Stem Cell & Hematologic Malignancies
- Occupation: Assistant Professor of Medicine, University of California San Diego
- Alternative career choice: Criminal Law Prosecutor
- What do rock stars and scienctists have in common: Creativity
- Musical Instrument I Play: None
- I tend to approach life: Optimistically
- Biggest misconceptions about me or my work: I'm not aware of any misconceptions; what you see is what you get.
- Worst part-time job ever: I had two--working at a gas station and working at a bank because I got equally dirty at both jobs.
- Longest med school study session: Group medical school study session on friend's boat.
- Best moment in medicine/research: Translating stem cell discoveries to the clinic and realizing that they have had a positive impact on people's lives.
About My Research
Disease Area: Hematologic Malignancies
Research Area: Stem Cell Research
Science Impact/Accomplishments or Goal: Dr. Jamieson's team at UC San Diego discovered the in vivo identity of candidate leukemic stem cells (LSC) involved in the progression of a well-known myeloproliferative neoplasm, chronic myeloid leukemia (CML) to blast crisis, and a mechanism that promotes activation of LSC self-renewal. A key self-renewal antagonist and central regulator of the Wnt self-renewal pathway, beta-catenin, is activated in a large proportion of patients with blast crisis CML as a result of hematopoietic stage specific missplicing of GSK3beta. This was the first demonstration of epigenetic deregulation of a self-renewal pathway regulator through missplicing. Because GSK3beta also regulates the Sonic hedgehog (Shh) pathway, Dr. Jamieson's team collaborated with Shh pathway experts Professors Reya and Beachy, and demonstrated together that aberrant Shh signaling promotes leukemia stem cell propagation in mouse models of CML and in imatinib resistant human CML progenitors. Consequently, her team has identified a potent and selective Shh antagonist that significantly inhibits human LSC engraftment providing the impetus for a Pfizer sponsored Phase l Shh inhibitor clinical trial for advanced phase CML and other refractory hematologic malignancies, which is now accruing patients at UC San Diego, as well as in Seattle and Bologna.
Research Description: Dr. Jamieson specializes in myeloproliferative disorders (MPDs) and leukemia. Myeloproliferative neoplasms are a family of uncommon but not rare degenerative disorders in which the body overproduces blood cells. Myeloproliferative neoplasms can cause many forms of blood clotting including heart attack, stroke, deep venous thrombosis, and pulmonary emboli and can develop into acute myelogenous leukemia. Although some effective treatments are available, they are laden with serious side effects. In addition, individuals can become resistant to the treatments. Dr. Jamieson studies the mutant stem cells and progenitor cells in myeloproliferative neoplasms. These cells can give rise to cancer stem cells. Cancer stem cells may lie low to evade chemotherapy and then activate again later, causing disease progression and resistance to treatment. Her goal is to find more selective, less toxic therapies. In the past two years, Dr. Jamieson's stem-cell research studies have taken a great leap: from identifying a promising treatment in the laboratory to opening and completing the first clinical trial to target cancer stem cells in humans. This trial is the result of teamwork that has brought together her discoveries in myeloproliferative neoplasms and a local pharmaceutical company's drug development track.
2003-2005 Instructor, Medicine, Hematology, Stanford University, Stanford, CA
2005-present Assistant Professor of Medicine, Hematology/Oncology, UCSD
2006-present Director, Stem Cell Research Program, Moores UCSD Cancer Center
2008-present Hematology Team Leader, Division of Hematology/Oncology, UCSD
2009-present Member, UCSD Division of Biomedical Sciences
2009-present Member, UCSD Cancer Biology Program
Most Recent Peer-reviewed Publications
1. Perrotti D, Jamieson C, Goldman J, Skorski T. Chronic myeloid leukemia: mechanisms of blastic transformation. J Clin Invest. 2010 Jul 1;120(7):2254-64.
2. Rice KN, Jamieson CH. Molecular pathways to CML stem cells. Int J Hematol. 2010 Jun;91(5):748-52. Epub 2010 Jun 10.
3. O’Brien CA, Kreso A, Jamieson CH. Cancer stem cells and self-renewal. Clin Cancer Res. 2010 Jun 15;16(12):3113-20. Epub 2010 Jun 8.
4. Jamieson C. Split ends in CML: divergent roles of Hes1. Blood. 2010 Apr 8;115(14):2726-7.
5. Goff D, Jamieson C. Cycling toward elimination of leukemic stem cells. Cell Stem Cell. 2010 Apr 2;6(4):296-7.
6. Gutierrez A, Sanda T, Ma W, Zhang J, Grebliunaite R, Dahlberg S, Neuberg D, Protopopov A, Winter SS, Larson RS, Borowitz MJ, Silverman LB, Chin L, Hunger SP, Jamieson C, Sallan SE, Look AT. Inactivation of LEF1 in T-cell acute lymphoblastic leukemia. Blood. 2010 Feb 1. [Epub ahead of print]
7. Goldman JM, Green AR, Holyoake T, Jamieson C, Mesa R, Mughal T, Pellicano F, Perrotti D, Skoda R, Vannucchi AM. Chronic myeloproliferative diseases with and without the Ph chromosome: some unresolved issues. Leukemia. 2009;23:1708-1715.
8. Jaiswal S, Jamieson CH, Pang WW, Park CY, Chao MP, Majeti R, Traver D, van Rooijen N, Weissman IL. CD47 is upregulated on circulating hematopoietic stem cells and leukemia cells to avoid phagocytosis. Cell. 2009;138:271-285. PMC2775564.
9. Abrahamsson A, Geron I, Gotlib J, Dao K-H, Barroga C, Durocher J, Creusot R, Giles F, Karimi M, Jones C, Zehnder J, Keating A, Negrin R, Weissman IL, Jamieson CHM. Glycogen Synthase Kinase 3beta Missplicing Contributes to Leukemia Stem Cell Generation. Proc Natl Acad Sci U S A. 2009;106:3925-3929.