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Nikki M. Heller, PhD

Dr. Nicola Heller

   Assistant Professor
   Department of Anesthesiology/Critical Care Medicine

   The Johns Hopkins University School of Medicine
   720 Rutland Avenue, Ross 367
   Baltimore, MD 21205
   Phone: (410) 955-1743
   Fax: (410) 614-0083
   nheller@jhmi.edu

 

 

Research Interests

The focus of Dr. Heller's laboratory is the role of IL-4/IL-13 signaling in asthma and allergic disease. She is interested in the basic mechanisms of signaling from the biology of the IL-4/IL-13 receptor, signal transduction, and its regulation to the role of M2 or “alternatively activated” macrophages in the pathogenesis of allergic inflammation. M2 macrophages differentiate from resting macrophages in the presence of IL-4 or IL-13 (and other stimuli) and are involved in mediating Th2-type inflammation, such as immune responses to helminth worms and allergens. Because their phenotype contrasts with “classically activated” or “inflammatory” macrophages, M2 macrophages are considered “anti-inflammatory.” Nevertheless, this term is somewhat of a misnomer. M2 macrophages can promote fibrosis through release of chitinase-like molecules, MMPs/TIMPs, and fibronectin, and they secrete chemokines that recruit inflammatory leukocytes. M2-like macrophages also promote tumor progression. However, when these alternatively activated macrophage responses become chronic or are dysregulated, they can result in pathogenesis as seen in lung fibrosis and tissue remodeling in asthma.

It is becoming increasingly clear that the balance between alternatively activated and classically activated macrophages centrally regulates the pathology of many diseases with an inflammatory basis, including obesity, cardiovascular disease, and cancer. Although alternatively activated and classically activated macrophage phenotypes can be useful designations, it is apparent that macrophages exist along a phenotypic spectrum and may have the capacity to convert their phenotypes. This is an exciting new area of macrophage immunobiology in which Dr. Heller is actively engaged. New projects include elucidating the links between asthma and obesity and how sex and race affect asthma and obesity in humans.  Her emphasis is to utilize a variety of techniques, including molecular and cellular biology, biochemistry, mouse models, cultured cell lines, and human patient samples to uncover cellular and molecular pathways that will be relevant targets for human clinical benefit.  In this regard, Dr. Heller maintains active collaborations with faculty members of the Division of Allergy and Clinical Immunology at the Johns Hopkins Asthma and Allergy Center on the Bayview Campus.

Dr. Heller has mentored more than 15 trainees from high school students to MD/PhD’s during her academic career, and she welcomes motivated and interested students. She is a faculty member of the Immunology Graduate Program at the School of Medicine and also serves on thesis committees for other graduate programs, including Molecular Microbiology and Immunology and Environmental Health Sciences at the Johns Hopkins Bloomberg School of Public Health. Many potential projects in the lab can be tailored to fit the interests of students and fellows with either a short-term or longer-term time-frame.  Students/fellows will gain hands-on experience with a variety of cutting-edge techniques in their own project and be able to observe and/or participating in other ongoing research projects in the lab.  Students/fellows will have the opportunity to interact with Dr. Heller on a daily basis, often at the bench.

Laboratory members

Postdoctoral Fellows
Sarah M. McCormick, PhD (McMaster University, Hamilton, ON)
Aleksander Keselman, PhD (Georgetown University, Washington, DC)
Mireya Becerra Diaz, PhD (National Autonomous University of Mexico, Mexico City)

Undergraduates
Preston White (Johns Hopkins University)

  • Dr. Heller welcomes inquiries from interested postdoctoral fellows, graduate students, and undergraduates about research opportunities in the lab.

Selected Publications

  1. Ford AQ, Heller NM, Stephenson L, Boothby MR, Keegan AD. An atopy-associated polymorphism in the ectodomain of the IL-4R(alpha) chain (V50) regulates the persistence of STAT6 phosphorylation.  J Immunol  183(3):1607-1616, 2009.
    • This paper was highlighted for its clinical relevance on MDLinx.com (Allergy/Immunology section).
  2. Heller NM, Qi X, Junttila IS, Shirey KA, Vogel SN, Paul WE, Keegan AD. Type I IL-4Rs selectively activate IRS-2 to induce target gene expression in macrophages.  Sci Signaling  1(51): ra17, 2008.
    • This paper was the subject of a Perspective Review in the same issue:  
      Wills-Karp M, Finkelman FD. Untangling the complex web of IL-4- and IL-13-mediated signaling pathways.  Sci Signal. 1: pe55, 2008.
    • and a Highlight in the Journal of Allergy and Clinical Immunology:
      Rothenberg ME, Nelson HS. News Beyond Our Pages.  J Allergy Clin Immunol  123: 517, 2009.
  3. LaPorte SL, Juo ZS, Vaclavikova J, Colf LA, Qi X, Heller NM, Keegan AD, Garcia KC. Molecular and structural basis of cytokine receptor pleiotropy in the interleukin-4/13 system. Cell  132:259-272, 2008.
    • We provide the functional data, i.e. signal transduction analyses, to complement the structural data from the Garcia laboratory.
    • This paper was the basis of the Cover art and a Review in that issue: Zdanov A, Wlodawer A. A new look at cytokine signaling. Cell 132: 179, 2008.
    • and a Research Highlight in Nature Reviews Immunology: Minton K. Allergy and Asthma: What 'drives' IL-4 versus IL-13 signalling? Nat Rev Immunol 8:166, 2008.
  4. Heller NM, Matsukura S, Georas SN, Boothby MR, Rothman PB, Stellato C, Schleimer RP.  Interferon-γ inhibits STAT6 signal transduction and gene expression in human airway epithelial cells.  Am J Respir Cell Mol Biol  31(5):573-582, 2004.
  5. Heller NM, Matsukura S, Georas SN, Boothby MR, Stellato C, Schleimer RP. Assessment of STAT6 as a target of glucocorticoid action in human airway epithelial cells.  Clin Exp Allergy 34(11):1690-1700, 2004.
  6. Fan J, Heller NM, Gorospe M, Atasoy U, Stellato C. The role of post-transcriptional regulation in chemokine gene expression in inflammation and allergy.  Eur Respir J  26(5): 933-47, 2005.
  7. Gao PS, Heller NM, Walker W, Chen CH, Plunkett B, Roberts MH, Schleimer RP, Hopkin JM, Huang SK. Variation in dinucleotide (GT) repeat sequence in the first exon of the STAT6 gene is associated with atopic asthma and differentially regulates the promoter activity in vitro.  J Med Genet  41(7): 535-9, 2004.
  8. Kurosawa S, Myers AC, Chen L, Wang S, Ni J, Plitt JR, Heller NM, Bochner BS, Schleimer RP. Expression of the costimulatory molecule B7-H2 (inducible costimulator ligand) by human airway epithelial cells.  Am J Respir Cell Mol Biol 28(5): 563-73, 2003.
  9. Hubbard WC, Blum AE, Bickel CA, Heller NM, Schleimer RP. Detection and quantitation of fatty acid acyl conjugates of triamcinolone acetonide via gas chromatography-electron-capture negative-ion mass spectrometry.  Anal Biochem 322(2):243-50, 2003.