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Nicholas H. Carbonetti, PhD

Academic Title:

Professor

Primary Appointment:

Microbiology and Immunology

Location:

685 W Baltimore St

Phone (Primary):

410-706-7677 (Office)

Phone (Secondary):

410-706-0097 (Lab)

Fax:

410-706-6970

Education and Training

  • B.Sc. - Biological Sciences, University of Birmingham, UK (1981)
  • Ph.D. - Genetics/Microbiology, University of Leicester, UK (1985)
  • Postdoc - Department of Microbiology and Immunology, University of North Carolina at Chapel Hill (Dr. P. Frederick Sparling) (1985-1989)
  • European Community Senior Postdoctoral Fellowship - Sclavo Research Center, Siena, Italy (Dr. Rino Rappuoli) (1989-1991)

Biosketch

Dr. Carbonetti started working on pertussis with Dr. Rino Rappuoli at Sclavo Research Centre, Siena, Italy in 1989. In 1991 Dr. Carbonetti was hired to his current position as a faculty member in the Department of Microbiology and Immunology at the University of Maryland School of Medicine in Baltimore. His research is primarily on the basic biology of pertussis infection and disease in mouse models, with a focus on the role of pertussis toxin.

Currently his group is investigating mechanisms by which pertussis toxin exacerbates pertussis infection and disease, through (i) upregulation of host factors that contribute to pathogenesis and (ii) inhibition of host mechanisms of attenuating and resolving airway inflammation. This has led to two different therapeutic possibilities that his group is testing in preclinical models, utilizing drugs that are either already FDA approved for other diseases or in clinical trials for treatment of inflammatory conditions. Dr. Carbonetti had the honor of organizing and hosting the ninth International Bordetella Symposium in Baltimore in Sept-Oct, 2010.

Dr. Carbonetti served as program director for the Molecular Microbiology and Immunology graduate program at the University of Maryland School of Medicine from 2005-2015. He is Deputy Editor-in-chief for the journal Pathogens and Disease and serves on the editorial board for the journal Infection and Immunity. He has also served on numerous NIH study sections.

Research/Clinical Keywords

Bordetella, pertussis, respiratory infection, host response, lung inflammation, sphingosine-1-phosphate receptor signaling, pendrin, adult and neonatal mouse models, interferons

Highlighted Publications

Scanlon, KM, Snyder, YG, Skerry, C, Carbonetti, NH (2017) Fatal pertussis in the neonatal mouse model is associated with pertussis toxin-mediated pathology beyond the airways. Infection & Immunity 85:e00355-17 

Skerry, C, Scanlon, KM, Ardanuy, JG, Roberts, D, Zhang, L, Rosen, H, Carbonetti, NH (2017) Reduction of pertussis inflammatory pathology by therapeutic treatment with sphingosine-1-phosphate receptor ligands by a pertussis toxin-insensitive mechanism. Journal of Infectious Diseases 215:278-286

Carbonetti, NH (2016) Pertussis leukocytosis: mechanisms, clinical relevance and treatment. Pathogens and Disease 74:ftw087

Plaut, RD, Scanlon, KM, Taylor, M, Teter, K, Carbonetti, NH (2016) Intracellular disassembly and activity of pertussis toxin require interaction with ATP. Pathogens and Disease 74:ftw065

Carbonetti, NH (2015) Contribution of pertussis toxin to the pathogenesis of pertussis disease. Pathogens and Disease 73:ftv073 PMCID: PMC4626579

Skerry, C, Scanlon, KM, Rosen, H, Carbonetti, NH (2015) Sphingosine-1-phosphate receptor agonism reduces Bordetella pertussis-mediated lung pathology. Journal of Infectious Diseases 211:1883-1886 PMCID: PMC4836722

Scanlon, KM, Gau, Y, Skerry, C, Soleimani, M, Wall, SM, Carbonetti, NH (2014) The epithelial anion transporter pendrin contributes to inflammatory lung pathology in Bordetella pertussis infection. Infection & Immunity 82:4212-4221 PMCID: PMC4187853

Additional Publication Citations

Carbonetti, NH, Wirsing von König, CH, Lan, R, Jacob-Dubuisson, F, Cotter, PA, Deora, R, Merkel, TJ, van Els, CA, Locht, C, Hozbor, D, Rodriguez, ME (2016) Highlights of the 11th International Bordetella Symposium: From Basic Biology to Vaccine Development. Clinical and Vaccine Immunology 23(11):

Wang, X, Shaw, DK, Hammond, HL, Sutterwala, FS, Rayamajhi, M, Shirey, KA, Perkins, DJ, Bonventre, JV, Velayutham, TS, Evans, SM, Rodino, KG, VieBrock, L, Scanlon, KM, Carbonetti, NH, Carlyon, JA, Miao, EA, McBride, JW, Kotsyfakis, M, Pedra, JHF (2016) The prostaglandin E2-EP3 receptor axis regulates Anaplasma phagocytophilum-mediated NLRC4 inflammasome activation. PLoS Pathogens 12:e1005803 PMCID: PMC4970705

Carbonetti, NH (2016) Bordetella pertussis: New concepts in pathogenesis and treatment. Current Opinion in Infectious Diseases 29:287-294 PMCID: PMC4846492

Guevara, C, Mooi, FR, Greenberg, DP, Decker, MD, Carbonetti, N, Starner, TD, McCray, PB, Iqbal, J, Gómez-Duarte, OG (2016) Primary human airway epithelial cells: a model to study Bordetella pertussis fimbrial-mediated adherence. Infectious Diseases 48:177-188

Scanlon, KM, Skerry, C, Carbonetti, NH (2015) Novel therapies for the treatment of whooping cough. Pathogens and Disease 73:ftv074 PMCID: PMC4626598

Connelly, C, Sun, Y, Carbonetti, NH (2012) Pertussis toxin exacerbates and prolongs airway inflammatory responses during Bordetella pertussis infection. Infection & Immunity 80:4317-4332 PMCID: PMC3497438

Worthington, ZEV, van Rooijen, N, Carbonetti, NH (2011) Enhancement of Bordetella parapertussis infection by Bordetella pertussis in mixed infection of the respiratory tract. FEMS Immunology and Medical Microbiology 63:119-128 PMCID: PMC3170498

Ayala, VI, Teijaro, JR, Farber, DL, Dorsey, SG, Carbonetti, NH (2011) Bordetella pertussis infection exacerbates influenza virus infection through pertussis toxin-mediated suppression of innate immunity. PLoS ONE 6(4): e19016 PMCID: PMC3080395

Research Interests

We are interested in the pathogenesis of infection and disease caused by Bordetella pertussis, the agent of pertussis or whooping cough. We use animal models and in vitro approaches to investigate this host-pathogen interaction, with an emphasis on the host response. Current projects include the following:

  1. Role of interferons in lung inflammatory pathology caused by Bordetella pertussis infection. We identified the type I and III IFN receptors as significant activators of lung gene upregulation during peak B. pertussis infection. We are studying the activation of type I and III IFN expression and their link to lung inflammatory pathology in adult and neonatal mouse models.
  2. Sphingosine-1-phosphate receptors as potential therapeutic targets for treatment of pertussis. Sphingosine-1-phosphate (S1P) signals through G protein-coupled receptors (GPCRs) that are sensitive to PT inhibition. We hypothesized that PT inhibits signaling through this receptor that would normally attenuate inflammation after infection, thereby exacerbating inflammation. Treatment of B. pertussis-infected mice with S1P receptor ligands dramatically reduced cytokine production and lung inflammatory pathology, and treatment of B. pertussis-infected neonatal mice reduced lethality, identifying another potential therapeutic avenue for pertussis treatment. However, these effects were not inhibited by PT, and we are currently attempting to dissect the molecular mechanism by which these ligands cause their effect.
  3. Neonatal mice infection with Bordetella pertussis as a model of critical pertussis in human infants. As in humans, neonatal mice are susceptible to fatal B. pertussis infection. We found that this lethality is completely dependent on PT activity and that the pathogenesis of disease is quite different from that caused by B. pertussis infection in adult mice.

Grants and Contracts

R01 AI101055
NIH/NIAID
Carbonetti (PI)
5/15/13 - 4/30/18 (NCE to 4/30/19)
Exacerbation of pertussis airway inflammation and pathology by pertussis toxin

R21 AI117095
NIH/NIAID
Carbonetti (PI)
1/1/16 - 12/31/17 (NCE to 12/31/18)
Host-targeted therapeutics for pertussis in infants

R21 AI122248
NIH/NIAID
Pasetti (PI)
1/1/16 - 12/31/17 (NCE to 12/31/18)
Role of maternal and infant vaccine-induced IgG in protection against pertussis (Role: Collaborator)

R21 AI135465
NIH/NIAID
Carbonetti (PI)
12/13/17 - 11/30/19
Type I interferon signaling in Bordetella pertussis pathogenesis

R21 AI137778
NIH/NIAID
Carbonetti (PI)
1/25/18 - 12/31/19
Repurposing S1P receptor drugs as therapeutics for pertussis in the baboon model

Professional Activity

  • 2017-present: Deputy Editor-in-chief, Pathogens and Disease
  • 2017: Chair, ZGM1 MBRS-SCORE Study Section, NIH
  • 2016: Scientific Organizing Committee, 11th International Bordetella Symposium, Buenos Aires, Argentina, April 5-8, 2016 – Chair, Immune Responses session; Chair, Pertussis Vaccines Roundtable Discussion session
  • 2014: Chair, ZGM1 MBRS-SCORE Study Section, NIH
  • 2013-present: Editor, Pathogens and Disease
  • 2010: Organizing Committee Chair and Host, 9th International Bordetella Symposium, Baltimore, MD, Sept 30 - Oct 3, 2010
  • 2009-present: Editorial Board Member, Infection and Immunity