ADVANCING RESEARCH FROM LAB TO LIFE A Biannual Research Digest of the University of Tennessee Medical Center
Amyloidosis Clinical Trial Offers Hope
On the Horizon: Dean Hauptman
Research Spotlight: From student to scientist
News in Brief: Goldman retires NIH funds bone regeneration study NIH common rule Contraceptive Access Oncofreeze Scans
Summer/Fall 2019
Wisdom for Your Life.
Observations
Our final issue of “Advance� But only the beginning of our progress in research. We will be publishing a digest of research developments in The Scope, a quarterly newsletter for the GSM. Please become a UTGSM Scope Subscriber! Send your name and preferred email address to: GSMNews@utmck.edu Thank you for your continued support of our research endeavors in medicine.
Table of Contents
This is my final editorial for Advance. I have stepped down as Assistant Dean for Research in the Graduate School of Medicine. It has been a wonderful opportunity to work with some outstanding researchers, to explore interesting ideas and concepts well outside my knowledge base, to meld collaborations and to help grow the research effort at the institution. It has been a great pleasure for me to see the significant resurgence in research interest in all of the departments of the Graduate School. This growth is essential to the success of our institution. Scholarly activity keeps our faculty on the forefront of medicine bringing high quality care to our patients. It enhances the education of our trainees, creating critical thinkers as well as good clinicians. The opportunity to do both clinical and translational research helps us recruit higher quality faculty and students creating an environment that is continuously looking for new solutions for patients and the medical community. I have been proud to work with a crew that is passionate about creating that atmosphere. From the Deans and Chairpersons to the administrative support personnel, I have seen a tireless commitment to increasing our research portfolio, to creating collaborative opportunities with our sister campuses at UTK and ORNL, and to develop the support structures within the Graduate School to enable further growth. So, like the good skipper, I am stepping ashore with the knowledge that boat is shipshape and the mission is in good hands and will have fair winds and following seas.
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Featured Researcher: Dean Hauptman Amyloidosis Clinical Trial Offers Hope From student to scientist In Brief: Goldman retires In Brief: NIH funds bone regeneration study In Brief: NIH common rule In Brief: New Grant Champions Contraceptive Access In Brief: Oncofreeze Scans News
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Advance
Issue 16: Summer/Fall 2019 Managing Editor Kandi Hodges Contributors Paul J. Hauptman, M.D. Mitch Goldman, M.D. Kandi Hodges Photography Kandi Hodges Design Jerry Tracy 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 Telephone: 865-305-6377 E-mail: GSMNews@utmck.edu Web: http://gsm.utmck.edu
Mitchell H. Goldman, M.D.
Professor of Surgery University of Tennessee Graduate School of Medicine
Wisdom for Your Life.
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FEATURED RESEARCHER »»»»»»
A New Dean:
Heart Failure Expert Leads GSM Education and Research Programs
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The University of Tennessee Graduate School of Medicine has welcomed Paul J. Hauptman, MD, in October 2018 as its fourth dean to lead academic and research endeavors. Hauptman’s experience in these areas will help open doors to new studies, new treatments, and a healthier community. He also serves as Senior Vice President and Chief Academic Officer of The University of Tennessee Medical Center. President and CEO Joe Landsman said, “I am excited to welcome Dr. Hauptman to the medical center. Heart disease is the number two medical condition affecting the region, so his expertise in heart failure medicine and research are going to be a great asset to our community.” Hauptman is board certified in advanced heart failure by the American Board of Internal Medicine. He said heart failure became his primary clinical focus in the early 1990s when options for patients were limited and not many physicians were choosing to specialize in the field. “Over the past 25 years, I have seen an evolution, if not a revolution, in the options patients now have for heart failure treatment. In the 1990s and before, heart failure was associated with a very limited life expectancy and was
considered a disheartening field to work in. As a consequence of breakthrough research, advances in technology, and with clinicians collaborating across specialties, heart failure treatment now offers considerably more options for patients.” As editor-in-chief of the Journal of Cardiac Failure, the leading heart failure journal, Hauptman is exposed to the latest information and advances in his field. He said, “What I enjoy is that for every question answered, we come up with at least one or two more questions. There are countless research avenues to explore.” And this applies to all areas of medicine. “My overriding vision is to find ways to expand upon current research initiatives at the medical center, further enhancing our reputation while growing very specific areas of research excellence,” Hauptman said. His professional research interests include outcomes assessment in cardiovascular disease and advanced heart failure, evaluation of care delivery, and clinical trials in congestive heart failure. He has garnered support through federal, foundation, and industry-sponsored research grants, including from the National Institutes of Health and the American Heart Association. He has also served as an expert panelist for the FDA and has authored over 145 papers in publications including JAMA and the New England Journal of Medicine. Hauptman came to the medical center from a position with Saint Louis University School of Medicine. Most recently he was Assistant Dean of Clinical and Translational Research, Professor of Internal Medicine at the SOM, and Director of the Heart Failure program at Saint Louis University Hospital. He served as an adjunct professor in the College for Public Health and Social Justice. In addition, Hauptman was director of SLU’s Clinical Trials Office, the regulatory authority for contracting, budgeting and invoicing of clinical trials. Prior to his tenure at SLU, Dr. Hauptman held faculty appointments at Harvard Medical School.
CURRENT MEDICAL CENTER RESEARCH AT A GLANCE Office of Clinical Trials Update: As of June 30, 2019, there are 74 active clinical trials with 100 participants. The number of trials and participants has nearly doubled since 2016.
Current Investigations within our Centers of Excellence: • Cancer – hematology, gynecological oncology, surgical oncology and radiation oncology • Brain & Spine – Alzheimer’s disease, Multiple Sclerosis, aneurysm, and stroke • Heart Lung Vascular – arteriovenous fistula (AVF) with end stage renal disease, Cystic fibrosis, heart failure, cardiovascular imaging • Women & Infants – heavy menstrual bleeding, premature birth, sterilization, endometriosis associated pain, chlamydia, uterine fibroids
Current faculty research explores: • various aspects of opioid use in our patient population. • radiological imaging agents that may assist in the staging, diagnosis, and treatment of cancers and other serious diseases. • neurodegenerative diseases in our aging population. • how simulation-based programs may improve patient outcomes.
Current resident and fellow studies 357
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Amyloidosis Clinical Trial Offers Hope
A first-in-man clinical trial being conducted at The University of Tennessee Medical Center may lead to earlier, more accurate diagnoses for patients affected by amyloidosis. This rare and devastating disease is associated with the accumulation of complex protein clumps or aggregates (fibrils) in the heart, kidneys, nerves and other organs. More than 30 amyloid-associated diseases have been identified but significant challenges remain in accurate diagnosis and treatment. The protein that forms amyloid fibrils and the pattern of organ involvement can be different in each patient and the condition is often detected in its late stages. Another challenge is that the U.S. Food and Drug Administration has not yet approved any methods that allow doctors to comprehensively detect the specific locations of amyloid accumulation in patients or
monitor the course of disease. This capability could aid in more accurate diagnoses, improve patient management, and potentially increase the patient’s quality of life and survival once the extent of disease is fully appreciated. To address these barriers, the research team in the Amyloidosis and Cancer Theranostics Program (ACTP) at the Graduate School of Medicine, led by Jonathan Wall, PhD, has been working to develop a new reagent capable of imaging the diverse forms of systemic amyloidosis in organs and nerves throughout the body. This research has resulted in the identification of a synthetic peptide, designated “p5+14�, which when labeled with iodine-124, can be used to detect amyloid using positron emission tomographic (PET) imaging. This scan also offers the potential of assessing the burden of disease and changes in that burden over time. This is also
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significant since the FDA has approved three novel medications in the last year that are the first truly viable treatment options for patients with amyloidosis. In 2014, Dr. Wall obtained early grant support from the National Heart, Lung, and Blood Institute at the National Institutes of Health to produce human-grade peptide p5+14 and gather data in support of using this peptide in an amyloid imaging clinical trial. In 2018, the FDA approved his application to perform the ongoing safety and efficacy trial in patients with all of the major forms of systemic amyloidosis. ACTP is collaborating with teams from the UT Cancer Institute, Department of Radiology, and Nuclear Medicine, to recruit patients to the trial, perform the imaging studies, and evaluate results. The first patient was imaged in late Fall. Ronald Lands, MD, Associate Professor and Oncologist, monitored the
patient for several days as the team collected serial imaging and safety data. Since then, nine additional patients have been imaged for the study. While many patients are from Tennessee, Dr. Wall anticipates that over the next 18 months the trial will recruit a total of 43 patients from all over the U.S. Dr. Wall hopes the results of this clinical trial will lead to expanded clinical studies using larger patient populations. He hopes this technique may one day be approved by the FDA and made available to clinicians in order to allow them to confirm and quantify the presence of amyloid in the body. Ultimately, Dr. Wall and his multi disciplinary UT team hope to improve the prognosis and quality of life for patients with amyloidosis through the development of additional imaging agents, and most importantly new treatments designed to clear the amyloid aggregates from the body.
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From Student to Scientist When Trey Fisher joined the Vascular Research Laboratory (VRL) as a Research Technician in August 2010, he didn’t plan on pursuing a PhD. He had already earned his BS in Biochemistry and Molecular Biology and his MS in Kinesiology at the University of Tennessee Knoxville. But in the VRL it didn’t take long for Trey to become captivated by the world of biomedical research and realize his love for basic translational science. Research in the VRL is focused on defining the mechanisms behind vascular restenosis, a common cause of vascular intervention failure, and in designing translational drug delivery systems aimed at improving those outcomes. What started as a mere employment opportunity during a transitional phase of life for Trey became a career choice. “He started thinking at a high level very early on in his time in the lab. He was very good on the bench, and as a technician he would come to me with a problem and a solution all at once. That was very telling,” says Deidra Mountain, PhD, Associate Professor of Surgery and Scientific Director of the VRL. They began to discuss experimental designs and hypothesis-driven research on a higher level, and Dr. Mountain began to give Trey more responsibility in the laboratory for his own protocol development and some degree of freedom in experimental direction. “It didn’t take long for me to realize Trey had huge potential, but I needed to test him. The day he came to me and started talking about completely switching gears in our drug delivery studies and starting from the ground up with an entirely new nanocarrier system, I knew he was ready for the challenge of a PhD program.” Dr. Mountain encouraged Trey to explore doctoral programs and think about his potential as a Research Scientist. She gave him the option to stay in the VRL
to continue his graduate training or go elsewhere, whatever he decided was the best fit for where he wanted to take his career. In the end that perfect fit ended up being with the VRL and the perfect offering was the Comparative and Experimental Medicine (CEM) program administered by UT College of Veterinary Medicine (UTCVM). CEM is an interdisciplinary graduate program in biomedical sciences that pools resources from both veterinary and human medicine, with faculty members from UTCVM, UTGSM, UT Medical Center, and UT Knoxville’s life sciences departments. For Dr. Fisher the choice was clear. He entered the CEM program in January of 2013 and chose to pursue a concentration in Cellular and Molecular Biology with Dr. Mountain as his doctoral advisor. He was already enthralled with the liposomal drug delivery studies he and Dr. Mountain had begun launching in the VRL, and he was excited about its potential for clinical impact. After 6 years of classes, countless late nights in the lab, and multiple manuscript drafts and revisions, Trey successfully defended his dissertation “The Development of a Dualligand PEGylated Liposome Nanotechnology for Cell-selective Targeted Vascular Gene Therapy” in March 2019. He received his PhD in Comparative and Experimental Medicine and was officially hooded as Dr. Richard K. Fisher, III on May 9, 2019. “The work Trey has done in our lab over the last several years has been instrumental in our studies in targeted drug delivery. His successes are demonstrated by his numerous national presentations and multiple manuscripts he has authored and coauthored. He will undoubtedly have a very successful scientific career, and I am honored to now call Dr. Fisher my colleague.”
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IN BRIEF »»»»»»
IN BRIEF »»»»»»
Goldman Retires
After serving for 9 years in his role as Assistant Dean for Research, Dr. Goldman has transitioned back to his primary professional home in the Department of Surgery, where among other tasks he helps direct the department’s research effort in his role as mentor and advisor. Dr. Goldman is a legendary leader at the GSM, having served in multiple positions, including Chair of Surgery and Surgical Director of the fully accredited UT Center for Advanced Medical Simulation. The recipient of multiple professional awards, including the Rudolph Matas Award from the Southern Association for Vascular Surgeons, Dr. Goldman was recently selected to join the American College of Surgeons Academy of Master Surgeon Educators. From the bedside to the laboratory, Dr. Goldman has been deeply committed to our tripartite mission of excellence in clinical care, teaching and research. In that context, he has encouraged countless students, residents, fellows and attending staff to pursue educational and research endeavors, and has played a pivotal role in their professional development. A native of Massachusetts and a Red Sox fan, Dr. Goldman earned his MD degree from Harvard Medical School and joined the UT Graduate School of Medicine in 1985. That same year, he performed the first kidney transplant at UTMC. His research endeavors have largely focused on vascular injury and intimal hyperplasia.
NIH funds bone regeneration study Millions of Americans are affected by a musuloskeletal condition that can lead to pain and disability. Specifically, bone diseases and injuries ranging from simple fractures to face/jaw defects, catastrophic bone loss, and bone cancers affect roughly 6.8 million people each year in the United States. These bone injuries and diseases result in significant pain, distress, and loss of quality of life, as well as considerable financial hardships for patients and the health care system. Current approaches include transplanting bones from other sites in the patient’s body (autograft), from cadavers (allografts) or polymers/bioactive ceramics/composites. However, each of these has limitations such as pain and morbidity, high costs, host responses to foreign tissue and lack of structural integrity/mechanical strength. Thus the development of a new strategy is necessary to overcome these limitations. Bone tissue engineering is an interdisciplinary field that applies the principles of material science, engineering and life sciences in the development of biological substitutes that can restore, maintain, or improve bone tissue function. Combining a scaffold-matrix with viable human cells and/or biologically active molecules into an implantable construct is now being recognized as a viable strategy for the treatment of musculoskeletal disorders. The team of Stacy Stephenson, MD, and Tom Masi, PhD, both of the Graduate School of Medicine, Madhu Dhar, PhD, from the University of Tennessee College of Veterinary Medicine Large Animal Clincial Sciences, and Shawn
Bourdo, PhD, University of Arkansas, Little Rock, Center for Integrative Nanotechnology Sciences have recently received a new three-year grant from the National Institutes of Health entitled “Bone regeneration: mesenchymal stem cells and graphenebiomimetic nanomaterials.” The investigators have discovered that when human mesenchymal stem cells (hMSCs) are placed on a low oxygen form of a carbon-based polymer (graphene) scaffold, the stem cells change into bone cells (osteobalsts) and start to make the components of bone matrix without the addition of any external factors/stimuli. For this project the interdisciplinary team will focus on figuring out the mechanism/signaling pathway(s) that are triggered during the interaction of the graphene scaffold and the stem cells that tell the cells to become bone cells. Once the mechanism is known, the graphene scaffold can be modified to make the process of bone formation occur faster and more efficiently. Graphene can be molded into any shape or form and therefore the team will also focus on developing a 3D scaffold containing hMSCs for implantation in vivo. This will allow the investigators to evaluate bonehealing capacity of the scaffold/stem cells as well as biotoxicity and biodegradation. The long term goal of this research is to develop an optimal scaffold design that when combined with stem cells, results in bone healing of a critical sized defect and a return to normal form and function in veterinary or human patients.
Why this matters:
Bone injuries and diseases result in significant pain, distress, and loss of quality of life, as well as considerable financial hardships for patients and the health care system. The new grant will allow the investigators to evaluate the bone-healing capacity of both scaffold and stem cells as well as biotoxicity and biodegradation. 8
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IN BRIEF »»»»»»
New Grant Champions Contraceptive Access
NIH Common Rule The highly anticipated revisions to the Common Rule became effective, in their entirety, on January 21, 2019. For studies approved by the University of Tennessee Graduate School of Medicine IRB (UTGSM IRB), prior to January 21, 2019, the “old” rules apply and the IRB process remain the same. For studies submitted or approved after January 21, 2019, the revised rules apply. Under the revised rules, the most relevant updates include the addition and expansion of exempt categories based on level of participant risk, new consent form requirements designed to increase participant understanding, and the elimination of the regulatory required “continuing review” for most minimal
risk studies. To make this transition as seamless as possible, updates have been made to iMedRIS (the electronic, web-based software system for study submission and tracking). iMedRIS now includes expanded selections with descriptions to enable researchers to initiate the appropriate study application. These revisions are designed to ease researcher burden while enhancing the protection of human research participants. Additional information can be found on the UTGSM IRB website at: http://gsm.utmck. edu/irb/main.cfm. Any questions related to either the revised rules or the updates to iMedRIS may be directed to the UTGSM IRB office at (865) 305-9781 or (865) 305-6892.
Why this matters:
Being aware of rule changes prior to grant submission can improve the efficiency of the process. 10
without insurance or with plans that exclude LARC can reach thousands of dollars. Dr. Zite says there have been many policy change “wins” in Tennessee for Tenncare and CoverKids recipients in terms of contraceptive access over the last few years. However, policy change alone does not result in increased LARC access, particularly immediately postpartum (IPP), which is a convenient time to have contraceptive needs met, and these policy changes do not improve access for all women. “While academic centers like UT Medical Center and Vanderbilt have been able to implement changes in order to offer IPP LARC relatively quickly for some women, we need champions across the entire state at the provider, pharmacy, nursing, billing, and electronic health record levels to improve access for more women,” Dr. Zite said. To assist hospitals in developing protocols to offer IPP LARC, Dr. Zite said they are creating a tool-kit with examples of barriers in implementing LARC that hospitals have experienced and overcome to act as guidance. Dr. Zite said, “The current focus of the project is to overcome billing and cost barriers for all women. Another priority is to emphasize patientcentered counseling in order to help women fully understand the pros and cons of IPP LARC, and how and where to have the device removed if they desire to do so.”
The University of Tennessee Medical Center is helping women obtain better access to longterm family planning protocols, particularly immediately postpartum. Nikki Zite, MD, Professor and Vice-Chair of Education and Advocacy, has been awarded a grant from the National Institute of Reproductive Health to help women gain better access to longacting reversible contraception (LARC). Dr. Zite is collaborating with Vanderbilt University Medical Center in Nashville, Tennessee, and SisterReach, a Reproductive Justice organization, in Memphis, Tennessee, on a multi-phase project known as “LARC Access and Infrastructure in Tennessee: Building a sustainable culture of patientcentered immediate postpartum LARC through collaboration, education, and dissemination.” Common types of LARC currently available at the medical center include Nexplanon, a contraceptive implant placed in the arm and effective for 3 years; hormonal intrauterine devices (IUDs) such as Liletta and Mirena and effective for 5 years; and non-hormonal IUDs such as ParaGard, a copper IUD effective for 10 years. While these contraceptives are available in the U.S., access to them has been a challenge both for women in low-income families and women of higher socio-economic status on private health insurance. In the absence of insurance coverage for LARC, out-of-pocket expenses include the cost of the device ($800-$1,000), insertion fees, and then when desired, removal costs. Total costs
Why this matters:
Overcoming barriers to LARC will make it easier for all women seeking this type of contraceptive in Tennessee to have access. 11
IN BRIEF »»»»»»
Oncofreeze PET/CT Scans Deliver Faster, Better Diagnosis Thanks to a unique partnership between the Graduate School of Medicine and Siemens, The University of Tennessee Medical Center has access to some of the most cutting-edge scan research in the world. The Molecular Imaging & Translational Research Program (MITRP), directed by Dustin Osborne, PhD, has worked with Siemens for more than 10 years to bring the latest in scanning technology to our area. Through this partnership, the medical center was the first in the country to begin using a PET/ CT scanner with FlowMotion. FlowMotion scans in a single, continuous sweep, making imaging more efficient. UTMC is the first in the country to use OncoFreeze, creating even better images in less time. Dr. Osborne said, “When added to the FlowMotion technology, OncoFreeze doesn’t just reduce the blurring caused by natural breathing, it also speeds up scan time, dropping it from 30 minutes to 9 minutes.” The combination of FlowMotion and Oncofreeze gives medical center physicians the highest quality scans in the shortest time of anywhere in the region. PET/CT scanning technology plays an important role in cancer treatment. This type of scan detects cancer cells, providing for early diagnosis, precise localization and more accurate tumor detection. Physicians also use PET/CT scans to track how well cancer treatments, like chemotherapy and radiation, have worked. For Harold B., a patient at UTMC, a scan with Oncofreeze caught his lung cancer early. For many patients with cancer, this new tool can lead to better decision making and a longer life. Specifically, in 2016 Mr. B was diagnosed and treated for throat cancer. Last year, he came back for a follow-up PET/CT scan, which showed his throat was clear of cancer. However, the medical center’s state-of-the-art PET/CT scanner, with a unique technology called OncoFreeze, detected something new: a small spot on his lung. For the patient, the shorter scan time meant not having to stay in the imaging system for
Karlstad receives NIH Grant
longer than necessary, allowing him to get back to teaching and playing with his grandson. The improved image quality from the new scanner led his physician, Joseph Kelley, MD, PhD, Assistant Professor in the Department of Radiology, to discover the spot on his lung. That spot may have been missed without motion correction imaging. And Mr. B isn’t alone. Now that the scans are so fast, the radiology technicians have time to do more of them, which means all of the medical center’s patients with cancer who receive a PET/ CT scan have access to the Oncofreeze technology and motion-free images. Dr. Osborne’s team was also recently granted a patent for a new motion tracking algorithm that enables monitoring of lesion specific motion for even more accurate data correction. This tracking technology combined with tools like OncoFreeze give the highest quality images with the least amount of invasive monitoring. Cancers like Mr. B’s, which might not have been detected in a traditional scan, can now be caught and treated early. Also, the physicians who read them have clearer scans than ever before, which means better diagnoses and even more customized treatment for patients. Dr. Kelley said, “Very few hospitals in the world have access to this world-class scanner. We’re incredibly fortunate.” Mr. B is grateful for this topline scanner, too. “Without OncoFreeze, the cancer would have been more progressed and I might not be alive today.”
Why this matters:
Shorter scan time and improved image quality are beneficial to patients and clinicians. 12
News»
Michael Karlstad, PhD, Director of Shock Trauma and Nutrition Research Laboratory, has received a two-year grant for a collaborative study with researchers at Pennington Biomedical Research Center in Baton Rouge, Louisiana, on type 1 diabetes. The study hypothesizes that pro-inflammatory stimuli can be used to reduce disease-causing mechanisms leading to type 1 diabetes. Preliminary studies have shown promising results.
Wexner Medical Center. The symposium was led by Dr. John Bell, Professor and UT Cancer Institute Medical Director. Wall named Research Director Dr. Jonathan Wall has been named Director of Research at the Graduate School of Medicine effective June 1, 2019. Dr. Wall will be responsible for helping the Dean to oversee the basic and translational science initiatives and will replace Dr. Mitchell H. Goldman who, after nearly a decade of service, will be stepping down from his position as Assistant Dean for Research.
Ferris earns master’s degree Jennifer Ferris graduated from George Washington University with a Master of Science in Health Sciences in Clinical Research Administration. As part of the six-semester program, Ferris completed a Capstone project on People and Quality: Identifying Strategic Priorities in Clinical Research. The project included in-depth exploration into bioethical issues in clinical research and the overall impact on the U.S. healthcare system.
Acuff receives award Shelley Acuff, Research Leader, was presented with 1st Place Editors’ Choice Award for her article published in the Journal of Nuclear Medicine Technology titled, “Practical Consideration for Integrating PET/CT in Radiation Therapy Planning for Patient Care” at the Society of Nuclear Medicine and Molecular Imaging’s 2019 annual conference.
5th annual cancer research symposium The UT Cancer Community of Scholars Research Symposium was held April 25th at UT Medical Center including a poster session to share research and keynote address by Raphael Pollock, MD, PhD, Division of Surgical Oncology/ Department of Surgery, Ohio State University
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 visit online: http://gsm.utmck.edu/research/main.cfm.
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