NIH BIOGRAPHICAL SKETCH

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1 NAME: Jaime L. Hook era COMMONS USER NAME: JLHOOK NIH BIOGRAPHICAL SKETCH POSITION TITLE: Assistant Professor of Medicine, Columbia University Medical Center, New York, NY EDUCATIONAL INSTITUTION AND LOCATION DEGREE OR POSITION START END FIELD OF STUDY Univ. of Wisconsin, Madison, WI BS, Medical Scholar 08/ /2004 Mol. Biology (PBK) Univ. of Wisconsin School of Med. MD 08/ /2008 Medicine (AOA) and Public Health, Madison, WI Univ. of Wisconsin School of Med. Research Fellow 05/ /2005 Clinical Epidemiology and Public Health, Madison, WI New York Univ. Med. Ctr., NY, NY Intern 07/ /2009 Internal Medicine Columbia Univ. Med. Ctr., NY, NY Resident 07/ /2011 Internal Medicine Columbia Univ. Med. Ctr., NY, NY Columbia Univ. Med. Ctr., NY, NY Clinical Fellow T32 Research Fellow 07/ / / /2015 Pulm. & Crit. Care Med. Lung Biology A. Personal Statement I study the physiological responses of lung alveoli to inhaled pathogens that lead to lung infection-induced Acute Lung Injury. I use real-time optical imaging of live, intact mouse and human lungs, among other methods, to determine alveolar mechanisms of lung infection initiation and lung microvascular barrier loss. My initial project in the Bhattacharya lab revealed a novel mechanism by which inhaled staphylococci stabilize in lung alveoli, induce alveolar damage, and resist antibiotic therapy. My ongoing and future work will leverage the live lung imaging approach to understand how juxtacrine and paracrine communication among lung alveolar cells determines epithelial viability, barrier restoration, and regeneration in influenza- and Staphylococcus aureus-infected alveoli. The goal of my research is to develop new approaches to therapy. My research background includes postdoctoral research training in clinical epidemiology ( ) and basic science (2013-present). I am currently a Tenure Track Assistant Professor at Columbia. I allocate 80% of my time to research, which is supported by a highly competitive (26% success rate, application scored in the 0.1 percentile), K99/R00-equivalent, Fellow-to-Faculty Transition Award from the AHA ($526,000; ). Results from my initial project in the Bhattacharya lab were recently published as a first-author paper in the Journal of Clinical Investigation, in which we report a new mechanism of bacterial stabilization in lung alveoli. We found that inhaled bacteria of the S. aureus family, USA300 form stable, solute-impermeable microaggregates in alveolar corners, where they induce toxin-mediated epithelial damage, deteriorate the alveolar barrier, and inhibit antibiotic penetration. Since the alveolar corners are critical to microaggregate formation, these findings uncover a novel role for organ microanatomy in the initiation of bacterial infection, development of organ injury, and efficacy of antibiotic therapy. My two-year research plan is to use findings generated from my current project, in which I am investigating mechanisms of alveolar bacterial stabilization and barrier loss in influenza-s. aureus coinfection, as preliminary data for my first NIH R01 application in June My five-year plan is to use influenza and S. aureus lung infection as models for investigating the role of alveolar cell-cell communication in promoting epithelial cell survival, barrier restoration, and regeneration. For example, my live lung imaging approach may be useful in understanding how juxtacrine and paracrine signals are conveyed in Notch1 and Wnt signaling cascades to strengthen the alveolar barrier and regenerate the epithelium. My career vision is to understand how alveolar epithelial survival and repair mechanisms change across the lifespan, with an eye to how failure of these mechanisms might induce age-related lung diseases. My ultimate goal is to develop new therapeutic approaches that target epithelial injury and repair, thereby circumventing microbial anti-infective resistance, and perhaps interrupting the pathogenesis of age-related lung disease.

2 B. Positions and Honors Academic Appointments: 7/2015-6/2017 Instructor in Medicine at CUMC, Pulmonary and Critical Care Medicine, Columbia, NY 7/ present Assistant Professor of Medicine, Pulmonary and Critical Care Medicine, Columbia, NY Invited Lectures and Oral Presentations at National and International Meetings: American Thoracic Society meetings: 2012 Mini Symposium Talk, Scientific & Clinical Innovations in Lung Transplantation, San Francisco, CA 2014 Mini Symposium Talk, Molecular Underpinnings of Acute Lung Injury, San Diego, CA 2015 Oral Presentation at Poster Discussion, Acute Lung Injury and Inflammation, Denver, CO 2016 Mini Symposium Talk, Mitochondrial Dysfunction in Lung Disease, San Francisco, CA 2018 Abstract Award Presentation, Science and Innovation Center, San Diego, CA 2018 Mini Symposium Talk, Redefining ALI Pathogenesis, San Diego, CA FASEB and Gordon meetings: 2014 Short Talk, The Lung Epithelium in Health and Disease Conference, Federation of American Societies for Experimental Biology (FASEB), Saxtons River, VT 2016 Invited Lecture (30 min), Gordon Research Conference, The Biology of Acute Respiratory Infection, Galveston, TX 2016 Short Talk, Gordon Research Seminar, The Biology of Acute Respiratory Infection, Galveston, TX 2018 Short Talk, Gordon Research Conference, The Biology of Acute Respiratory Infection, Ventura, CA Roles in Professional Organizations and Societies: Research meeting organizing roles: 2018 Gordon Conference and Seminar on the Biology of Acute Respiratory Infection, Ventura, CA Co-Chair, Gordon Research Seminar Organizer & Facilitator, Power Hour seminar to address challenges faced by women in science 2018 American Thoracic Society Conference, San Diego, CA Member, Respiratory Cell & Molecular Biology Assembly Program Committee Organizer, Respiratory Cell & Molecular Biology Assembly Mentoring Program Facilitator, Epithelial Cell Biology in Respiratory Disease Thematic Poster Session American Thoracic Society roles: present Society Member present Respiratory Cell & Molecular Biology Assembly Early Career Professionals Working Group Member Wisconsin Medical Society roles: Society Member Board of Directors Member Council on the Health of the Public Member University of Wisconsin School of Medicine and Public Health Medical Student Association roles: Member President (elected by peers to serve as the primary representative of the 700-student body and lead organizer of student events and fundraisers) Other memberships and positions: American Medical Association Medical Student Representative present Wisconsin Medical Alumni Association Class of 2008 Representative present American Heart Association Member present Columbia Virginia Kneeland Frantz Society for Women Faculty Member

3 Honors: Undergraduate: 2000 Medical Scholar (granted pre-admission to the University of Wisconsin School of Medicine and Public Health based on high school performance) 2002 Beta Beta Beta Biological Honor Society Member 2004 Graduation with Distinction (top 20% of graduating class) 2004 Phi Beta Kappa Medical school: 2005 Wisconsin Medical Society Charity Roast Scholarship 2005 Lora L. Marshall Scholarship for Academic Achievement 2006 Wisconsin Medical Society Foundation General Medical Education Scholarship 2006 Wisconsin Medical Alumni Association Scholarship for Leadership 2006 Eugene M. Polo Scholarship for Dedication to Education 2007 Wisconsin Medical Society Foundation Presidential Scholar Award for Leadership 2007 University League Endowed Scholarship for Leadership 2008 Department of OB/GYN Award for Academic Excellence 2008 Gold Humanism Honor Society Member 2008 Alpha Omega Alpha Post-graduate and junior faculty: 2010 Arnold P. Gold Foundation Award for Humanism and Excellence in Clinical Teaching 2012 Travel Award, American Thoracic Society Assembly on Clinical Problems 2014 Abstract Award, American Thoracic Society Assembly on Respiratory Cell & Molecular Biology 2014 Travel Award, Federation of American Societies for Experimental Biology 2015 Travel Award, American Thoracic Society Assembly on Allergy, Immunology, and Inflammation 2016 Scholarship, American Thoracic Society Assembly on Respiratory Cell & Molecular Biology 2018 Science and Innovation Center Abstract Award, American Thoracic Society Assembly on Respiratory Cell & Molecular Biology 2018 Jo Rae Wright Award in recognition of outstanding scientific achievement by a young investigator, American Thoracic Society Assembly on Respiratory Cell & Molecular Biology Institutional Academic Service: present Division of Pulmonary, Allergy, and Critical Care Medicine Fellowship Applicant Interviewer 2016 Department of Medicine, Junior Faculty Panelist, Academic and Research Career Guidance Seminar for Fellows Licensure and Board Certifications (all active): 2008 American Heart Association Basic and Advanced Cardiac Life Support 2009 Physician License, New York State (#255534) 2011 Internal Medicine, American Board of Internal Medicine 2013 Pulmonary Medicine, American Board of Internal Medicine 2014 Critical Care Medicine, American Board of Internal Medicine C. Contributions to Science 1. Predoctoral Training: As an undergraduate student, I worked in an immunology lab harvesting mouse reticuloendothelial tissue and analyzing leukocyte populations by flow cytometry. In medical school, I received a Research Fellowship to support my clinical epidemiologic project studying frailty in order adults with cancer. My research mentor, Dr. Maureen Smith, MD, MPH, PhD, is an expert in population health research. I identified that frailty, a biological syndrome of vulnerability to stressors, was described in the literature by cyclical models. Cyclical models are not conducive to testing over time to determine predictive factors. I developed a novel longitudinal model relating the presence of symptoms to frailty development, and I tested my model using longitudinal data from a cohort study. My findings show that the presence of symptoms, particularly exhaustion and slowness, predicted frailty development ten years later, indicating that an

4 individual s perception of poor health was a sensitive marker of physical decline. Identification of these symptoms at early time points may provide new opportunities to prevent frailty development. I designed the model, analyzed the data, and presented the findings as a research poster. a. Abstract and Poster: Hook JL and Smith MA. A longitudinal model for progressive decline leading to frailty in cancer patients. Medical Student Summer Research Fall Forum, UWSMPH. November 17, 2005; Madison, WI. 2. Postdoctoral Training in Clinical Epidemiology: As a medical resident and clinical fellow at CUMC, I worked on a prospective epidemiologic cohort study examining outcomes in patients with idiopathic pulmonary fibrosis (IPF), a disease with high mortality and no therapy. My mentor, Dr. David Lederer, MD, MS, is an expert in clinical epidemiology, pulmonary fibrosis, and lung transplantation. My projects with Dr. Lederer focused on two areas. First, we identified a novel bedside measure, the Titrated Oxygen Requirement (TOR), that predicts one-year mortality in IPF patients. The TOR provides a non-invasive, inexpensive, and standardized approach for estimating IPF disease severity and identifying patients at high risk of death. This study led to a first-author paper (2012), two first-author poster presentations at national ATS meetings (2010, 2011), and an ATS Travel Award (2012). I used STATA and R statistical programs to perform independent data analysis, and I wrote and edited the manuscripts with assistance from Dr. Lederer. My second project focused on predictors of outcomes after lung transplantation. One-fifth of lung transplant recipients die in the first year after transplant, suggesting that there may be unrecognized pre-transplant risk factors for poor clinical outcomes. In a prospective cohort study of lung transplant candidates, we found that pre-transplant frailty was prevalent and tended to associate with post-transplant reintubation, need for additional surgical procedures, and 30-day mortality. These preliminary findings indicate that frailty may identify high-risk lung transplant candidates, and that the incorporation of frailty into candidate risk assessments may improve lung transplant outcomes. This project resulted in an invited oral presentation at a national ATS meeting (2012). In addition, I wrote and edited a first-author review (2012) and editorial (2012) on related topics under the guidance of Dr. Lederer. a. Hook JL, Arcasoy SM, Zemmel D, Bartels MN, Kawut SM, Lederer DJ. Titrated oxygen requirement and prognostication in idiopathic pulmonary fibrosis. Eur Respir J. 2012;39(2): PMID b. Hook JL, Lederer DJ. Socioeconomic barriers to lung transplantation: balancing access and equity. Am J Respir Crit Care Med. 2012;186(10): PMID c. Hook JL, Lederer DJ. Selecting lung transplant candidates: where do current guidelines fall short? Expert Rev Respir Med. 2012;6(1): PMID d. First-author abstracts are published in ATS International Conference Abstracts, 2010 (no. A2969), 2011 (A1516), and 2012 (A5328) editions. 3. Postdoctoral Training in Basic Science: I am currently a post-doctoral research fellow under the mentorship of Dr. Jahar Bhattacharya, MD, DPhil, an internationally recognized expert in lung biology research. I joined the Bhattacharya lab in 2013 as a T32 Fellow to gain training in the biology of Acute Lung Injury (ALI), a common disease with high mortality and no specific therapy. ALI is defined by loss of the lung alveolar barrier, which is comprised of two physiologically and spatially distinct components alveolar epithelium and microvascular endothelium. It is not known how alveolar activation by inhaled pathogens, a major cause of ALI, deteriorates both barrier components. The current understanding is derived from studies of cultured cells, which cannot replicate the in vivo structure and physiology of the barrier. I have learned to study the alveolar barrier in situ using methods of real-time, optical imaging of live, intact perfused mouse and human lungs, a method which Dr. Bhattacharya pioneered. These established methods afford mechanistic examination of spatial, temporal, and physiological factors underlying pathogen-induced ALI. My novel findings show that inhaled bacteria of the S. aureus family, USA300 rapidly form stable, solute-impermeable microaggregates in structural niches of lung alveoli, where they secrete a-hemolysin toxin and induce localized epithelial injury. The injury induces increase of epithelial cytosolic Ca 2+, which spreads to uninfected alveoli through intercellular gap junctions, causing widespread pulmonary edema. Although antibiotics have no effect on mice infected with wild type USA300, they are protective against lung injury by mutant USA300 lacking the aggregationpromoting factor, PhnD. These findings uncover a critical role for alveolar niches, hence alveolar micro-

5 anatomy in lung infection initiation, alveolar barrier loss, and antibiotic efficacy. My new project, in which I am investigating mechanisms of influenza-induced ALI, will define my academic independence. a. Hook JL, Islam MN, Parker D, Prince AS, Bhattacharya S, Bhattacharya J. Disruption of staphylococcal aggregation protects against lethal lung injury. J Clin Invest. 2018;128(3): PMID This paper was highlighted by the journal editors in the March 2018 issue of JCI This Month, a digest of featured publications. b. First-author abstracts are published in ATS International Conference Abstracts, 2014 (no. A3963), 2015 (A3687), 2016 (A4597), 2017 (A4398), and 2018 (no. TBD) editions. Additional first-author abstracts were presented at the 2014 FASEB Conference on the Lung Epithelium in Health and Disease and the 2016 and 2018 Gordon Research Conferences and Seminars on the Biology of Acute Respiratory Infection. 4. Other Research as Columbia Pulmonary Faculty: As a member of the Columbia Lung Transplantation Program, I take part in clinical research that is ongoing in the Pulmonary Division. My contributions include research participant data and manuscript editing. a. Benvenuto LJ, Anderson DR, Kim HP, Hook JL, Shah L, Robbins HY, D Ovidio F, Bacchetta M, Sonett JR, Arcasoy SM. Geographic disparities in donor lung supply and lung transplant waitlist outcomes: A cohort study. Am J Transplant In press. PMID Complete list of published work in MyBibliography: bibliography/ /public/?sort=date&direction=descending D. Research Support Pending: Columbia University Irving Institute/Clinical Trials Office Pilot Award 7/1/18-6/30/19 Novel mechanisms of post-influenza staphylococcal lung injury This award supports junior investigators to obtain pilot data that will lead to independent, external funding. Role: PI ($75,000) Ongoing: AHA Association Wide Fellow-to-Faculty Transition Award (scored in the 0.1 percentile) 7/1/16-6/30/21 Pulmonary microvascular responses to methicillin-resistant Staphylococcus aureus lung infection This career development award critically supports the transition from trainee to independent investigator. Role: PI ($526,000) Completed: Research Fellowship, UW Institute for Clinical and Translational Research 5/15/05-8/15/05 Self-rated health as a predictor of future functioning in older adults after a diagnosis of cancer The goal of this project was to receive training in clinical epidemiology research. Role: PI ($4,000) NHLBI T32 HL105323, Columbia Training Program in Lung Science (PI: Bhattacharya) 7/1/13-6/30/15 The goal of this Fellowship was to receive training in basic and translational lung biology. Role: Fellow ($103,032) Stony Wold-Herbert Fund Research Training Fellowship and Competitive Renewal 7/1/15-6/30/17 The goal of this Fellowship was to receive training in the investigation of respiratory diseases. The Renewal (7/1/16-6/30/17) was relinquished due to overlapping support with the AHA Award. Role: PI ($25,000)