Christopher J. Hogan, Ph.D.

Return to Faculty Page

Associate Professor
Department of Medicine
Integrated Department of Immunology
Associate Director, Charles C. Gates Regenerative Medicine
and Stem Cell Biology Program
University of Colorado Denver
Phone: 303-724-3113
Email: chris.hogan@uchsc.edu

 

 

Professional Activities
Director, University of Colorado Cancer Center Flow Cytometry Core
Graduate School and Center Affiliations:
Associate Professor, Integrated Department of Immunology
Member, University of Colorado Cancer Center
Education:
Ph.D., Colorado State University, 1987
Postdoctoral Training:
NSF Postdoctoral Fellowship, University of California, Berkeley, 1987-1990
NIH Postdoctoral Fellowship, University of California, Berkeley, 1990-1993
Research Interests
My research program focuses on the biology and developmental potential of human hematopoietic stem cells. Most of our knowledge of the mammalian hematopoietic hierarchy, including stem and progenitor cell potentials and lineage relationships, has been derived from the mouse system, from studies employing either experimental transplantation or embryonic stem (ES) cell technology. Comparable studies have not been practical in the human system until recently. With the advent of xenotransplantation models and the recent isolation of human ES cells we now have at hand the means to dissect early embryonic hematopoietic developmental pathways through in vitro analysis of human ES cells, as well as assess the hematopoietic potential of various adult precursor populations in vivo through experimental transplantation into immunocompromised mouse models.
We have characterized the developmental potential in vivo of various rare populations of post-natal human stem cells, isolated from bone marrow, growth factor-mobilized peripheral blood, and umbilical cord blood, in the non-obese diabetic (NOD)/severe combined immunodeficiency (SCID) mouse model. Using this model we have defined cell populations responsible for short-term hematopoietic reconstitution, as well as populations that comprise long-term, multi-lineage repopulating elements. Likewise we have been able to define cell populations that exhibit lineage-restricted potential in vivo, as well as those that are capable of reconstituting all cell types of the hematopoietic system.
Interestingly, engraftment of primitive stem cells from cord blood leads to repopulation of the mouse thymus with human double and single positive (CD4/CD8) T cells. Currently we are investigating the progression of human T cell development that occurs in the mouse thymus to determine if this scenario recapitulates development in the human thymus. The goal is to be able to study human T cell repertoire development in this system and ultimately to create a functional human immune system in the mouse model.
Recently multi-potential stem cells found in both mouse and human bone marrow have been shown to be capable of differentiating into various cell types of ectodermal, mesodermal, and endodermal origin. Currently we are investigating the developmental potential of primitive stem cell fractions found in cord blood. Recently we have isolated a rare population of adherent cells that do not express any hematopoietic markers. These cells can be expanded in culture over extended periods of time without phenotypic change and can be induced to differentiate into various mesodermal lineages in vitro. We hypothesize that this population may consist of multi-potential precursors capable of giving rise to hematopoietic stem cells, as well as stem cells of various other lineages. We are in the process of determining their capacity to form hematopoietic cells, both in vitro and in vivo, as well as their potential to produce cells of ectodermal and endodermal lineages. Once characterized this cell population could have great impact on clinical strategies focused on cellular therapies for a number of pathologies. These cells, because of their capacity to expand in vitro without differentiation, will give us access to primitive stem cell populations that are too rare or fleeting for practical analysis in vivo. Our ultimate goal is to use such a system to understand the early molecular and biochemical events leading to mesodermal induction and commitment of stem cells to hematopoietic fates.

Selected Publications:

  1. Yingzhu Li, Nancy Clough, Xiaolin Sun, Weidong Yu, Brian L. Abbott, Christopher J. Hogan1, andZonghan Dai. Bcr-Abl induces abnormal cytoskeleton remodeling, 1 integrin clustering and increased cell adhesion to fibronectin through the Abl interactor 1 pathway. J. Cell Sci. 120: 1436-1446. 2007.
  2. Li, F.X., Zhu, J.W., Tessem, J.S., Beilke, J., Varella-Garcia, M., Jensen, J., Hogan, C.J., DeGregori, J. The development of diabetes in E2f1/E2f2 mutant mice reveals important roles for bone marrow-derived cells in preventing islet cell loss. Proc. Nat. Acad. Sci. (USA) 100: 12935-12940. 2003.
  3. Li, F.X., J.Z. Zhu, C.J. Hogan and J. DeGregori. Defective gene expression, S phase progression and maturation during hematopoiesis in E2F1/E2F2 mutant mice. Mol. Cell. Biol. 23: 3607-3622. 2003.
  4. Lacaud, G., Gore, L., Kennedy, M., Kouskoff, V., Palis, J., Kingsley, P., Speck, N., Hogan, C.J., Carlsson, L., Keller, G. Runx1 is required for hemangioblast development. Blood 100: 458-466. 2002
  5. Hogan, C.J., Shpall, E.J., Keller, G. Differential long-term and multilineage engraftment potential from subfractions of human CD34+ cord blood cells transplanted into NOD/SCID mice. Proc. Nat. Acad. Sci. (USA) 99: 413-418. 2002.
  6. Shpall, E.J., Quinones, R., giller, R., Zeng, C., Baron, A.E., Jones, R.B., Bearman, S.I., Nieto, Y., Freed, B., Madinger, N., Hogan, C.J., Slat-Vasquez, V., Russell, P., Blunk, B., Schissel, D., Hild, E., Malcolm, J., Ward, W., McNiece, I.K. Transplantation of ex-vivo expanded cord blood. Biol. Blood Marrow Transplant 8: 368-376. 2002.
  7. Varella-Garcia, M., Hogan, C.J., Odom, L.F., Murata-Collins, J.L., Ai, H., Chen, L., fichkind, K., Paskulin, G., Andreeff, M., Brizard, A., McGavran, L., Gemmill, R.M., Berger, R., Drabkin, H.A. Minimal residual desease (MRD) in remission t(8;21) AML and in vivo differentiation detected by FISH and CD34+ cell sorting. Leukemia 15: 1408-1414. 2001.
  8. McNiece, I., Jones, R., Bearman, S., Cagnoni, P., Nieto, Y., Franklin, W., Ryder, J., Steele, A., Stoltz, J., Hartsough, K., Russell, P., McDermitt, J., Hogan, C.J., Murphy, J., Shpall, E.J. Ex vivo expanded peripheral blood progenitor cells provide rapid neutrophil recovery in breast cancer patients following high dose chemotherapy. Blood 96: 3001-3007. 2000.
  9. Hogan, C.J., Shpall, E.J., McNiece, I., Keller, G. Multilineage engraftment in NOD/LtSz-scid/scid mice from mobilized human CD34+ peripheral blood progenitor cells. Biol. Blood and Marrow Transpl. 3: 236-246. 1997.
  10. Hogan, C.J., Shpall, E.J., McNulty, O., McNiece, I., Dick, J.E., Shultz, L.D., Keller, G. Engraftment and development of human CD34+-enriched cells from umbilical cord blood in NOD/LtSz-scid/scid mice. Blood 90: 85-96. 1997.