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Bruce David Levy
Physician, Brigham and Women's Hospital
Parker B. Francis Professor of Medicine, Harvard Medical School

Brigham and Women's Hospital
Department of Medicine
Pulmonary
75 Francis Street
Boston, MA 02115

Research Location: Harvard Institute of Medicine


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Research Narrative:

Dr. Levy is a Professor in Medicine at Brigham and Women’s Hospital and serves as the Division Chief of the Pulmonary and Critical Care Medicine Division. Research undertaken in the Levy laboratory focuses on the roles of endogenous counter-regulatory mediators in the lung. The lab’s mission is “to identify novel pathways and cellular targets that promote resolution of pulmonary inflammation or injury and to determine roles for naturally-derived, specialized pro-resolving mediators in lung health and disease as well as their potential as templates for rational new drug design.”

To this end, we have identified a novel series of bioactive polyisoprenyl phosphates in neutrophils (Levy et al, Nature. 1997). One of these compounds, presqualene diphosphate, undergoes rapid phosphate remodeling upon cell activation and carries inhibitory properties in bioassays of neutrophil activation, such as superoxide anion generation. These were the first results to indicate novel roles for cholesterol biosynthetic intermediates as lipid-derived anti-inflammatory signals. We have also elucidated mechanisms for lipid mediator class switching during acute inflammation in vivo that lead to the formation of lipoxins, a potent family of eicosanoids with leukocyte-specific counter-regulatory properties. We identified protective roles for lipoxins and lipoxin A4 receptors in the development of allergy, airway inflammation and airway hyper-responsiveness. Determining the molecular mechanism of action for polyisoprenyl phosphate signaling, elucidation of pivotal presqualene diphosphate metabolic enzymes, as well as uncovering the potential for lipoxins and related compounds to promote resolution of pulmonary inflammation are major areas of current emphasis in the laboratory.


Education:
University of Pennsylvania School of Medicine, 1988, MD

Publications (Pulled from Harvard Catalyst Profiles):

1. Wu W, Bang S, Bleecker ER, Castro M, Denlinger L, Erzurum SC, Fahy JV, Fitzpatrick AM, Gaston BM, Hastie AT, Israel E, Jarjour NN, Levy BD, Mauger DT, Meyers DA, Moore WC, Peters M, Phillips BR, Phipatanakul W, Sorkness RL, Wenzel SE. Multiview Cluster Analysis Identifies Variable Corticosteroid Response Phenotypes in Severe Asthma. Am J Respir Crit Care Med. 2019 Jun 01; 199(11):1358-1367.

2. Lachowicz-Scroggins ME, Dunican EM, Charbit AR, Raymond W, Looney MR, Peters MC, Gordon ED, Woodruff PG, Lefrançais E, Phillips BR, Mauger DT, Comhair SA, Erzurum SC, Johansson MW, Jarjour NN, Coverstone AM, Castro M, Hastie AT, Bleecker ER, Fajt ML, Wenzel SE, Israel E, Levy BD, Fahy JV. Extracellular DNA, Neutrophil Extracellular Traps, and Inflammasome Activation in Severe Asthma. Am J Respir Crit Care Med. 2019 May 01; 199(9):1076-1085.

3. Fitzpatrick AM, Gillespie SE, Mauger DT, Phillips BR, Bleecker ER, Israel E, Meyers DA, Moore WC, Sorkness RL, Wenzel SE, Bacharier LB, Castro M, Denlinger LC, Erzurum SC, Fahy JV, Gaston BM, Jarjour NN, Larkin A, Levy BD, Ly NP, Ortega VE, Peters SP, Phipatanakul W, Ramratnam S, Teague WG. Racial disparities in asthma-related health care use in the National Heart, Lung, and Blood Institute's Severe Asthma Research Program. J Allergy Clin Immunol. 2019 Jun; 143(6):2052-2061.

4. Duvall MG, Krishnamoorthy N, Levy BD. Non-type 2 inflammation in severe asthma is propelled by neutrophil cytoplasts and maintained by defective resolution. Allergol Int. 2019 Apr; 68(2):143-149.

5. Dell DS, Baldwin K, Bell EJ, Lehmann CU, Webber EC, Mohan V, Leu MG, Hofmann JM, Kaelber DC, Landman AB, Hron J, Silverman HD, Levy B, Elkin PL, Poon E, Luberti AA, Finnell JT, Safran C, Palma JP, Forman BH, Kileen J, Arvin D, Pfeffer M. Characteristics of the National Applicant Pool for Clinical Informatics Fellowships (2016-2017). AMIA Annu Symp Proc. 2018; 2018:225-231.

6. Downing NS, McMullan CJ, Rennke HG, Levy BD, Loscalzo J. Complements from the Lung. N Engl J Med. 2018 Nov 01; 379(18):1767-1773.

7. Karra L, Singh Gangwar R, Shamri R, Puzzovio PG, Cohen-Mor S, Levy BD, Levi-Schaffer F. Leukocyte CD300a Contributes to the Resolution of Murine Allergic Inflammation. J Immunol. 2018 Nov 15; 201(10):2998-3005.

8. Loynes CA, Lee JA, Robertson AL, Steel MJ, Ellett F, Feng Y, Levy BD, Whyte MKB, Renshaw SA. PGE2 production at sites of tissue injury promotes an anti-inflammatory neutrophil phenotype and determines the outcome of inflammation resolution in vivo. Sci Adv. 2018 09; 4(9):eaar8320.

9. Krishnamoorthy N, Douda DN, Brüggemann TR, Ricklefs I, Duvall MG, Abdulnour RE, Martinod K, Tavares L, Wang X, Cernadas M, Israel E, Mauger DT, Bleecker ER, Castro M, Erzurum SC, Gaston BM, Jarjour NN, Wenzel S, Dunican E, Fahy JV, Irimia D, Wagner DD, Levy BD. Neutrophil cytoplasts induce TH17 differentiation and skew inflammation toward neutrophilia in severe asthma. Sci Immunol. 2018 08 03; 3(26).

10. Dela Cruz CS, Wunderink RG, Christiani DC, Cormier SA, Crothers K, Doerschuk CM, Evans SE, Goldstein DR, Khatri P, Kobzik L, Kolls JK, Levy BD, Metersky ML, Niederman MS, Nusrat R, Orihuela CJ, Peyrani P, Prince AS, Ramírez JA, Ridge KM, Sethi S, Suratt BT, Sznajder JI, Tsalik EL, Walkey AJ, Yende S, Aggarwal NR, Caler EV, Mizgerd JP. Future Research Directions in Pneumonia. NHLBI Working Group Report. Am J Respir Crit Care Med. 2018 Jul 15; 198(2):256-263.