UTGSM Advance Summer 2014

Advancing Research from Lab to Life A Biannual Research Digest of the University of Tennessee Medical Center and UT Graduate School of Medicine

The Future of Research: Students Clinically Immersed

On the Horizon: New Researchers Pursue Studies of the Brain

Research Spotlight:

Engineering Students Create Lung Phantom

Studies in Brief: • Bass Bone Scan • Handling Dental Emergencies with Human Simulation

Summer 2014

Wisdom for Your Life.

Spirit of Discovery‌

Observations

Table of Contents

As I look over the last 45 years of my involvement in medicine and specifically medical research, one of the very exciting things I have realized is how far we have come in our knowledge of disease and its treatment, and how advanced are the tools we have to work with.

From the diagnostic tools like PET CT to a pharmacopeia that has grown exponentially to robotic and minimally invasive surgery and innovations that have made the practice and delivery of medicine exciting and rewarding. If you think about it, it was only 100 years ago that physicians could, in many cases, only sit by the bedside and hope that the person’s body would effect their recovery and people honestly felt that hospitals were a place to go to when you were about to die. Almost all of the innovations we take for granted today are the results of individuals who are stimulated to not only care for patients, but to look for better ways to do that care.

This edition of Advance highlights the efforts of the faculty of the GSM and the staff of UMTC to engage young people in the quest for medical solutions. I am reminded of Thomas Fogarty who as a medical student invented the embolectomy catheter that we use routinely in vascular surgery and subsequently went on to a distinguished career in surgery. These efforts by undergraduates, medical students, and residents offer the promise of similar biomedical advances in the future. By engaging young people in research, we are not only ensuring these advances, but we are providing a service to the Tennessee community through enhancing their education. In return, very bright and very excited students stimulate and challenge the faculty to push ahead. It is a benefit for all. I. Reid Collmann saw this when he was a medical student and as a very successful practitioner and educator at UTMC. He remembered the value his research experience had for his career. Through his generosity, we are able to enable the growth of medical knowledge for the future. We should honor his foresight and his commitment and remember what our predecessors did for our careers. This is a very exciting time for the future of medicine and it’s wonderful that the medical center has faculty who are willing to promote that future.

Featured Researchers: Lydic and Baghdoyan

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Featured Researcher: Stephenson 4 Collmann Endowment

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In Brief: Bass Bone project

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In Brief: Lung Phantom

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In Brief: Capstone Design Course 10 In Brief: Clinical Documentation 11 In Brief: Handling Dental Emergencies 12 News

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Advance

Issue 7: Summer 2014 Publishers James Neutens, Ph.D. Mitch Goldman, M.D. Eddie Moore, M.D. Managing Editors Kristen Bass, M.S. Rachel Echols Contributors Mitch Goldman, M.D. Photography Kandi Hodges Design Jerry Tracy/J Squared Graphics Advance is produced by the University of Tennessee Graduate School of Medicine. The mission of the digest is to spotlight research programs at the institution and explain how the work of our researchers impacts health care in East Tennessee and beyond.

Institutional Review Board All research using human volunteers follows stringent federal regulations that require a review by an Institutional Review Board (IRB) before it is approved. The IRB committee is comprised of physicians, pharmacists, scientists, researchers and non-scientific community representatives. The members review research protocol to ensure protections are in place.

Faculty from the UT Graduate School of Medicine influence medical care across the world by publishing and presenting. For a comprehensive list of publications and presentations, visit http://gsm.utmck.edu/scholars Contact Us Advance UT Graduate School of Medicine 1924 Alcoa Highway, U-11 Knoxville, TN 37920 Telephone: 865-305-9749 E-mail: kbass@utmck.edu Web: http://gsm.utmck.edu

Mitchell H. Goldman, M.D.

Professor and Chairman, Department of Surgery Assistant Dean of Research University of Tennessee, Graduate School of Medicine

Wisdom for Your Life.

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FEATURED RESEARCHERS

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New Anesthesiology Pursue Studies of

New research in the Department of Anesthesiology is aimed at understanding the chemical and electrical difference between consciousness and unconsciousness, an effort which could also lead to understanding disorders such as autism and schizophrenia.

To lead this endeavor, Ralph Lydic, Ph.D., and Helen Baghdoyan, Ph.D., considered one of the most productive couples-collaborations in the history of anesthesiology research, have brought their skills and expertise to The University of Tennessee Medical Center.

They hold joint appointments with the Department of Anesthesiology in the UT Graduate School of Medicine, the Department of Psychology in the UT College of Arts and Sciences, and the Oak Ridge National Laboratory, creating an environment of collaboration among facilities with some of the most advanced technologies and researchers.

Robert M. Craft, M.D., Professor and Vice-Chair of Anesthesiology, said, “I want to understand how consciousness works. Anesthesia reversibly interrupts consciousness and thus offers an opportunity to study both states in the same individual.

“The aim is to find a common change in brain chemicals or electrical activity (EEG) across the spectrum of anesthetic agents. Whatever process goes away and comes back with the onset and reversal of anesthesia – that is the minimum requirement for consciousness.”

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Over the past 20 years, Dr. Lydic and his collaborators have shown evidence for the “shared circuit hypothesis,” which contends that the brain regions and mechanisms involved in physiologic sleep have similarities with anesthesia-induced sleep.

Researchers the Brain Studying sleep from a different angle, Dr. Baghdoyan’s research has concentrated on identifying the chemical differences between physiologic sleep, wakefulness and anesthesia as they relate to EEG. She has shown that some of the systems involved in sleep cycles are also involved in anesthesia.

Dr. Craft believes that by understanding the basic requirements for consciousness, they can also understand disorders of consciousness, such as autism and schizophrenia. Establishing a broad neuroscience effort across the multiple institutions in Knoxville is the ultimate goal for his recruitment of Dr. Lydic and Dr. Baghdoyan.

Prior to coming to the medical center, Dr. Lydic and Dr. Baghdoyan established research programs, first at Penn State University and most recently at the University of Michigan, which have gained national notoriety for their contributions. Since 1988, Dr. Lydic and Dr. Baghdoyan’s research has been continuously funded by grants from the National Heart, Lung, and Blood Institute.

In 2012, The American Society of Anesthesiologists presented Dr. Lydic with its Excellence in Research Award. He is a founding member of the Society for Anesthesia and Sleep Medicine, and he serves on the board. In addition, he is chairman of the External Advisory Council for the National Space Biomedical Research Institute.

Dr. Craft said, “We are proud to have Dr. Lydic and Dr. Baghdoyan at our research facility, and we look forward to making new contributions toward an understanding of how the brain works.”

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FEATURED RESEARCHER

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Dr. Stacy Stephenson Brings Life to Research Lab Stacy M. Stephenson, M.D., joined the Department of Surgery as an Assistant Professor in the Division of Plastic and Reconstructive Surgery in November 2013. She previously held an Assistant Professor position with the University of Toledo Medical Center, Division of Plastic Surgery, while also specializing in treating melanoma with Surgical Oncology.

Her background includes a Bachelor of Science from Auburn University. She obtained her M.D. from Ohio State University in 2000, followed by a one-year Post-Doctoral Fellowship with the Division of Pharmaceutics at OSU. In 2007, she completed her General Surgery Residency at St. Agnes Hospital in Baltimore, MD. In 2010, while at the University of Texas in San Antonio, Dr. Stephenson completed a residency in Plastic Surgery receiving the Cronin Award from the

Texas Society of Plastic Surgeons for Best Senior Resident Paper in 2009. She also held honors in Plastic Surgery Rotation, Ambulatory Rotation, and Comprehensive Head and Neck Surgery rotation.

Since joining The Graduate School of Medicine, Dr. Stephenson has been vital in establishing a research lab within the division, starting clinical work in February. Her research involves vascularization of tissue engineered constructs with adipose derived stem cells, having focused on Biomedical Engineering as part of her doctoral education at Ohio State University under the Division of Pharmaceutics, Dr. Stephenson has had extensive experience with grant writing and publications.

In March 2014, Tom Masi, Ph.D., joined Dr. Stephenson in the lab as a Research Specialist.

Dr. Masi’s previous work includes Research Associate Professor in

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the Department of Microbiology at UT as well as Post-Doctoral Research Associate at the UT College of Veterinary Medicine. His education includes a Bachelor of Science in Biology from the University of Central Florida followed by a Ph.D. in Biology from Florida State University.

Dr. Masi specializes in techniques including harvesting fat tissue from research specimens, purifying non-embryonic stem cells, and differentiating and verifying their cell type.

Dr. Stephenson and Dr. Masi are generating a bioluminescent cassette which will be used to permanently “label� the stem cells and differentiated cell types such that they will be able

image them live in vivo in an animal model.

Reflecting on the future of the research lab, Dr. Stephenson states that she has three goals she expects to accomplish; to validate the differentiation of adipose derived stem cells into endothelial cells by culture in specific media, evaluate the capacity of endothelial differentiated adipose devised stem cells to form microvascular networks in vitro, and develop methodologies to track the fate of endothelial differentiated adipose derived stem cells in vivo. With her high expectations for the research lab and abundant experience in non-embryonic stem cell research, the future looks promising for Dr. Stephenson.

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Collmann Summer R

Dr. I. Reid Collmann was a former Dean of the Graduate School of Medicine. To honor his years of leadership and service, the I. Reid Collmann, M.D. Medical Student Educational Endowment was established. The purpose of this endowment is to insure and enhance the quality of medical student education programs.

Dr. Collmann initiated the I. Reid Collmann, M.D. Medical Student Education Fund to give students an opportunity similar to his own student research experience. The awareness of research’s impact on patient care is information that will build a solid foundation for the remainder of the student’s medical career.

Once awarded, the endowment requires an eight week commitment from the student. This year, three students were selected to participate in the program.

Travis Potter pictured left, is a rising M2 medical student at ETSU Quillen College of Medicine working in the Vascular Research Lab under the direction of Deidra Mountain, Ph.D., and Stacy Kirkpatrick. His project focuses on RNAi, or the use of short interfering RNA (siRNA) to degrade mRNA in the cytoplasm and transiently attenuate intracellular proteins, which shows promise in the

inhibition of vascular pathogenesis. In this study various polymer classes are being screened in vitro for their cellular toxicity and inhibition efficiency compared to our laboratory’s standard transfection methods. Our aim is to establish polymeric carrier molecules for targeted RNAi in the treatment of vascular pathogenesis.

Ben Pomy, pictured right, is a rising M2 medical student at the UTHSC College of Medicine who is doing research in the lab of Michael Karlstad, Ph.D. His study addresses the possibility that a diet restricted in methionine will decrease diabetes frequency using the nonobese diabetic (NOD) mouse, a genetically susceptible autoimmune model. In his study, Ben proposes using female NOD/ShiLtJ mice fed a commercially-available methionine-restricted (MR) diet for 12 weeks. Currently, NOD/ShiLtJ female mice develop type-1 diabetes at a frequency of between 70-80% by 18 weeks of age. This makes female NOD/ShiLtJ mice useful for testing the hypothesis that MR dietary intervention will suppress the islet inflammation that drives destruction of the pancreatic beta-cell.

Casey Smith, pictured center, is a rising M2 medical student at the UTHSC College of 6

Research Program

that had a fever while in labor. Â Currently if the mother is diagnosed with an unexplained fever, they are assumed to have an infection and the baby must start antibiotics. The goal of this research is to determine what markers are valuable in helping to diagnose babies that are truly at risk of infection to ultimately provide better care to the mother and baby.

Medicine working with Nikki Zite, M.D., in the Department of Obstetrics and Gynecology.

Her summer project is evaluating fever in labor. Â Her project is a retrospective review of all women delivering at the The University of Tennessee Medical Center in the last three years

Why this matters:

Research is the force behind advances in medicine.

By participating in research during medical school, students are empowered to remain on the cutting edge of an evolving field while discovering new information and developing state of the art treatment methods leading to the improvement of the lives of their patients. This research experience changes the way students learn to think as a physician. Additionally, research may spark an interest in academic medicine as a career. Without research, the understanding of disease processes would remain stagnant and treatment options would fail to progress.

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IN BRIEF

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Examining Signs of Osteoporosis and Bone Characterization of the Bass Bone Collection

years of age. Samples were grouped according to sex and age for analysis. Findings from this study showed no significant correlation (p>0.05) of expected osteoporosis parameters within male samples, however, this was not the case for females. Several analysis categories showed statistical significance (p<0.05) between age groups 1 and 2 as well as 1 and 3, including: bone density, Z- and T-score, trabecular spacing and thickness, and bone surface. This work clearly showed signs of osteoporosis across aging populations of women sampled from the Bass bone collection.

Undergraduate anthropology student, Sarah Depew, has been working with Dustin Osborne, Ph.D. and Shelley Acuff, CNMT in the Molecular Imaging and Translational Research Program to examine signs of osteoporosis and bone characterization of the Bass bone collection.

For this study, she used high resolution microCT to acquire high resolution bone images of approximately 40 microns to perform advanced trabecular bone and standard bone mineral density analysis. This work took 24 samples from three different patient populations ranging in age from 50-59 (1), 60-69 (2), and 70-79 (3)

Why this matters:

Characterization of the Bass Donated Skeletal Collection adds to forensic scientists’ ability to better identify unknown individuals.

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»»»»»» Engineering Students Design Respiratory System for Simulated Image Testing

IN BRIEF

during imaging. The phantom simulates the movement of nodules in the lung as well as liver lesions that are most affected by respiratory motion.

This new phantom will be used to test the functionality and accuracy of advanced gating technologies developed at the University of Tennessee and to develop new methods of calibrating and testing nuclear medicine imaging equipment with radiation therapy hardware.

Gating technologies for PET/CT imaging enable the capture of motion information within the respiratory or cardiac cycle so that physicians can either visualize the motion or reduce motion artifacts in the final images. In radiation therapy, gating technologies are used to synchronize the therapy beam to activate during a certain phase of the cycle so that the therapy occurs at the proper time in the motion cycle.

This work is made possible by the biomedical engineering senior design program in MABE headed by Jeff Reinbolt, Ph.D., and is partially funded by the National Institutes of Health.

Mechanical, Aerospace, and Biomedical Engineering (MABE) students from the University of Tennessee are working in conjunction with the Molecular Imaging and Translational Research Program to design a new respiratory phantom that enables accurate imaging of lung nodules during simulated respiratory motion for use in testing advanced gating technologies for PET/CT imaging as well as radiation oncology applications.

MABE students working on the project are Geneva Doak, Michael Harris, Kayla Stone, and John Taylor.

Their system uses a basic design that is similar to the standardized shape of the Society of Nuclear Medicine Clinical Trials Network Chest Phantom, but it is outfitted with systems that enable accurate representation of respiratory motion

Why this matters:

Correction for respiratory motion during imaging is critical to enable the most accurate diagnoses.

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IN BRIEF »»»»»» Engineering students work with GSM to turn knowledge into skills

This program is characterized by collaborations rare in undergraduate engineering. The multiinstitutional environment: UT Mechanical, Aerospace, and Biomedical Engineering; UT Graduate School of Medicine (GSM); and Oak Ridge National Laboratory – is an important and novel approach. The alliance with GSM is a practical source for patient-driven design projects.

For the past three summers, the Graduate School of Medicine has participated in the clinical engineering partnership. Doctors from several departments have allowed the Biomedical Engineering students to participate in a clinical immersion throughout the summer. By shadowing clinical faculty, these students are then able to begin designing projects based on the needs they see in the hospital. Clinical shadowing, literature/ patent searches, and project planning take place over a 10-week period to provide an immersive training environment through daily activities in a clinical setting and discussions about treatment protocols.

The National Institutes of Health (NIH) National Institute of Biomedical Imaging and Bioengineering (NIBIB) awarded an R25 research education grant to Jeff Reinbolt, Ph.D., University of Tennessee Mechanical, Aerospace, and Biomedical Engineering, for his application titled “FUTURE (Furthering University of Tennessee Undergraduate Research Education) for TeamBased Design in Biomedical Engineering.”

The senior capstone design course is the last bridge between theory-based education and a problem-solving profession. The project addresses an important research education problem where a gap exists between the education of biomedical engineers and their roles in the engineering workforce. It introduces a new period of clinical immersion and planning over the summer that that serves as a springboard for future design activities. A combination of student teams, clinical environment, and open-ended biomedical design projects are used to overcome a critical barrier and bridge the gap to progress in scientific knowledge, technical capability, and clinical practice in biomedical engineering.

Why this matters:

This research education program fosters undergraduate biomedical engineering students to build upon their theoretical knowledge and develop multidisciplinary team-based problemsolving skills for careers related to public health. Program participants - future generations of biomedical engineers - will be better prepared to pursue careers creatively involved in problem solving and the design of solutions for the health care of the future.

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IN BRIEF

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Documentation Training Benefits Patient Care and Costs

David Jeffcoach, M.D., recently presented his findings on documentation patterns of surgery residents in order to meet the challenges of increasingly complex surgical resident education standards. These standards included meeting the Next Accreditation System education milestones, the national implementation of the Patient Protection and Affordable Care Act, and decreasing resident education funding. In order to meet these standards, Dr. Jeffcoach developed a training intervention focused on improving patient documentation, hypothesizing that such improvements would enhance documentation patterns, thus increasing geometric mean length stay, case mix index, and overall patient care.

All general surgery residents participated, with each resident undergoing a one-on-one 30 minute intervention with Trey La Charite, M.D., Clinical Documentation Integrity Specialist for The University of Tennessee Medical Center,

in order to review the quality of their notations using current medical documentation practices.

Charts were reviewed for all patients discharged from four surgical services over a one month period. Patient demographics, length of stay, geometric mean length of stay (GMLOS), case mix index (CMI), and the improvement of patient care.

Following the intervention, a subsequent sample of surgical patients was evaluated using the same endpoints. All goals of the project were met: increased GMLOS, increased CMI, and overall improved patient care.

Dr. Jeffcoach’s statistical data concluded that the intervention was a success in improving the practices of General Surgery residents in documentation; was a valuable resource for preparing residents for practice; and provided the necessary strategies to improve patient care.

Why this matters:

Improved awareness of accurate documentation patterns prepares residents for successful practice, benefiting both the medical community and patient care during treatment.

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IN BRIEF »»»»»» Handling Dental Emergencies with Human Simulation of the simulation is to teach residents to identify a developing problem, determine the need for assistance from emergency medical personnel, manage the situation, and stabilize or refer the patient to an appropriate medical facility for complete care. Dental residents from the UT General Dentistry Residency program practiced in a room replicating a dental operatory at the UT Center for Advanced Medical Simulation, while instructors and colleagues assessed the participants through audio/visual streaming. Participants were then debriefed and provided metrics on their performance. The response from the Dentistry residents was positive, noting they are more likely to have protocols committed to memory and have increased their confidence levels in preparation for dealing with reallife emergencies. The simulation course is currently being offered in the residents’ academic curriculum permanently. In the future, the course will be included twice: once in the beginning of residency to determine a baseline competency and again at the end of the residency to determined individual improvement.

Chelsea L. Balderson, D.D.S., was given the opportunity to present at the AEI annual consortium of ACS-Accredited education institutes in March 2013 with her simulation poster entitled “Medical Emergencies in the Dental Office.” Imitating real-life experience using medical simulation, dental residents were submerged into an environment where skills can be learned and practiced with feedback from peer and faculty observers. Part of that simulation involved emergency situations but has only been used with inanimate mannequins in the past. Recently residents have been training with the use of human simulators that allow for the sophistication and complexity of the human body compared to that of a mannequin. The main purpose

Why this matters:

Dentists, physicians, students, and other members of the healthcare team attain not only improvement in individual skills, but also learn and practice team skills that are essential for patient safety. This type of multi-faceted, orchestrated training improves critical thinking, decision making, and clinical techniques - all without imparting risk to a real patient.

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News»

POT OF GOLD Winner Announced:

Berger, M.D., Brian Freeman, M.D., Kyle Basham, M.D., Austin Bourgeois, M.D., and Megan Rooney Thompson, M.D.

The Graduate School of Medicine and the University of Tennessee, Knoxville campuses created a grant pool for investigators conducting collaborative research between our two campuses.

The funding pool was simply named “POG” or pot of gold. Both campuses combined dollars to create a $15,000 pool. The winners are: (1) “Peptide targeting of nanoparticles”, Jon Wall Ph.D. (Department of Medicine) and Michael Best Ph.D. (Department of Chemistry); $10,000. The goals of this collaborative research project are: to synthesize and characterize liposome nanoparticles coated with cancer-targeting peptides, and determine the biodistribution of radiolabeled nanoparticles in mice with pulmonary melanoma metastases and subcutaneous HCC xenografts, by using small animal SPECT/CT imaging, autoradiography, and measurement of tissue-associated radioactivity.

Dr. Kestler retires:

The Department of Medicine wishes to congratulate Dan Kestler, Ph.D. on his retirement on June 30th after over 20 years with the Department of Medicine. Dr. Kestler has been an important member of the research team here at the Graduate School of Medicine. He has performed novel research with odontogenic ameloblast-associated protein (ODAM) and its relation to certain cancers, which was supported by a grant from the Komen Foundation. We have greatly appreciated Dr. Kestler’s contributions to GSM, and he will be missed. We wish him the very best in his future endeavors.

IRB hires new Director:

Becky West has joined the UT Graduate School of Medicine as the new assistant director of the Institutional Review Board, following Reni Leslie’s retirement. She brings with her more than 20 years of IRB experience, most recently as administrator for Convenant Health. IRB Chair Kim Mason, PharmD, said, “I am thrilled to have Becky aboard as she brings a wealth of knowledge and experience from her prior work with large academic medical centers and her familiarity with cutting edge IRB process and technology.

(2) “Role of Neutriphil CXCR2 Activation in Diabetes Development”, Michael Karlstad Ph.D. (Department of Surgery), Tim Sparer Ph.D., (Department of Microbiology), and Jason Collier PhD (Pennington biomedical Research Center), $5,000. The overall goals of this study are to understand the mechanism of CXCR2 activation that promotes neutrophil inflammatory responses and whether blocking CXCR2 signaling in vivo using a pre-clinical rodent model of diabetes will prevent Type 1 diabetes mellitus.

Sudden Cardiac Death Topic of Winning Research:

MITRP wins awards:

Dustin Osborne, Ph.D., Director, and Shelley Acuff, CNMT, Clinical Research Leader, in the Molecular Imaging and Translational Research Program won one of three young investigator awards from the Computer and Instrumentation Council at the Society of Nuclear Medicine and Molecular Imaging Annual Meeting.

The UT Graduate School of Medicine and Academy of Scholars Committee held Resident and Fellow Research Day on Wednesday, May 28, where 21 residents and fellows from 8 programs presented their original research or case study in a five-minute oral presentation. Winners are Erik

Your Chance to Advance The people at the UT Graduate School of Medicine would be happy to discuss our research programs and how your support can help advance healthcare. For information about philanthropic giving to the UT Graduate School of Medicine Office of Research, please contact the development office at 865-305-6611 or development@utmck.edu.

If you would like more information about any research programs described in this issue of Advance, please contact the UT Graduate School of Medicine’s Research Coordinator, Kristen Bass, at 865-305-9749 or visit online: http://gsm.utmck.edu/research/main.cfm.

Thank you.

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