Leopoldo Segal M.D.

Assistant Professor of Medicine

 A. Personal Statement My lab has been studying the human microbiome since 2010. As a pulmonologist, I sample the lower airways by bronchoscopy and we conducted early 16S rRNA surveys of the lower airways in humans to understand the interactions between lung microbiome and host immune response. As part of the NYU Human Microbiome Program, I exploit state of the art next generation sequence techniques and bioinformatic approaches to define complex microbial communities in the lung. More recently, I have been exploring microbiome changes that could be fueling metabolic derangements that might have important effects on the immune system. 1.Wu BG, Segal LN. Lung Microbiota and Its Impact on the Mucosal Immune Phenotype. Microbiol Spectr. 2017 Jun;5(3)PubMed PMID: 28643622; PubMed Central PMCID: PMC5484071. 2.Segal LN, Clemente JC, Li Y, Ruan C, Cao J, Danckers M, Morris A, Tapyrik S, Wu BG, Diaz P, Calligaro G, Dawson R, van Zyl-Smit RN, Dheda K, Rom WN, Weiden MD. Anaerobic Bacterial Fermentation Products Increase Tuberculosis Risk in Antiretroviral-Drug-Treated HIV Patients. Cell Host Microbe. 2017 Apr 12;21(4):530-537.e4. PubMed PMID: 28366509; PubMed Central PMCID: PMC5465639. 3.Segal LN, Clemente JC, Wu BG, Wikoff WR, Gao Z, Li Y, Ko JP, Rom WN, Blaser MJ, Weiden MD. Randomised, double-blind, placebo-controlled trial with azithromycin selects for anti-inflammatory microbial metabolites in the emphysematous lung. Thorax. 2017 Jan;72(1):13-22. PubMed PMID: 27486204; PubMed Central PMCID: PMC5329050. 4.Segal LN, Clemente JC, Tsay JC, Koralov SB, Keller BC, Wu BG, Li Y, Shen N, Ghedin E, Morris A, Diaz P, Huang L, Wikoff WR, Ubeda C, Artacho A, Rom WN, Sterman DH, Collman RG, Blaser MJ, Weiden MD. Enrichment of the lung microbiome with oral taxa is associated with lung inflammation of a Th17 phenotype. Nat Microbiol. 2016 Apr 4;1:16031. PubMed PMID: 27572644; PubMed Central PMCID: PMC5010013. B. Positions and Honors Positions and Employment 1999 - 2000 Intern, Internal Medicine, Hospital Español de Buenos Aires, Buenos Aires 2000 - 2002 Resident, Internal Medicine, Hospital Español de Buenos Aires, Buenos Aires 2002 - 2003 Chief Resident, Internal Medicine, Hospital Español de Buenos Aires, Buenos Aires 2003 - 2004 Intensive Care Attending, Juncal Hospital, Buenos Aires 2004 - 2005 Intern, Internal Medicine, Morristown Memorial Hospita, Morristown, NJ 2005 - 2007 Resident, Internal Medicine, Morristown Memorial Hospita, Morristown, NJ 2007 - 2010 Fellow, Pulmonary, Critical Care and Sleep Medicine, NYU School of Medicine, New York, NY 2010 - 2012 Instructor of Medicine, NYU School of Medicine, New York, NY 2012 - Assistant Professor of Medicine, NYU School of Medicine, New York, NY Other Experience and Professional Memberships Honors 2010 - 2011 Physician Scientist Training Program, NYU Schoo of Medicine 2012 - 2014 Translational Research Scholars Program , NYU School of Medicine 2014 - 2015 Gerald Weissmann Young Scholars Society, NYU School of Medicine 2016 - 2019 Chairman's Circle Scholar, NYU School of Medicine C. Contribution to Science 1. Lung microbiota in health. The use of culture independent techniques has allowed us to characterize the microbial communities uncovering a very diverse microbiome in the lung. By sampling the respiratory tract using bronchoscopy, I have focused on understanding the composition of the lower airway human microbiome in relation to the upper airways, the main source of microbes through micro aspiration. These investigations have shown an association between the lower airway microbiota and the immunological phenotype of healthy hosts. a. Segal LN, Clemente JC, Tsay JC, Koralov SB, Keller BC, Wu BG, Li Y, Shen N, Ghedin E, Morris A, Diaz P, Huang L, Wikoff WR, Ubeda C, Artacho A, Rom WN, Sterman DH, Collman RG, Blaser MJ, Weiden MD. Enrichment of the lung microbiome with oral taxa is associated with lung inflammation of a Th17 phenotype. Nat Microbiol. 2016 Apr 4;1:16031. PubMed PMID: 27572644; PubMed Central PMCID: PMC5010013. b. Segal LN, Rom WN, Weiden MD. Lung microbiome for clinicians. New discoveries about bugs in healthy and diseased lungs. Ann Am Thorac Soc. 2014 Jan;11(1):108-16. PubMed PMID: 24460444; PubMed Central PMCID: PMC3972985. c. Segal LN, Blaser MJ. A brave new world: the lung microbiota in an era of change. Ann Am Thorac Soc. 2014 Jan;11 Suppl 1:S21-7. PubMed PMID: 24437400; PubMed Central PMCID: PMC3972973. d. Segal LN, Alekseyenko AV, Clemente JC, Kulkarni R, Wu B, Gao Z, Chen H, Berger KI, Goldring RM, Rom WN, Blaser MJ, Weiden MD. Enrichment of lung microbiome with supraglottic taxa is associated with increased pulmonary inflammation. Microbiome. 2013 Jul 1;1(1):19. PubMed PMID: 24450871; PubMed Central PMCID: PMC3971609. 2. Immunological implications of lung microbiome in disease. With the use of functional microbiomics to study microbial genes (metagenome) and microbial metabolites (metabolome) we can evaluate pathways implicated in determining immunological phenotypes in disease states. These investigations have shed light into microbial metabolic pathways that are important immunological regulators in COPD and HIV. a. Wang J, Lesko M, Badri MH, Kapoor BC, Wu BG, Li Y, Smaldone GC, Bonneau R, Kurtz ZD, Condos R, Segal LN. Lung microbiome and host immune tone in subjects with idiopathic pulmonary fibrosis treated with inhaled interferon-γ. ERJ Open Res. 2017 Jul;3(3)PubMed PMID: 28717640; PubMed Central PMCID: PMC5507144. b. Segal LN, Clemente JC, Li Y, Ruan C, Cao J, Danckers M, Morris A, Tapyrik S, Wu BG, Diaz P, Calligaro G, Dawson R, van Zyl-Smit RN, Dheda K, Rom WN, Weiden MD. Anaerobic Bacterial Fermentation Products Increase Tuberculosis Risk in Antiretroviral-Drug-Treated HIV Patients. Cell Host Microbe. 2017 Apr 12;21(4):530-537.e4. PubMed PMID: 28366509; PubMed Central PMCID: PMC5465639. c. Segal LN, Clemente JC, Wu BG, Wikoff WR, Gao Z, Li Y, Ko JP, Rom WN, Blaser MJ, Weiden MD. Randomised, double-blind, placebo-controlled trial with azithromycin selects for anti-inflammatory microbial metabolites in the emphysematous lung. Thorax. 2017 Jan;72(1):13-22. PubMed PMID: 27486204; PubMed Central PMCID: PMC5329050. d. Segal LN, Dickson RP. The Lung Microbiome in HIV. Getting to the HAART of the Host-Microbe Interface. Am J Respir Crit Care Med. 2016 Jul 15;194(2):136-7. PubMed PMID: 27420358; PubMed Central PMCID: PMC5003221. 3. Lower airway cellular phenotyping. With the use of lower airway samples obtained through bronchoscopies, we characterize the phenotype of bronchial epithelial cells and bronchoalveolar cells. These investigations contribute to our understanding of phenotypic signatures associated with inflammation and cancer. a. Wang J, Lesko M, Badri MH, Kapoor BC, Wu BG, Li Y, Smaldone GC, Bonneau R, Kurtz ZD, Condos R, Segal LN. Lung microbiome and host immune tone in subjects with idiopathic pulmonary fibrosis treated with inhaled interferon-γ. ERJ Open Res. 2017 Jul;3(3)PubMed PMID: 28717640; PubMed Central PMCID: PMC5507144. b. Tsay JC, Li Z, Yie TA, Wu F, Segal L, Greenberg AK, Leibert E, Weiden MD, Pass H, Munger J, Statnikov A, Tchou-Wong KM, Rom WN. Molecular characterization of the peripheral airway field of cancerization in lung adenocarcinoma. PLoS One. 2015;10(2):e0118132. PubMed PMID: 25705890; PubMed Central PMCID: PMC4338284. c. Weiden MD, Naveed B, Kwon S, Segal LN, Cho SJ, Tsukiji J, Kulkarni R, Comfort AL, Kasturiarachchi KJ, Prophete C, Cohen MD, Chen LC, Rom WN, Prezant DJ, Nolan A. Comparison of WTC dust size on macrophage inflammatory cytokine release in vivo and in vitro. PLoS One. 2012;7(7):e40016. PubMed PMID: 22815721; PubMed Central PMCID: PMC3399845. d. R12Kobayashi H, Nolan A, Naveed B, Hoshino Y, Segal LN, Fujita Y, Rom WN, Weiden MD. Neutrophils activate alveolar macrophages by producing caspase-6-mediated cleavage of IL-1 receptor-associated kinase-M. J Immunol. 2011 Jan 1;186(1):403-10. PubMed PMID: 21098228; PubMed Central PMCID: PMC3151149. 4. Distal Airway Physiology. Many respiratory diseases start in the small airways. With the use of cutting edge pulmonary physiology testing, I have studied the small airway physiology to uncover early physiological events that may explain important inflammatory pathways and the onset of symptoms when routine pulmonary physiological tests are otherwise normal. a. Berger KI, Pradhan DR, Goldring RM, Oppenheimer BW, Rom WN, Segal LN. Distal airway dysfunction identifies pulmonary inflammation in asymptomatic smokers. ERJ Open Res. 2016 Oct;2(4)PubMed PMID: 27995132; PubMed Central PMCID: PMC5165724. b. Oppenheimer BW, Berger KI, Ali S, Segal LN, Donnino R, Katz S, Parikh M, Goldring RM. Pulmonary Vascular Congestion: A Mechanism for Distal Lung Unit Dysfunction in Obesity. PLoS One. 2016;11(4):e0152769. PubMed PMID: 27035663; PubMed Central PMCID: PMC4817979. c. Oppenheimer BW, Berger KI, Segal LN, Stabile A, Coles KD, Parikh M, Goldring RM. Airway dysfunction in obesity: response to voluntary restoration of end expiratory lung volume. PLoS One. 2014;9(2):e88015. PubMed PMID: 24505355; PubMed Central PMCID: PMC3913722. d. Segal LN, Goldring RM, Oppenheimer BW, Stabile A, Reibman J, Rom WN, Weiden MD, Berger KI. Disparity between proximal and distal airway reactivity during methacholine challenge. COPD. 2011 Jun;8(3):145-52. PubMed PMID: 21513433. Complete List of Published Work in My Bibliography: https://www.ncbi.nlm.nih.gov/myncbi/leopoldo.segal.1/bibliography/40161959/public/

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