Hannah Dorando
Program: Molecular Genetics and Genomics
Current advisor: Jacqueline Elise Payton, MD, PhD
Undergraduate university: University of Michigan-Ann Arbor
Research summary
Inhibitory immune receptors are critical for maintaining immune homeostasis; they modulate host response to infection while limiting autoimmunity and immunopathology. Two members of this group, leukocyte-associated immunoglobulin-like receptors 1 and 2 (LAIR1 and LAIR2), are elevated in Cutaneous T-cell Lymphoma (CTCL) patients susceptible to S. aureus skin and soft tissue infection. We therefore predicted that expression of these receptors would be altered in response to inflammatory stimuli. We found that LAIR1 is regulated in contrasting ways in human and mouse: in humans, LAIR1 increases with LPS and decreases with IFNg, while in mouse, LAIR1 increases with IFNg and decreases with LPS. We additionally used luciferase reporter assays and novel integrative bioinformatics techniques to identify candidate regulatory elements and distinct sets of transcription factors involved in regulation of human and mouse LAIR1 and LAIR2. The expression changes we observed in LAIR1 in response to inflammatory stimuli associated with bacterial infection led us to hypothesize that LAIR1 would play a critical role in the host immune response to S. aureus infection. Therefore, we tested loss of LAIR1 in mice in a model of skin and soft tissue infection. LAIR1 loss resulted in formation of much larger abscesses and inflammatory tissue damage, with no difference in infection control. We additionally identified similarities in cytokine responses between LAIR1 loss and CTCL skin lesions that may link our findings in mice to immune defects observed in CTCL. Together, these data demonstrate a novel role for LAIR1 in bacterial infection and represent an opportunity for therapeutic intervention in CTCL.
Graduate publications
Cubitt CC, Wong P, Dorando HK, Foltz JA, Tran J, Marsala L, Marin ND, Foster M, Schappe T, Fatima H, Becker-Hapak M, Zhou AY, Hwang K, Jacobs MT, Russler-Germain DA, Mace EM, Berrien-Elliott MM, Payton JE, Fehniger TA. 2024 Induced CD8α identifies human NK cells with enhanced proliferative fitness and modulates NK cell activation. J Clin Invest, 134(15):e173602.
Dorando HK, Mutic EC, Li JY, Perrin EP, Wurtz MK, Quinn CC, Payton JE. 2024 LPS and type I and II interferons have opposing effects on epigenetic regulation of LAIR1 expression in mouse and human macrophages. J Leukoc Biol, 115(3):547-64.
Pei J, Beri NR, Zou AJ, Hubel P, Dorando HK, Bergant V, Andrews RD, Pan J, Andrews JM, Sheehan KCF, Pichlmair A, Amarasinghe GK, Brody SL, Payton JE, Leung DW. 2021 Nuclear-localized human respiratory syncytial virus NS1 protein modulates host gene transcription. Cell Rep, 37(2):109803.
Pyfrom SC, Quinn CC, Dorando HK, Luo H, Payton JE. 2020 BCALM (AC099524.1) Is a Human B Lymphocyte-Specific Long Noncoding RNA That Modulates B Cell Receptor-Mediated Calcium Signaling. J Immunol, 205(3):595-607.