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Craig Jordan
University of Colorado Denver, Anschutz Medical Campus

Our goal is to perform high-resolution molecular characterization of human leukemia stem cells (LSCs). We have developed an integrated set of single-cell techniques that will assess transcriptional, genomic, and phenotypic features of primary LSC populations obtained from patients undergoing varying forms of treatment. We expect to create a molecular atlas of primary LSCs that will provide the leukemia research community with a powerful resource for the development of improved therapies.

Project Term: October 2, 2024 - September 30, 2027

Hao Jiang
University of Virginia

Genetic changes of ASXL1 are very frequent in human blood cancers. We found that the altered forms of ASXL1 protein promote blood cancers through forming tiny liquid-like droplets in the cell. In this project, we aim to develop a method to specifically break these droplets to inhibit its activity in driving blood cancers.

Project Term: October 1, 2024 - September 30, 2027

Brian Walker
University of Miami

Multiple myeloma is characterized by severe changes in chromosomes that result in gains or losses of genetic material. Several key events disrupt the genome of myeloma cells and are important in defining poor patient outcome, but the biological mechanisms of how they cause high-risk disease is not known. We will perform comprehensive genomic studies, involving six different cutting-edge techniques, to examine the interactions of these high-risk events and identify the mechanisms leading to them.

Project Term: October 1, 2024 - September 30, 2027

Ari Melnick
Josep Carreras Leukemia Research Institute

This project is the first to explore the origin of a newly discovered type of lymphoma called “BN2-DLBCL”. Mutations in a gene called “SPEN” are a defining feature of these tumors. Strikingly, SPEN mutations are more common in females and cause more deadly disease. Our proposal will reveal for the first time how these tumors originate from the immune system, how they are intimately linked to autoimmune disorders such as Lupus, why they occur preferentially in women, and how to cure them. 

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

Eirini Papapetrou
Icahn School of Medicine at Mount Sinai

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

Lucy Godley
Northwestern University

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

Michael Kharas
Memorial Sloan Kettering Cancer Center

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

Siddhartha Jaiswal
Stanford University

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

Saar Gill
Perelman School of Medicine at the University of Pennsylvania

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

Courtney Jones
Princess Margaret Cancer Centre, University Health Network

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

Jun Qi
Dana-Farber Cancer Institute

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

Peter Klein
Perelman School of Medicine at the University of Pennsylvania

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