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Collaborative Studies on Lung Stem Cell Biology and Cell Based Therapy
 
 


Judith Shizuru, MD, Ph.D.
Stanford University Medical Center
Stanford School of Medicine

Dr. Judith Shizuru is an Associate Professor of Medicine, Blood and Marrow Transplantation Division and in the Division of Blood and Marrow Transplantation at Stanford University Medical Center.

She received her medical degree and Ph.D. from Stanford University School of Medicine.

Along with her work at Stanford University Medical Center, she is also:

  • Associate Professor, Stanford School of Medicine
  • Member, Stanford Cancer Center

Email Dr. Shizuru

Consortium Research Title: Isolation and Transplantation of Candidate Alveolar Progenitor Cells.

Consortium Research Description:

The alveoli of the lung are composed of a delicate web of endothelial and epithelial cells, which interface between the environment and the blood stream. As part of maintenance and response to injury, these structures must undergo constant repair. Repair and maintenance of adult alveoli is not well understood. The hypothesis tested in this application is that endothelial and epithelial alveolar progenitor cells can be identified in dissociated and young adult lungs by a composite phenotype of surface markers, and this phenotype can be used to isolate these cells. We further hypothesize that these cells, when infused into recipients that have undergone lung injury, will participate and augment alveolar repair. Our preliminary data suggest that using such an approach, we have isolated a population of lung cells, that when infused into lethally irradiated recipients by intravenous injection, appears to be enriched for endothelial progenitor cell (EPC) activity demonstrated by participation in regeneration of alveolar capillaries. Our observation that donor cells can participate in the generation of endothelial clusters in lung, is a novel finding. We have additionally determined that introduction of dissociated lung populations by direct intratracheal route results in successful dispersion of the cells throughout the lung of recipients and observed cells in alveoli which appear to be of epithelial origin. The research proposed in this proposal will aim to further purify and characterize the putative alveolar EPCs, and determine if alveolar epithelial progenitor cells (AepPc) can be similarly isolated and participate in lung repair.

 

Shizuru Lab Information: 
Stanford University
340 Panama Street
Stanford CA 94305-6203
919-668-7762
(650) 725-8950

The research interests are to understand the cellular and molecular basis of resistance to engraftment of transplanted allogeneic bone marrow (BM) cells and to understand the way in which BM grafts modify immune responses. This research complements our interest in clinical BM transplantation and aspects of these studies are aimed at solving some of the major problems of BM transplantation which include graft-vs-host disease and BM engraftment failure. Conventional BM transplantation involves the transfer of heterogeneous populations of cells composed of rare hematopoietic stem cells (HSCs) and differentiated blood cell types. To study these issues our approach has been to transplant phenotypically purified cells under defined conditions. The specific projects in my laboratory include:

1) Identification of the cells and molecules responsible for resistance to engraftment of purified allogeneic HSCs. We and others have shown that cells with NK determinants constitute a significant barrier to allogeneic HSC engraftment, and that transplanted whole BM contains a population that facilitates engraftment. In these experiments our approach to identify the cell population(s) and mechanism by which HSC engraftment is resisted is to use recipient mice from strains that lack defined immune functions. We are studying the cells in BM and spleen that are bound and/or depleted by a-ASGMI, and in this way identify the candidate barrier populations.

2) Use of transplants of purified HSCs to induce tolerance to allo- and autoantigens, and study of the mechanisms by which such tolerance is induced. We continue to develop preclinical models for organ tolerance induction and treatment of autoimmune disease by using cell specific therapy. One goal is to decrease the morbidity of the recipient preparative regimen and to determine the lowest level of chimerism needed to induce immune tolerance.

Recent Publications

  • Shizuru JA, Bhattacharya D, Cavazzana-Calvo M. The biology of allogeneic hematopoietic cell resistance. Biol Blood Marrow Transplant. 2010 Jan;16(1 Suppl):S2-7. Epub 2009 Nov 12.

  • Gyurkocza B, Cao TM, Storb RF, Lange T, Leisenring W, Franke GN, Sorror M, Hoppe R, Maloney DG, Negrin RS, Shizuru JA, Sandmaier BM. Salvage allogeneic hematopoietic cell transplantation with fludarabine and low-dose total body irradiation after rejection of first allografts. Biol Blood Marrow Transplant. 2009 Oct; 15(10):1314-22. Epub 2009 Aug 3.