Research we fund

We want to understand how leukemia inhibits blood production as this is one of the main causes of death in leukemia patients. We use new microscopy techniques developed by our group to image—for the first time—all types of blood cells and how they are eradicated by leukemia cells. Identification of the mechanisms through which leukemia inhibits blood production will be the foundation for new studies to develop drugs to maintain normal blood levels and prevent death in leukemia patients.

Children get different types of leukemias than adults. Even if the leukemias look the same under the microscope, the mutations are different. We are trying to understand why the mutations are different and what the implications are for treatment. 

We have found that changes in normal developing blood cells can determine whether a mutation will cause leukemia. For example, a mutation might only activate pathways that drive leukemias at one specific age. It may therefore only cause leukemia at that specific age. We have indeed identified several genes that are activated by infant leukemia mutations, but only shortly after birth. More recently, we have identified genes that actually protect fetal cells from leukemia formation, potentially accounting for the extreme rarity of leukemia prior to birth.

Differences between childhood and adult leukemias might have other implications. A mutation found only in children might require treatments that are unique to children. Work in our lab has identified mechanisms that help drive childhood-specific leukemias, which we are currently working to target.

Finally, we need better tools to model childhood leukemias so that drug screens use specimens that faithfully reflect the effects of childhood-specific mutations. We developed a new technology to efficiently model childhood leukemias using mouse cells. We are using this new technology to look for new drug targets that account for the unique properties of childhood leukemia.

By studying unique features of childhood leukemia - where and when they arise - we can develop treatments that account for unique properties of the childhood malignancies.

Coming soon.

CAR T-cells are highly effective in lymphoma but limited by a profound and potentially fatal toxicity involving the central nervous system (CNS). Little is known about how CAR T-cells eliminate lymphoma cells in the CNS nor how this therapy causes toxicity. I will study CAR T-cells in patients with CNS lymphomas with the goal of expanding CAR T-cell indications. I will also examine serial blood and CNS samples to understand neurologic toxicity to inform new therapies to control this toxicity.

Coming soon.

My ultimate goal is to develop more effective, better tolerated, and individualized treatment for patients with AML. This project focuses on AML patients with IDH1 or IDH2 mutations, with a clinical trial evaluating a combination of three agents which are effective in IDH-mutated AML. While these therapies are not curative on their own, my hope is that this combination will lead to a practice changing all-oral, outpatient, and well-tolerated curative strategy for patients with IDH-mutated AML.

In this proposal, the Choi lab is investigating mechanisms that underlie aggressive forms of T cell lymphoma. They have found a gene mutation that is found exclusively in aggressive subtypes. There is a gene that encodes for PD1 that suppresses tumor progression. In a subset of T cell lymphomas, this gene is lost or inactivated, leading to increased tumor progression and aggressiveness. Here they propose three complementary approaches to understand how this gene constrains T cell lymphomas and importantly, they are now proposing to leverage this information to generate novel treatments for the patients who need it most. 

Dr Tasian’s scientific passion is successful development of precision medicine therapies for high-risk childhood leukemia. Her translational laboratory research program focuses upon investigation of kinase inhibitors and chimeric antigen receptor (CAR) T cell immunotherapies in childhood ALL and AML using primary patient specimens and patient-derived xenograft models. Through her laboratory and clinical research, she aspires to improve cure rates and minimize toxicities for children with leukemia.

My research focuses on why and how risk of acute myeloid leukemia (AML) increases with aging. Studying naturally aged mouse models in combination with mice engineered to express mutations commonly found in human blood stem cells with aging, we are investigating whether certain inflammatory factors that increase during aging increase the risk of leukemia. My goal is to identify biomarkers to assess risk of AML development in aging individuals and define new therapeutic targets to prevent AML.