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.