Research we fund

We study the mechanisms of clonal hematopoiesis (CH), a process by which mutations provide hematopoietic stem cells (HSCs) with a fitness advantage. CH can precede the development of blood cancer. We use cutting-edge techniques to understand the effects of these mutations on HSC behavior. Our long-term goal is to identify ways to inhibit the growth of these mutant HSCs while sparing normal HSCs in people with CH. This may someday provide a blood cancer prevention method by eliminating the cells which carry the initial cancer-driving mutations.

Project Term: July 1, 2018 - June 30, 2023

We seek to elucidate the mechanisms by which aging of the vascular system contributes to the decline in blood stem cell function and leads to diseases such as hematopoietic malignancies. We have developed novel model systems that have led to the discovery of rejuvenation factors that can restore the functional capacity of an aging blood and vascular system. These studies lay the foundation for the development of therapeutic strategies to not only rejuvenate an aged blood system, but to also give a competitive advantage to non-malignant blood cells while directly targeting cancer cells following chemotherapy regimens commonly utilized to treat hematological malignancies.

Project Term: July 1, 2018 - June 30, 2023

We seek to understand the mechanisms of Cytokine Release Syndrome (CRS), the most common and potentially life-threatening toxicity associated with CAR-T cell therapies. We are using cutting-edge approaches to determine the cascade of events leading to the development of CRS and therefore define new candidates for CRS prevention and/or resolution. We will describe a cellular and molecular atlas associated with CRS development and severity, thus providing more specific and reliable candidates for therapeutic targeting. These findings may inform strategies to prevent CRS of cancer patients receiving CAR-T therapies.

Project Term: January 1, 2021 - December 31, 2023

The goal of my research is to characterize the role of the cellular metabolic regulator AK2 in multiple myeloma (MM) pathogenesis and therapy resistance. A series of molecular, biochemical, and functional assays will be performed using laboratory models to define the basis of MM cell dependence on AK2 and elucidate its role in MM progression and drug resistance. This work will highlight novel metabolic vulnerabilities in MM that can be targeted to further enhance therapeutic outcomes.

Project Term: October 1, 2021 - September 30, 2024

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.

Project Term: October 1, 2021 - September 30, 2026

Transcription factors are components of a cell which control our genetic information and are known to have altered function in diseases such as Acute Myeloid Leukemia (AML). I am investigating how we can better understand and use novel transcription factor drugs as therapy for AML. This involves using CLICK-chemistry drug localization studies and creating transcription factor occupancy maps of the genome. Overall, my work will help to understand the inner workings of transcription factors in disease and provide a new therapeutic option for the treatment of AML.

Project Term: July 1, 2018 - June 30, 2021

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.

Project Term: January 1, 2021 - December 31, 2025

This proposal aims to understand the molecular mechanisms underlying response to AZA therapy in MDS, as a basis for developing more effective therapies. A ribonucleotide, AZA’s effects on RNA remain unknown. Here, we will investigate the impact of in vivo AZA therapy on RNA alternative splicing and DNA demethylation in MDS patients. Secondly, we will investigate whether AZA treatment exposes neoepitopes in the dysplastic cells of patients, which could be exploited for cancer immunotherapy in MDS

Project Term: October 1, 2021 - September 30, 2023

There are widely recognized but unexplained sex differences in cancer incidence and outcomes, including in blastic plasmacytoid dendritic cell neoplasm (BPDCN), an aggressive leukemia that occurs over 3 times more frequently in men. We aim to identify male-female differences in plasmacytoid dendritic cells, the blood cell involved in BPDCN, to better understand this disease. Our goal is to use what we learn to improve the treatment of BPDCN and related blood cancers for both men and women.

Project Term: July 1, 2019 - June 30, 2022

Drug resistance in AML can develop via a non-genetic process which remains poorly understood. Using our novel cellular barcoding technology that can trace the growth of thousands of cancer cells, our research will identify genes that are switched on or off in AML cells that lead to drug resistance and relapse. This work will reveal the factors underpinning non-genetic drug resistance that may be targeted with new drugs to prevent relapse and ultimately improve quality of life and survival.

Project Term: October 1, 2021 - September 30, 2024

Most T cell acute lymphoblastic leukemia (T-ALL) patients respond to chemotherapy, however many relapse with limited therapy options. To address this problem, we are utilizing a newly-developed human T-ALL system to study two potential therapy targets (NOTCH1 and MLL1) and their interaction, to determine if they can be co-inhibited to eradicate disease. Since compounds that inhibit NOTCH1 and MLL1 are already in development, this novel combination strategy could lead to clinical approval sooner.

Project Term: January 1, 2021 - December 31, 2023

Children with Down syndrome (Trisomy 21) have an increased risk of childhood leukemia and, in these cases, the initiating genetic alterations already occur during the development of the fetus. In 30% of newborns with Down syndrome, a pre-leukemia disease occurs, which in some cases can progress to acute myeloid leukemia. I am planning to determine why children with Down syndrome have an increased risk of developing leukemia with the goal to identify potential therapeutic targets.

Project Term: April 1, 2021 - March 31, 2023