Research we fund

We have long standing experience in the field of HCL research. The aim of this research proposal is to characterize HCL on single cell level across multiple layers to uncover interactions of HCL with its microenvironment, which supports HCL cell survival. We will further explore metabolic and functional dependencies of primary HCL cells, and we hypothesize that their attenuation compromises HCL cell survival. Finally, we aim to pharmacologically disrupt these pro-survival pathways in HCL cells.

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. 

Pediatric AML is a disease with poor outcomes and a need for improved therapeutic options. Pediatric AML is characterized by diverse lesions that often do not overlap with adult AML, which therefore means therapeutic development must be done using pediatric AML models. Recent advances in patient derived xenograft (PDX) modeling have made possible the successful development of PDX models of diverse pediatric AML subtypes.

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.

Hairy cell leukemia (HCL) is very sensitive to chemotherapy, whose toxicity to the bone marrow and the immune system is however concerning. We have established vemurafenib plus rituximab as a very effective chemotherapy-free regimen in relapsed/refractory HCL (NEJM, in press). Here, we will test it in a clinical trial against a chemotherapy-based standard of care represented by cladribine plus rituximab, aiming at lower toxicity and similar efficacy.

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.

In this proposal, we have combined clinical and research expertise in HCL across Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, the University of Pennsylvania, and Yale University to develop newer targeted therapeutics for every stage and subtype of hairy cell leukemia. Capitalizing on this combined expertise, our proposal stands to significantly advance treatment strategies for hairy cell leukemia through the following aims: to test BRAF inhibition for initial treatment of classical hairy cell leukemia, test new oral inhibitors of the MAP kinase signaling pathway known as ERK inhibitors in both classical and variant hairy cell leukemia, evaluate totally new treatments that degrade BRAF, and develop T-cell immunotherapies for the first time in hairy cell leukemia.