Mandy J Mcgeachy
Cornell University, NY·Microbiology & Immunology
The immune system has to be forceful enough to control microbes and restrained enough not to wreck the body's own tissues. A family of immune responses called type-17, named for the signaling molecule IL-17, sits right on that line: it defends the body's barrier surfaces such as skin, gut and lung against bacteria and fungi and helps repair tissue, but when it runs unchecked it drives chronic autoimmune damage, as in multiple sclerosis.
- Fields
Microbiology & Immunology
Medicine & Clinical Research
Biology
- Topics
Th17 cells
interleukin-17
type-17 immunity
- Grants
- 3 known grants, through Apr 2031
What they work on
- Determine how the interaction between PIP5K1a, an enzyme making the nuclear lipid PIP2, and ARS2, an mRNA cap-binding protein, is regulated as Th17 cells differentiate, using primary human T cells and CD28-humanized CD28A210P mice.
- Define how the PIP5K1a-ARS2 axis controls which proteins Th17 cells produce, testing whether this post-transcriptional route governs IL-17 and additional pathogenic effector functions beyond IL-17 itself.
- Test the therapeutic potential of blocking PIP5K1a or deleting ARS2 in effector Th17 cells during inflammatory responses in vivo, including the EAE mouse model of multiple sclerosis and T cells from people with multiple sclerosis responding to the antigen MBP.
- Identify which cells produce the IL-17 that rises as LCMV clone 13 infection becomes chronic in mice, using genetic and antibody-mediated blockade of IL-17 to link that source to T cell activation and exhaustion.
- Test whether fibroblastic reticular cells, the scaffold-forming stromal cells of lymph nodes, are the targets through which IL-17 limits antiviral T cell responses during chronic LCMV infection.
- Determine how excess interferon-gamma drives CD8 and Th1 T cell exhaustion and tissue damage when IL-17 signaling is absent, combining gene expression analysis with antibody blockade in chronically infected mice.
- Map the cellular interactions and communication networks by which IL-17 signaling in lymph node fibroblastic reticular cells promotes B cell activation while moderating inflammatory T cell responses.
- Test how far IL-17-driven stromal cell adaptation observed in lymph nodes applies to stromal cells in other inflamed tissues, specifically skin and lung, using models shared across the program projects.
More about the research
Across three projects the common question is what dials these responses up and down. One project dissects the molecular switches inside the IL-17-producing T cells themselves (Th17 cells). The other two turn the usual story around and ask what IL-17 does to the structural cells of lymph nodes, finding that it can actually restrain inflammation rather than fuel it.
Why it matters
The same type-17 immune pathway drives damage in multiple sclerosis and other chronic inflammatory and fibrotic diseases yet protects barrier tissues from infection, so blocking it wholesale carries costs. Identifying PIP5K1a and ARS2 as controllers of IL-17 production, validated in T cells from people with multiple sclerosis, points to drug targets that could interrupt established autoimmune disease. The lymph node work suggests that IL-17 signaling in stromal cells might be harnessed to make vaccines and antiviral responses more protective with less tissue damage, which matters for people living with chronic viral infections and their long-term cancer risk.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Laurie Harrington
University of Alabama at Birmingham, AL·Microbiology & Immunology
Determine how the transcription factor STAT4 directs the accumulation of Th17 cells, a pro-inflammatory CD4 T cell subset, in inflamed peripheral tissues.
Bumsuk Hahm
University of Missouri-Columbia, MO·Microbiology & Immunology
Determine how influenza virus lowers S1P lyase (SPL), the enzyme that degrades the lipid messenger S1P, and raises sphingosine kinase 2 (SK2), which makes it, and how these shifts speed viral replication in infected cells.
Reza Abdi
University of California-Los Angeles, CA·Microbiology & Immunology
Optimize the stability, binding and body distribution of nanoparticles carrying an antibody against PNAd, a molecule found only on high endothelial venules, in NOD mice that develop type 1 diabetes.
The school
Cornell University: 37 labs on PI Pages, $1.6B a year on research, 537 research doctorates a year.
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