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Craig T. Jordan, PhD


Dr. Craig Jordan
Craig T. Jordan PhD
University of Colorado School of Medicine
  • Division Chief, Division of ​Hematology
  • Nancy Carroll Allen Professor of Hematolo​gy
  • Vice Chair of Basic Research, Department of Medicine
  • Professor of Medicine

 

Publications​

See Craig T. Jordan's Colorado Profiles for a complete listing of publications.

 

Contact information​

Anschutz Medical Campus
12700 East 19th Ave, Room 9122
Research Complex 2, Campus Box B170
Aurora, CO  80045
303-724-8165
craig.jordan@ucdenver.edu
Jordan Lab

Dr. Jordan completed his bachelor’s degree at the University of California, Berkeley, followed by doctoral studies at Princeton University with a focus on the molecular biology of hematopoietic stem cells.  He then went on to perform post-doctoral studies at MIT’s Whitehead Institute.  He next spent several years working in the biotechnology industry before rejoining the academic ranks in 1997 at the University of Kentucky as an Assistant Professor of medicine. In 2003 he moved to the University of Rochester, where he became the Director of Translational Research for Hematologic Malignancies at the James P. Wilmot Cancer Center.  In 2013 he was recruited to his present position at the University of Colorado Denver.

Dr. Jordan has been and is an editorial board member or academic editor for several journals including Leukemia, Stem cells, PLoS Biology, Blood, and Cell Stem Cell, and is ad hoc reviewer for numerous journals including Science, Nature, New England Journal of Medicine, Nature Medicine, Cancer Cell, Nature Reviews Cancer, Lancet, Nature Reviews Drug Discovery, Drug Discovery Today, etc.  Dr. Jordan has participated in numerous NIH/NCI grant review panels, and has published over 125 peer-reviewed original research articles, review articles and book chapters. He has successfully maintained national level grants including awards from the NIH/NCI, Department of Defense, Leukemia and Lymphoma Society, and American Cancer Society.  His honors include the Helen Hay Whitney Fellowship, the Stohlman Scholar Award from the Leukemia and Lymphoma Society, and the Philip and Marilyn Wehrheim endowed chair in cancer research.

  • University of California, Berkeley, AB, 1984
  • Princeton Un​iversity, PhD, 1991​

Since first establishing my independent academic laboratory in 1997, my research has been focused on characterization and targeting of leukemia stem cells (LSCs).  In leukemia, like many forms of cancer, a small subset of so-called “cancer stem cells” are thought to be key drivers of pathogenesis and relapse.  While therapies that reduce bulk tumor have been devised for many forms of cancer, effective eradication of cancer stem cells is more challenging, and represents an important goal towards improved therapies.  In the most prevalent forms of adult acute leukemia, long-term survival rates are only ~20%, hence, better therapies are urgently needed.

My laboratory was the first to describe properties of human LSCs that are relevant to therapeutic targeting (1,2).  These observations have led to multiple clinical trials using antibodies, small molecules and cell-based immunotherapies designed to target the biological properties first reported from our studies.  Our research was also the first to describe a drug regimen specifically designed to target LSCs in patients (3).

  1. Jordan, C. T., Upchurch, D., Szilvassy, S. J., Guzman, M. L., Howard, D. S., Pettigrew, A. L., Meyerrose, T., Rossi, R., Grimes, B., Rizzieri, D. A., Luger, S. M., and Phillips, G. L. (2000) The interleukin-3 receptor alpha chain is a unique marker for human acute myelogenous leukemia stem cells. Leukemia 14, 1777-1784. PMID: 11021753

  2. Guzman, M. L., Neering, S. J., Upchurch, D., Grimes, B., Howard, D. S., Rizzieri, D. A., Luger, S. M., and Jordan, C. T. (2001) Nuclear factor-kappaB is constitutively activated in primitive human acute myelogenous leukemia cells. Blood 98, 2301-2307. PMID: 11588023

  3. Guzman, M. L., Swiderski, C. F., Howard, D. S., Grimes, B. A., Rossi, R. M., Szilvassy, S. J., and Jordan, C. T. (2002) Preferential induction of apoptosis for primary human leukemic stem cells. Proceedings of the National Academy of Sciences of the United States of America 99, 16220-16225. PMC138592

  4. ​​​Building on our initial basic science studies, in subsequent years we developed drug screening and identification methods to identify improved therapeutic agents to target LSCs.  We were the first group to report a single agent (known as parthenolide) capable of selectively eradicating LSCs (4).  We subsequently collaborated with a leading medicinal chemistry group to develop a candidate clinical compound that was based on parthenolide (5).  That agent, known as DMAPT is currently being tested in phase I clinical trials.

  5. Guzman, M. L., Rossi, R. M., Karnischky, L., Li, X., Peterson, D. R., Howard, D. S., and Jordan, C. T. (2005) The sesquiterpene lactone parthenolide induces apoptosis of human acute myelogenous leukemia stem and progenitor cells. Blood – Plenary Paper, 105(11):4163-69. PMC1895029

  6. Guzman, M. L., Rossi, R. M., Neelakantan, S., Li, X., Corbett, C. A., Hassane, D. C., Becker, M. W., Bennett, J. M., Sullivan, E., Lachowicz, J. L., Vaughan, A., Sweeney, C. J., Matthews, W., Carroll, M., Liesveld, J. L., Crooks, P. A., and Jordan, C. T. (2007) An orally bioavailable parthenolide analog selectively eradicates acute myelogenous leukemia stem and progenitor cells. Blood 110, 4427-4435​. PMC2234793

  7. In parallel to our efforts to develop novel drugs, we have also generated new methods for drug characterization and new strategies to identify the most basic molecular properties of leukemia stem cells (6,7).  Intriguingly, in recent studies we have identified a distinct subpopulation of LSCs characterized by unique metabolic properties (8,9).  This discovery has led to a new therapeutic strategy for targeting LSCs based on pharmacological inhibition of Bcl-2, a concept that is currently being tested in ongoing clinical trials (10).  We have also identified non-hematopoietic organs that provide protective niches for leukemia stem cells and are working to identify more effective strategies for targeting tissue specific reservoirs (11).

  8. Hassane, D. C., Guzman, M. L., Corbett, C., Li, X., Abboud, R., Young, F., Liesveld, J. L., Carroll, M., and Jordan, C. T. (2008) Discovery of agents that eradicate leukemia stem cells using an in silico screen of public gene expression data. Blood, 111(12):5654-62. PMC2424160

  9. Ashton, J. M., Balys, M., Neering, S. J., Hassane, D. C., Cowley, G., Root, D. E., Miller, P. G., Ebert, B. L., McMurray, H. R., Land, H., and Jordan, C. T. (2012) Gene sets identified with oncogene cooperativity analysis regulate in vivo growth and survival of leukemia stem cells. Cell Stem Cell, 11, 359-372. PMC4023631

  10. Pei S, Balys M, Callahan KP, Minhajuddin M, Ashton JM, Neering SJ, Lagadinou ED, Corbett C, Ye H, Becker MW, Liesveld JL, O’Dwyer KM, Li Z, Shi L, Greninger P, Settleman J, Benes C, Hagen F, Munger J, Crooks PA, and Jordan CT.  Targeting aberrant glutathione metabolism to selectively eradicate human leukemia cells.  Journal of Biology Chemistry. 2013 Nov 22;22(47):33542-58. PMC3837103.

  11. Pei S, Minhajuddin M, D’Alessandro A, Nemkov T, Stevens BM, Adane B, Khan N, Hagen FK, Yadav VK, De S, Ashton JM, Hansen KC, Gutman JA, Pollyea DA, Crooks PA, Smith C and Jordan CT.  Rational Design of a Parthenolide-based Drug Regimen that Selectively Eradicates Acute Myelogenous Leukemia Stem Cells.  Journal of Biology Chemistry. 2016, in press.

  12. Lagadinou, E. D., Sach, A., Callahan, K., Rossi, R. M., Neering, S. J., Minhajuddin, M., Ashton, J. M., Pei, S., Grose, V., O'Dwyer, K. M., Liesveld, J. L., Brookes, P. S., Becker, M. W., and Jordan, C. T. (2013) BCL-2 inhibition targets oxidative phosphorylation and selectively eradicates quiescent human leukemia stem cells. Cell Stem Cell 12, 329-341. PMC3595363​

  13. Ye H, Adane B, Khan N, Sullivan T, Minhajuddin M, Gasparetto M, Stevens B, Pei S, Balys M, Ashton JM, Klemm DJ, Woolthuis CM, Stranahan AW, Park CY, Jordan CT.  Leukemic Stem Cells Evade Chemotherapy by Metabolic Adaptation to an Adipose Tissue Niche. Cell Stem Cell. 2016 Jul 7;19(1):23-37. doi: 10.1016/j.stem.2016.06.001. Epub 2016 Jun 30. PubMed PMID: 27374788; PubMed Central PMCID: PMC4938766.