POSITION TITLE: Professor OG and Urology, Female Pelvic Medicine and Reconstructive Surgery

Transcription

1 NAME: Linda Brubaker, M.D, M.S. OMB No and (Rev. 10/15 Approved Through 10/31/2018) BIOGRAPHICAL SKETCH Provide the following information for the Senior/key personnel and other significant contributors. Follow this format for each person. DO NOT EXCEED FIVE PAGES. era COMMONS USER NAME (credential, e.g., agency login): LBRUBAKER POSITION TITLE: Professor OG and Urology, Female Pelvic Medicine and Reconstructive Surgery EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable. Add/delete rows as necessary.) INSTITUTION AND LOCATION DEGREE (if applicable) Completion Date MM/YYYY FIELD OF STUDY University of Illinois BA/ Honors 1977 English Rush Medical School MD 1984 Medicine Rush Presbyterian St. Luke s Medical Center Residency 1988 Ob-Gyn Rush Presbyterian St. Luke s Medical Center Fellowship 1990 Urogynecology University of Michigan M.S CRDSA (Clinical Research Design & Statistical Analysis) A. Personal Statement This proposal requests funds for a collaborative project to comprehensively survey populations of bacteriophage (viruses that infect bacteria) within the bladder and begin to understand how they contribute to lower urinary tract symptoms. We believe that the discovery of new principles and generation of foundational information in this area requires an integrated, multidisciplinary & systematic approach. As an experienced clinical and translational investigator, I am well qualified to serve as an investigator for this work. In other proposals, I have a proven track record of successful research, both clinical and translational, as evidenced by my past research productivity that includes multiple NIH research networks, the NIDDK Urinary Incontinence Treatment Network, NICHD Pelvic Floor Disorders Network and the NIDDK PLUS Consortium. Together with Dr. Wolfe, I co-founded the Loyola research group (LUEREC) that discovered the female urinary microbiome and has done the foundational work to date. Our research collaborations have remained strong and we are excited by the new discoveries of bacteriophages in the urinary microbiome. My ability to provide clinical and translational guidance is enhanced as I have recently stepped away from major administrative roles to devote more time and effort to this important research effort. My time and effort for this research are set aside, prioritized and allocated within the scope of my overall professional activities. B. Positions and Honors Academic Positions Instructor, Dept. OB-GYNE Rush Medical College, Chicago Director, Division of Female Pelvic Medicine and Reconstructive Surgery Assistant Professor, Dept. OB-GYNE Rush Medical College, Chicago Associate Professor, Division of Female Pelvic Medicine and Reconstructive Director Departments of Obstetrics & Gynecology, and Surgery Rush Medical College, Chicago Professor and Director, Division of Female Pelvic Medicine and Reconstructive Surgery Departments of Obstetrics and Gynecology, Surgery Rush Medical College, Chicago Professor, Division of Female Pelvic Medicine and Reconstructive Surgery Departments of Obstetrics and Gynecology, Urology, Loyola University Medical Center (Director ) Assistant Dean Clinical and Translational Research, Stritch School of Medicine, Loyola

2 University Chicago Vice-Chair, Gynecology, Stritch School of Medicine, Associate Dean, Clinical and Translational Research, Stritch School of Medicine, Loyola University Chicago Senior Associate Dean, Clinical and Translational Research, Stritch School of Medicine, Loyola University Chicago Dean, Stritch School of Medicine, Interim Provost, Health Sciences Division 2017-present Clinical Professor, Division of Female Pelvic Medicine and Reconstructive Surgery, Department of Reproductive Medicine, University of California San Diego NIH Positions Member: National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK) External Advisory Committee for the Interstitial Cystitis Clinical Trials Group (ICCTG/EAC) Member and Committee Co-Chair Bladder Review Group Report Meeting (NIDDK) Member: UDA-EAC/NIDDK Urologic Diseases in America-External Advisory Committee Consultation and Advisory Committee ORWH-SCOR Review Committee 2007 ORWH-SCOR Review Committee Chair Permanent Member, Urologic & Kidney Development & Genitourinary Diseases Study Section 2009 ZHD1 K12 Review Panel (x 2) Chair, Special Emphasis Panel 1DKUS A Chair, Urologic and Kidney Development and Genitourinary Diseases Study Section 2012 Special Emphasis Panel ZDK1 GRB-G-C1: The NIDDK Genetics Repository Contract 2013 Chair, Special Emphasis Panel: ZRG1 DKUS-P(80) 2014 Member, External Experts Panel (EEP) for the Multidisciplinary Approach to the study of Chronic Pelvic Pain (MAPP) Research Network 2014 Chair, Special Emphasis Panel: ZDK1 GRB-G(M3+4) NIDDK MAPP 2014 ZRG1 DKUS-P (80)S: Small Grants for New Investigators to Promote Diversity Honors 1992 Faculty Teaching Award 1998 Outstanding service on the Education Commission of ACOG 1998 Ortho Pharmaceutical/CREOG Faculty Teaching award 2002 National Association for Continence (NAFC) Urogynecologist of the Year 2003 Rush Medical College Distinguished Alumnus 2007 APGO Excellence in Teaching Award 2007 Best Clinical Paper Presentation, International Continence Society Meeting, Rotterdam 2011 Aetna Susan B. Anthony Award for Excellence in Research on Older Women and Public Health 2013 Alpha Omega Alpha 2013 Alpha Sigma Nu, Jesuit Honor Society C. Contribution to Science 1) Co-director of team that discovered the female urinary microbiome (FUM). Along with my collaborator, Alan J. Wolfe, PhD, we envisioned the science that had led to the discovery of the female urinary microbiome. Our collaborative work has introduced multiple other non-urologic investigators to this exciting field, as we continue to make insights into how the lower urinary systems modulates a resident bacterial community in health and disease. We have already made important insights into the relationship of this community with urinary symptoms, symptom severity and treatment response. Brubaker L. et al. Nager CW, Richter HE, Visco A, Nygaard I, Barber M, Schaffer J, Meikle S, Wallace D, Shibata N, Wolfe AJ. Urinary Bacteria in Adult Women with Urgency Urinary Incontinence. Int Urogynecol J Feb 11 [Epub ahead of print]. PMID: Wolfe A, Toh E, Shibata N, Rong R, Kenton K, FitzGerald MP, Mueller ER, Schreckenberger P, Dong Q, Nelson D, Brubaker L. Evidence of Uncultivated Bacteria in the Adult Female Bladder. J Clin Microbiol 2012 Apr; 50(4) PMID:

3 Hilt E, McKinley K, Pearce MM, Rosenfeld AB, Zilliox MJ, Mueller ER, Brubaker L, Gai X, Wolfe AJ, Schreckenberger P. Urine is not Sterile: Use of Enhanced Urine Culture Techniques to Detect Resident Bacterial Flora in the Adult Female Bladder. J Clin Microbiol 2013 Dec 26. [Epub ahead of print]. PMID: Pearce M, Hilt E, Rosenfeld A, Zilliox M, Thomas-White K, Fok C, Kliethermes S, Schreckenberger P, Brubaker L, Gai X, Wolfe A. The Female Urinary Microbiome: A Comparison of Women with and Without Urgency Urinary Incontinence. MBio Jul 8;5(4). PMID: ) Team-scientist. I have participated in multiple collaborative venues, within and beyond my own specialty. I have honed my skills at producing high-quality research with individual from other disciplines including basic scientists. My current research collaborations include a wide variety of individuals across institutions and multiple disciplines. I serve as a multiple PI for the Prevention of Lower Urinary Symptoms in Women (PLUS), a large NIDDK funded Consortium that emphasizes transdisciplinary, team science. Our first publications are coming to fruition at this time. Other efforts have included large NIH-networks that have produced a wide variety of science aimed at improving human health. Chai T, Moalli P, Richter H, Lake A, Kim H, Nager C, Sirls L, Brubaker L and Kusek J. Preoperative Urodynamic Parameters (Valsalva Leak Point Pressure and Maximum Urethral Closure Pressure), Urinary Collagen and Plasma Vitamin D Levels as Predictors of Mid Urethral Sling Surgery Outcome The Journal of Urology, Volume 196, Issue 3, Neinhouse V, Gao X, Dong Q, Nelson D, Toh E, McKinley K, Schreckenberger P, Shibata N, Fok C, Mueller E, Brubaker L, Wolfe A, Radek K. Interplay Between Bladder Microbiota and Urinary Antimicrobial Peptides: Mechanisms for Human Urinary Tract Infection Risk and Symptom Severity. PLoS One Dec; 8:9(12). PMID: Le P, Pearce M, Zhang S, Campbell E, Fok C, Mueller E, Brincat C, Wolfe A, Brubaker L. IL22 Regulates Human Urotherlial Cell Sensory and Innate Functions through Modulation of the Acetylcholine Response, Immunoregulatory Cytokines and Antimicrobial Peptides: Assessment of an in vitro Model. PLOS ONE 2014 Oct 29;9(10). PMID: Spirka T, Kenton K, Brubaker L, Damaser M. Effect of Material Properties on Predicted Vesical Pressure during a Cough in a Simplified Computational Model of the Bladder and Urethra. Ann Biomed Eng 2013: Jan 41(1) PMID: ) Pivotal research that challenges dogma, including first randomized studies of intravesical onabotulinumtoxin A in women. I have contributed to (and often co-led) pivitol studies studies, including the first randomized study of botulinum injection into the bladder in women with refractory urgency urinary incontinence. This study highlighted the efficacy and adverse event profile with this treatment for this indication. The initial study laid the groundwork for subsequent studies including the ABC study within which we collected pre-treatment urine samples and documented the female urinary microbiome (see #4, below). In addition, our study on the utility of urodynamic testing prior to stress incontinence surgery was a major non-surgical RCT. Brubaker L, Richter HE, Visco A, Mahajan S, Nygaard I, Braun TM, Barber MD, Menefee S, Schaffer J, Weber AM, Wei J; Pelvic Floor Disorders Network. Refractory Idiopathic Urge Urinary Incontinence and Botulinum a Injection. J Urol July; 180(1): PMID: NIHMS Visco A, Brubaker L, Richter H, Nygaard I, Paraiso MF, Menefee S, Schaffer J, Lowder J, Khandwala S, Sirls L, Spino C, Nolen T, Wallace D, Meikle S. Anticholinergics Therapy vs OnabotulinumtoxinA for Urgency Urinary Incontinence. New Engl J Med Nov; 8;367(19): PMID: Nager CW, Brubaker L, Litman HJ, Zyczynski HM, Varner RE, Amundsen C, Sirls LT, Norton PA, Arisco AM, Chai TC, Zimmern P, Barber MD, Dandreo KJ, Menefee SA, Kenton,K, Lowder J, Richter HE, Khandwala S, Nygaard I, Krause SR, Johnson HW, Lemack GE, Mihova M, Albo ME, Mueller E, Sutkin G, Wilson TS, Hsu Y, Rozanski TA, Rickey LM, Rahn D, Tennstedt S, Kusek JW, Gormley EA. A Randomized Trial of Urodynamic Testing Before Stress Incontinence Surgery. N Engl J Med 2012 May 24;366(21): [Epub ahead of print] 2012 May 2. PMID:

4 4) Collator of evidence-based research and practice in FPMRS. Having devoted my career to date to the highest quality evidence possible, I have led a variety of teams in evidence-based reviews of literature. I have participated in the International Consultation on Incontinence (ICI) and chaired multiple committees since the inception of this group. The proceedings of this process are regularly published in order to help elevate the clinical care for affected individuals (adults and children, males and females) across the globe. The group most recently meet in September 2016 and the publication should be forthcoming shortly. A prior publication is below: Abrams P, Andersson KE, Birder L, Brubaker L, Cardozo L, Chapple C, Cottenden A, Davila W, de Ridder D, Dmochowski R, Drake M, DuBeau C, Fry C, Hanno P, Hay Smith J, Herschorn S, Hosker G, Kelleher C, Koelbl H, Khoury S, Madoff R, Milsom I, Moore K, Newman D, Nitti V, Norton C, Nygaard I, Payne C, Smith A, Staskin D, Tekgul S, Thuroff J, Tubaro A, Vodusek D, Wein A, and Wyndaele JJ and the Members of the Committees. Fourth International Consultation on Incontinence Recommendations of the International Scientific Committee: Evaluation and Treatment of Urinary Incontinence, Pelvic Organ Prolapse, and Fecal Incontinence. Neurourol Urodyn 2010;29: Complete List of Published Work in MyBibliography: D. Research Support Ongoing Research Support ACTIVE R01DK A1 Brubaker, Wolfe (Multiple PI) 03/01/16-02/28/ calendar The Female Urinary Microbiome and Urinary Incontinence Determine the relationship between the female urinary microbiome and urgency urinary incontinence. 1U01DK Brubaker, Mueller (Multiple PI) 07/01/15 06/30/ calendar PLUS Loyola Clinical Center In the proposed PLUS-LCC studies, we will explore the community, cultural context by engaging in a Chicagowide participatory, mixed methodological community-based Pelvic Health Assessment by conducting the first Chicago LUTS and community health survey, first large scale qualitative study on community members pelvic health perceptions, behaviors and knowledge groups, and conduct landscape assessment to characterize Chicago s health care system where women interface. 1R01DK (Kramer PI, Brubaker Co I) 8/25/16-5/31/ calendar NIH UKNOW 1P20DK (Wolfe: PI) 09/15/15 07/31/ calendar NIH The Female Urinary Microbiome: Adjacent Microbiomes and Clinical Associations The aim of this study is to use previously collected urine, vaginal and perineal specimens previously collected to study the relationship between the bacteria detected in these three different niches Completed Research Support 1R56DK Brubaker, (Multiple PI) 07/15/15 06/30/ calendar NIH/NICHD The Female Urinary Microbiome and Urinary Incontinence The aim of is to understand the role of the urinary microbiome in urinary incontinence RFC/LU Brubaker, (Multiple PI) 04/01/15 03/31/ calendar

5 Recurrent Urinary Tract Infection: Linking the Host Genome and to the Urinary Microbiota The aim of is to understand the role of the urinary microbiome in urinary incontinence. U10-DK58229 Brubaker (PI) 02/01/14-06/30/14 Urinary Incontinence Treatment Network (NERi) The Microbial Milieu to Female Stress Urinary Incontinence This project will use baseline urine samples obtained from participants in the UITN s ValUE study to assess the microbial milieu of SUI. The generated data will guide future research to validate any initial discoveries and to further correlate the FUM with clinical phenotypes and treatment outcomes. 1R21DK Brubaker (Multiple PI) 9/15/13-8/31/ calendar Urinary Bacterial Communities in Urge Incontinence Women. In this study we propose the novel hypothesis that bacterial colonization of the lower urinary tract influences UUI symptoms 3U10 HD Brubaker (PI) 07/01/11-06/30/ calendar NIH/NICHD RFC/LU (Brubaker) 04/01/15 03/31/ calendar Recurrent Urinary Tract Infection: Linking the Host Genome and to the Urinary Microbiota The aim of this study is to understand the role of the urinary microbiome in urinary tract infections RFC/LU (Brincat) 10/01/15 09/30/ calendar Host Response to Pessaries in microbial communities of the postmenopausal vagina The aim of this study is to determine the predominant vaginal microorganisms of older women with and without a pessary.