American Urological Association - AUA Investigator 2018: Issue I

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AUA Investigator 2018: Issue I

  AUA Investigator
2018 Issue I
Feature Articles
 
 

Research Gets Political at the Annual Urology Advocacy Summit

By Aria Olumi, MD, AUA Research Council Chair

 Early-Career Investigators
Image 1. Hari Koul, PhD (right), immediate past president of SBUR, met with Congressman Ralph Abraham, DVM, MD (R, Louisiana) at the Capitol.

Members of the AUA research community participated in the inaugural Annual Urology Advocacy Summit 2018 to advocate for research support from the federal government between March 12-14, 2018 in Washington, DC. Prior to meeting with leaders in the Capitol and the NIH, we presented our case within our own community and heard from Dr. Ganesh Raj (President, Society for Basic Urologic Research), Dr. David Albala (Chief of Urology, Crouse Hospital, Syracuse, NY, AUA Northeastern Section), Dr. Ben Chew (Research Chair, Endourology Society) and Mr. Bryan Lewis (Kidney Cancer Action Network). We made a strong argument that research functions as a robust "economic engine" for our society. With over 200,000 scientists involved in research at academic institutions, we are responsible for many of the innovative discoveries that lead to new start-up companies that create new private and public-sector jobs. Therefore, our coalition has a powerful voting voice and, when banded together, can make a stronger case to support biomedical research at the federal level. In addition to making a convincing point for biomedical support, we rallied community practicing urologists to consider clinical research programs for their practices as the means of developing a niche, which can advance clinical science while generating a positive revenue. Teamwork between the private practice and academic groups leads to speedier progress and earlier adaptation of advances that can benefit our patients. Lastly, we discussed the power of patient advocacy at Capitol Hill and its value in targeting federal dollars toward specific diseases. For example, the Kidney Cancer Action Network has been extremely successful with its grassroots efforts to unite patients and scientists and has led to increased research funding for kidney cancer, a disease that is significantly underfunded compared to other cancers.

Early-Career Investigators
Image 2. Urology research representatives met with NIH leaders: (bottom row, left to right): Barry Kogan, MD; Aria Olumi, MD; Gail Prins, PhD; Toby Chai, MD; (top row, left to right): Jessica Bateman, MA; Steven Kaplan, MD; Michael Hsieh, MD, PhD; John Lynch, MD; Robert Flanigan, MD; Carolyn Best, PhD.

After rallying our scientific representatives with a united message and focus, members of our community visited representatives at the Capitol and the NIH. While some made a plea to our senators for more urologic research dollars (Image 1), others (Images 2 & 3) discussed the challenges that face our community with NIH leaders at NCI, NIA, NICHD and NIDDK – institutes that are closely aligned with supporting urologic research. We identified funding opportunities with specific diseases that our community could leverage for a higher likelihood of funding (topics of future AUANews articles).

In addition to meeting with several NIH‘s leaders, some members of our coalition met with representatives of the Center for Scientific Review (CSR) branch of the NIH responsible for the peer review of grant applications. One agenda item was the peer review process and ensuring appropriate expert review of applications that are submitted for review by the urology-focused panels. The CSR leadership was very receptive to our group and welcomed partnering with our research community to better identify experts who can effectively and appropriately review submitted grants to the NIH.

Early-Career Investigators
Image 3. Rosalyn Adam, PhD (left) and Dolores Lamb, PhD met with CSR leaders at NIH.

Overall, the inaugural Annual Urology Advocacy Summit meeting was a distinct success, and the research community was well represented in planning and implementing the meeting. We made key connections with leaders in the federal government who can better serve our needs as a scientific community and advance urologic research with the hope of delivering better care to our patients.


 

NIDDK Advisory Council – Role of the Urology Members

By Craig A. Peters, MD – NIDDK Advisory Council 2014-2017 University of Texas Southwestern
Paul H. Lange, MD – NIDDK Advisory Council 2016-2019 University of Washington

As part of its role to support research and improve human disease management, the NIH is required to establish and maintain advisory councils of its various institutes to provide oversight* and offer guidance as to the direction and strategies of its activities related to extramural research. Members selected to the Council by the NIH are usually members of the academic urologic research community with experience in NIH research and related activities. Councilors serve a single 3 to 4-year term. To potentially improve the value of urologic representation on the NIDDK Advisory Council, we have attempted below to clarify the role of the councilors and how their positions may better support urologic research development.

The basic responsibilities of the Advisory Council members are to provide guidance to the Institute on matters of research strategies, how to identify important research topics, to respond most effectively to the relevant health needs of their Institute, and foster a closer collaboration between the Institute and the research community.

For each of three Council meetings per year, councilors are asked to review the various grants being considered for that cycle, not to repeat the formal review process, but to look for potentially important topics that might miss the likely pay line, and that may be eligible for consideration of funding based on programmatic reasons. There is often a degree of funding available at the discretion of the program officers if it is thought that the topic or approach may be valuable to the broader research effort. Similarly, there may be programmatic priorities that can be supported even when not falling within the pay line. Councilors are advisory in these cases, but can offer the perspective of urologists with a broad view of the research field and its potential impact. Other considerations may relate to larger projects and funding mechanisms where Council input as to the suitability and value of particular projects is taken into consideration for final funding decisions. Councilors are also required to sign off on certain funding questions such as restorations of funding amounts or grants over a certain amount of dollars. Ultimately, the Council must formally approve the funding recommendations of the reviews, again, not to second-guess the reviewers, but to monitor the general direction and scientific relevance of the proposals.

The Council is divided into the three sections of NIDDK, and Urology is within the Kidney, Urology and Hematology (KUH) section. Each section meets separately to discuss relevant specific topics during each Council meeting. These section meetings include specific topics to provide insight into specific aspects of the activities of the section, including research direction and strategy, advocacy activities (each section has non-scientific public members from various advocacy groups), and ways in which the research activities might be enhanced. Councilors are asked to present their perspectives on important topics of urologic research and where NIDDK should potentially focus its resources through specific funding initiatives or programs. These presentations often lead to discussions as to the best way in which such priorities may be developed in the research community and how to leverage both the NIH and AUA resources. Various options can include funding workshops, collaborative studies and research initiatives.

A major topic of discussion over the last several years relates to improving training initiatives supported by NIH and how to best attract young talent into urologic research. Keeping that talent in research has also been a major issue of consideration. For example, T32 training grants, the largest part of the KUH training portfolio, yield the fewest downstream R01 grant applications. The value of this mechanism has to be reviewed as well as ways to enhance its contributions to our research community.

The value of the NIDDK Council members to the urology research community is one of "soft" influence and communication. It is a line of communication critically important to a large and complex government organization such as the NIDDK. The staff at NIDDK with whom the councilors interact are extremely committed to improving research in our areas of interest and passion. They have a high level of expertise in many areas of similar interest and often have their own substantive research endeavors. They want, and indeed need, our input, as our success is their success. It must be recognized that they work within a system that has constraints and a great deal of process. While we can voice our ideas and perspectives, we as councilors are advisors, not executives. We all may have our individual priorities and areas of interest, yet the NIDDK staff must consider a wide variety of perspectives and interests from scientists, patient advocacy groups and Congress in their decision-making. The Council offers a line of direct communication for the urologic research community to the NIH. Urology investigators should reach out to the councilors for information and to convey their interests and perspectives. Keep in mind that the councilors are not going to be able to move a grant into the fundable range; their role is much broader and with a longer time horizon. Maintaining a credible line of communication with the NIDDK team will benefit urologic research in many ways, and we should work to keep this collaboration active and productive.

*Established by law and charter, the National Diabetes and Digestive and Kidney Diseases Advisory Council meets three times annually to advise the NIDDK about its research portfolio. The Council typically undertakes broad issues of science policy. Members of the Advisory Council are drawn from the scientific and lay communities, are appointed for 4-year terms, and represent all areas within the Institute's research mission. An important role of the Council is to provide second-level peer review of grant applications that have been scored by scientific review groups. The Council members are an important liaison between the research communities they represent and the NIDDK, which supports each community's research efforts.​ (https://www.niddk.nih.gov/about-niddk/advisory-coordinating-committees/national-diabetes-digestive-kidney-diseases-advisory-council)

 
Urology Researchers Making a Difference
 
 

Margot S. Damaser, PhD – Innovator in Regenerative Medicine and Urinary Incontinence

 Dr. Margot Damaser

Dr. Margot Damaser earned her PhD in Bioengineering from the joint University of California Berkeley and San Francisco Bioengineering Program. It was during this graduate training where she began her urologic research career, receiving guidance from, among others, urologist Marshall Stoller, MD, and earning a National Science Foundation Creativity in Engineering scholarship to better understand the mechanics and control of the urinary bladder. She continued her early urologic research with her postdoctoral fellowship, funded in part by the Urology Care Foundation and at the University of Pennsylvania, where she studied the "Effect of Hypertrophy and Overdistension on Mechanics and Structure of the Urinary Bladder." Together this training built the foundation for a thriving career at the forefront of bioengineering research in urology. Since then, she has mentored many young investigators towards successful careers in urologic research, six of whom also received Urology Care Foundation support for their research training.

Dr. Damaser is now Professor of Molecular Medicine at the Cleveland Clinic Lerner College of Medicine at Case Western Reserve University with appointments in the Department of Biomedical Engineering at the Lerner Research Institute and in the Glickman Urological & Kidney Institute. She is also Senior Research Career Scientist in the Advanced Platform Technology Research Center at the Louis Stokes Cleveland Department of Veterans Affairs Medical Center and directs a laboratory there as well as at the Cleveland Clinic.

Her interdisciplinary background and continuous learning model of collaborative research has enabled Dr. Damaser to pioneer in seemingly divergent areas of urologic applications of technology. Her research group at both Cleveland VA and the Lerner Research Institute currently focuses on two major programs: 1) developing regenerative medicine approaches to treat and/or prevent pelvic floor disorders including stress urinary incontinence with a focus on non-cellular regenerative methods; and 2) developing devices to improve diagnosis and treatment of urinary incontinence and voiding dysfunction. Her overriding goals in both programs is to minimize the invasiveness of diagnostic methods, longer term monitoring methods and methods of treatment or therapy.

Dr. Damaser's group, funded by the NIH and the VA, has demonstrated that either mesenchymal stem cells or their secretions alone from culture (the stem cell secretome) can prevent stress incontinence in animal models even if given systemically. One of the active elements in the secretome is brain-derived neurotrophic factor (BDNF), which her group has previously shown can act to regenerate the urethra and pudendal nerve if given exogenously. They recently used siRNA transfection methods to conduct a dose-response study of BDNF levels in stem cell secretome, demonstrating its importance for regeneration and restoration of continence in an animal model. BDNF is upregulated in nerves by low-frequency, low-amplitude subthreshold electrical stimulation, which may provide a minimally invasive therapy for postpartum incontinence that could prevent or ameliorate later development of stress incontinence in women. Current experiments in Dr. Damaser's laboratory are designed to assess if the mechanism of nerve regeneration from electrical stimulation is BDNF-mediated, and future experiments will be designed to identify a less invasive method of using electrical stimulation to regenerate the pudendal nerve.

Inspired by the cardiac Holter monitor and in collaboration with a team of engineers and urologists, Dr. Damaser's group has pioneered the development of novel, wireless catheter-free methods of monitoring bladder function for both diagnostic and therapeutic applications. Their goal is to develop a device that could be inserted non-invasively into the bladder via the urethra and enables full ambulatory urodynamic monitoring at home for several days with improved comfort. Dr. Damaser expects that physiological data collected during activities of daily living will facilitate greater detail in phenotyping incontinence beyond current methods for differentiating and treating types of incontinence. This will ultimately enable individualized and precision therapies with improved success rates, reduced complication rates and side effects, and reach a greater number of patients suffering from incontinence. Her group is also developing devices designed for chronic use to provide bladder-state feedback to neuromodulation systems and to notify individuals without bladder sensation, such as those with neurogenic bladder, of the need to empty the bladder. Such devices would communicate wirelessly with an external device or an app on the phone. Discussions with companies interested in licensing the technology are currently in progress.

In addition to her own research programs, Dr. Damaser has most recently begun a four-year term as a member of the NIH National Diabetes and Digestive and Kidney Diseases (NIDDK) Advisory Council, one of only two members advising on urologic research. In her new role as a member of the NIH NIDDK Council, she hopes to help coordinate efforts between NIH and the AUA Research Council to enable creative ways to facilitate state of the art research in urology and develop the careers of urology researchers and physician scientists.

"I am so grateful to the AUA and the Urology Care Foundation for their support of pioneering research in Urology to both PhDs and MDs and their collaborative groups," said Dr. Damaser. "Their efforts to build and sustain the research community not only fostered my career, but also the careers of so many others, enabling our work to move forward and ultimately help patients."

Concluding note: Dr. Damaser is now serving as a member of the AUA Research Education, Conferences & Communications (RECCC) Committee, where she is helping to expand and deepen their research education mission.

For more information on the NIDDK Research Council and the role of urology advisors, please see the article by Drs. Craig Peters and Paul Lange in this issue of AUA Investigator.


 

Ganesh V. Raj, MD, PhD – Finding Better Ways to Combat Therapeutic Resistance in Prostate Cancer

 Ganesh V. Raj, MD, PhD

Ganesh V. Raj, MD, PhD is a urologic surgeon-scientist with both an active clinical practice and flourishing research laboratory at UT Southwestern Medical Center. His expertise as a physician helps identify critical needs for patients with advanced cancer and forms the basis for the translational research efforts in his laboratory. Dr. Raj's research group is focused on understanding the mechanisms of, and developing drugs to overcome, therapeutic resistance in prostate and breast cancers.

Dr. Raj's group has identified nuclear receptors and their variants as critical drivers of resistance to both targeted drug therapies and radiation. A major thrust of their efforts is in defining molecular pathways that are activated in therapy resistance, with a view towards defining either biomarkers of resistance or novel therapeutic targets. For example, their recent work showing that the DNA protein kinase C (DNA-PKC) is critically important in mediating resistance to radiation has led to evaluation of drugs targeting DNA-PKC in combination with radiation to enhance prostate cancer cell kill.

In order to target nuclear receptor signaling, they have developed a novel class of compounds, oligobenzamide peptidomimetics, that target protein-protein interactions between nuclear receptors and their co-regulators, with structural and sequence-driven specificity. They have shown that these drugs are orally bioavailable, are non-toxic, and can effectively target the growth of cancer cells in animal models. These first-in-class molecules, for which Dr. Raj holds a patent, are in advanced preclinical testing in both breast and prostate cancers for translation to the clinic.

To accelerate the development of testing these drugs in preclinical models that are both biologically and clinically relevant, the Raj Lab has used the ex vivo cultures of patient primary tumors. As they are tissue-based, these explants adequately recapitulate the cellular heterogeneity, complex tissue architecture and cell-to-cell communication axes that are the critical determinants of tissue responses to exogenous agents. Dr. Raj's laboratory has the largest experience in the world with primary tumor explants, which, when combined with next generation sequencing approaches, enables the systematic analyses of tumor drug vulnerabilities. Their ex vivo culture models have been published and funded in breast, pancreatic, lung and prostate cancers.

The Raj Lab is funded by the U.S. Department of Defense, National Cancer Institute, Cancer Prevention Research Institute of Texas and multiple private foundations including the Prostate Cancer Foundation. Dr. Raj is a co-recipient of the first ever U.S. Department of Defense Prostate Cancer Research Program Transformative Impact Grant. As a clinical scientist, he is actively involved in research and works closely with his basic science students and clinical residents and fellows. His primary goal is to make a difference in the lives of patients with prostate cancer.Dr. Raj is a member of the AUA Research Council and the AUA Research Grants and Investigator Support Committee, as well as serving as the President of the Society for Basic Urologic Research (SBUR), a major AUA partner organization.

 
Research Funding Highlights
 
 

Physician Scientist Residency Training Award Competition Now Open!

Eligible medical students and recent medical school graduates with a passion for urology and research are invited to apply for the Urology Care Foundation’s new Physician Scientist Residency Training Award (PSRTA). Although common in other medical and surgical fields, this program is unique in the field of urology. The PSRTA supports three years of intensive research training embedded within residency and is intended to develop urologic surgeon-scientists who can effectively engage with basic scientists, successfully compete for independent research funding and ultimately lead robust research programs.

The PSRTA resident will complete an eight-year training program in urology beginning in July 2019. The trainee will complete the first two years of clinical training and then matriculate into the three-year research training program. The final three years of clinical training will conclude the PSRTA training program. The Urology Care Foundation will provide $75,000 per year ($225,000 total) to support the trainee during the three years of research training. Institutional cost-sharing is required. In addition, the trainee will receive conference travel support, focused didactic research courses, strong research skills and exceptional mentorship.

Fourth-year medical students or medical student graduates not more than two years beyond graduation by July 1, 2018 are invited to apply for the inaugural PSRTA resident position. Applicants will participate in an early selection process, separate from the both the Residency Match Program and the National Residency Match Program (NRMP). The following institutions have been selected as eligible Program Sites: University of California, Los Angeles; University of Michigan; University of Washington; and Wake Forest University. The successful candidate will begin residency in July 2019.

Importantly, candidates for this program must register for the Society of Academic Urologists (SAU)/American Urological Association’s (AUA) Residency Match Program. Applications must be submitted through the Electronic Residency Application Service (ERAS), as well as additional materials submitted directly to the AUA. Selection and notification of the PSRTA recipient will be completed no later than October 31, 2018 so that applicants not selected for the Physician Scientist Residency Training Award will remain eligible for the regular urology residency match.

Additional details are provided in the Physician Scientist Residency Training Award Program Announcement – Research Resident, available at http://www.auanet.org/research/funding-opportunities/physician-scientist-residency-training-award.


 

2019 Urology Care Foundation Research Scholar Awards – Request for Applications

Research Scholar Awards provide $40,000 per year for one- or two-year mentored research training for clinical and postdoctoral fellows or early-career faculty. Sponsoring institutions provide additional funds and ensure that the scholar receives the necessary research support to successfully complete the study. Pre-applications are required and due by August 9, 2018. Apply today!


 

AUA Hosts Webinar on DoD Kidney Cancer Research Program Funding

The AUA recently partnered with Department of Defense (DoD) Congressionally Directed Medical Research Program (CDMRP)'s program manager to host an informational webinar on applying for research funding through the Kidney Cancer Research Program. This webinar is a valuable tool for anyone seeking support for kidney cancer research. KCRP funding is made possible thanks to the tireless advocacy efforts of Action to Cure Kidney Cancer (ACKC), AUA, Kidney Cancer Action Network (KCAN) and Kidney Cancer Research Alliance (KCCure). View the webinar!

 
Research Resources
 
 

AUA Big Data Advances Urology Research

The topic of how data can be used to positively influence advances in healthcare has been debated for many years, but the challenge has been how to gather reliable real-world data. As more practices embrace the use of electronic health records, however, the process of collecting such data has become virtually effortless, thereby increasing the opportunities to analyze current practice trends.

Recognizing this increasingly important role of Big Data in urology and urologic research, the AUA has been collecting urology practice data through the AUA Quality (AQUA) Registry, the Annual Census, and other venues since 2014. As the data repository continues to grow, researchers are taking advantage of this critical data set as an invaluable resource for studies in healthcare informatics and quality improvement.

Through analyzing data from the AQUA Registry and the AUA Annual Census concurrently, Jeremy B. Shelton, MD, MHS, Assistant Professor of Urology at the University of California, Los Angeles, along with the AUA's team of statisticians, were able to identify current practice patterns in the U.S. and the prevalence of adhering to recommended guidelines. The study, supported through Dr. Shelton's 2017 AUA Data Grant, evaluated how AQUA is being utilized among participating practices. Additionally, as part of his project, Dr. Shelton collaborated with several other AQUA participants to design a pilot implementation trial. The goal of the trial is to explore ways of optimizing AQUA for quality improvement purposes. According to Dr. Shelton, "What's really exciting to me about working with the AUA's AQUA Registry, Census, and Statistical Services is that the AUA, through these investments, has brought together the pieces to begin to realize and enable the 20-year old vision of learning healthcare systems from urologists across the country."

The current progress of Dr. Shelton's study was presented as an abstract at the AUA2018 meeting in San Francisco, titled Characteristics of Participants in the AUA Quality (AQUA) Registry and Early Impact of Participation on Quality of Care, and was published in the April edition of The Journal of Urology.


 

2017 AUA Census Data Available to Researchers

The AUA Census collects critical information about urologic providers' geographic distribution, demographic characteristics, education and training and patterns of urology practice. It also identifies cross-sectional and longitudinal variations across the specialty nationwide. De-identified, census-based public use micro-datasets are available to clinicians, health services and policy researchers, residents, medical students and industry groups for research and analysis. Learn more!


 

National Clinical Trials Network (NCTN) Navigator – Biospecimens Available to Urology Researchers

The National Cancer Institute NCTN Navigator is a publicly searchable database of specimens from completed National Clinical Trials Network Phase 3 adult cancer trials. Nearly 900,000 specimens are available from over 61,000 patients. Investigators can search Navigator's inventory of high-quality specimens that are linked to clinical trials outcomes data, including bladder, kidney and prostate samples. Learn more!

 
Research and Patient Advocacy
 
 

Research Advocacy Poster Session Featured at AUA2018's Patient Advocacy Hub

The Patient Advocacy Hub, an integral component of the AUA Annual Meeting, promotes collaboration among urologic patient advocacy organizations, physicians and researchers in effort to effectively promote an urgency to secure research funding that results in advances of urologic treatments and medical discoveries.

New this year, the Patient Advocacy Hub featured a research poster presentation that showcased the work of patient advocacy organizations who collaboratively lead, fund, and facilitate developments of urologic research. During this hour, meeting attendees including members of the Research Advocacy Committee and Research Council, engaged in conversation with advocacy organizations who work to promote the value urologic research and drive forward research agendas that benefit the urologic community. This experience offered a valuable opportunity to initiate dialogue with research focused advocates who are eager to collaborate on legislative issues surrounding the value of research and cultivate Congressional champions of urologic research.

The 2018 Patient Advocacy Hub featured 20 patient advocacy organizations who represented all facets of the urologic community. Several of these organizations are key collaborators with the AUA's Research Council including Bladder Cancer Advocacy Network, Interstitial Cystitis Association, KCCure, Kidney Cancer Action Network, Kidney Cancer Association, Prostate Cancer Foundation, Spina Bifida Association and United Spinal Association. These organizations offer valuable perspectives from the patient community that are needed to effectively advocate for the AUA's legislative priorities, which include obtaining and securing funding for urologic research.

In line with past years, the Advocacy Hub provided a platform for patient advocates to generate conversations and dialogue with meeting attendees around some of the key legislative issues in urology. The Hub offered patient advocates the opportunity to converse with urological experts and healthcare providers to showcase organization resources and identify areas of advocacy collaboration.

The patient perspective is a vital component of the AUA’s advocacy work and collaboration opportunities created at the Patient Advocacy Hub allow members of the urologic community to partake in critical conversations that significantly boost the visibility of advocacy priorities at both local and federal levels. The AUA Research Council supports the overall mission of the Patient Advocacy Hub and values the role that patient advocacy organizations play in advancing urologic research initiatives. These collaborative advocacy efforts ultimately secure funding for groundbreaking research proposals that result in groundbreaking medical breakthroughs.

 
Did You Know?
 
 

The AUA Hosts an Online Research Resource Hub

The AUA, working with its Research Council and Research Education, Conferences and Communications Committee, now hosts an online hub for researchers interested in:

  • Research funding
  • Training and career opportunities
  • Biorepositories with urology-relevant samples
  • Research symposia and workshops
  • And more!

Learn more!


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Calendar of Research Events
 

Aug 3-5

Third Global Summit on Precision Diagnosis and Treatment of Prostate Cancer

Boston Marriot Long Warf | Boston, MA


Aug 28-31

International Continence Society 48th Annual Meeting

Pennsylvania Convention Center | Philadelphia, PA


Sep 20-23

36th World Congress of Endourology and SWL

Paris, France


Nov 8-11

19th Annual Fall Scientific Meeting of SMSNA

Loews Miami Beach Hotel | Miami, FL


Nov 8-11

Society for Basic Urologic Research (SBUR) Annual Meeting

Westin Mission Hills Golf Resort & Spa | Rancho Mirage, CA


Nov 28-30

19th Annual Meeting of the Society of Urologic Oncology

Sheraton Grand Phoenix | Phoenix, AZ

Opportunities in Urologic Research

Postdoctoral Position

Klausner/Speich Bladder Biomechanics and Urodynamics Laboratory
Virginia Commonwealth University


Postdoctoral Position

Hyung L. Kim, MD Laboratory
Cedars-Sinai Medical Center


Postdoctoral Position

University of Tennessee Health Science Center


Faculty Position

University of Tennessee Health Science Center

 
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