The Medical I.B.I.S., Issue 3, 2015

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

At the University of Miami, we transform lives through teaching, research, and service.

Discoveries in our laboratories advance prevention, diagnosis, treatments and cures for the diseases and conditions that afflict humankind. They also advance what is taught in our classrooms, because medical students – just like practicing physicians – must have access to the latest knowl-

edge. Under the guidance and mentoring of our faculty, our students take their first important steps in the career to which they have been called.

The breakthrough research presented in this issue is truly impressive. The 12 articles span a wide range of interests, including cancer, ophthalmology, neurology, orthopedics, microbiome and community service. Our students are just entering the field of medicine, yet they are already making significant contributions to medical knowledge. Their research is an important element in our mission to transform lives every day, and we know there will be more great work to come.

Pascal J. Goldschmidt, M.D. Senior Vice President for Medical Affairs and Dean University of Miami Miller School of Medicine CEO, University of Miami Health System 2 The Medical I.B.I.S. Spring 2015

From the Editor-in-Chief:

The Power of Imagination We are all born full of light and imagination – able to look up into the sky and see animals in the clouds, to create elaborate stories and games in our minds. Most people lose their propensity to wonder and dream somewhere along the way; the routine and menial tasks associated with adulthood can strip us of our creativity. Some people, however, carry this gift of spirited imagination through their lifetime. It can express itself in many ways: being an artist, a playwright, a novelist, a photographer, and yes, a scientist. Cultivating imagination and creativity through medical research is the heart and soul of The Medical I.B.I.S. As scientists, we spend much

Laura Bloom Editor-in-Chief

of our days learning the facts that were discovered yesterday and discovering new truths that will be taught tomorrow.

We owe essentially all of what we know to the discoveries of those before us, but we owe equally as much to the curious imagination that preceded that discovery. Much of what we now hold as true was once believed to be false or even downright crazy: a round Earth, the Earth revolving around the Sun, that all living things are composed of the same nucleic acids. These were the audacious ideas of yesterday – many of which were shunned. We in the field of scientific research must have the audacity to continue to dream – to push the boundaries of what

Kevin Moore Managing Editor

is believed to be possible.

Welcome to the third edition of The Medical I.B.I.S. – the first and only entirely studentrun research magazine of the University of Miami Miller School of Medicine. Our masthead has grown from four members in our first year to nearly thirty in our third year. We have the honor of being supported by Student Government, Medical Education, and the Alumni Association. At The Medical I.B.I.S., we foster both the scientific aptitude and the creativity of medical students. We explore not only the scientific discoveries of our student researchers but also who they are as people and what drew them to their scientific pursuits. This is what

Melissa Stone Senior Editor

inspired me to become a writer for the magazine last year and the Editor-in-Chief this year.

Being integrally involved with The Medical I.B.I.S. is one of the highlights of my medical school career. With great pride and pleasure, we share our latest edition with the Miller community.

Collectively, all of us in medical school: We are the next big thing in medicine. What we accomplish – the ideas we put forth – are what will propel us and our field into the future.

Dare to dream big, dare to be audacious, dare to discover, dare to be the next big thing in medical innovation.

Laura Bloom

Richa Taneja Senior Editor Spring 2015 The Medical I.B.I.S. 3

VOL. 3

ISSUE 1

SPRING 2015

Editor-In-Chief Laura Bloom

Managing Editor Kevin Moore

Senior Editors Melissa Stone Richa Taneja

Laura Bloom, Kevin Moore, Melissa Stone, Richa Taneja

Selection Committee Chair Matthew Phillips

Selection Committee Matthew Field Michael Durante Joshua Parker Spencer Summers

Layout & Production Editors Ladan Afifi Reshma Muppala

Directors of Photography

Michael Durante, Spencer Summers, Joshua Parker, Matthew Phillips

Nikesh Doshi Stephen Allegra

Publishing & Advertising Editor Jennifer Rodriguez

Director of Communications Adam Jaffe

Cover Illustrator Jared Tannenbaum

4 The Medical I.B.I.S. Spring 2015

Adam Jaffe, Reshma Muppala, Ladan Afifi, Stephen Allegra, Nikesh Doshi, Jennifer Rodriguez

Section Editors

Laura Huang Devon Cohen Houda Boucekkine Cory Patrick Michelle Caunca

Writers

Devon Cohen, Cory Patrick, Houda Boucekkine, Michelle Caunca

Sapir Karli Caroline Chen Whitney Hang Nisreen Ezuddin Cathy Cichon Genevieve Wiehl Emily Chen

Faculty Advisor

Emmanuel Thomas, M.D., Ph.D.

Advisory Board

Pascal Goldschmidt, M.D. Alex J. Mechaber, M.D.

Genevieve Wiehl, Whitney Hang, Emily Chen, Cathy Cichon

The 2015 Medical I.B.I.S. Masthead

The Medical I.B.I.S. is published by the University of Miami Miller School of Medicine Student Government. We reserve the right to edit any submissions, solicited or unsolicted, for publication.

This magazine is the work of University of Miami medical students, and the University of Miami is not responsible for its contents. Perspectives expressed by authors do not necessarily reflect the opinions of the University of Miami. We retain the right to reprint contributions, both text and graphics, in future issues as well as a non-exlcusive right to reproduce these in electronic form. The Medical I.B.I.S. welcomes comments and feedback. Please send questions and comments to medical.ibis@gmail.com.

Spring 2015 The Medical I.B.I.S. 5

university of miami’s medical student research publication

LAURA STONE MCGUIRE

8

DUSTIN MASSEL

16

SARAH TEPLICKI

9

DIANA BOTROS & SAMUEL BECKERMAN

18

The development of non-convulsive seizures following mild traumatic brain injury with hyperthermia in the rat

Critical roles of mesenteric lymph nodes in gut-associated T cell development

The effect of viscosity on cement penetration in total knee arthroplasty: an application of the squeeze film effect

Project Serve: engaging medical students and patient families in a non-clinical environment

ROY ELIAS

10

PATRICK AZCĂ RATE

20

NIKESH SHAH

12

MIRELYS BARRIOS

21

KATYAYINI ARIBINDI

14

ALIZA EPSTEIN

22

FRANCESCA RAFFA

15

NIMA SHARIFAI

24

Placental-derived cell-based gp96-Ig vaccine as a multivalent cancer treatment

Total body radiotherapy dose comparison in patients with relapsed acute lymphoblastic leukemia

Phospholipid profiles of control and glaucomatous human aqueous humor

Changing trends of speech outcomes after total laryngectomy in the 21st century: a single-center study

Androgen deficiency and dry eye syndrome in the aging male

Investigation of intraperitoneal carboplatin, intravenous and intraperitoneal paclitaxel in the management of advanced stage ovarian carcinoma: a pilot study

Outcomes of same-day versus delayed removal of lens fragments after cataract surgery

In situ visualization of protein-protein interactions: converging signals and dendrite morphogenesis

THE ROLE OF RESEARCH IN PREPARING FOR RESIDENCY

25

REPEAT OFFENDERS: KATYAYINI and NIKESH

26

HOW TO GET INVOLVED IN RESEARCH

28

GETTING STARTED: TYPES OF RESEARCH

30

Special thanks to

UMMSM

Executive Student Government

The development of non-convulsive seizures following mild traumatic brain injury with hyperthermia in the rat

By Whitney Hang With her sights set on neurosurgery, Laura Stone McGuire decided to take a year off between her third and fourth years of medical school to conduct neuroscience research. She became a research associate for Dr. W. Dalton Dietrich, Ph.D. and Dr. Helen Bramlett, Ph.D., both of whom conduct research for the Miami Project to Cure Paralysis with a grant from the Department of Defense. Laura’s research specifically focused on two main questions: (1) whether an elevation in brain temperature worsens the outcome after mild traumatic brain injury (TBI), and (2) how do outcomes compare after repetitive brain injuries versus single injury. This research has important implications for both soldiers and athletes who are in danger of becoming concussed multiple times in warm climates that result in elevated body temperatures.

Using the Marmarou weight drop model of closed-head traumatic brain injury, mild TBIs were given to five groups of rats: a

Laura Stone McGuire M.D. Candidate Class of 2015

control group, a TBI-normothermia group, a TBI-hyperthermia group, a multiple injury normothermia group, and a multiple injury hyperthermia group. The normothermia and hyperthermia groups had their temperatures maintained at 37°C and 39°C, respectively. The effects of elevated temperature and multiple injuries on post-traumatic outcomes were observed via behavioral and electrophysiological testing.

Laura performed behavioral testing by utilizing the Morris Water Maze to examine the memory capacities of the rats; this was done at 12 weeks post-injury. In order to observe the effect of injury on the sensorimotor skills of the rats, Laura also performed a cylinder test at the following time points: pre-injury, one week post-injury, and 12 weeks post-injury. These results revealed no statistically significant differences between the experimental groups. To obtain the electrophysiology data, Laura performed a one-hour video electroencephalography (EEG) at 12 weeks post-injury. The

8 The Medical I.B.I.S. Spring 2015

EEG data was then processed via a custom-written program in MATLAB. Seizures, as characterized on EEG recordings by an increase in power across all frequency bands, were not seen in the acquired EEG recordings of the different animal samples.

However, paroxysmal events were observed on the recordings. These events are illustrated by an increase in the power of some, but not all, frequency bands, and they possibly represent early electrographic manifestations of seizures. The number of paroxysmal events varied between the different experimental groups and was observed to increase in the following order: control group, the normothermia TBI group, the hyperthermia TBI group, the multiple injury normothermia group, and the multiple injury hyperthermia group. Therefore, the gathered data suggests a possible increase in non-convulsive seizure susceptibility among animals with hyperthermia and multiple brain injuries.

The next steps of this project include investigating the effects

that hyperthermia in the context of TBI may have on the histopathology of the rats’ brains, specifically at 12 weeks post-injury.

Furthermore, to fully understand the relationship between temperature manipulation and TBI, the therapeutic effects of hypothermia that have previously been recorded in the literature will be examined. The next aspect of the project that Laura will personally be conducting is the utilization of proton spectroscopy to analyze the concentration of metabolites in bodily fluids pre-TBI and twenty-four hours post-TBI to investigate the potential effects of metabolite changes on post-traumatic outcomes.

Laura has presented this project at the National Neurotrauma Society Symposium and continues to find the time to remain involved in this study. She loves the process of discovery and says that she has been bitten by the “research bug.” As such, Laura hopes to incorporate research into her future career as a neurosurgeon.

Sarah Teplicki M.D./M.P.H. Candidate Class of 2015

Sarah pictured with Dr. Chen, M.D., Ph.D.

Critical roles of mesenteric lymph nodes in gut-associated T cell development

By Caroline Chen The immune system provides our natural defense against infectious agents such as bacteria or viruses. CD4 and CD8 T cells are critical players in the immune system. How these cells mature or differentiate is extremely important in determining our body’s natural ability to fight infection while protecting the tissue in our body from immune-mediated damage.

The focus of Sarah Teplicki’s project, conducted with Dr. Zhibin Chen, M.D., Ph.D., Associate Professor of Microbiology and Immunology, was to understand the role of mesenteric lymph nodes in T cell differentiation.

Lymph nodes are areas of tissue in which the cells of our immune system, including T cells, collect and filter lymph fluid draining from various parts of our body.

Mesenteric lymph nodes are located around our intestines and therefore receive information regarding a normal flora of gut-living bacteria that outnumber human cells in the entire body by at least ten times.

In this study, Sarah’s hypothesis is that the mesenteric lymph nodes are important for gut-associated T cell differentiation. To definitively test this hypothesis, she developed a surgical procedure to remove the mesenteric lymph nodes, together with Jen Bon Lui,

a graduate student in Dr. Chen’s lab. Sarah and Jen Bon perfected a procedure of survival surgery that enables them to remove the mesenteric lymph nodes in young animals under general anesthesia and then bring the animals to healthy recovery.

One month later, the animals were analyzed for the CD4 and CD8 population of T cells with flow cytometry, a device that looks at individual cells and identifies them based on their surface proteins. Through this surgical approach, they found that mesenteric lymph nodes played an important role in the conversion of CD8 T cells to CD4 T cells. This demonstrated that the development of the CD8 T cell lineage could be influenced by the gut microenvironment and the normal flora of bacteria living in the gut. This project

also sparked Sarah’s interest in anesthesia. She acknowledges, “It was fascinating to see how improving the resuscitation measures during dissection and removal of the mesenteric lymph nodes improved survival.” Her work has been submitted as part of a manuscript titled “Crossdifferentiation from the CD8 lineage to CD4 T cells in the gutassociated microenvironment with a nonessential role of microbiota.” The paper has been accepted for publication by Cell Reports, a peer-reviewed journal by the Cell Press. Sarah learned throughout this project how much work truly goes into basic science research and developed an immense amount of respect for those who dedicate their lives to research. She also learned the value of surgical approaches for definitively testing a hypothesis in medical research.

Spring 2015 The Medical I.B.I.S. 9

Placental-derived cell-based gp96-Ig vaccine as a multivalent cancer treatment

By Cathy Cichon Over the last decade, cancer vaccines have quietly made their way to the forefront of clinical trials, harkening a new and promising era of cancer treatment distinct from the current standards of chemotherapy and anticancer drugs. Already, the FDA has approved cancer vaccination (immunotherapy) as a treatment option for metastatic prostate cancer (Provenge), with clinical trials ongoing for several other types of cancers, including non-small cell lung carcinoma (NSCLC), melanoma, and breast cancer. Working under the guidance of Dr. Eckhard Podack, M.D., Ph.D., Chair of Microbiology & Immunology, second-year student Roy Elias has been researching ways to expand the scope of extant cancer vaccines.

The aim is to create a multivalent cancer vaccine in the hope of advancing and streamlining this emerging cancer care.

Roy first became involved in cancer research and treatment as an undergraduate student, during which time he participated in drug discovery research at the Moffitt Cancer Center in Tampa, Florida. It was while searching for a related project here at the University of Miami Miller School of Medicine that he discovered Dr. Podack’s research on tumor vaccines. Roy recognized the amazing potential of immunotherapy and found himself particularly intrigued by Dr. Podack’s innovative approach to it.

Roy Elias M.D. Candidate Class of 2017

Dr. Podack’s lab develops therapeutic tumor vaccines, which are vaccines that treat existing cancers by stimulating an immune response to cancerous cells. Typically, cancer cells are able to subvert the immune system, either by evading it or actively suppressing it, rendering the body’s natural defenses against the disease useless. This hallmark of cancer cells forces doctors to employ widely destructive toxic agents – which often have debilitating side effects – in the fight against cancer. Immunotherapy, on the other hand, allows the body to recognize mutated cancer cells as pathogenic and to respond accordingly. It harnesses the power of our own immune system to treat cancer, avoiding the destruction caused by more standard, yet toxic, substances.

10 The Medical I.B.I.S. Spring 2015

In September of 2013, Roy began studying the Podack lab’s NSCLC vaccine, which had recently undergone phase I human trials at the Sylvester Comprehensive Cancer Center. In his studies, he learned that the vaccine was based on the heat-shock protein gp96. This protein is normally present in the lumen of the endoplasmic reticulum (ER), where it is a protein chaperone that plays a critical role in immune response regulation. When a cell undergoes necrosis (premature cell death due to injury, infection, or abnormal growth), gp96, together with its client peptides, is released into the extracellular environment. The gp96-peptide complex is then taken up by antigen presenting cells (APCs), such as macrophages and dendritic cells, and the native peptides are presented by major histocom-

patibility complex (MHC) class I molecules. Foreign peptides and tumor peptides bound to MHC I molecules then mediate white blood cell interactions in order to generate killer cells that dispose of the diseased cell.

To synthetically initiate this process in tumor cells from “donor” cancer cell lines, the lab creates a DNA construct by fusing the Fc portion of immunoglobulin to the gp96 protein, deleting the ER retention sequence that usually keeps gp96 localized to the lumen. As a result, in the cells transfected by this construct, a chimeric gp96-Ig protein is released into the extracellular space. The lab then irradiates these cells (so they cannot replicate) and injects them into the patient.

Once inside the patient, the transfected cells secrete massive

amounts of gp96-Ig attached to a tumor specific antigen (TSA). This entire complex is subsequently taken up by APCs, broken down, and presented by MHC class I molecules to white blood cells known as cytotoxic T cells (CTLs or CD8+ T cells).

These CTLs, with the directions provided by the MHC class I molecules, are able to target and kill both the injected cancer cells and the host cancer cells. Roy has been working to build off of this research by attempting to apply the approach to many different types of cancer, rather than NSCLC alone.

While working under Dr. Podack, Roy has spent the majority of his time synthesizing and testing possible vaccines.

Because cancer cells often express embryonic proteins, Roy hypothesizes that using proteins from placental-derived cell lines as the antigen source in these experimental vaccines will make them effective against multiple types of cancer. In the immunology lab, Roy works with these placental cells in the hope of creating a viable vaccine that works to slow or even stop the tumors cells’ progress in mice.

Given time, such a vaccine could be applied to humans, in more cases than just cancer. In fact, a malaria vaccine based on similar principles should be ready for human trials this year, with vaccines for HIV and Hepatitis C in close pursuit.

In the future, Roy plans to pursue a residency in internal medicine and hopes to continue conducting cancer research.

His ongoing cancer vaccine research has given him a glimpse into the thrilling and constantly changing world of cancer treatment. He enjoys the diversity of knowledge required to carry out cancer research and believes it offers the broad range of experience necessary to become a well-rounded doctor from bench to bedside. The world of cancer treatment depends on such knowledge, and these long months working with Dr. Podack will give Roy the tools necessary to eventually translate cutting-edge findings into tangible results for patients.

Until then, Roy stands shoulder to shoulder with the pioneers of therapeutic cancer vaccines, poised to bring immunotherapy to the front lines of cancer treatment. In this new era of cancer research, Roy, his mentor, and the rest of the laboratory team have learned to take advantage of the body’s own defense systems in order to attack tumors, and the results so far are promising. Although still in its infancy, the approach could improve cancer outcomes – and has indeed already begun to do so in clinical trials.

Thanks to Roy and his mentor’s research, a universal cancer vaccine may be possible.

Conflict of interest statement: Dr. Podack is the scientific cofounder and equity owner of Heat Biologics, Inc

“

The beauty of the system is that you vaccinate against so many antigens that the tumor can’t escape.

”

Spring 2015 The Medical I.B.I.S. 11

Total body radiotherapy dose comparison in patients with relapsed acute lymphoblastic leukemia

By Cathy Cichon “Your child has cancer,” may very well be four of the most terrifying words any parent can imagine. Now imagine hearing, “Your child has cancer again.”

Unfortunately, this latter scenario is the norm in third-year student Nikesh Shah’s research, which focuses on treatment of childhood relapsed acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer (accounting for about 34% of all cancers in children) and one of the most treatable. However, between 15 and 20% of pediatric patients will eventually experience a relapse, usually occurring within

two years of treatment completion. Relapsed acute lymphoblastic leukemia (RALL) remains the most significant cause of treatment failure among pediatric ALL patients. In fact, RALL accounts for more cancer deaths in children than any other malignancy.

Nikesh first became involved with these patients and their families three years ago when he began to shadow Dr. Joseph Panoff, M.D., Assistant Professor of Radiation Oncology, in Radiation-Oncology at the Sylvester Comprehensive Cancer Center. Subsequently, under Dr. Panoff’s guidance, Nikesh began a project comparing palliative radiation therapies in children at the end of life. It was while

12 The Medical I.B.I.S. Spring 2015

analyzing the medical charts of past patients that he discovered the challenges faced by pediatric patients and their families. “Seeing all these people’s stories was eye-opening,” he said. “You’re not just treating disease but talking to family about care and end of life…that’s hard especially for kids.”

After completing that first project, Nikesh was drawn to his current research project, which analyzes the total body irradiation (TBI) doses used for pediatric patients with RALL. When traditional treatment fails to achieve lasting remission, physicians may consider RALL patients for more novel therapies, such as hematopoietic stem cell transplant (HSCT), in the hope

of achieving a more durable remission. In order to prepare for HSCT, patients must first undergo TBI to suppress their immune system and prevent rejection of the donor’s bone marrow or blood stem cells.

One large TBI dose is divided into smaller fractions and typically administered twice daily over three or four days.

The overall doses can vary (depending on physician preference), but the two most commonly used doses are 1320 cGy and 1200 cGy. To date, there have been no studies analyzing these dose regimens – and their potential toxicity – for children specifically. This is largely because patients receiving TBI and HSCT only receive

such treatment after a second or third relapse, making it difficult to gather a large enough sample size for evaluation. Despite this challenge, Nikesh set out to discover whether a higher total dose divided into more fractions (1320 cGy/8 fractions) had different patient outcomes than a lower dose divided into fewer fractions (1200 cGy/6 fractions).

Pulling retrospective data from 54 pediatric medical records from 1994 through 2014, Nikesh analyzed patients’ overall survival, relapse-free survival, and toxicity resulting from the TBI regimen. It quickly became clear that the data from earlier years reflected more inconsistent TBI doses, whereas

Nikesh Shah M.D. Candidate, Class of 2016

in more recent years physicians held closer to the two accepted doses previously mentioned.

Despite these variations, statistical analysis revealed no overall survival, relapse-free survival, or toxicity differences between the two doses. Fortunately, these findings indicate that physicians have not inadvertently caused more toxicity or premature death to the young patients by giving inappropriate TBI doses.

Over the course of his research, Nikesh also found that patients treated in 1990-1999 had a greater incidence of acute graft-versus-host-disease (GVHD) than those treated in 2000-2009 or 2010-present. He conjectured this was the result of less sophisticated transplant

matching during those years, not TBI dose toxicity. Nikesh further discovered that patients who received more than seven TBI fractions or less than 200 cGy per fraction had a greater incidence of acute GVHD. This finding may influence physicians’ decisions regarding TBI doses and hopefully reduce GVHD incidence in future pediatric transplant patients.

With Nikesh’s results in hand, Dr. Panoff quickly spread the word to fellow radiation-oncologists and Nikesh discovered the speed with which his research could impact care in the small world of RALL patients. Among pediatric cancer patients, such direct and global research dissemination could save lives.

“You’re privileged to have such an impact,” Nikesh mused. Indeed, that opportunity to directly impact patients’ lives has driven him to pursue a career in internal medicine. He hopes to match into a radiation-oncology or hematology-oncology residency program.

Although Nikesh’s research has thus far been fruitful and was recently presented at the American Society for Radiation Oncology conference in San Francisco, he freely admits there is still much to learn. For example, Nikesh believes the TBI dose effects would be better evaluated via a prospective randomized controlled trial rather than a retrospective study. While this may not be an option, he plans to further investigate some interesting secondary findings from his study, such as outcome differences between patients from different backgrounds (Hispanic, Caucasian, etc.). These future studies and others could further clarify the consequences of differential treatment plans on the outcomes of pediatric patients with RALL. Relapsed acute lymphoblastic leukemia remains one of the most treatable childhood cancers, yet many patients still experience one or more relapses. Ultimately, physicians must keep the children’s own comfort and wellbeing in mind, and Nikesh’s research on RALL treatment can begin to provide that guidance.

Spring 2015 The Medical I.B.I.S. 13

Katyayini Aribindi M.D. Candidate Class of 2017

Phospholipid profiles of control and glaucomatous human aqueous humor

By Sapir Karli Glaucoma is a leading cause of irreversible blindness in the world, affecting 60 million people worldwide. Glaucoma is a chronic, progressive optic neuropathy characterized by optic disc cupping and a corresponding visual field defect.

Understanding the pathophysiology of the disease may contribute to the creation of novel treatments; the physiological and mechanical changes, however, are equally important in understanding the foundation of the disease and have not been previously explored.

Katyayini Aribindi, a secondyear medical student, has been working tirelessly to improve the therapeutic modalities available for glaucoma.

Katyayini has always enjoyed physics and computer science, and as an undergraduate student she began working with mass spectrometry under the mentorship of Dr. Sanjoy Bhattacharya, Ph.D., at the Bascom Palmer Eye Institute.

In hopes of characterizing lipids involved in glaucoma, she explored the phospholipid profiles of human control and glaucomatous aqueous humor.

The methodology of class-

specific mass spectrometry is a novel way of characterizing ocular lipids, and the lipid species themselves have not been previously identified.

Katyayini and her collaborators extracted lipids from normal and glaucomatous aqueous humor, separated them using organic and aqueous phase distribution, and analyzed the species of lipids. They concluded that the majority of lipids were the same between control and glaucomatous aqueous humor; however, a few species differed and were unique to either control or glaucomatous tissues. The lipids identified will provide an important foundation for further studies in terms of metabolic importance and the role of each lipid in glaucoma neuropathy or any other ocular disease.

With this foundation, Katyayini and her collaborators can track the enzymatic pathway to gain an understanding of the function of those selected lipids.

In the future, Katyayini would like to utilize her research skills by identifying clinical problems without an efficacious treatment plan and collaborating with research colleagues to create novel therapeutic modalities.

14 The Medical I.B.I.S. Spring 2015

“

The entire project is very cutting edge and has vast implications as it establishes a very important foundation for future projects.

�

Changing trends of speech outcomes after total laryngectomy in the 21st century: a single-center study

By Caroline Chen Imagine you had cancer and your best shot at surviving was having your larynx - the part of your body that contains your vocal cords - surgically removed.

This is the reality for patients who undergo a total laryngectomy (TL). Historically, TL was the standard of care for patients with advanced laryngeal cancer. In the past decades, a more conservative approach of organ preservation through the use of alternatives such as chemotherapy and radiation has become more common, with “salvage TLs” reserved for cases refractory to chemoradiation.

Finding the best way to restore the voices of patients who have had TLs or salvage TLs has been the goal of Francesca Raffa’s research. Francesca conducted basic science research on HIV in college, and decided to switch to the clinical arena upon entering medical school, specifically in a field at the intersection of surgical and clinical medicine. Francesca found her perfect mentors in Dr. Donna Lundy, Ph.D., an Associate Professor and Co-Director of the Vocal Disorders Laboratory and Dr. Seo Moon, M.D., Chief Resident in Otolaryngology. Their project involved patients who underwent tracheo-esophageal puncture (TEP), a procedure in

which a hole is made connecting the trachea and the esophagus.

Patients then learn to use the air from their esophagus to speak, which is termed “tracheo-esophageal speech.” As there has been an increase in salvage TLs, there has been an associated increase in patients who undergo TL after receiving radiation to the neck. Radiation therapy can cause scarring of the surrounding area. One concern with performing a TEP in a patient following salvage TL is the potential for failure secondary to the scarring.

In their study, they included 167 patients from 2000-2012 who received a TEP following a TL, which were then divided into two groups: those who had previously received radiation therapy (salvage TLs), and those who had not (TL only). Francesca then looked at the one- year follow up for these patients to determine the success rates of the TEP and the patients’ tracheo-esophageal speech.

Francesca’s study revealed similar speech outcome success rates between patients who had received a TEP following a salvage TL, and those who had received a TEP following TL without radiation therapy.

This study suggests that TEP remains a good option for voice reconstruction in patients who underwent salvage TL, which is

increasingly the case in laryngeal cancers. This would allow physicians to maximize the voice rehabilitation for these patients and continue to have TEP as one of the options to improve their quality of life. These findings have been presented at the 2014 Eastern-Atlantic Student Research Forum in addition to being published in Laryngoscope.

Through her experience with Dr. Lundy’s project, Francesca has found the blend of surgery, clinical medicine, and human touch that she was looking for. “Reading about their stories and the progression of their illness was very humbling and gave me an appreciation for how voice rehabilitation and speech pathology can impact patients,” explained Francesca, who hopes to include similar clinical research in her career.

Francesca Raffa M.D. Candidate Class of 2016

Spring 2015 The Medical I.B.I.S. 15

Dustin Massel

M.D. Candidate Class of 2016

The effect of viscosity on cement penetration in total knee arthroplasty: an application of the squeeze film effect

By Nisreen Ezuddin Total knee arthroplasty (TKA), or total knee replacement, is an important procedure for restoring quality of life in patients impacted by damaged or arthritic joints. While there have been many improvements in implant design and procedural techniques over the past few decades, aseptic loosening re-

16 The Medical I.B.I.S. Spring 2015

mains a major complication of total knee arthroplasty. This led Dustin Massel, a third-year student at UMMSM, and his team to look at the best timing for cement application – liquid phase vs. dough phase – in hopes of preventing or reducing this complication.

The focus of Dustin’s project

was to evaluate the effect of cement viscosity on the penetration of cement via the squeeze film effect in total knee arthroplasty. Under the mentorship of Dr. Raymond Robinson, M.D., F.A.C.S., Professor of Clinical Orthopedics at UMMSM, and Dr. Edward Silverman, M.D., PGY5 in Orthopedics, Dustin conducted a prospective, randomized, blinded cadaver study. Five matched pairs of cadaver tibias were implanted with the tibial component of TKA, using either liquid or dough phase cement.

The results on anterioposterior fluoroscopic imaging showed that the dough phase cement penetrated deeper than the liquid in all four x-ray zones. Dustin’s study, built upon previous studies, revealed that the deeper the cement

penetration, the stronger the cement-bone interphase. These findings suggest that the dough phase cement should be the recommendation for achieving optimal cement penetration in total knee arthroplasty surgeries. Dustin hopes that his research will help set a standard for optimal cement preparation to provide the most effective interphase, thereby reducing the rate of aseptic loosening.

Dustin’s interest in medicine began at an early age. When he was five years old, he went to work with his father, an internist, on “Take Your Child to Work Day.” While there, one patient in particular left a lasting impression on Dustin when he stated, “Your dad is the best doctor in the world…he saved my life.”

Dustin knew in that moment that

he wanted to pursue a career in medicine.

After he matriculated to college at the University of Illinois at Urbana-Champaign, Dustin travelled to Ghana for a medical aid trip, between his second and third years. While there, he experienced life in the Emergency Department, as he witnessed innumerable trauma cases. On his experience in Ghana, Dustin said, “I saw 11 people die, due to the lack of appropriate health care available...it was unbelievable. I realized that if I have the ability to help someone, in any aspect, who is injured, [then] that’s the reason you go into medicine—to help people.”

Dustin’s particular interest in orthopedic surgery occurred as a result of unexpected circumstances. With a 16-year career

in wrestling, Dustin has had his fair share of personal injuries.

From a fractured vertebrae, to tearing both menisci and breaking his nose nine times, Dustin never allowed an injury to interfere with his love for the sport.

When asked what made Dustin work so hard at wrestling after having broken his nose nine times, Dustin replied, “If you love what you’re doing, nothing will stand in your way of accomplishing your goals.” Trips in and out of the hospital gave Dustin ample exposure to the field of Orthopedic Surgery, with each subsequent visit reaffirming his interest in orthopedics.

Dustin’s determination holds true far beyond the four corners of the wrestling mat. As the co-director for the Department of Community Service (DOCS),

Dustin devotes the few hours when he is not in the hospital to providing healthcare to the underserved populations of South Florida. He helps to manage and execute a total of nine health fairs per year, with the help of Miller students and faculty.

Dustin’s favorite part of the project was seeing his work culminate in the final draft that was published in the October 2014 edition of The Journal of Arthroplasty. He intends to continue his research throughout medical school, as obtaining evidence that helps find solutions to a long-standing problem is not only rewarding, but is also a crucial aspect of promoting progress in the medical field.

Spring 2015 The Medical I.B.I.S. 17

Project Serve: engaging medical students and patient families in a non-clinical environment

By Nisreen Ezuddin It all started at a clinical case presentation in the 5th floor auditorium of the Rosenstiel Medical Science Building. Some students presented the case of a pediatric patient who, along with

student, not only attends to her patients’ medical needs, but also, as part of Project Serve, serves free, healthy, homecooked meals to families staying at RMH. Along with Sam Beckerman, an M.D./Ph.D. student, they have expanded the scope of

communities. Medical students exchange their white coats for chef aprons to cook meals for and share dinner with patients in their “home.” This allows families to voice their true concerns freely while medical students can learn from patients and en-

Sam and Diana pictured with Dr. Byrne, Ph.D.

her family, had been living at Ronald McDonald House (RMH) on the UM Medical campus for two months. During the presentation, the medical student came to the realization that this child with a chronic illness and her family were separated from their community when they needed support the most. It was an eye-opening experience for the students and they were compelled to do and learn more.

A few years later, Diana Botros, a fourth-year medical

Project Serve to include an epidemiological research aim under the mentorship of Dr. Margaret M. Byrne, Ph.D., Associate Professor of Surgery and Public Health Sciences.

In addition to providing the meals, Project Serve endeavors to help medical students achieve a better understanding of patients from different cultures and to increase their awareness of the challenges faced by families who access care away from the comfort of their homes and

18 The Medical I.B.I.S. Spring 2015

hance their communication skills in this informal setting.

Diana and Sam were captivated by RMH and its mission after they volunteered there during college and medical school, respectively. Similar to one of Project Serve’s co-founders, Juliet Nissan, M.D. ‘12, Diana’s love for RMH stems from her sorority roots. Diana began volunteering at RMH, Alpha Delta Pi’s national charity, as a college freshman here in Miami. Sam, on the other hand, loves cooking as much as

he loves seeing patients or working in the lab. When he found out about the dinners at RMH, he simply had to get involved.

Both students found their experiences with RMH families to be educational and inspirational. They felt that much could be learned from these families and that similar experiences could help other medical students develop into more holistic healthcare providers. Sam believes that the RMH dinners serve both the students and patients: “The delivery of healthcare is complex…

Project Serve is a tool to expose students to many important aspects of social medicine while providing a great meal to burdened families.” When talking about her favorite part of the project, Diana notes, “It’s seeing the patients enjoying their meals and getting to sit down and talk with them. The families were just so grateful for everything and they taught us so much.”

Under Dr. Byrne’s mentorship, Diana and Sam hypothesized that through the RMH dinners, it was possible to: (1) improve medical students’ ability to communicate with patients, (2) enhance medical students’ understanding of obstacles facing families who have children with chronic health issues, and (3) improve medical students’ cultural competency. To test this, surveys with open-ended, free-response and quantitative Likert scale questions were administered to medical students after each dinner. Subsequently, these surveys, from over 180 medical students who participated in Project Serve from 2009-2011, were analyzed

and statistical analysis was performed in Stata v.13. Diana and Sam found that 74% of students agreed that Project Serve gives participants a unique opportunity to interact with people from different backgrounds and a majority of students strongly felt that this experience enhanced their medical training.

Diana and Sam are already busy initiating a follow-up prospective study to complement their existing data sets. Along with M.D./M.P.H. student Jennifer Schwenk, they have instituted a pre- and post-experience metrics in an effort to determine causality between changes in medical student attitudes/knowledge and their participation in Project Serve. Thus far, participation in Project Serve has been limited to medical students, but the two would like to study how this service-learning experience might affect other members

Sam Beckerman

of the mediM.D./Ph.D. Candidate cal community, including Class of 2017 nursing, public health and biomedical graduate students. Diana and Sam hope their efforts with Project Serve will continue to help mold them and other UMMSM students into outstanding future physicians who treat patients and not just their disto Alex Mechaber, M.D., Jeffrey eases.

Importantly, Diana and Sam Brosco, M.D., Ph.D., Lee Sanders, emphasize that their work is M.D., M.P.H., and Kenneth Goodthe product of a team effort. man, Ph.D., for helping to estabThis study could not have been lish and sustain the program. accomplished without the tre- Along with the faculty’s continmendous support of the Miller ued support, the Project Serve School, its students and the com- team received funding from munity. A special thanks is given Academic Societies, as well as a

Diana Botros

M.D. Candidate Class of 2015

Hunger Outreach Grant from the Walmart Foundation and a Community Outreach Grant from the Winn-Dixie Foundation. In addition, money was raised from the Medical Faculty Association and institutional support was obtained from various departments. In total, Project Serve has received more than $5000 in funding. This money has enabled the group to continue to serve meals and to send numerous students to present their research at national conferences.

Last year alone, Diana received a John K. Robinson Travel Grant for presenting at the American Medical Women’s Association Conference in Washington D.C., and gave an oral presentation at Eastern-Atlantic Student Research Forum in February 2014.

Finally, the team is really excited about the manuscript they are preparing in order to share their work with other members of the medical education community at UMMSM and beyond.

Spring 2015 The Medical I.B.I.S. 19

Androgen deficiency and dry eye syndrome in the aging male

By Emily Chen Amid hectic schedules and consuming daily activities, it’s often easy to overlook simple things that allow us to be independent. How many times in a day does an individual make a conscious effort to be thankful for their sight, their speech, or even their motility? Syndromes such as dry eye syndrome (DES) affect a large portion of the aging population by decreasing quality of life through eye irritation, light sensitivity and blurred vision. An avid researcher and photographer, student researcher Patrick Azcárate seeks clinical applications of the ophthalmology research in which he participated early in his medical school career, in the hope that it will encourage further investigation of DES cures. Under the guidance of Associate Professor of Clinical Ophthalmology at Bascom Palmer Eye Institute, Dr. Anat Galor, M.D., Patrick evaluated the relationship between androgen levels in males and DES. Dry eye syndrome is caused by a deficiency in tear production or complication of the tear film. The tear film is composed of three layers (an aqueous, a lipid and a mucous layer); but the root cause of dry eye syndrome within a specific layer of the film is still unknown.

Moreover, there seems to be little data from research on the cause of DES that are specifically found in the male population.

Reviewing data from 263 patients of the Miami Veterans Affairs Medical Center, Patrick evaluated patients with DES and corresponding androstenedione levels. Androstenedione can be measured within the serum and is a precursor of androgen

Patrick Azcarate M.D. Candidate Class of 2016 production, like testosterone.

As middle-aged men get older, they may enter andropause, which is comparable to menopause. In andropause, males begin to lose testosterone and enter a deficient state. There’s a need for increased investigation into andropause, since not all males will experience testosterone deficiency, and not all those who are deficient will be symptomatic. The purpose of this study was to investigate if there was any significant correlation between androgen levels and occurrence of DES, and if androgen therapies could be used to target a specific, problematic layer of the tear film.With androgen supplementation as an increasingly popular treatment for low libido, declining muscle mass, and thinning skin in aging men, Patrick and Dr. Galor hoped to see if such supplementation would warrant exploration as a viable treatment for DES as well.

20 The Medical I.B.I.S. Spring 2015

Patients completed the Dry Eye Questionnaire 5, and their serum androgen levels were measured. The study found that there was a weak but statistically significant correlation between higher levels of androstenedione and healthier tear film. Patrick hopes that the significant correlation warrants future studies to examine a treatment for DES that targets the underlying etiology, since current treatment is based around management of dry eye symptoms. A potential cure could have far-reaching effects on a continuously growing population of people that is affected with DES. Undoubtedly, Patrick is grateful for the research experience he has had at Bascom Palmer Eye Institute, with Dr. Galor being an invaluable teacher. Patrick, who was involved in basic science research during his undergraduate career, feels that this experience has given him early exposure

to a clinical study that holds far-reaching implications, affecting the large aging population as well as those affected by DES. This incredible opportunity gave him the responsibility of reviewing the data, running statistical analyses, and writing a manuscript with Dr. Galor. Patrick also had the honor of presenting his findings at the American College of Physicians Florida Chapter Annual Conference in 2014.

Patrick witnessed the devoted team of consultant physicians, endocrinologists, and lab specialists that fostered an environment of academia, all in search of a solution to better patients’ quality of life. This research study, as well as others that are currently being undertaken, gives Patrick confidence that his future lies within ophthalmology, working together with a team of physicians, scientists, and students, in search of viable treatments for future patients in need.

Mirelys Barrios

M.D. Candidate Class of 2016

Investigation of intraperitoneal carboplatin, intravenous and intraperitoneal paclitaxel in the management of advanced stage ovarian carcinoma: a pilot study

By Genevieve Wiehl During the summer of 2013, Mirelys Barrios was awarded the Dr. Robert C. Knapp Medical Student Award to participate in the Hearing the Ovarian Cancer Whisper Internship Program. Ovarian cancer is sometimes called the “whisper killer” because the disease is usually asymptomatic until it has progressed to a very late stage. This award allowed Mirelys to conduct research under the guidance of Dr. John Diaz, M.D., a private practice physician with the South Miami Gynecologic Oncology Group.

Traditional treatment for ovarian cancer is surgical resection followed by intravenous chemotherapy. However, recent research has demonstrated that intraperitoneal (IP) chemotherapy, which is infused directly into the abdominal cavity, is associated with improved survival for

ovarian cancer patients. Unfortunately, the standard IP chemotherapy, cisplatin, has a high rate of toxicity. Due to side effects, over 50% of patients are unable to complete the recommended six courses of therapy.

The goal of this retrospective study was to determine if a modified treatment regimen would produce comparable outcomes with lower toxicity. These patients received IP carboplatin in combination with IP and intravenous paclitaxel. Carboplatin has been shown to have similar results to cisplatin when given intravenously, but is associated with fewer adverse effects.

This study found that a significantly higher proportion of patients were able to complete all six cycles of IP carboplatin compared to the landmark study that demonstrated the efficacy of IP cisplatin. These results suggest that the IP carboplatin regimen

is more tolerable by patients.

The other outcomes of the study, including progression-free survival and five-year overall

“

spiration to pursue advances in our treatment approach to this unforgiving killer,” she explained.

Mirelys found working with

The project really helped me understand current treatment protocols and how they can be modified for better patient outcomes. survival, were on par with those of the landmark study. Mirelys’ research may serve as a stepping-stone for a phase III trial to investigate the IP carboplatin regimen compared to IP cisplatin, with the goal of optimizing the IP chemotherapy regimen.

One of Mirelys’ favorite parts of this project was getting to meet many of the patients during their follow-up visits.

“These brave women fighting ovarian cancer were my daily in-

”

Dr. Diaz at the clinic to be a very rewarding experience. Currently, they are working on other clinical studies investigating the safety and outcomes of robotic secondary cytoreduction for recurrent ovarian cancer. “There is still so much left to be discovered about ovarian cancer,” Mirelys concluded. “We won’t give up the fight!”

Spring 2015 The Medical I.B.I.S. 21

Outcomes of same-day versus delayed removal of lens fragments after cataract surgery

Aliza Epstein M.D. Candidate Class of 2015

22 The Medical I.B.I.S. Spring 2015

By Emily Chen As a first-year medical student, Aliza Epstein actively sought an opportunity to get involved in clinical research.

Considering ophthalmology as a possible career path, Aliza attempted to gain greater exposure to the field and contacted Dr. Yasha Modi, M.D., an ophthalmology resident at the time at Bascom Palmer Eye Institute for possible shadowing and research opportunities. When Aliza met with Dr. Modi, he happened to be chatting with his colleague, Dr. Harry W. Flynn, Jr., Professor of Ophthalmology. Having overheard Aliza discussing her interest in becoming involved in ophthalmology research, Dr. Flynn offered Aliza an exciting opportunity to join his project investigating the timing of removal of retained lens fragments (RLFs) after cataract surgery.

Cataracts are clouding of the eye’s natural lens causing a reduction in sharpness of vision.

They are most commonly associated with aging individuals due to protein clumping and clouding that may occur over time.

A possible complication of cataract surgery is RLFs, which occur when the entire lens or lens fragments are displaced into the vitreous cavity in the back of the eye during the course of cataract surgery. The complication itself

is usually detected at the time of cataract surgery but may not present itself until days or weeks later. Pars plana vitrectomy (PPV) is a procedure that is used to remove the RLFs in a closed system, and reduces many of the vision-threatening complications of RLFs. This study sought to define the relationship between the optimal time necessary between cataract surgery and PPV for removal of RLFs. Under the direction of Dr. Flynn, Aliza contributed to the data collection of all patients who underwent PPV for RLFs at Bascom Palmer Eye Institute, which included 569 eyes of 568 patients.

Best-corrected visual acuity after PPV procedure was compared between the patients and results were organized into three groups: those who received PPV on the same day as cataract surgery, within one week after cataract surgery, or greater than one week after cataract surgery.

Patients undergoing same-day versus delayed (within one week or greater than one week) PPV had similar visual acuity outcomes and complication rates.

The study showed that there were no significant differences between groups when assessing complications including cystoid macular edema, retinal detachment, intraocular inflammation, intraocular pressure, vitreous hemorrhage and suprachoroidal

hemorrhage.

The study addresses the question of whether or not the removal of RLFs is time sensitive. Although same day surgery may offer advantages such as avoiding additional trips to the operating room and limiting anesthesia, a patient may not be disadvantaged if the vitrectomy does not occur on the same day. In fact, there may be reasons why a same day vitrectomy cannot be done, such as corneal edema limiting visualization, patient fatigue, and lack of an available retinal surgeon. The timing of PPV should instead depend on the patient’s clinical picture, performing surgeon’s opinion, availability of the retinal surgeon and operating room space. Overall, the study addresses clinical decision-making in the context of a surgical complication with regard to how a patient-centered treatment plan should be formed.

The study is unique in that it is the largest study to examine visual acuity outcomes of patients undergoing same-day versus delayed PPV for RLFs. Because of its important contributions to the field, the project has garnered many accolades, exemplifying the high quality research tin which UM medical students are involved. Aliza presented the project at the Eastern-Atlantic Student Research Forum in February 2011, while Dr. Modi

presented the project at the Association for Research in Vision and Ophthalmology conference in May 2013 in Seattle, WA, and Dr. Flynn presented at the American Academy of Ophthalmology in November 2013, where it earned the Best of the Posterior Segment Meetings award.

Aliza’s involvement in research early on in her first year at UMMSM illustrates the opportunities afforded to medical students at UM as soon as they begin their training. Her research exposed her to the expansive and dynamic field of ophthalmology, as well as allowed her to interact and network with research faculty. The guidance of her mentor Dr. Flynn inspired Aliza to have dedication and passion for clinical research.

From her research experience, Aliza appreciates the use of medical records of patients of the past to better envision patient care for the future. Aliza’s work emphasizes the need to cater treatment to the patient considering how to best achieve a good clinical outcome for that patient. The opportunity to be a part of such a large and monumental study solidified her passion for the field of ophthalmology. Aliza will be completing her ophthalmology residency at the renowned Kresge Eye Institute in Detroit, MI.

Spring 2015 The Medical I.B.I.S. 23

Nima Sharifai

M.D./Ph.D. Candidate Class of 2017

In situ visualization of protein-protein interactions: converging signals and dendrite morphogenesis

By Whitney Hang Visualizing protein interactions within a living system is a novel approach that Nima Sharifai is currently using as he studies the interactions between Cdc42 (cell division control protein 42 homolog) and WASp (Wiskott– Aldrich Syndrome protein) within a developing Drosophila brain.

A better understanding of this molecular interaction could potentially lead to the ability to recreate cellular processes. More specifically, Cdc42 and WASp interactions are believed to influence synaptogenesis in neurons; therefore, having a better understanding of this relationship during embryogenesis could lead to therapies for neurodegenerative diseases that are caused by synaptic problems, such as Alzheimer’s and dementia.

Proteins are too small to distinguish individually with live imaging. Thus, in order to visualize protein interactions, flu-

orescence donor and acceptor molecules are attached to the proteins being examined. In this study, under the supervision of his mentor Dr. Akira Chiba, Ph.D., Professor of Biology, Nima used mEGFP as the fluorescence donor and mCherry as the fluorescence acceptor to visualize the interaction between Cdc42 and WASp. When mEGFP and mCherry come within approximately 8 nm of each other, which occurs only when Cdc42 and WASp physically associate, the fluorescence lifetime of mEGFP decreases. This decrease in lifetime is due to a phenomenon known as FRET (fluorescence resonance energy transfer), in which energy is transferred from an excited state fluorophore to a second chromophore nearby. By measuring the fluorescence lifetime of mEGFP, Nima was able to determine when and where the interaction between Cdc42 and WASp took place within growing Drosophila neurons.

In order to ascertain wheth-

24 The Medical I.B.I.S. Spring 2015

er the fluorescence lifetime of a mEGFP-labeled protein did in fact decrease as a result of a protein-protein interaction, a baseline donor lifetime of 2.56 ns was first determined. Once this baseline value was set, the fluorescence lifetime of mEGFP was measured in multiple Drosophila embryos in which Cdc42 and WASp were labeled with mEGFP and mCherry, respectively. Analysis of these embryos revealed a statistically significant decrease in the fluorescence lifetime of mEGFP from the baseline value to a mean value of 2.45 ns, indicating that Cdc42 and WASp do indeed interact during Drosophila nervous system development. Although both Cdc42 and WASp are expressed throughout embryogenesis, interaction between the two proteins did not become apparent until after hour 15 of embryological development. Peak interaction occurred several hours later in the center of the nerve cord, called the neuropil, which co-

incides with the time and place of dendritic growth and synapse formation in the central nervous system.

This project proves that FRET can be detected between fluorescently labeled proteins in vivo, and Nima hopes that more researchers will use this novel approach to investigate how molecular interactions influence cellular processes. His most recent work has gone a step further to study these interactions within single neurons in order to determine the specific subcellular compartments in which they take place. Nima, who will graduate with a M.D., Ph.D., particularly enjoys this project because he is part of a team that is the first to utilize this cutting edge technique to visualize protein interactions within a living animal. He hopes to incorporate the knowledge he has learned in his future career in psychiatry or neurology at an academic research center.

The role of research in preparing for residency

By Sapir Karli Conducting research is a selfless, highly valuable experience.

Research allows for personal growth and development, and residencies place great value on medical students who conduct research to complement their clinical and academic work.

The secret to your medical student success in research: take ownership of your project! By doing so, you will learn to work with a variety of people on an inter-professional level, learn how to orchestrate many details, and act as a leader. By being actively involved in every stage of the project, you will learn to appreciate the process of translating research results into clinical developments.

Additionally, when you are considering getting involved in a research project, don’t jump in at the end stage of a project.

Develop a research question in a field of your interest. Cultivate a hypothesis and research plan.

Mobilize available resources and execute your research plan.

Through this extensive process, you will learn to be an analytical thinker, critically assess existing literature, and objectively evaluate your own work. Conducting research is just as much about

the journey as it is about the results. Nonetheless, the feeling of drawing conclusions that could be translated into clinical practice and improve diagnostic and therapeutic modalities in medicine is extraordinary.

Now you may wonder, “So how does this help me get into residency?� The answer lies in the discussion above. As just described above, residency programs know the enormous amount of time, energy, and effort that goes into a well thought-out research project and the qualities you gain in the process.

Last, but definitely not least, some of your greatest mentors will likely arise from your research project. By being actively involved in the research process with your principal investigator (PI), you will have the opportunity to form a strong collaborative relationship. You will find yourself reaching out to your PI for advice and guidance, and he or she may become your greatest advocate when the time comes to apply to the residency of your choice. The faculty members at the University of Miami Miller School of Medicine are unbelievably supportive, and you are likely to carry their mentorship with you for life.

Conducting research, or more specifically, taking ownership of a research project, illustrates several characteristics: Hard work and dedication to a medical field Selflessness Refined critical thinking skills Leadership

Spring 2015 The Medical I.B.I.S. 25

Repeat Offenders:

Katyayini and Nikesh Neither Katyayini Aribindi nor Nikesh Shah is a stranger to The Medical I.B.I.S. Having been featured in both the 2014 and 2015 editions, we wanted to give readers a more in-depth insight into who these researchers are and how they got involved in the incredible research they do.

For Katyayini, her mentor has been a major player in the research she does and her continuation in it. “I will count myself as successful if I become a fraction of the person he is, and that’s just the truth,” she says about Dr. Bhattacharya, a mentor that is “knowledgeable about everything” and is “the type of person to go out of his way to help those around him.” Katyayini’s unending praise for Dr. Sanjoy Bhattacharya, Ph.D., proved her true admiration for him and exemplified a relationship built on many years of working together.

Katyayini started her research in August 2010, her freshman year at the University of Miami, making her a five-year veteran student researcher. When asked why she chose the field she was researching, she stated, “the work was incredibly fascinating and very challenging, so I really delved into it.” Yet, when Katyayini applies to residencies,

26 The Medical I.B.I.S. Spring 2015

By Ladan Affifi & Reshma Muppala

she is not limiting her options.

Although Ophthalmology is one of her fields of interest, she wants to keep an open mind throughout wards and rotations.

Her favorite part of the research, she states, is “when the method or a machine works exactly the way we would like it to,” and her least favorite part is “all the work it takes to finally get that method or machine to work the way we want it to.” Katyayini’s advice for students thinking of research is to do research in a field they truly enjoy, so long hours and difficulties can be justified by your passion.

Nikesh developed an interest in research during high school when he began volunteering at a local university. As an undergraduate, he was fortunate enough to make his way to Philadelphia where he took a summer internship which focused on Radiation Oncology. This field made a lasting impression on Nikesh, and in his first year of medical school he began shadowing Dr. Joseph Panoff, M.D., where he gained an appreciation for the clinical applications of the field and began clinical research. He further explains that Dr. Panoff’s mentorship taught him how to be a successful physician by not

only learning how to conduct research, but also how to provide excellent patient care. Nikesh plans to continue his career in Radiation Oncology, and when asked what drew him to this specialty he was researching, he explained, “It is an incredible combination of research, technology, and oncology, all centered around direct patient care.” He describes that the most challenging aspect of research is “coping with results that you didn’t expect, or results that don’t support your theories. But as a researcher, it is your duty to publish and report results, regardless of their impact. At the same time, the best part of research is discussing your findings at conferences with peers who share similar interests.” While Nikesh plans on dedicating the majority of his time to patient care, he hopes to continue incorporating research throughout residency and further into his career. Nikesh advises students who are interested in research to be persistent. He reveals that “not all research produces breaking news, but amid the hours of sifting through data, research is the only way to improve patient care.”

Katyayini Aribindi

Nikesh Shah

If you were given a grant with however much money you want, what would you research?

“This is going to sound really nerdy: a high resolution imaging mass spectrometer, and the facilities to synthesize our own lipid standards.”

“I would love to learn more about the genetics of cancer and find novel ways to target cancer cells, and especially to prevent cancers before they even develop.”

If you could have a dinner date with any scientist or researcher dead or alive who would you pick?

“Nikola Tesla. He was someone way ahead of his own time. He was also incredibly human; he could have been a humanitarian with his idea of electricity for all. I’d like to know what his real motivations were and if he really did build the Teleforce.”

“I would follow cliche and choose Albert Einstein. His story shows you can achieve greatness regardless of your past. I would love to learn what motivated him to pursue his passion in the face of adversity.”

If you were on deserted island, what lab item would bring with you?

“Some really strong antibiotics and antifungals.”

“Ethyl alcohol - to sanitize things of course...”

Spring 2015 The Medical I.B.I.S. 27

How to get involved in research

By Laura Bloom “Wait a second…I have to get published how many times?”

This is the shocking question that will run through the minds of almost every first and second year medical student. Being involved in research and publishing papers have become cornerstones of the medical school experience and necessities for getting into top residency programs for all specialties – from plastic surgery to pediatrics. Plastic surgery interns published an average of twelve times in medical school, and pediatric interns published an average of three times (NRMP Charting Outcomes in The Match, 2014). What a daunting task for a new medical student!

The thought of getting involved in research in medical school for the first time is intimidating. Oftentimes the scariest part is trying to figure out how to get involved in research in the first place. Thinking back on my first year, I was terrified – I didn’t know where to begin. The purpose of this article is to share with you how some of your fellow classmates here at UMMSM

went about getting involved in research and also to provide strategies that you can use as you embark on this part of your medical school journey.

Two different approaches to choosing your research interest: 1. Decide on your field 2. Pick a research topic After discussing the research process with several current UMMSM medical students, there were two distinct approaches to deciding what to research: either decide on the field in which you’re interested (ex. orthopedic surgery) or on a topic in which you’re interested (ex. stem cells). We all have had different pathways into research, but one theme ran through all of our recommendations: use upperclassmen as a major resource!

Despite the highly competitive nature of medical school, we are a tight-knit community here at UMMSM, and your upperclassmen are always willing to provide advice and guidance.

28 The Medical I.B.I.S. Spring 2015

Advice from the upperclassmen:

Laura Bloom (me), MS2: As a writer for The Medical I.B.I.S. last year, I had the opportunity to write an article on fellow student Zach Gersey and his research on stem cells in the brain cancer glioblastoma multiforme. I find both stem cells and the brain to be fascinating topics, and so I reached out to Zach for his advice. Through him, I was lined up with a mentor in whose lab I worked all summer between first and second year. The rest has just fallen into place. The hardest part is that first step of choosing your area of interest and reaching out; the process is largely downhill from there. My advice to you is that any research is better than no research – even if you don’t know what type of doctor you want to be and even if your initial research projects end up being in a different field

than that in which you ultimately end up. Also, certain topics (like stem cells) span many different disciplines and are thus at least somewhat applicable across fields.

Roy Elias, MS2, had a similar philosophy about approaching a research topic. “Find what you are interested in – not which specialty, but a disease or research subject that is really important to you. Then see what type of research in that field is going on here. Educate yourself on the project - by reading the publications by the principal Investigator (PI) - then go set up a meeting and get started.” This is exactly what Roy did, and now he is being featured in this edition of The Medical I.B.I.S. for his work that marries cancer and immunology.

“

Ask your elders: your upperclassmen are your key to getting involved in research in medical school

Laura Stone McGuire, MS4, also found faculty to be approachable and helpful. “I found that faculty were generally very receptive to student interest in research projects. By reaching out and discussing your academic interests, they usually respond positively, connecting you to their research team.” Laura’s work on traumatic brain injury is featured in this year’s The Medical I.B.I.S. Allison Silverstein, MS3, was guided by the type of research project she was interested in pursuing. (For more on the different types of research, please see our article on page 30-31.)

Allison had already been heavily involved in bench work during high school and undergrad, and set off looking for clinical research opportunities. She admits that finding true clinical opportunities can be difficult, but found it helpful to ask upperclassmen about their mentors or people on the wards with whom they had enjoyed working, and even approach a speaker after a lecture if the topic is of particular interest to you. Allison says: “In many ways, I have found that emails, persistence, and a little bit of luck are all necessary.”

Dustin Massel, MS3, suggests that if you know what field in which you are interested, you’ll be amazed how much beneficial advice you can get through talking to upperclassmen planning on going into that field. Dustin found that through upperclassmen friends he was able to contact the PI for the recommended lab, but he also says: “If that fails, the next best thing is to email the physician directly. Most of the physicians are open to students interested in research, especially if they are reaching out.” Dustin’s research on joint replacements is featured in this edition of The Medical I.B.I.S.

Zach Gersey, MS3 and the student to whom I personally reached out, had the following advice – short and to the point: “Find out what field you want to go into. Find a great mentor with a good project. Work hard. Get published.”

What’s next Once you have some leads from your upperclassmen, the next step is to select a mentor who is doing research in that field/ topic. One great place to start is SciVal (http://www.experts. scival.com/miami). If you have specific researchers in mind, you can search for them here – most importantly to see if they publish often and in particular if they’ve been publishing recently. On the other hand, you can search in SciVal for your topic of interest and it will pull up the names of people who are doing research within that topic. When you have your short list of names, it is the time to write those researchers emails, explaining your interests and asking if they have advice on getting involved in research in the field. Make sure to

attach your curriculum vitae to this email. After you’ve established contact, you’ll meet with one or several researchers to get a sense of one another and the research. Make sure it’s a good fit! Then in no time, you’ll be on your way.

You’re not alone The thing I can tell you that I hope will bring you a sense of relief as you begin to pursue your research endeavors is this: you are not alone. Uncertainty is not something that we as medical students tend to handle well.

”

Whether they show it or not, most of your fellow classmates are feeling the same anxiety as you are. And your upperclassmen who look so cool and collected – we’ve been there too.

I hope that this article offers you some insight, perspective, and tangible advice about the different approaches to getting involved in research, but also about the common thread that runs through all of them: put your anxiety aside, reach out, and watch the opportunities unfold.

“

The only thing to do with good advice is to pass it on. It is never of any use to oneself.

”

Oscar Wilde Spring 2015 The Medical I.B.I.S. 29

Getting started: types of research

By Jennifer Rodriguez & Michelle Caunca Because medical science is dynamic and constantly developing, medical students at the UM Miller School of Medicine are incredibly involved in research projects on campus. However, many students currently seeking research opportunities are often unaware of the various types of research available. Though students may consider the specific scientific field in which they are interested, they may not think about research spanning from basic science at the bench to epidemiological studies to case reviews. This article will outline the different types of research along with their pros and cons, as well as the typical time commitment expected of students involved in these research projects.

When it comes to deciding in what kind of research to get involved, students should ask themselves these questions: How much time do you intend to spend conducting research?

In what field are you interested?

What kind of outcome are you looking to gain from a project?

After deciding what is best, the next step would be to search for projects that interest the student and reach out to the principal investigator (PI) about getting involved. The skills gained from research experience will not only look great on a resume or a residency application, but will also impact the scientific and medical field.

Retrospective

Retrospective studies are a type of longitudinal epidemiological study that evaluates the factors leading to a health outcome by studying past information from a cohort. Retrospective studies are incredibly useful in establishing risk factors for and potential causes of disease. Students can execute these studies in a timely manner if their research group has a well-established data set, cohort, study design and protocol.

However, students usually need to have experience in epidemiological data analysis and training in statistical analyses programming, which may require a greater time commitment by the student and the research group. In addition, if the student needs to acquire new data, it lengthens the time commitment significantly.

Time commitment: medium to high (depends on the student’s dedication and PI’s investment in student) Publication potential: low to medium for a first author publication, but medium to high for authorship in general Pros: gaining of statistical analysis experience, which is helpful in any field of medical science; can give student introduction into epidemiology Cons: no bench work; may include data entry work which can be time-consuming

Case Reports

Case reports are a formal write-up of a single patient with unusual or unique presentation of a medical condition. Unlike bench or clinical research, case reports are not hypothesis-driven, but rather are motivated by observation of patients with unique clinical presentation or who have been treated with new therapies. Students can effectively write and submit case reports for publication in as little as a month. Subsequently, writing a case report is a great way to boost a student’s CV, but does not necessarily demonstrate hypothesis-driven thinking or ability to design and execute experiments.

Time commitment: low Publication potential: high; if student assigned the project, there’s a good chance of a first authorship Pros: great writing experience; good way to obtain publications quickly Cons: no real scientific experience

30 The Medical I.B.I.S. Spring 2015

Clinical

Research

Basic Science

Basic science research is a systematic study aimed at advancing knowledge of a phenomenon. The general knowledge obtained in basic research provides the means of answering a large number of practical problems and it can include all branches of science and engineering. Basic science research involves a lot of lab time, creativity and intellectual rigor since there isn’t a defined problem or goal, and can take years to complete. If a student’s motivation is knowledge for knowledge’s sake, then doing basic science is the way to go; however, if the motivation is to get results that reach an end goal, applied research may be the better route.

Time commitment: high

Clinical research involves human subjects and helps translate basic research from labs into new treatments and information to benefit patients. Clinical research includes: •Patient-oriented research – seeks insight on mechanisms of human disease, therapeutic interventions, clinical trials, and development of new technologies •Behavioral studies – examines the distribution of disease, the factors that affect health, and how people make health-related decisions •Outcomes and health services research – identifies the most effective and efficient treatments and services Clinical research requires a blend of medical and research skills such as familiarity of bioethics, protection of human subjects, scientific writing, and experimental design. As medical students, it’s also exciting to work directly with patients; however, clinical research can be tedious since it involves a lot of paperwork and adheres to a strict protocol.

Time commitment: medium (6+ weeks) Publication potential: medium for first authorship, high for authorship in general Pros: work with patients Cons: can be tedious

Publication potential: low Pros: viewed as highly valuable research when completed Cons: results unpredictable; long experiment can have no useful data

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