Research we fund

Dr. Signer is investigating how the process of building defective proteins (inaccurate protein synthesis) plays a role in the development of a type of blood cancer called acute myeloid leukemia (AML) in the hopes of developing targeted therapies to treat this condition.

Project Term: July 1, 2020 - 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

Myeloproliferative neoplasms (MPNs) carry JAK2(V617F), MPL(W515L) and mutations in calreticulin (CALRmut) often accompanied by mutations in TET2, ASXL1, DNMT3A, EZH2, and other genes. We will develop a strategy based on gene mutation profiling to identify MPNs displaying specific defects in DNA repair. These defects will be then explored by specific DNA repair inhibitors to eliminate quiescent and proliferating MPN stem and progenitor cells without affecting normal cells and tissues.

Project Term: July 1, 2021 - June 30, 2024

We will test if Gene Expression and Mutation Analysis (GEMA) could be applied as personalized medicine tool to identify individual patients with AML displaying specific preferences for repairing spontaneous and drug-induced DNA damage. These preferences will predispose leukemia stem and progenitor cells to synthetic lethality triggered by already approved as well as novel DNA repair inhibitors.

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

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. Starczynowski is investigating the role and potential benefit of therapeutic targeting of a protein called UBE2N in acute myeloid leukemia (AML).

Project Term: July 1, 2020 - June 30, 2023

Dr. Kimberly Stegmaier is performing pre-clinical research to identify promising therapeutic strategies for pediatric leukemia. Pediatric blood cancers comprise about 40% of all pediatric cancers. The most common pediatric blood cancer is acute lymphoblastic leukemia (ALL), which is curable in most patients through the use of chemotherapy. Though beneficial in the short term, destroying the cancer through chemotherapy often leads to long term health problems. For those that do not respond to chemotherapy, there are fewer therapeutic options. Another pediatric blood cancer is acute myeloid leukemia (AML), which is a more aggressive and lethal disease. Therefore, many pediatric acute leukemia patients require better therapeutic options, and a precision medicine approach targeting specific mutations will likely lead to a better clinical benefit.

Project Term: October 1, 2020 - September 30, 2022

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.

Project Term: July 1, 2021 - June 30, 2023

Refractory pediatric B- and T- lymphoid cancers exhibit hyperactivation of MYC and its downstream pathways. Experimentally, MYC inactivation sustains tumor regression. However, MYC’s requirement in normal B/T-cells has hampered the development of MYC inhibitors. Recently, we showed that MYC-High B/T-Lymphoid Neoplasms (B/T-MLN) evade Natural Killer (NK) cell surveillance. Hence, we propose to develop targeted off-the-shelf NK therapies as an alternative to MYC inhibition for treating B/T-MLN.

Project Term: July 1, 2021 - June 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

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.

Project Term: January 1, 2023 - December 31, 2025