Two to Tango: Dialog between Immunity and Stem Cells in Health and Disease.

Stem cells regenerate tissues in homeostasis and under stress. By taking cues from their microenvironment or “niche,” they smoothly transition between these states. Immune cells have surfaced as prominent members of stem cell niches across the body. Here, we draw parallels between different stem cell niches to explore the context-specific interactions that stem cells have with tissue-resident and recruited immune cells. We also highlight stem cells’ innate ability to sense and respond to stress and the enduring memory that forms from such encounters. This fascinating crosstalk holds great promise for novel therapies in inflammatory diseases and regenerative medicine.

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Wound, heal thyself

Naik S. Nature Medicine. 24, 1311–1312 (2018)

An in vivo cellular reprogramming strategy to generate epithelial cells from wound mesenchymal cells promotes healing and provides a new avenue for the treatment of nonhealing wounds.

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The healing power of painful memories

Naik, S. The healing power of painful memories. Science 359(6380): 1113 March 2018

Our body’s epithelia are barriers that interface with the terrestrial environment and routinely experience inflammation. Although a vast majority of these inflammatory reactions resolve, they imprint the tissue with a memory. Cells of the immune system are traditionally thought to be the bearers of this memory, allowing them to react faster to subsequent inflammatory pressures (1, 2). Yet, barrier tissues are composites of epithelial, mesenchymal, nervous, vascular, and immunological networks working in unison to sustain optimal function in health and disease. The question of whether tissue-resident cells, distinct from the immune system, are entrained in response to a perturbation remains to be addressed.

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Inflammatory memory sensitizes skin epithelial stem cells to tissue damage.

Naik S*, Larsen SB*, Gomez N, Alaverdyan K, Sendoel A, Polak L, Kulukian A, Chai S and Fuchs E. Inflammatory memory sensitizes skin epithelial stem cells to tissue damage. *Equal author contribution. Corresponding author. Nature. 550(7677): 475-480 Oct 2017

Here we report that acute inflammation trains epithelial stem cells to respond faster to subsequent stressors. This work is the first to identify inflammatory memory in a non-immune cells and has significant implications for our understanding of inflammatory diseases and cancer.

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Translation from Unconventional 5’ Start Sites Drives Tumor Initiation

Sendoel A, Dunn J, Gonzales E, Naik S, Gomez N, Hurwitz B, Levorse J, Dill BD, Schramek S, Molina H, Weissman J and Fuchs E. Translation from Unconventional 5’ Start Sites Drives Tumor Initiation. Nature. 541(7638):494-499 Jan, 2017

We are just beginning to understand how translational control affects tumour initiation and malignancy. Here we use an epidermis-specific, in vivo ribosome profiling strategy to investigate the translational landscape during the transition from normal homeostasis to malignancy.

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