S.

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Effect CAMPUS of Colon Transection on Spontaneous High-Amplitude Propagating Contractions BY GABE WEINGROD-NEMZOW

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iddish is the language of choice when constructing insults for your nemesis. Rather than being vulgar, they are elegant and witty phrases PHDQW WR LQYRNH XWWHU FRQWHPSW IWV UHSHUWRLUH RI FXUVHV LQFOXGHV ´PD\ \RX JURZ OLNH DQ RQLRQ with your head in the groundâ€? or “may I live long enough to DWWHQG \RXU IXQHUDOÂľ BXW WKH ZRUVW SRVVLEOH FXUVH WKH RQH WKDW should only be said to your worst enemy, is “may you have HLUVKVSUXQJ’V DLVHDVHÂľ

“Having a family member with Hirschsprung¡s inspired me to understand why some may still have problems even after “curativeâ€? therapy.â€? HLUVFKVSUXQJ’V DLVHDVH HD LV FKDUDFWHUL]HG E\ DJDQJOLDQRVLV of the rectum, which in normal terms is an absence of the motor neurons (ganglion cells) controlling the rectum and lower large LQWHVWLQH TKLV UHVXOWV LQ VHYHUH FRQVWLSDWLRQ II QRW UHFRJQL]HG DQG WUHDWHG WKH ODUJH LQWHVWLQH ZLOO SRS OLNH D EDOORRQ OHDGLQJ WR D VHYHUH EDFWHULDO LQIHFWLRQ ZLWK D KLJK GHDWK UDWH HLUVFKVSUXQJ’V LV XVXDOO\ GLDJQRVHG ZLWKLQ WKH Ă€UVW ZHHN RI OLIH ZKHQ D EDE\ is found not to soil its diaper, and is treated by removing the diseased intestine through a procedure called colonic transection. AOWKRXJK WKH\ DUH ´FXUHGÂľ RI HLUVFKVSUXQJ’V ZLWK WKH VXUJHU\ many suffer from a minor loss of neurons throughout the rest RI WKHLU LQWHVWLQHV UHVXOWLQJ LQ FKURQLF FRQVWLSDWLRQ TKLV ODVWLQJ neuronal dysfunction is a highly researched topic. SKDURQ :ROIVRQ D VHFRQG \HDU PHGLFDO VWXGHQW DW WKH MLOOHU SFKRRO LV Ă€JKWLQJ WR FXUH WKHLU FRQVWLSDWLRQ TKLV Ă€JKW LV SHUVRQDO :KHQ VKH ZDV  D FORVH IDPLO\ UHODWLYH ZDV GLDJQRVHG ZLWK HLUVFKVSUXQJ’V SKH EHFDPH LQYROYHG LQ WKH WUHDWPHQW DQG ZKLOH VHDUFKLQJ RQ WKH LQWHUQHW WR OHDUQ PRUH DERXW HD VKH IRXQG DQ DUWLFOH E\ DU PDXO H\PDQ D PURIHVVRU RI PHGLDWULFV 30

The Medical I.B.I.S. | Spring 2014

DW LSU DQG CKLHI RI PHGLDWULF *I DQG NXWULWLRQ DW CKLOGUHQV HRVSLWDO RI NHZ OUOHDQV SKDURQ FDOOHG KLP WR GLVFXVV SRVVLEOH WUHDWPHQWV IRU KHU UHODWLYH DU H\PDQ ZDV LPSUHVVHG ZLWK WKH NQRZOHGJH RI WKLV  \HDU ROG LQYLWHG KHU WR FRQGXFW UHVHDUFK with him the following summer of 2007, and she presented her RZQ UHVHDUFK DW DLJHVWLYH DLVHDVH :HHN ZKLFK VKH GHVFULEHV as the “biggest and baddest international Gastro-Intestinal conference in the entire world.â€? SKDURQ WRRN VRPH WLPH RII IURP VWXG\LQJ HLUVFKVSUXQJ’V ZKLOH VWXGLQJ BLRPHGLFDO EQJLQHHULQJ DW BRVWRQ UQLYHUVLW\ DQG instead did research in both a respiratory mechanics lab (to cure DVWKPD DQG DQ DXGLWRU\ QHXURSK\VLRORJ\ ODE HHU LPSUHVVLYH resume and personality landed her a prestigious $4000 grant IURP WKH NRUWK APHULFDQ SRFLHW\ IRU PHGLDWULF *I HHSDWRORJ\ DQG NXWULWLRQ NASP*IHN WR GR PRUH UHVHDUFK ZLWK DU H\PDQ GXULQJ KHU Ă€UVW PHGLFDO VFKRRO VXPPHU EUHDN LQ  :RUNLQJ ZLWK DQ LSU VWXGHQW CRXUWQH\ -DFREV SKDURQ GLG a retrospective study on the constipation that 500 children VXIIHUHG IURP ZLWK DQ DYHUDJH DJH RI  \HDUV UVLQJ D FRORnoscopy probe that detects the strength of muscle contractions, WKH\ PHDVXUHG WKH QXPEHU RI HLJK APSOLWXGH PURJDJDWLQJ FRQWUDFWLRQV RU HAPCV WKDW IRXU JURXSV RI FKLOGUHQ KDG LQ WKHLU ODUJH LQWHVWLQHV ERWK EHIRUH DQG DIWHU HDWLQJ D PHDO TKHVH JURXSV FRQVLVWHG RI D VHW RI FKLOGUHQ ZLWK HD D FRORVWRP\ control group consisting of children who had a colon resection IRU DQ\ UHDVRQ H[FHSW HLUVFKVSUXQJ’V FKLOGUHQ ZLWK IXQFWLRQDO FRQVWLSDWLRQ HYHU\WKLQJ ZRUNV EXW WKH\ DUH XQDEOH WR UHOD[

Sharon Wolfson DHJUHH PURJUDP M.D. E[SHFWHG *UDGXDWLRQ 2016 MHQWRU PDXO H\PDQ MD HRQRUV NASP*HAN SXPPHU RHVHDUFK FHOORZVKLS  EDUOH DQG MLOGUHG BDLOH\ MHPRULDO AZDUG AFWLYLWLHV Genetics and Genomics Pathway of Emphasis, DOCS -DFN DQG -LOO HHDOWK FDLU PURMHFW MDQDJHU FXWXUH *RDOV NHXURVXUJHU\ *DVWURHQWHUROJ\ sg.mededu.miami.edu/medicalibis


their pelvic muscles out of fear of defecating) and children with chronic abdominal pain. IQ QRUPDO LQGLYLGXDOV WKHUH DUH SHULRGLF HAPCV WKDW VHUYH WR help propel food through the colon. Eating tends to accentuate WKLV SURFHVV DV LI WR PDNH URRP IRU WKH QHZ IRRG PUHYLRXV research has found that colonic transection causes an increase LQ WKH IUHTXHQF\ RI HAPCV ERWK EHIRUH DQG DIWHU HDWLQJ IQ WKH H[SHULPHQW FKLOGUHQ’V HAPCV ZHUH PHDVXUHG EHIRUH DQG DIWHU HDWLQJ SKDURQ IRXQG WKDW SDWLHQWV ZLWK HD DQG WKH FRORVWRP\ FRQWURO SDWLHQWV KDG PRUH HAPCV RQ DYHUDJH WKDQ FKLOGUHQ ZLWK IXQFWLRQDO FRQVWLSDWLRQ RU FKURQLF DEGRPLQDO SDLQ TKLV ZRXOG PHDQ WKDW WKH KLJKHU IUHTXHQFLHV RI HAPCV REVHUYHG LQ HD patients were due to the colonic transection and not due to the QHXURQDO G\VIXQFWLRQ LQ HD USRQ IXUWKHU DQDO\VLV SKDURQ DQG KHU FROOHDJXHV DOVR IRXQG WKDW WKH HD SDWLHQWV KDG D ELPRGDO GLVWULEXWLRQ RI HAPCV TKLV PHDQV WKDW WKHUH ZHUH WZR VXEVHWV RI HLUVFKVSUXQJ’V DLVHDVH SDWLHQWV VRPH ZLWK KLJK IUHTXHQFLHV RI HAPCV DQG VRPH ZLWK ORZ IUHTXHQFLHV RI HAPCV TKHVH WZR HLUVFKVSUXQJ’V DLVHDVH groups averaged out to a similar value to the colostom control patients, which originally led her to believe that this was the effect RI WKH FRORQLF UHVHFWLRQ ´IW ZDV WULFN\ WR ÀJXUH LW RXW WKDW WKH\

ZHUH GLIIHUHQWÂľ VKH VDLG ´:H MXVW VWDUWHG FUXQFKLQJ QXPEHUVÂľ IQWHUHVWLQJO\ WKH HLUVFKVSUXQJ’V DLVHDVH SDWLHQWV ZLWK IUHTXHQW HAPCV DOVR UHSRUWHG KDYLQJ IHFDO LQFRQWLQHFH TKRVH HD FKLOGUHQ ZLWK IHZHU HAPCV KRZHYHU UHSRUWHG FRQVWLSDWLRQ TKHVH FRQVWLSDWHG FKLOGUHQ VHHPHG MXVW OLNH FKLOGUHQ ZLWK a general functional constipation, simply unable to relax their SHOYLF Ă RRU PXVFOHV EHFDXVH RI IHDU RI SRRSLQJ TKLV LQGLFDWHV WKHUH LV D VXEVHW RI HLUVFKVSUXQJ’V DLVHDVH SDWLHQWV WKDW KDYH abnormal neuronal control. Sharon believes that if these neurons FRXOG EH FRQWUROOHG PDQ\ FKLOGUHQ ZLWK HLUVFKVSUXQJ’V DLVHDVH could have some relief for their symptoms. SKDURQ LV KRSHIXO WKDW KHU UHVHDUFK ZLOO SURYLGH UHOLHI WR HD SDWLHQWV B\ GHĂ€QLQJ VXEJURXSV RI SDWLHQWV WUHDWPHQWV FDQ EH devised to limit or control the side-effects. “If we did a different type of surgery,â€? Sharon wondered, “would that prevent WKH LQFRQWLQHQFH" CRXOG WKH LQFRQWLQHFH EH JHQHWLFDOO\ OLQNHG"Âľ FXWXUH VWXGLHV FRXOG KRSHIXOO\ EULQJ PDQNLQG D VWHS FORVHU WR DOOHYLDWLQJ WKH V\PSWRPV RI HLUVFKVSUXQJ’V DLVHDVH OQH GD\ VRRQ ´PD\ \RX KDYH HLUVFKVSUXQJ’VÂľ ZLOO EH D laughable curse.

Sharon in front of the Lois Pope fountain. sg.mededu.miami.edu/medicalibis

Spring 2014 | The Medical I.B.I.S.

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