Kai Mesa, PhD

PhD Genetics, Yale University, 2017

In my PhD, I focused on understanding how adult stem cells balanced cell death, differentiation, and division to maintain proper tissue regeneration. A major challenge in addressing this question has been the inability to study cells in their native tissue environment. I helped to overcome this limitation through the development of a two- photon microscopy-based imaging approach to track the skin stem cell populations in live mice. By these means, I uncovered how the local tissue niche extrinsically coordinates stem cell fate, including stem cells acting as the phagocytes to clear apoptotic neighbors, and that epidermal stem cell differentiation triggers neighboring stem cells to rapidly and accurately replenish the stem cell pool. In my postdoctoral studies, I joined the lab of Dan Littman to examine how the principle of tissue niches shapes immune cell fates over the lifetime of the organism. Tracking the 3D tissue distribution of skin macrophages in the same mice over several months, I found resident macrophages were lost with age in a niche-specific manner. Moreover, time-lapse recordings revealed that loss of macrophages from the capillary niche led to impaired resolution of microvasculature clots. However, this aging defect was reversible through microenvironmental changes, including local tissue damage, to recruit new CAMs from the blood and improve capillary resilience to future ischemic events. Looking forward, I propose to understand how a spectrum of inputs, from local cellular interactions to tissue-wide cues, synergistically control the activity of immune cells in a tissue. My long-term goals are to build a comprehensive framework of tissue immunity laws that link the needs of a tissue to the behaviors of its immune cells and understand how these laws shape tissue regeneration and aging.

 
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Publications:

  1. Mesa KR#, O'Connor KA, Ng C, Salvatore S, Littman DR#. Niche-specific macrophage loss promotes skin capillary aging. bioRxiv. 2023 2023.08.25.554832; doi: https//doi.org/10.1101/2023.08.25.554832. (#co-corresponding authors)

  2. Cockburn K, Annusver K, Gonzalez DG, Ganesan S, May DP, Mesa KR, Kawaguchi K, Kasper M, Greco V. Gradual differentiation uncoupled from cell cycle exit generates heterogeneity in the epidermal stem cell layer. Nat Cell Biol. 2022 Dec;24(12):1692-1700. doi: 10.1038/s41556-022-01021-8. Epub 2022 Nov 10. PubMed PMID: 36357619; PubMed Central PMCID: PMC9729105.

  3. Kedmi R, Najar TA, Mesa KR, Grayson A, Kroehling L, Hao Y, Hao S, Pokrovskii M, Xu M, Talbot J, Wang J, Germino J, Lareau CA, Satpathy AT, Anderson MS, Laufer TM, Aifantis I, Bartleson JM, Allen PM, Paidassi H, Gardner JM, Stoeckius M, Littman DR. A RORγt+ cell instructs gut microbiota-specific Treg cell differentiation. Nature. 2022 Oct;610(7933):737-743. doi: 10.1038/s41586-022-05089-y. Epub 2022 Sep 7. PubMed PMID: 36071167; PubMed Central PMCID: PMC9908423.

  4. Xu H, Wu L, Nguyen HH, Mesa KR, Raghavan V, Episkopou V, Littman DR. Arkadia-SKI/SnoN signaling differentially regulates TGF-β-induced iTreg and Th17 cell differentiation. J Exp Med. 2021 Nov 1;218(11). doi: 10.1084/jem.20210777. Epub 2021 Sep 2. PubMed PMID: 34473197; PubMed Central PMCID: PMC8421263.

  5. Ng C, Aichinger M, Nguyen T, Au C, Najar T, Wu L, Mesa KR, Liao W, Quivy JP, Hubert B, Almouzni G, Zuber J, Littman DR. The histone chaperone CAF-1 cooperates with the DNA methyltransferases to maintain Cd4 silencing in cytotoxic T cells. Genes Dev. 2019 Jun 1;33(11-12):669-683. doi: 10.1101/gad.322024.118. Epub 2019 Apr 11. PubMed PMID: 30975723; PubMed Central PMCID: PMC6546056.

  6. Mesa KR*, Kawaguchi K*, Cockburn K*, Gonzalez D, Boucher J, Xin T, Klein AM, Greco V. Homeostatic epidermal stem cell self-renewal is driven by local differentiation. Cell Stem Cell. 2018 Nov 1;23(5):677-686.e4. doi: 10.1016/j.stem.2018.09.005. Epub 2018 Sep 27. PubMed PMID: 30269903; PubMed Central PMCID: PMC6214709. (* equal contribution)

  7. Park S, Gonzalez DG, Guirao B, Boucher JD, Cockburn K, Marsh ED, Mesa KR, Brown S, Rompolas P, Haberman AM, Bellaïche Y, Greco V. Tissue-scale coordination of cellular behaviour promotes epidermal wound repair in live mice. Nat Cell Biol. 2017 Mar 1;19(2):155-163. doi: 10.1038/ncb3472. [Epub ahead of print] PubMed PMID: 28248302; PubMed Central PMCID: PMC5581297.

  8. Rompolas P*, Mesa KR*, Kawaguchi K, Park S, Gonzalez D, Brown S, Boucher J, Klein AM, Greco V. Spatiotemporal coordination of stem cell commitment during epidermal homeostasis. Science. 2016 Jun 17;352(6292):1471-4. doi: 10.1126/science.aaf7012. Epub 2016 May 26. PubMed PMID: 27229141; PubMed Central PMCID: PMC4958018. (* equal contribution)

  9. Pineda CM, Park S, Mesa KR, Wolfel M, Gonzalez DG, Haberman AM, Rompolas P, Greco V. Intravital imaging of hair follicle regeneration in the mouse. Nat Protoc. 2015 Jul;10(7):1116-30. doi: 10.1038/nprot.2015.070. Epub 2015 Jun 25. PubMed PMID: 26110716; PubMed Central PMCID: PMC4632978.

  10. Mesa KR, Rompolas P, Greco V. The dynamic duo: niche/stem cell interdependency. Stem Cell Reports. 2015 Jun 9;4(6):961-6. doi: 10.1016/j.stemcr.2015.05.001. Epub 2015 May 28. Review. PubMed PMID: 26028534; PubMed Central PMCID: PMC4471832.

  11. Mesa KR, Rompolas P, Zito G, Myung P, Sun TY, Brown S, Gonzalez DG, Blagoev KB, Haberman AM, Greco V. Niche-induced cell death and epithelial phagocytosis regulate hair follicle stem cell pool. Nature. 2015 Jun 4;522(7554):94-7. doi: 10.1038/nature14306. Epub 2015 Apr 6. PubMed PMID: 25849774; PubMed Central PMCID: PMC4457634.

  12. Rompolas P, Mesa KR, Greco V. Spatial organization within a niche as a determinant of stem-cell fate. Nature. 2013 Oct 24;502(7472):513-8. doi: 10.1038/nature12602. Epub 2013 Oct 6. PubMed PMID: 24097351; PubMed Central PMCID: PMC3895444.

  13. Mesa KR, Greco V. Linking morphogen and chromatin in the hair follicle. Dev Cell. 2013 Apr 29;25(2):113-4. doi: 10.1016/j.devcel.2013.04.009. PubMed PMID: 23639438; PubMed Central PMCID: PMC3666555.

  14. Prakash A, Mesa KR, Wilhelmsen K, Xu F, Dodd-o JM, Hellman J. Alveolar macrophages and Toll-like receptor 4 mediate ventilated lung ischemia reperfusion injury in mice. Anesthesiology. 2012 Oct;117(4):822-35. doi: 10.1097/ALN.0b013e31826a4ae3. PubMed PMID: 22890118; PubMed Central PMCID: PMC3477877.

  15. Wilhelmsen K, Mesa KR, Lucero J, Xu F, Hellman J. ERK5 protein promotes, whereas MEK1 protein differentially regulates, the Toll-like receptor 2 protein-dependent activation of human endothelial cells and monocytes. J Biol Chem. 2012 Aug 3;287(32):26478-94. doi: 10.1074/jbc.M112.359489. Epub 2012 Jun 15. PubMed PMID: 22707717; PubMed Central PMCID: PMC3410990.

  16. Wilhelmsen K, Mesa KR, Prakash A, Xu F, Hellman J. Activation of endothelial TLR2 by bacterial lipoprotein upregulates proteins specific for the neutrophil response. Innate Immun. 2012 Aug;18(4):602-16. doi: 10.1177/1753425911429336. Epub 2011 Dec 20. PubMed PMID: 22186927; PubMed Central PMCID: PMC3444510.