Dr. Nikki Heller is a researcher and associate professor of anesthesiology and critical care medicine at the Johns Hopkins University School of Medicine. The focus of Dr. Heller’s laboratory is the role of macrophages in promoting and resolving disease, particularly in lung diseases, such as asthma and acute respiratory distress syndrome (ARDS). Improper regulation of macrophage polarization can promote pathogenesis, exemplified by the abundance of M2 or “alternatively activated” macrophages during allergic inflammation of the lung. Dr. Heller is interested in how IL-4 or IL-13 (and other stimuli) induce differentiation of resting macrophages into the M2 phenotype. Her research program focuses on the basic molecular mechanisms of signaling from the biology of the IL-4/IL-13 receptor, signal transduction, and its regulation.
Current research projects include determining how sex and sex hormones affect macrophage polarization in asthma. New projects are investigating novel interventions (peptide inhibitors) to block macrophage differentiation in asthma and utilizing nanoparticle-treated monocytes as cellular immunotherapy for ARDS. 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. She has a joint appointment in this Division. Dr. Heller is the Director of the ACCM Flow Cytometry Core.
Dr. Heller has mentored many 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 (MMI) and Environmental Health and Engineering (EHE) 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.
Aleksander Keselman, PhD (Georgetown University, Washington, DC)
Mireya Becerra Diaz, PhD (National Autonomous University of Mexico, Mexico City, Mexico)
Deepa Walia, Ph.D. (Jamia Hamdard University, Delhi, India)
Dr. Heller welcomes inquiries from interested postdoctoral fellows, graduate students, and undergraduates about research opportunities in the lab.
Selected Publications (Trainees are underlined)
- Warren KJ, Fang XJ, Gowda NM, Thompson JJ, Heller, NM. The TORC1-Activated Proteins, P70S6K and GRB10, Regulate IL-4 Signaling and M2 Macrophage Polarization by Modulating Phosphorylation of Insulin Receptor Substrate-2. J Biol Chem. 2016 Oct 14. pii: jbc.M116.756791. [Epub ahead of print]. PMID: 27742835.
- McCormick SM, Gowda N, Fang JX, Heller NM. Suppressor of Cytokine Signaling (SOCS)1 Regulates IL-4-Activated Insulin Receptor Substrate (IRS)-2 Tyrosine Phosphorylation in Monocytes and Macrophages via the Proteasome. J Biol Chem. 2016 Aug 9. pii: jbc.M116.746164. [Epub ahead of print]. PMID: 27507812.
- D’Alessio FR, Craig JM, Singer BD, Files DC, Mock JR, Garibaldi BT, Fallica J, Tripathi A, Mandke P, Gans JH, Limjunyawong N, Sidhaye R, Heller NM, Mitzner W, King LS, Aggarwal NR. Enhanced Resolution of Experimental ARDS through IL-4-Mediated Lung Macrophage Reprogramming. Am J Physiol Lung Cell Mol Physiol., 2016 Apr 15; 310(8): L733-46. PMCID: PMC4836113.
- Johns RA, Takimoto E, Meuchel LW, Elsaigh E, Zhang A, Heller NM, Semenza GL, Yamaji-Kegan K. Hypoxia-Inducible Factor 1α Is a Critical Downstream Mediator for Hypoxia-Induced Mitogenic Factor (FIZZ1/RELMα)-Induced Pulmonary Hypertension. Arterioscler Thromb Vasc Biol. 2016 Jan; 36(1):134-44. PMID: 26586659.
- Keselman A, Heller N. Estrogen Signaling Modulates Allergic Inflammation and Contributes to Sex Differences in Asthma. Front Immunol. 2015 Nov 16; 6:568. PMCID: PMC4644929 Invited Review in a Research Topic Section focused on enhanced immune reactivity in females.
- McCormick SM, Heller NM. Regulation of Macrophage, Dendritic Cell, and Microglial Phenotype and Function by the SOCS Proteins. Front Immunol. 2015 Oct 27;6:549. PMCID: PMC4621458.
- Berga-Bolaños R, Sharma A, Steinke FC, Pyaram K, Kim YH, Sultana DA, Fang JX, Chang CH, Xue HH, Heller NM, Sen JM. β-Catenin is required for the differentiation of iNKT2 and iNKT17 cells that augment IL-25-dependent lung inflammation. BMC Immunol. 2015 Oct 19; 16:62. doi: 10.1186/s12865-015-0121-0. PMID: PMC 4615569.
- McCormick SM, Heller NM. Commentary: IL-4 and IL-13 Receptors and Signaling. Cytokine. 2015 Sep; 75(1):38-50. PMCID: PMC4546937 Invited Review in a Special Section of this Issue focused on the IL-4/IL-13 Family.
- 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).
- 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.
- 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.
- 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.