Research we fund

Bispecific antibodies are a new, highly effective immunotherapy for multiple myeloma. Most bispecific antibody therapies have been tested as continuous therapies in which patients continue receiving the treatment until the myeloma starts growing again. Preliminary results suggest that patients with good responses may be able to stop therapy and enjoy a period of time off-therapy with close observation, which may limit long term toxicities caused by continuous therapy. We propose a clinical trial to test this limited-duration approach with recently approved bispecific antibodies for multiple myeloma.

Project Term: February 7, 2024 - June 30, 2027

Although many patients with IgM MGUS remain asymptomatic, some of them progress to Waldenstrom Macroglobulinemia (WM) requiring treatment. Recently, we have found that the hereditable alteration of IRF4 gene increases the risk to develop WM, however little is known on the molecular mechanisms responsible for this feature. In this project, we aim to elucidate the role of the germline alteration of IRF4 in promoting WM through oncogenic cooperation with MYD88 and dysregulated immune microenvironment, ultimately paving the way for novel precision therapies for this patient population.

Project Term: August 21, 2023 - August 20, 2025

The MULTIPLY is a large multi-institutional project aimed at characterization of a variety of clinical predictors, both baseline and at relapse through three interconnected Work Packages (WP) with the following objectives: I) Identification of clinical factors affecting prognosis and characterization of relapses; II) Identification of lymph node biomarkers III) characterization of liquid tissue associated biomarkers. All parameters will be integrated through biostatistical and artificial intelligence tools to establish a comprehensive model of relapse prediction and optimal salvage treatment. The proposal is conducted by the Eu-MCL-Network which is the largest group conducting clinical and translational research worldwide in MCL including the largest phase III trials ever conducted. MULTIPLY will exploit the extensive dataset and tissue bank of the TRIANGLE trial that will be presented as abstract #1 at the ASH plenary session. This study will establish a novel standard by the addition of ibrutinib to first-line treatment, but will also raise relevant issues for prediction and management of disease relapse in first-line BTK-era. The expected results will be the generation of comprehensive integrated models for relapse prediction MCL and development of an effective platform to develop rational chemotherapy-free strategies based on genetic alterations of the malignant cell and innovative biomarker-driven strategies.

Project Term: July 1, 2023 - June 30, 2027

Angioimmunoblastic T-cell lymphoma is a rare, aggressive form of T-cell lymphoma associated with poor clinical outcomes in response to current therapeutic approaches. Recurrent oncogenic mutations in isocitrate dehydrogenase 2 (IDH2) have been identified in patients with angioimmunoblastic T-cell lymphoma and this represents a targetable lesion in other malignancies. However, comprehensive investigations of mutant IDH2 inhibition in angioimmunoblastic T-cell lymphoma are lacking, and this may represent a new therapeutic avenue for a patient population in need of newer treatments

Project Term: July 2, 2023 - June 30, 2026

We are conducting a clinical trial testing a novel form of immunotherapy, called a bispecific antibody, as part of initial treatment for patients with follicular lymphoma. The goal of the trial is two-fold: 1) to establish a highly effective, chemotherapy-free treatment option for patients with follicular lymphoma, and 2) to establish predictors of response and toxicity that can guide treatment decisions for future patients with follicular lymphoma.

Project Term: July 1, 2024 - June 30, 2027

Our project’s goal is to change how multiple myeloma is understood and treated by interrogating a novel part of the cellular “soil” (the bone marrow adipocyte), in which myeloma cells, or “seeds”, land and grow. We will discover new forms of cancer drug resistance that are driven by adipocyte-derived factors and the fatty acid binding proteins. This work will expose new ways to overcome drug resistance to improve survival and quality of life for myeloma and other hematological cancer patients.

Project Term: July 1, 2024 - June 30, 2029

Outcomes for acute myeloid leukemia (AML) and multiple myeloma (MM) patients remain inadequate and new treatment options to combat resistance against existing agents are urgently needed. My research aims to identify and target selective vulnerabilities of AML and MM cells. I am particularly interested in epigenetic and metabolic pathways that control self-renewal and differentiation of hematopoietic cells and that can be leveraged to modulate cell fate for therapeutic benefit.

Project Term: July 1, 2024 - June 30, 2029

The primary focus of research is to better understand mechanisms of resistance to immunotherapies and design treatment approaches to improve outcomes. I hope to accomplish this by conducting clinical trials that concurrently target both BCMA and GPRC5D in patients with advanced multiple myeloma and by studying antigen expression, tumor genetics, and T cell characteristics to better understand mechanisms of resistance. The goal is to develop more effective immune treatments for myeloma.

Project Term: July 1, 2024 - June 30, 2029

Mutations in RNA splicing factors, particularly those involving the core splicing factor SF3B1 are amongst the most common mutations found in myeloid neoplasms. We recently identified a cofactor protein known as GPATCH8 which is required for the aberrant function of mutant SF3B1. We now seek to understand and target the ways in which GPATCH8 and SF3B1 interact. In so doing we hope to develop new treatments for leukemias containing mutant splicing factors.

Project Term: July 1, 2024 - June 30, 2027

We are evaluating two parallel clinical trials with synergistic immunotherapies in mantle cell lymphoma (MCL), including 1) tafasitamab and lenalidomide and 2) glofitamab and lenalidomide. We will investigate how these treatments impact the MCL immune microenvironment and mediate anti-tumor immune responses, and will correlate these changes with outcome.Our goal is to develop safe, effective, and "off-the-shelf" immunotherapies to improve outcomes for patients with relapsed, refractory MCL.

Project Term: July 1, 2024 - June 30, 2029

Advances in the treatment of Langerhans cell histiocytosis and Erdheim-Chester disease have led to a growing survivor population; however, there is a lack of information regarding the long-term outcomes, healthcare needs, and health-related quality of life in the era of targeted therapies. We propose the creation of a large national cohort of survivors with histiocytosis to address unanswered questions, eventually leading to targeted survivorship programs for this vulnerable population.

Project Term: July 1, 2024 - June 30, 2029

Vitamin A is safe, well tolerated and positively affects gut immune health. Graft versus host disease (GVHD) is a life-threatening complication of bone marrow transplant (BMT) which happens due to inflammatory changes in the gut. We harnessed the anti-inflammatory properties of vitamin A by giving it to children before bone marrow transplant (BMT) and showed reduction in acute gut and moderate/severe chronic GVHD. We will validate our findings in this currently proposed study of an independent group of adult BMT patients. We will give vitamin A or placebo before BMT to adult BMT patients and observe for reduction of chronic GVHD in vitamin A recipients compared to placebo. This study will be a step forward in adoption of vitamin A as a universal strategy to prevent GVHD which is affordable ($1.25 for entire treatment), non-toxic, and doesn’t suppress the immune system.

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