Institution Name: Degree: Completion Date: Field of Study: University of Groningen, The Netherlands PhD 12/2006 Pharmacology

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1 Harm Maarsingh, PhD Associate Professor of Pharmaceutical Sciences Lloyd L. Gregory School of Pharmacy Palm Beach Atlantic University 901 S Flagler Drive West Palm Beach, FL (phone) (fax) harm_maarsingh@pba.edu EDUCATION/TRAINING Institution Name: Degree: Completion Date: Field of Study: University of Groningen, The Netherlands PhD 12/2006 Pharmacology University of Groningen, The Netherlands MSc 08/2001 Pharmacy Certifications: 2016 Good Clinical Practice (awarded by Dr. Gizurarson, University of Iceland) Certified Pharmacologist (awarded by Dutch Pharmacological Society) Legal status (art. 9) to ethically conduct animal experiments and to apply for research projects grants involving animal experimentation (The Netherlands) Legal status to conduct experiments involving radioactivity at the 5B level (The Netherlands) Safe microbiological experimentation, providing legal status for experimentation at the ML-1 and ML-2 level (The Netherlands).

2 POSITIONS AND HONORS Positions and Employment: 2013 present: Associate Professor of Pharmaceutical Sciences, Lloyd L. Gregory School of Pharmacy, Palm Beach Atlantic University, West Palm Beach, FL : Lecturer, Department of Molecular Pharmacology, University of Groningen, Groningen, The Netherlands (0.5 fte) : Post-doctoral fellow at the department of Molecular Pharmacology, University of Groningen on a research grant funded by the Schering-Plough Research Institute (later MSD). Part of this research was performed at the department of Physiology, University of Massachusetts Medical School, Worcester, MA. (0.5 fte from September 2009) : Post-doctoral fellow at the department of Molecular Pharmacology, University of Groningen on a research grant funded by NV Organon, Oss (later Schering- Plough). Part of this research was performed at the department of Asthma, Allergy and Lung Biology, King s College London (UK). Awards: 2010 International Trainee Travel Award - granted by the American Thoracic Society 2007 Thesis Award - granted by the Netherlands Society for Pharmaceutical Sciences for the best thesis in the field of Pharmaceutical Sciences defended in International Trainee Travel Award - granted by the American Thoracic Society RESEARCH STATEMENT Main expertise is in airway pharmacology, specifically in relation to preclinical in vivo, ex vivo and in vitro models of asthma and COPD. Within this context, the role of the L-arginine metabolome (arginase, nitric oxide synthase), the camp signaling pathway (β-agonists, camp effectors and A- kinase anchoring proteins) and the Fstl1/BMP4 pathway in airway inflammation, hyperresponsiveness and remodeling is studied. An important strength is the integration of mechanistic in vitro and ex vivo studies with proof of concept in vivo studies, which enables not only the identification of new drug targets but also the mechanisms of action. Research collaborations exist with Drs Nornoo, Santini and Mitroka (Palm Beach Atlantic University), Drs Schmidt, Meurs, Gosens, Hirsch and Dekker (University of Groningen, The Netherlands), Dr Halayko (University of Manitoba, Canada) and Dr. Van den Hoff (Amsterdam Medical Center, The Netherlands). For a complete list of publications follow this link: Publication List Harm Maarsingh

3 CONTRIBUTION TO SCIENCE Using guinea pig models of acute and chronic allergic asthma, I studied the role of the L-arginine metabolome, specifically the interactive role of arginase and nitric oxide synthase (NOS), in the development of airway hyperresponsiveness (AHR), airway inflammation and airway remodeling. We were the first to demonstrate that the activity of arginase is increased after the early and late asthmatic reaction in models of acute and chronic asthma, which limits the bioavailability of L- arginine to NOS leading to a deficiency of bronchodilating NO. Targeting this increased arginase activity ex vivo using the specific arginase inhibitor nor-noha prevents allergen-induced AHR by restoring normal levels of bronchodilating nitric oxide and preventing the formation of pro-contractile peroxynitrite. Increased arginase also contributes to the deficiency of neuronal NOS-derived NO in allergic asthma by limiting the bioavailability of L-arginine to neuronal NOS. Treatment with the inhaled arginase inhibitor in vivo greatly reduced the sensitivity to inhaled allergens in vivo and reduced AHR and inflammation in a guinea pig model of acute asthma. ABH also prevented allergen-induced airway remodeling, inflammation and AHR in a guinea pig model of chronic asthma. We also demonstrated that arginase activity is increased in an LPS-induced guinea pig model of COPD and that treatment with inhaled ABH in vivo prevents LPS-induced inflammatory processes and fibrosis. ABH also prevented the development of right ventricular hypertrophy a marker for pulmonary hypertension. Taken together, increased arginase represents a novel therapeutic target for the treatment of asthma and COPD. Key publications L-arginine metabolome studies: a. Meurs H, McKay S, Maarsingh H, Hamer MAM, Macic L, Molendijk N, Zaagsma J. 2002; Increased arginase activity underlies allergen-induced deficiency of cnos-derived nitric oxide and airway hyperresponsiveness. Br J Pharmacol 136(3): b. Maarsingh H, Leusink J, Bos IST, Zaagsma J, Meurs H. 2006; Arginase strongly impairs neuronal nitric oxide-mediated airway smooth muscle relaxation in allergic asthma. Respir Res 7:1. c. Maarsingh H, Zuidhof AB, Bos IS, van Duin M, Boucher JL, Zaagsma J, Meurs H. 2008; Arginase inhibition protects against allergen-induced airway obstruction, hyperresponsiveness, and inflammation. Am J Respir Crit Care Med 178(6): d. Maarsingh H, Bossenga BE, Bos IST, Volders HH, Zaagsma J, Meurs H. 2009, L-Arginine deficiency causes airway hyperresponsiveness after the late asthmatic reaction. Eur Respir J 34: e. Maarsingh H, Dekkers BG, Zuidhof AB, Bos IS, Menzen MH, Klein T, Flik G, Zaagsma J, Meurs H. 2011; Increased arginase activity contributes to airway remodelling in chronic allergic asthma. Eur Respir J. 38: f. Pera T, Zuidhof AB, Smit M, Menzen MH, Klein T, Flik G, Zaagsma J, Meurs H, Maarsingh H. 2014; Arginase inhibition prevents inflammation and remodeling in a guinea pig model of COPD. J Pharmacol Exp Ther. 349(2):

4 Another ongoing research line is focused on the role of the camp signaling pathway in health and disease. The camp pathway is an important second messenger pathway and plays a crucial role in the efficacy of β-agonist, a mainstay bronchodilator. We have established the functional role of the camp effector Epac (Epac1 and Epac2) in the airways and demonstrated that activation of Epac induces airway relaxation, prevents mitogen-induced phenotypic modulation of airway smooth muscle and inhibits cigarettes smoke-induced airway inflammation. Importantly, the expression of Epac1 is reduced in lung tissue of COPD patients. Using knockout mice, we demonstrated that Epac1 and Epac2 are differentially involved in regulating inflammatory and remodeling processes in the lungs that are induced by cigarette smoke. A-kinase anchoring proteins (AKAPs) play an important role in compartmentalizing camp signaling by forming a scaffold for various proteins involved in camp signaling, such as receptors and effector proteins. Our studies revealed that AKAP-PKA interactions play an important role in regulating (patho)physiological processes in the lungs. AKAPs contribute to loss of E-cadherin expression and subsequent reduction in epithelial barrier function induced by cigarette smoke extract (CSE). AKAPs also coordinate CSE-induced inflammatory cytokine release from airway smooth muscle cells as well as the responsiveness towards β-agonists. I have also studied the effect of (a combination of) a long-acting anti-cholinergic (tiotropium), an ultra-long acting β-agonist (olodaterol) or a glucocorticosteroid (ciclesonide) on airway hyperresponsiveness, airway inflammation and airway remodeling in guinea pig models of asthma. These studies demonstrated that olodaterol synergistically enhanced the bronchoprotective effect of tiotropium in allergen-induced asthma. Key publications camp studies: a. Roscioni SS, Maarsingh H, Elzinga CRS, Schuur LJ, Menzen MH, Halayko AJ, Meurs H, Schmidt M. 2011; Epac as a novel effector in airway smooth muscle relaxation. J Cell Mol Med 15: b. Roscioni SS, Prins AG, Elzinga CR, Menzen MH, Dekkers BG, Halayko AJ, Meurs H, Maarsingh H, Schmidt M. 2011; Protein kinase A and the exchange protein directly activated by camp (Epac) modulate phenotype plasticity in human airway smooth muscle. Br J Pharmacol. 164: c. Oldenburger A, Roscioni SS, Jansen E, Menzen MH, Halayko AJ, Timens W, Meurs H, Schmidt M, Maarsingh H. 2012; Anti-inflammatory role of the camp effectors Epac and PKA: implications in chronic obstructive pulmonary disease. PLoS ONE. 7(2):e d. Schmidt M, Dekker FJ, Maarsingh H. 2012; Exchange protein directly activated by camp (epac): a multidomain camp mediator in the regulation of diverse biological functions. Pharmacol Rev. 65(2): e. Smit M, Zuidhof AB, Bos SI, Maarsingh H, Gosens R, Zaagsma J, Meurs H. 2014; Bronchoprotection by olodaterol is synergistically enhanced by tiotropium in a guinea pig model of allergic asthma. J Pharmacol Exp Ther. 348(2): f. Oldenburger A, Poppinga WJ, Kos F, de Bruin HG, Rijks W, Heijink I, Timens W, Meurs H, Maarsingh H, Schmidt M. 2014; A-kinase anchoring proteins contribute to loss of E-cadherin and bronchial epithelial barrier by cigarette smoke. Am J Physiol Cell Physiol. 306(6):C585-C597. g. Poppinga WJ, Heijink IH, Holtzer LJ, Skroblin P, Klussmann E, Halayko AJ, Timens W, Maarsingh H, Schmidt M. 2015; A-kinase-anchoring proteins coordinate inflammatory responses to cigarette smoke in airway smooth muscle. m J Physiol Lung Cell Mol Physiol. 308(8):L766- L775.

5 RESEARCH SUPPORT As main applicant $275,000 Netherlands Asthma Foundation (NAF grant ) - granted in 2012 study the role of the bone morphogenic protein (BMP) antagonist Follistatin-like 1 (Fstl1) in the pathophysiology of COPD. $275,000 Netherlands Asthma Foundation (NAF grant ) - granted in 2011 study the role of A-kinase anchoring proteins in the pathophysiology and pharmacological treatment of COPD. $22,000 Stichting Astmabestrijding - granted in 2010 study the relation between airway responsiveness and airway remodeling in COPD $2,000 Palm Beach Atlantic University Quality Initiative - granted in 2015 study the relation between allergen-induced airway constriction and histamine release in asthma $525,000 Novartis (2 grants) - granted in 2013, 2015 study the effectiveness of drugs in preventing airway constriction. As co-applicant $270,000 Netherlands Asthma Foundation (NAF grant ) - granted in 2009 study the role of the camp effector Epac (exchange protein directly activated by camp) in the pathophysiology and pharmacological treatment of COPD. $935,000 Technology Foundation STW, The Netherlands granted in 2015 developing and testing of novel arginase inhibitors for the treatment of allergic asthma. $550,000 Organon Oss (Netherlands) & Schering-Plough, Kenilworth, NJ (2 grants) - granted in 2006, 2008 study arginase as a drug target for airway hyperresponsiveness, airway inflammation and airway remodeling in in vivo guinea pig models of acute and chronic asthma and COPD. $685,000 Boehringer-Ingelheim, Ingelheim, Germany (3 grants) - granted 2009, 2010, 2011 study the (interaction) of therapeutic drugs in relation to airway hyperresponsiveness, airway inflammation and airway remodeling and in in vivo guinea pig models of acute and chronic asthma.

6 TEACHING My teaching responsibilities within the PharmD program focus mainly on pharmacology and pathophysiology of diseases in pharmaceutical sciences courses and pharmacotherapy series in the P1, P2 and P3 year. In addition, I precept APPE rotation students in various research projects in the P4 year. List of current courses: PRX 1103 PRX 1203 PRX 2145 PRX 2213 PRX 2253 PRX 2264 PHR 3152 PHR 3263 PHR 4512 PHR 4524 PHR 4534 Principles of Drug Action I Principles of Drug Action II Cardiovascular Pharmacotherapy Immunology, Biotechnology & Pharmacogenomics Gastrointestinal, Hepatic, and Renal Pharmacotherapy Endocrine and Musculoskeletal Pharmacotherapy Special Topics in Pharmacotherapy Hematologic, Oncologic, and Immunologic Pharmacotherapy Pharmacy Missions Advanced Biomedical and Pharmaceutical Research - Advanced Pharmacy Practice Experience I Advanced Biomedical and Pharmaceutical Research - Advanced Pharmacy Practice Experience II SERVICE Lloyd L. Gregory School of Pharmacy present Research & Resource Committee present Evaluation & Assessment Committee present Pharmacy Faculty Search Taskforce present Spiritual Advisory Council Curriculum & Academic Policy Committee 2014 Faculty promotion committee Strategic Plan Advisory Council Curricular Taskforce 2015 OSCE Taskforce 2016 Faculty Workload Taskforce Palm Beach Atlantic University present Faculty Promotion and Evaluation Committee Faculty Research Committee Joint Committee for Sabbatical Leaves and Course Load Reductions

7 Scientific Community present Reviewer for various International Scientific Journals & Grant Organizations 2013 Co-organizer of the 8th International Young Investigators Meeting on airway smooth muscle and fibroblasts, Groningen, The Netherlands Chairman of the Program Committee of the Dutch Pharmacological Society Member of the Scientific Committee of the FIGON Dutch Medicine Days Session Chair at the FIGON Dutch Medicine Days Judge for Best Poster Presenter Award FIGON Dutch Medicine Days Member of the Core Group and Management Committee of the European Union COST Action Epigenetics: bench to bedside (TD0905) Chairman of the COST working group Functional consequences of epigenetics (until May 2012)