NAME: Woo, Mary A. OMB No. 0925-0001/0002 (Rev. 08/12 Approved Through 8/31/2015) 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): Woo222 POSITION TITLE: Professor UCLA School of 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 California, Davis, CA Pasadena City College, Pasadena, CA Mt. St. Mary s College, Los Angeles, CA University of California, Los Angeles, CA University of California, Los Angeles, CA BS AA BSN MN PhD 06/1976 02/1980 05/1985 06/1988 06/1992 Genetics Cardiovascular A. Personal Statement I have the research and clinical experience to serve as the principal investigator on this project. I have almost 20 years of clinical and research experience in heart failure and have led previous NIH-funded research projects in the areas of heart failure and brain MRI. I have worked with the co-investigators and other key team members on other research studies in heart failure, obstructive sleep apnea, nursing education, congenital central hypoventilation syndrome, and brain MRI for many years, as evidenced by our multiple co-authored publications and grants in these areas. I believe that I have the research and clinical expertise and established multidisciplinary team to successfully carry out this project. 1. Woo MA, Stevenson WG, Moser DK. Six-minute walk test and heart rate variability: lack of association in advanced stages of heart failure. Am J Crit Care 1997;6:348-354. 2. Fonarow GC, Stevenson LW, Walden JA, Livingston NA, Steimle AE, Hamilton MA, Moriguchi J, Tillisch JH, Woo MA. Impact of a comprehensive heart failure management program on hospital readmission and functional status of patients with advanced heart failure. J Am Coll Cardiol 1997;30:725-732. PMID: 9283532 3. Pan A, Kumar R, Macey PM, Fonarow GC, Harper RM, Woo MA. Visual assessment of brain magnetic resonance imaging detects injury to cognitive regulatory sites in patients with heart failure. J Cardiac Failure 2013: 19(2): 94-100. PMC Journal In Process 4. Yadav, SK, Kumar R, Macey PM, Woo MA, Yan-Go FL, Harper RM. Insular cortex metabolite changes in obstructive sleep apnea. Sleep 2014; 37(5): 951-958. PMC Journal In process B. Positions and Honors Positions 1980-1981 School Nurse for Los Angeles Unified School District, Los Angeles, CA (full-time) 1981-1988 Staff/Charge nurse-cardiac Intensive Care, Huntington Memorial Hospital, Pasadena, CA 1988-1993 Clinical Research Nurse, Division of Cardiology, UCLA Medical Center, Los Angeles, CA 2001-2005 Associate Dean for Research, UCLA School of, Los Angeles, CA 1994-present Assistant to Full Professor, Acute Care Section, UCLA School of, Los Angeles, CA 2008-present Member of Research Mentorship Team, UCLA School of Honors 1988 Professional Nurse Traineeship 1988 Outstanding Student - Medical-Surgical Section - UCLA School of 1988 Thesis with Distinction - University of California at Los Angeles
1988-1992 Audrienne M. Moseley Fellowship 1989 Kaiser Foundation Scholarship 1990 Helene Fuld Grant - for promotion of technology in nursing education 1990 UCLA School of Alumni Association Research Award 1991 Sigma Theta Tau - Gamma Tau Chapter - Research Award 1992 Hewlett-Packard/AACN Critical Care Research Award 1993 New Investigator Award - Council on CV - American Heart Association 1995 Grant-in-Aid - American Heart Association 1997 Fellow of the American Heart Association - Council on Cardiovascular 2009 Fellow of the American Academy of 2009 Named a Pillar of Cardiovascular Research by Council on Cardiovascular of the American Heart Association 2013 NINR Director s Leadership Award C. Contributions to Science 1. Heart Rate Variability and Sudden Death in Heart Failure. Early in my career, I became interested in this area when I read that end-stage heart failure patients had one of the highest sudden death rates and that they were increasingly likely to die of sudden death rather than progressive ventricular failure. Unfortunately, at that time, there were no reliable or independent predictors of sudden death risk in persons with end-stage heart failure. After evaluation of the literature, it appeared that heart rate variability, a non-invasive measure of autonomic tone, might have promise in this identification. However, the heart rate variability techniques at that time were not predictive of mortality in heart failure. Therefore, after some consideration of Chaos theory, I was the first to apply Poincaré Plot (also known as Lorenz Plots) analyses to heart rate variability. This technique proved to be an independent predictor for one-year sudden death risk and overall mortality in heart failure. a. Woo MA, Stevenson WG, Moser DK, Trelease RB, Harper RM. Patterns of beat-to-beat heart rate variability in advanced heart failure. Am Heart J 1992;123:704-710. b. Woo MA, Stevenson WG, Moser DK. Effects of ventricular ectopy on sinus R-R intervals in patients with advanced heart failure. Heart Lung 1992;21:515-522. c. Woo MA, Stevenson WG, Moser DK, Middlekauff HM. Complex heart rate variability and serum norepinephrine levels in patients with advanced heart failure. J Am Coll Cardiol 1994;23:565-569 d. Woo MA, Stevenson WG, Moser DK. Comparison of four methods of assessing heart rate variability in patients with heart failure. Am J Crit Care 1996;5:34-41 2. Brain Structure Changes in Heart Failure. While I had identified and tested a method of heart rate variability analysis which was an independent predictor of sudden death in heart failure, I felt that in order to find effective interventions that I needed to understand WHY the Poincaré Plots could identify heart failure patients at high risk for mortality. Given my findings in heart rate variability and the literature, it appeared that the autonomic nervous system was involved. Also, both my clinical experiences and the literature indicated that there were significant decreases in cognition (especially short-term memory) in heart failure. However, there were few studies which examined brain status in these patients. Thus I obtained training and funding in brain magnetic resonance imaging (MRI) research and analytic methods and was the first to publish data indicating that heart failure patients had injury and functional abnormalities in specific brain regions. a. Woo MA, Macey PM, Fonarow GC, Hamilton MA, Harper RM. Regional brain gray matter loss in advanced heart failure. J Appl Physiol 2003; 95: 677-684. PMID: 12716866 b. Woo MA, Macey PM, Keens PT, Kumar R, Fonarow GC, Hamilton MA, Harper RM. Functional abnormalities in brain areas which mediate autonomic nervous system control in advanced heart failure. J Cardiac Failure 2005; 11: 437-446. PMID: 16105635 c. Woo MA, Macey PM, Keens PT, Kumar R, Fonarow GC, Hamilton MA, Harper RM. Aberrant central nervous system responses to the Valsalva maneuver in heart failure. Congestive Heart Failure 2007; 13: 29-35. PMID: 17272960 d. Woo MA, Yadav SK, Macey PM, Fonarow GC, Harper RM, Kumar R. Brain metabolites in autonomic regulatory insular sites in heart failure. Journal of Neurological Sciences 2014; (in press). PMC Journal In process
3. Sleep/Control of Breathing. While it was widely reported in the literature that sleep-disordered breathing was common in heart failure and linked to poorer outcomes in this patient population, I felt that I had to gain a greater understanding of brain changes in sleep-disordered breathing as well as exactly what parts of the brain control breathing in humans. This led to a series of studies and publications with my clinical and research colleagues which reported the incidence of sleep disturbance symptoms and provided greater understanding between cognitive and psychosocial symptoms, brain injury, and sleep-disordered breathing. a. Erickson VS, Westlake CA, Dracup KA, Woo MA. Sleep disturbance symptoms in patients with heart failure. AACN Clinical Issues: Advanced Practice in Acute and Critical Care 2003; 14: 477-487. PMID: 14595207 b. Macey PM, Woo MA, Kumar R, Cross RL, Harper RM. Relationship between obstructive sleep apnea severity and sleep, depression and anxiety symptoms in newly-diagnosed patients. PLoS One 2010; 5(4): e10211. PMCID: PMC2855711 c. Kumar R, Pham TT, Macey PM, Woo MA, Yan-Go FL, Harper RM. Abnormal myelin and axonal integrity in recently diagnosed patients with obstructive sleep apnea. Sleep 2014; 37(4): 723-732. PMC Journal In process d. Kumar R, Farahvar S, Ogren JA, Macey PM, Thompson PM, Woo MA, Yan-Go FL, Harper RM. Brain putamen volume changes in newly-diagnosed patients with obstructive sleep apnea. Neuroimage:Clinical 2014; 4: 383-391. PMC Journal In process 4. Cognition and Psychological Changes in Heart Failure. In addition to evaluation of a potential cause of brain injury in heart failure (sleep-disordered breathing), I also found it necessary to determine if there was a link between the brain injury and clinical symptoms in heart failure. This led to a series of studies, in conjunction with my students and research collaborators, which examined the relationships between cognitive changes and brain injury in heart failure. We discovered that important brain regions which control cognitive and psychological factors were damaged in heart failure and that this brain damage was reflected in their cognitive and psychological symptoms. a. Serber SL, Kumar R, Woo MA, Macey PM, Fonarow GC, Harper RM. Cognitive test performance and brain pathology. Nurs Res 2008; 57: 75-83. PMID: 18347478 b. Woo MA, Kumar R, Macey PM, Fonarow GC, Harper RM. Brain injury in autonomic, emotional, and cognitive regulatory areas in patients with heart failure. J Cardiac Failure 2009; 15: 214-223. PMCID: PMC2730774 c. Ogren JA, Macey PM, Kumar R, Fonarow GC, Hamilton MA, Harper RM, Woo MA. Impaired cerebellar and limbic responses to the Valsalva maneuver in heart failure. Cerebellum 2012; 11 (4): 931-938. d. Woo MA, Ogren JA, Abouzeid CM, Macey PM, Sairafian KG, Saharan PS, Thompson PM, Fonarow GC, Hamilton MA, Harper RM, Kumar R. Regional hippocampal damage in heart failure. European J Heart Failure 2015 (in press) Complete List of Published Work in MyBibliography: http://www.ncbi.nlm.nih.gov/sites/myncbi/mary.woo.1/bibliography/40790517/public/?sort=date&direction=asce nding D. Research Support Ongoing Research Support 1R01 HL113251 Kumar R (PI) NIH/NHLBI 08/15/2012-06/30/2016 Brain Axonal Injury in Obstructive Sleep Apnea Description: To examine the location and extent of white matter (axonal injury) in persons with obstructive sleep apnea. Role: co-pi
1R01 NR013625 Woo MA & Kumar R (MPIs) NIH/NINR 09/27/2012-06/30/2016 Central Autonomic Nervous System Regulation in Heart Failure Description: To compare functional brain response to autonomic nervous system challenge between heart failure and healthy control subjects and to determine if such functional brain responses are lateralized in heart failure. 1R01 NR013625 Pike N (PI) NIH/NINR 09/01/2013-08/31/2017 Memory and Brain Structure in Adolescents with Single Ventricle Heart Disease Description: To examine the relationship between cognitive status and brain injury in children after surgical repair of their congenital heart disease. Role: co-investigator 1R01 NR014669 Woo MA & Kumar R (MPIs) NIH/NINR 09/01/2014-08/31/2018 Blood-Brain Barrier Dysfunction and Brain Injury in Heart Failure Description: To examine the relationship between blood-brain barrier status and brain injury in heart failure patients. 1R01 NR015038 Kumar R (PI) NIH/NINR 04/01/2015-03/31/2019 Blood-Brain Barrier Deficits and Brain Injury in Obstructive Sleep Apnea Description: To evaluate the status of the blood-brain barrier, structural integrity of autonomic, cognitive, and breathing control brain areas, affective and cognitive issues, relationships between the blood-brain barrier function and those sites, and effects of CPAP treatment in blood-brain barrier integrity with time in obstructive sleep apnea patients. Role: co-investigator Completed Research Support 1R21NR011091 Woo MA (PI) NIH/NINR 06/01/2009-05/30/2012 Memory, Thiamine Levels, and Brain Structure in Heart Failure Description: To determine the relationship between plasma thiamine levels, short-term memory, and brain structure in heart failure patients. 1R21NR012292 Woo MA (PI) NIH/NINR 09/01/2010-08/31/2012 Passive Foot Movement and Sleep-Disordered Breathing in Heart Failure Description: To evaluate a novel method (passive foot movement) to treat sleep-disordered breathing in heart failure. R01 HD 22695 Harper RM (PI) NIH/NICHD 09/03/1989-06/30/2012 Physiological Development in SIDS Description: To use MRI to examine brain structure and function in developing children and children with Congenital Central Hypoventilation patients to evaluate potential mechanisms of failure in SIDS. Role: Co-Investigator
2R01 NR009116 Woo MA (PI) NIH/NINR 04/01/09-03/31/2013 Sleep and Brain Structure in Heart Failure Description: Examination of the relationship between brain gray matter loss and sleep-disordered breathing in advanced heart failure patients.