Heather H. Pua, Ph.D., M.D.

Assistant Professor

Faculty Appointments
Assistant Professor of Pathology, Microbiology and Immunology
M.D., Duke University, Durham, North CarolinaPh.D., Immunology, Duke University, Durham, North CarolinaB.S., Biology, Duke University, Durham, North Carolina
Research Description
In the Pua lab, we investigate the role of non-coding RNAs (especially miRNAs) in regulating immune responses and tissue inflammation. We are particularly interested in inflammatory disease in the lung and have identified two miRNAs that limit allergic lung inflammation in a mouse model of asthma. Ongoing studies in the lab seek to answer the following questions.
• Which miRNAs are critical for shaping effector cell programs in immune cells, particularly T lymphocytes?
• What is the mechanism by which miRNAs exert their effects? How do we identify critical miRNA:mRNA target interactions?
• Can miRNA-directed pathway discovery be used to identify novel genes and potential therapeutic targets, particularly in type2 inflammation?
• What is the role of extracellular RNAs in lung inflammation? What are the forms and cellular targets of these extracellular RNA species? What are their functions?

Our long-term goal is to define miRNA controlled regulatory networks in immune responses, determine their impact on pathologic inflammation and leverage our findings for the development of novel diagnostic and therapeutic approaches in inflammatory diseases. We use a broad range of techniques and tools to achieve these goals including classic immunology, molecular biology, cell culture, mouse models, and high-throughput sequencing.
Research Keywords
immune, inflammation, lung, miRNA, exRNA (extracellular RNA), extracellular vesicles, allergy, asthma, Th2
Singh PB, Pua HH, Happ HC, Schneider C, von Moltke J, Locksley RM, Baumjohann D, Ansel KM. MicroRNA regulation of type 2 innate lymphoid cell homeostasis and function in allergic inflammation. J. Exp. Med [print-electronic]. 2017 Dec 12/4/2017; 214(12): 3627-43. PMID: 29122948, PMCID: PMC5716040, PII: jem.20170545, DOI: 10.1084/jem.20170545, ISSN: 1540-9538.

Singh PB, Pua HH, Happ HC, Schneider C, von Moltke J, Locksley RM, Baumjohann D, Ansel KM. MicroRNA regulation of type 2 innate lymphoid cell homeostasis and function in allergic inflammation. J. Exp. Med [print-electronic]. 2017 Dec 12/4/2017; 214(12): 3627-43. PMID: 29122948, PMCID: PMC5716040, PII: jem.20170545, DOI: 10.1084/jem.20170545, ISSN: 1540-9538.

Slavotinek A, Pua H, Hodoglugil U, Abadie J, Shieh J, Van Ziffle J, Kvale M, Lee H, Kwok PY, Risch N, Sabbadini M. Pierpont syndrome associated with the p.Tyr446Cys missense mutation in TBL1XR1. Eur J Med Genet [print-electronic]. 2017 Oct; 60(10): 504-8. PMID: 28687524, PII: S1769-7212(17)30245-8, DOI: 10.1016/j.ejmg.2017.07.003, ISSN: 1878-0849.

Montoya MM, Maul J, Singh PB, Pua HH, Dahlström F, Wu N, Huang X, Ansel KM, Baumjohann D. A Distinct Inhibitory Function for miR-18a in Th17 Cell Differentiation. J. Immunol [print-electronic]. 2017 Jul 7/15/2017; 199(2): 559-69. PMID: 28607111, PMCID: PMC5508756, PII: jimmunol.1700170, DOI: 10.4049/jimmunol.1700170, ISSN: 1550-6606.

Winger BA, Foy E, Sud SR, MacKenzie JD, Pua HH, Lau AH, Heyman MB, Laszik Z, Tureen J. Mycobacterium bovis Enterocolitis in an Immunocompromised Host. J. Pediatr. Gastroenterol. Nutr. 2016 Jul; 63(1): e17-9. PMID: 26020480, PMCID: PMC4449326, DOI: 10.1097/MPG.0000000000000528, ISSN: 1536-4801.

Pua HH, Steiner DF, Patel S, Gonzalez JR, Ortiz-Carpena JF, Kageyama R, Chiou NT, Gallman A, de Kouchkovsky D, Jeker LT, McManus MT, Erle DJ, Ansel KM. MicroRNAs 24 and 27 Suppress Allergic Inflammation and Target a Network of Regulators of T Helper 2 Cell-Associated Cytokine Production. Immunity [print-electronic]. 2016 Apr 4/19/2016; 44(4): 821-32. PMID: 26850657, PMCID: PMC4838571, PII: S1074-7613(16)00004-2, DOI: 10.1016/j.immuni.2016.01.003, ISSN: 1097-4180.

Pua HH, Ansel KM. MicroRNA regulation of allergic inflammation and asthma. Curr. Opin. Immunol [print-electronic]. 2015 Oct; 36: 101-8. PMID: 26253882, PMCID: PMC4593751, PII: S0952-7915(15)00103-X, DOI: 10.1016/j.coi.2015.07.006, ISSN: 1879-0372.

Simpson LJ, Patel S, Bhakta NR, Choy DF, Brightbill HD, Ren X, Wang Y, Pua HH, Baumjohann D, Montoya MM, Panduro M, Remedios KA, Huang X, Fahy JV, Arron JR, Woodruff PG, Ansel KM. A microRNA upregulated in asthma airway T cells promotes TH2 cytokine production. Nat. Immunol [print-electronic]. 2014 Dec; 15(12): 1162-70. PMID: 25362490, PMCID: PMC4233009, PII: ni.3026, DOI: 10.1038/ni.3026, ISSN: 1529-2916.

Gordy C, Liang J, Pua H, He YW. C-FLIP protects eosinophils from TNF-a-mediated cell death in vivo. PLoS ONE. 2014; 9(10): e107724. PMID: 25333625, PMCID: PMC4204828, PII: PONE-D-14-27304, DOI: 10.1371/journal.pone.0107724, ISSN: 1932-6203.

Pua HH, Krishnamurthi S, Farrell J, Margeta M, Ursell PC, Powers M, Slavotinek AM, Jeng LJ. Novel interstitial 2.6 Mb deletion on 9q21 associated with multiple congenital anomalies. Am. J. Med. Genet. A. 2014 Jan; 164A(1): 237-42. PMID: 24501764, ISSN: 1552-4833.

Jia W, Pua HH, Li QJ, He YW. Autophagy regulates endoplasmic reticulum homeostasis and calcium mobilization in T lymphocytes. J. Immunol [print-electronic]. 2011 Feb 2/1/2011; 186(3): 1564-74. PMID: 21191072, PMCID: PMC3285458, PII: jimmunol.1001822, DOI: 10.4049/jimmunol.1001822, ISSN: 1550-6606.

Gordy C, Pua H, Sempowski GD, He YW. Regulation of steady-state neutrophil homeostasis by macrophages. Blood [print-electronic]. 2011 Jan 1/13/2011; 117(2): 618-29. PMID: 20980680, PMCID: PMC3031484, PII: blood-2010-01-265959, DOI: 10.1182/blood-2010-01-265959, ISSN: 1528-0020.

Pua HH, He YW. Mitophagy in the little lymphocytes: an essential role for autophagy in mitochondrial clearance in T lymphocytes. Autophagy [print-electronic]. 2009 Jul; 5(5): 745-6. PMID: 19398889, PII: 8702, ISSN: 1554-8635.

Pua HH, Guo J, Komatsu M, He YW. Autophagy is essential for mitochondrial clearance in mature T lymphocytes. J. Immunol. 2009 Apr 4/1/2009; 182(7): 4046-55. PMID: 19299702, PII: 182/7/4046, DOI: 10.4049/jimmunol.0801143, ISSN: 1550-6606.

Pua HH, He YW. Autophagy and lymphocyte homeostasis. Curr. Top. Microbiol. Immunol. 2009; 335: 85-105. PMID: 19802561, DOI: 10.1007/978-3-642-00302-8_4, ISSN: 0070-217X.

Miller BC, Zhao Z, Stephenson LM, Cadwell K, Pua HH, Lee HK, Mizushima NN, Iwasaki A, He YW, Swat W, Virgin HW. The autophagy gene ATG5 plays an essential role in B lymphocyte development. Autophagy [print-electronic]. 2008 Apr; 4(3): 309-14. PMID: 18188005, PII: 5474, ISSN: 1554-8635.

Pua HH, He YW. Maintaining T lymphocyte homeostasis: another duty of autophagy. Autophagy [print-electronic]. 2007 May; 3(3): 266-7. PMID: 17329964, PII: 3908, ISSN: 1554-8627.

Pua HH, Dzhagalov I, Chuck M, Mizushima N, He YW. A critical role for the autophagy gene Atg5 in T cell survival and proliferation. J. Exp. Med [print-electronic]. 2007 Jan 1/22/2007; 204(1): 25-31. PMID: 17190837, PMCID: PMC2118420, PII: jem.20061303, DOI: 10.1084/jem.20061303, ISSN: 0022-1007.