Research we fund

Myelodysplastic syndrome (MDS) is a blood disease with poor prognosis and frequent progression to acute myeloid leukemia (AML). There are currently no effective treatments. This proposal is based on a recent discovery by my group and proposes to investigate a protein called G⍺s (alpha subunit of the stimulatory G protein), as a novel therapeutic target for MDS. If successful, this work can lead to novel therapies that can transform the treatment of MDS, AML and possibly other cancers.

Project Term: October 1, 2022 - September 30, 2025

This proposal explores how inherited mutations in the DNA repair gene CHEK2 lead to blood cancers. Our work employs two unique resources: patient-derived cell lines and mice engineered with an inherited Chek2 variant that accurately models how bone marrow stem cells acquire DNA changes over time leading to bone marrow cancers. Our results may lead to new approaches that slow or prevent blood cancers in people with high risk.

Project Term: October 1, 2022 - September 30, 2025

Although molecular targeted therapy has dramatically changed how we treat cancer, the treatment for acute myeloid leukemia (AML) remains focused on the use of cytotoxic drugs with many patients eventually relapsing with their disease. Our studies have a uncovered a new nuclear structure that is dysregulated in myeloid leukemia. This proposal studies the identity and function of this nuclear body in human AML and strives to identify novel therapeutic strategies and targets in leukemia.

Project Term: October 1, 2022 - September 30, 2025

Mutations in a diverse set of genes can lead to pre-cancerous expansion of blood stem cells, but the factors that mediate the growth of these mutant clones are unknown. We recently discovered that many of these mutations lead to abnormal activation of a gene called TCL1A. Consequently, TCL1A may be an attractive target for treating or preventing blood cancers, but little is known about its function. Here, we will uncover how TCL1A influences the biology of pre-cancerous blood stem cells.

Project Term: October 1, 2022 - September 30, 2025

Most patients with acute myeloid leukemia (AML) are not cured with chemotherapy alone, and most long-term survivors of AML have undergone an allogeneic stem cell transplant (also known as bone marrow transplant). The outlook is quite grim for patients whose AML relapses after transplant. We have developed a new type of treatment for AML called chimeric antigen receptor (CAR) T cells for these patients. The goal of this project is to investigate how to improve CAR T cells for AML.

Project Term: October 1, 2022 - September 30, 2025

Acute myeloid leukemia (AML) is a devastating blood cancer. Most AML patients will initially respond to standard therapy; however, for many patients the disease recurs resulting in patient death. Consequently, there is an urgent need to develop new therapeutic strategies for relapsed AML patients. The objective of our proposal is to understand and target properties specific to relapsed AML cells with the overall goal of improving relapsed AML patient outcomes.

Project Term: October 1, 2022 - September 30, 2025

We identified that KDM5 can regulate important transcription factors in multiple myeloma (MM) and regulate the bone marrow (BM) microenvironment in providing protection toward MM, which also reduces anti-MM immunity. Thus, our study will utilize our novel potent and selective KDM5 inhibitor to fully dissect the interactions between MM cells, the BM microenvironment and the immune system in cellular and animal models to establish important mechanistic insights into MM.

Project Term: October 1, 2022 - September 30, 2025

Myelodysplasia (MDS) is a lethal stem cell disorder characterized by defective blood formation and progression to leukemia. MDS is frequently caused by mutations in splicing factors, but these mutations also create an Achille’s heel that can be targeted to kill MDS cells while sparing normal blood cells. We identified a group of clinically safe drugs that target this weakness and selectively kill MDS cells in vitro. We will test whether these drugs are effective in mouse models of MDS.

Project Term: October 1, 2022 - September 30, 2025

It has been demonstrated that most cases of AML are associated with mutations in multiple genes. Dr. Majeti's studies will provide novel insights into the genetic events and other factors such as the microenvironment that affect in the development of myeloid malignancies, particularly AML. This study will have significant implications for the prevention and treatment of myeloid malignancies, particularly AML.

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

Dr. Müschen studies mechanisms of tumor-initiation in B-cell malignancies, including acute lymphoblastic leukemia, mantle cell lymphoma and diffuse large B-cell lymphoma. These studies focus on negative regulators of the WNT/b-catenin pathway as potential diagnostic marker and therapeutic target.

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

Dr. Jamieson is examining the role of two enzymes (APOBEC3 and ADAR1) known to mutate DNA and RNA, and their role in acute myeloid leukemia (AML) and disease relapse, particularly in elderly patients.

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

T cell acute lymphoblastic leukemia (T-ALL) has a strong tendency to infiltrate the central nervous system (CNS). The goal is hope to develop strategies to treat CNS disease in T-ALL with less neurotoxicity and more efficacy than current chemotherapy.

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