Research Summary

The Halkias lab studies the cellular and molecular signals that drive human immune development with a focus on understanding how early life host-microbe interactions influence adaptive immune responses to perinatal inflammatory disorders such as preterm birth. Early life is a critical time in immune development marked by rapid exposure to environmental antigens. Microbial colonization of mucosal tissues plays a key role in the development and education of the host immune system and influences the susceptibility to immune-mediated disease later in life. Infants born preterm are predisposed to prenatal immune activation and inflammation, critical risk factors underlying much of the pathophysiology in this vulnerable population. In utero infection is the most frequently identified cause of spontaneous preterm birth and fetal T cell activation is associated with severe neonatal disease, yet the signals that drive the activation, differentiation, and regulation of fetal adaptive immunity are not known. We utilize immune and microbial transcriptomics, high parameter flow and mass cytometry, and humanized mouse models to understand the cellular and molecular interactions that instruct human immune cells during this critical window of development.

Research Funding

  • June 1, 2019 - April 1, 2023 - Harnessing immune regulatory mechanisms to target the fetal inflammatory response in preterm birth , PI . Sponsor: Burroughs Wellcome Fund, Sponsor Award ID: 1019828
  • July 1, 2017 - June 30, 2022 - Intrauterine sex steroids and human fetal T cell development , Principal Investigator . Sponsor: NIH, Sponsor Award ID: K08AI128007
  • July 1, 2017 - June 30, 2022 - Intrauterine sex steroids and fetal T cell development. , PI . Sponsor: NIH/NIAID, Sponsor Award ID: 5 K08 AI128007 02

Education

  • University of Pennsylvania, Philadelphia, B.A., 1995, Biology with Honors
  • Albert Einstein College of Medicine, M.D., 2001, Medicine
  • Children’s Hospital Los Angeles, Intern, 2002, Pediatrics
  • Children’s Hospital Los Angeles, Resident, 2004, Pediatrics
  • Children’s Hospital Los Angeles/University of Southern California, Fellow, 2007, Neonatal-Perinatal Medicine
  • University of California at Berkeley, Post-doctoral fellow, 2013, Immunology  

Honors & Awards

  • 2001
    Research Project Award, International Health Medical Education Consortium
  • 2007
    Carmel Scholar Award, Western Society for Pediatric Research
  • 2007
    Henry Christian Award, American Federation for Medical Research
     

Selected Publications

  1. Rackaityte E, Halkias J, Fukui EM, Mendoza VF, Hayzelden C, Crawford ED, Fujimura KE, Burt TD, Lynch SV. Corroborating evidence refutes batch effect as explanation for fetal bacteria. Microbiome. 2021 01 12; 9(1):10.  View on PubMed
  2. Rackaityte E, Halkias J. Mechanisms of Fetal T Cell Tolerance and Immune Regulation. Front Immunol. 2020; 11:588.  View on PubMed
  3. Rackaityte E, Halkias J, Fukui EM, Mendoza VF, Hayzelden C, Crawford ED, Fujimura KE, Burt TD, Lynch SV. Viable bacterial colonization is highly limited in the human intestine in utero. Nat Med. 2020 04; 26(4):599-607.  View on PubMed
  4. Halkias J, Rackaityte E, Hillman SL, Aran D, Mendoza VF, Marshall LR, MacKenzie TC, Burt TD. CD161 contributes to prenatal immune suppression of IFNγ-producing PLZF+ T cells. J Clin Invest. 2019 05 30; 129(9):3562-3577.  View on PubMed
  5. Ross JO, Melichar HJ, Halkias J, Robey EA. Studying T Cell Development in Thymic Slices. Methods Mol Biol. 2016; 1323:131-40.  View on PubMed
  6. Halkias J, Yen B, Taylor KT, Reinhartz O, Winoto A, Robey EA, Melichar HJ. Conserved and divergent aspects of human T-cell development and migration in humanized mice. Immunol Cell Biol. 2015 Sep; 93(8):716-26.  View on PubMed
  7. Halkias J, Melichar HJ, Taylor KT, Robey EA. Tracking migration during human T cell development. Cell Mol Life Sci. 2014 Aug; 71(16):3101-17.  View on PubMed
  8. Coombes JL, Charsar BA, Han SJ, Halkias J, Chan SW, Koshy AA, Striepen B, Robey EA. Motile invaded neutrophils in the small intestine of Toxoplasma gondii-infected mice reveal a potential mechanism for parasite spread. Proc Natl Acad Sci U S A. 2013 May 21; 110(21):E1913-22.  View on PubMed
  9. Halkias J, Melichar HJ, Taylor KT, Ross JO, Yen B, Cooper SB, Winoto A, Robey EA. Opposing chemokine gradients control human thymocyte migration in situ. J Clin Invest. 2013 May; 123(5):2131-42.  View on PubMed
  10. Podd BS, Thoits J, Whitley N, Cheng HY, Kudla KL, Taniguchi H, Halkias J, Goth K, Camerini V. T cells in cryptopatch aggregates share TCR gamma variable region junctional sequences with gamma delta T cells in the small intestinal epithelium of mice. J Immunol. 2006 Jun 01; 176(11):6532-42.  View on PubMed

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