Joji Fujisaki, MD, PhD
- Assistant Professor of Medical Sciences (in Pediatrics)
- Principle Investigator and Director of In Vivo Imaging, Columbia Center for Translational Immunology
The stem cell niche, a specialized microenvironment where stem cells reside, has been extensively studied as a site that regulates stem cell fate or functions. However, immunological attributes of the stem cell niche have remained unexplored. Interestingly, the testis and the placenta, organs for residence of stem cells, were shown in the 1950s to be immunological sanctuaries, termed immune privileged (IP) sites, where stem cells are protected from immune attack. Potent endogenous immune suppressive mechanisms in IP sites enable persistence of transplanted allogeneic or xenogeneic grafts in the absence of immune suppressive therapy, distinguishing IP sites from other tissues. There is little information about whether tissue-committed stem cell niches are IP sites, similar to the testis and the placenta.
Our long-term goal is to test if stem cell niches are IP sites. Our recent study (published in Nature 2011) has demonstrated evidence indicating that, one of the best-characterized stem cell niches, the hematopoietic stem and progenitor cell (HSPC) niche in the bone marrow is an IP site. We demonstrated that the HSPC niche meets the experimental criterion of an IP site, a tissue where transplanted allogeneic (allo-) grafts can survive without immune suppression: we demonstrated surprisingly prolonged persistence of allo-HSPCs in immune competent mice without immune suppression. Moreover, using novel high-resolution in vivo microscopy that enables to visualize the location and the dynamic movement of individual cells in live mice, we demonstrated that FoxP3+ regulatory T cells (Tregs), a T cell subset with immune suppressive potential, preferentially form clusters with HSPCs. Treg depletion results in the loss of allo-HSPCs. The data indicate that Tregs play a critical role in maintaining IP of the HSPC niche that protects HSPCs from immunity.
Our current focus is to unveil the clinical significance of IP of the HSPC niche, especially to malignancies. More specifically, we will test whether the niche shields malignant stem cells that share properties with stem cells. We will further elucidate mechanisms allowing the niche to provide immune protection, using in vivo multiphoton/confocal microscopy to visualize the dynamic movement and interaction of immune cells in the niche in live mice.
2015 Schaefer Scholar Award
2016 ASH Basic Science Junior Faculty Scholar Award
2016 NIH R01 HL129506-01A1 Fujisaki (PI) 07/01/2016-06/30/2021
2018 DOD w81xwh-17-pcrp-ida Fujisaki (PI) 09/01/2018-08/31/2021
2019 NIH R01 HL145154-01A1 Fujisaki (PI) 08/01/2019-06/30/2024
2020 NIH R01 DK121889 Fujisaki (PI) 04/01/2020-03/31/2024
IDENTIFICATION OF UNIQUE NITRIC OXIDE-EXPRESSING HEMATOPOIETIC STEM CELLS AND THEIR SPECIAL VASCULAR NICHE (Federal Gov)
Apr 1 2020 - Jan 31 2024
ROLES AND THERAPEUTIC POTENTIAL OF CD150HIGH NICHE-ASSOCIATED REGULATORY T CELLS IN BONE MARROW INJURY AND ENGRAFTMENT (Federal Gov)
Aug 15 2019 - May 31 2023
IMMUNE PRIVILEGE OF THE HEMATOPOIETIC STEM CELL NICHE IN THE BONE MARROW SHIELDS METASTATIC PROSTATE CANCER FROM IMMUNITY (Federal Gov)
Sep 1 2018 - Aug 31 2021
GLUCAGON-LIKE-PEPTIDE 2 (GLP-2) ANALOGUES AS A NOVEL STRATEGY FOR PREVENTION AND TREATMENT OF GRAFT-VERSUS-HOST DISEASE (Federal Gov)
Aug 15 2019 - Aug 14 2021
IMMUNE PRIVILEGE OF THE HEMATOPOIEITIC STEM CELL NICHE (Federal Gov)
Jul 1 2016 - Mar 31 2021
IMMUNE PRIVILEGE OF THE HEMATOPOIETIC STEM CELL NICHE (Private)
Jul 1 2016 - Jun 30 2019