Research we fund

Leukemia stem cells (LSCs) are highly heterogeneous populations and key contributors to AML progression. Here, I aim to employ heparan sulfate (HS) glycotyping to resolve LSC heterogeneity. Using complementary genetic and antibody-based approaches, I will delineate the functional roles of HS pathway during AML progression. The newer insights provided by these studies could potentially uncover novel LSC therapies and facilitate diverse training for me to become an independent leukemia researcher.

Project Term: July 1, 2024 - June 30, 2026

Overexpression of ID2 is a recurrent event in mature T-cell lymphoma (TCL), and its significance is yet to be established. We will use a multidisciplinary approach combining epigenetic, transcriptomic, and proteomic analysis in human and murine models to identify the mechanisms leading to ID2 overexpression and their effect on T-cell transformation. Our goal is to define the role of ID2 in lymphomagenesis and determine its potential as a novel therapeutic target in TCL.

Project Term: July 1, 2024 - June 30, 2026

My goal is to understand how cancer-associated gene fusions arise and cause disease. Specifically, I am studying how oncogenic fusions involving the gene KMT2A arise in different hematopoietic cell-types and how developmental context drives the development of leukemia. My long-term goals are to leverage an increased fundamental understanding of leukemogenesis provided by this research to improve treatment and lengthen lifespan for patients with KMT2A fusion-driven leukemias.

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

T-cell mediated therapies are all impeded by the same cause- tumoral antigen (Ag) escape: rare Ag– cells in tumors survive the initial attack and lead to relapse. We recently took an innovative approach by enhancing T cells' ability to attack the Ag- cells during the initial treatment. That process is modular by pharmaceutical intervention.The proposed project will analyze cryopreserved excisional B-NHL biopsies to identify possible pharmaceutical targets potentiating their 'vulnerability’.

Project Term: July 1, 2024 - June 30, 2026

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

Our focus is to unravel how clonal hematopoiesis (CH) progresses to leukemia. We will investigate how epigenetic heterogeneity affects Tet2-mutant hematopoietic stem cells (HSCs) during aging. We plan to simultaneously trace HSC clonal identity and clonal history by genetic barcode and single-cell multi-omics and determine their epigenetic configurations adaptive in the aged, inflammatory bone marrow. The long-term goal is to create innovative therapeutics to mitigate CH and prolong health span.

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

Acute myeloid leukemia is life-threatening and heterogeneous, and although classification models help guide treatment, they do not use detailed phenotypic information or dynamically update with new data during a patient’s course. We will develop computational methods to extract both mutations and phenotype from the electronic health record. Machine learning models will be built that adapt to new data over time so that all clinically relevant data is used when personalizing a patient’s therapy.

Project Term: July 1, 2023 - June 30, 2026