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Ricky Johnstone
The University of Melbourne

In recent work of our collaborating labs, the protein acetyltransferases P300 and CBP emerged as potent and preferential dependencies for multiple myeloma (MM) based on genetic depletion, catalytic inhibition or chemical degradation studies. Our current project will define distinct vs. redundant molecular and biological functions of P300/CBP in MM, identify the mechanisms of resistance to their inhibition/degradation and exploit these findings to develop new therapeutic modalities to treat MM.

Project Term: July 1, 2022 - June 30, 2025

Jane Oliaro
The University of Melbourne

Despite the promise of CAR-T cell immunotherapy for patients with lymphoma and multiple myeloma, a significant proportion of patients fail to respond or relapse following treatment. This project will focus on the clinical translation of a new treatment designed to improve durable response rates by combining CAR-T cell therapy with a new class of anticancer drugs called SMAC-mimetics. The results will provide the evidence base to drive a first-in-human clinical trial of this combination strategy.

Project Term: July 1, 2022 - June 30, 2025

Randall Davis
The University of Alabama at Birmingham

Evolving insights into the B cell-restricted FCRL1 surface protein reveal that it integrates with critical signaling pathways and is a promising immunotherapeutic target in CLL. Based on preclinical evaluation of novel FCRL1 monoclonal antibodies, we propose developing chimeric antigen receptor (CAR) T cells for targeting in unique mouse models and patient-derived cells. The results will form the basis for strategic drug development and clinical testing in CLL and related B cell malignancies.

Project Term: July 1, 2022 - June 30, 2025

Ravi Bhatia
The University of Alabama at Birmingham

The proposed studies will identify alterations in hematopoietic regulation that predict for risk for therapy-related myeloid neoplasm (TMN) and improve understanding of disease evolution to guide strategies to prevent TMN in patients receiving autologous hematopoietic cell transplantation (aHCT) for lymphoma. They will investigate alterations in hematopoietic function in peripheral blood stem cell used for aHCT, and serial evolution of hematopoietic defects leading to development of TMN.

Project Term: July 1, 2022 - June 30, 2025

Daniel Thomas
The University of Adelaide

Myelofibrosis is a severe myeloproliferative neoplasm with no known cure. We have obtained unique insights into the underlying mechanisms responsible for the emergence of myelofibrosis and designed new approaches to selectively control it. By combining our mutation-specific isolation methods with single cell sequencing, we will identify myelofibrosis-initiating stem cell populations, demonstrate efficacy of stem cell targeting and enumerate residual normal stem cells to inform a Phase I/II trial.

Project Term: July 1, 2022 - June 30, 2025

Suzanne Lentzsch
Columbia University Medical Center

Multiple myeloma is an incurable blood cancer complicated by bone diseases and compromised immune system. Our work indicated that checkpoint inhibitor PD-1H(VISTA) functions as the MMP-13 receptor, and the MMP-13/PD-1H signaling axis plays a critical role in multiple myeloma induced bone disease and immunosuppression. Therefore, immunotherapy targeting the novel MMP-13/PD-1H interaction module represents a novel approach to cure this devastating cancer.

Project Term: July 1, 2022 - June 30, 2025

Joachim Yahalom
Memorial Sloan Kettering Cancer Center

Extremely low dose radiation can improve blood cancer outcomes. But the mechanisms of how sublethal radiation (SRT) affects tumors, the microenvironment and immune system remain unclear. We envision a broad, nuanced role for SRT with benefits across diverse clinical situations and propose 3 clinical trials with deep translational components. Each can be paradigm-changing, but are thematically unified to improve mechanistic understanding of how such exceptionally small doses might offer so much.

Project Term: July 1, 2022 - June 30, 2025

Jolanta Grembecka
University of Michigan

Leukemia patients with chromosomal translocations of the Nucleoporin (NUP98) gene suffer from very poor prognosis. In this project we will identify new treatment for these patients by combining menin inhibitor with FDA approved drugs. We will evaluate effectiveness, mechanism of action and biomarkers of treatment response to these combinations in advanced pre-clinical models of NUP98 leukemia. We expect these studies will lead to future clinical trials in AML patients with NUP98 translocations.

Project Term: July 1, 2022 - June 30, 2025

Noemí Puig Morón
Institute of Biomedical Research from Salamanca

The present project will investigate the ability of quantitative immune precipitation mass spectrometry (QIP-MS) to anticipate relapsed or progressive disease in peripheral blood samples from patients with multiple myeloma. In the context of the GEM2014MAIN trial (lenalidomide and dexamethasone plus or minus ixazomib as maintenance), we will assess the presence of disease by QIP-MS in parallel with conventional methods in serum and next generation flow in bone marrow samples.

Project Term: July 1, 2022 - June 30, 2025

Mala Shanmugam
Emory University

Multiple myeloma (MM) relies on the bone marrow (BM) niche to progress to refractory disease. We found that beta blockers alter BM niche elements fostering MM growth and also reduce MM cell survival. Our objective is to elucidate the cellular and metabolic basis of how beta adrenergic signals impact the BM niche and MM progression. Knowledge of the prophylactic and therapeutic utility of beta blockers in MM will unravel new means to target neural niche remodeling fueling this fatal malignancy.

Project Term: July 1, 2022 - June 30, 2025

Christopher Porter
Emory University

The goal of this project is to explore a novel immunologic therapeutic target for hematologic malignancies, SIGLEC15 (Sig15). The central hypothesis is that Sig15 is aberrantly expressed in malignant B cells, is released to attenuate immune responses and can be targeted therapeutically to promote immune responses to malignant hematopoietic cells. This work will accelerate therapeutic exploitation of the immune system for the treatment of leukemia and lymphoma by targeting Sig15.

Project Term: July 1, 2022 - June 30, 2025

Amit Verma
Albert Einstein College of Medicine

The terrorist attacks on the World Trade Center (WTC) created an unprecedented environmental exposure to WTC aerosolized dust and gases that contained known and suspected carcinogens including polycyclic aromatic hydrocarbons, polychlorinated biphenyls, polychlorinated furans, dioxins and asbestos. Studies from Dr. Verma's group and others have reported an excess of cancer cases in the WTC-exposed Fire Department of the City of New York (FDNY) firefighters, including a trend towards higher incidence of multiple myeloma and leukemias. He now will be deep sequencing a large group of WTC-exposed firefighters to look for clonal hematopoiesis (CH) which is an acquisition of leukemia associated mutations associated with increases in the risk of hematologic cancer.

Project Term: June 1, 2022 - TBD