Research we fund

Cell-intrinsic metabolic processes are dysregulated in acute myeloid leukemia (AML) and can act to sustain an oncogenic state of differentiation arrest. Using AML cell lines and patient-derived material grown in sophisticated liquid culture medium that mimics human plasma, we will perform metabolically focused in vitro and in vivo CRISPR-Cas9 screens to reveal metabolic regulators of AML cell fate that can be exploited via dietary or pharmacologic intervention as a novel therapeutic strategy.

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

The focus of my research is to elucidate the core molecular regulators of malignant stem cell generation in multiple myeloma. My approach addresses the tumor cell-intrinsic versus niche-dependent mechanisms of myeloma regeneration by exploring transcription factor expression and stemness profiles within single cells from primary samples and patient-derived models. The central goal of my research is to uncover novel therapeutic strategies and translate these into new myeloma treatments.

Project Term: July 1, 2022 - June 30, 2027

The focus of this research project is to understand how therapeutic chimeric antigen receptor (CAR) T-cells mediate long-term remission of diffuse large B-cell lymphomas. I will use cell free DNA collected from patient plasma to understand if there is an association of CAR T-cell persistence and long-term tumor remission. The goal of this research is to define how CAR T-cells suppress tumors over time to develop better CAR T-cells in the future.

Project Term: July 1, 2022 - TBD

SIRPα+ macrophages mediate resistance to lenalidomide in B-cell lymphoma, limiting the activity of immunotherapy for these patients. Therefore, we propose a phase I/II study, investigating the safety and efficacy of ALX148, a novel fusion protein of the SIRPα binding domain, in combination with rituximab and lenalidomide in patients with B-cell lymphoma. We hypothesize that this combination will be safe and effective, providing a chemotherapy-free option for these patients.

Project Term: July 1, 2022 - June 30, 2027

Leukemia often results from aberrant gene expression caused by epigenetic alterations. Previously we discovered a novel histone acetylation reader domain in the ENL protein and demonstrated that this domain is essential for the survival of a wide range of acute leukemias, making it an attractive therapeutic target. We will develop specific inhibitors of ENL activity in acute leukemias and will use mouse models to define the role of ENL mutations identified in patients in leukemogenesis.

Project Term: July 1, 2022 - June 30, 2027

Our research program aims to gain a deeper understanding of the pathobiology of T-ALL and HSTL.To this end, we will use novel mouse models, cutting-edge techniques and comprehensive genetic, pharmacological and metabolic interventions. In addition, we will perform unbiased experiments to identify novel therapeutic targets.Our goal is to uncover new tools and targets for the treatment of T-ALL and HSTL, which could be used for the benefit of patients in the short/mid-term.

Project Term: July 1, 2022 - June 30, 2027

The long-term goal of my research program is to improve the outcomes for patients with high-risk myeloid blood cancers, particularly those with loss of chromosome 7 or CUX1. We are tackling this question using an arsenal of innovative methods and tools, including mouse models, human cells and patient samples, and state-of-the-art technologies to examine the cancer cell genome. Accomplishing this work will reveal new treatments and strategies for preventing blood cancers from arising.

Project Term: July 1, 2022 - June 30, 2027

My lab is focused on the immune regulatory mechanisms and ubiquitin-dependent machinery in lymphoma. We have established multiple high-throughput screening technologies and animal models to rapidly and accurately identify critical pathways that are suitable for targeted therapy and immunotherapy. Gaining insight into the pathological roles of these pathways can lead to improved understandings of the molecular circuitry that drives lymphoma pathogenesis and provide novel therapeutic strategies.

Project Term: July 1, 2022 - June 30, 2027

Our research program is focused on understanding the intersection between signaling and transcriptional dysfunction in myeloid leukemias. We leverage murine models, cell lines and human samples to uncover how biological context shapes the manifestation of oncogenic programs at the molecular level. Our long-term goal is to harness this knowledge to identify multipronged therapeutic strategies that improve outcomes for patients with myeloid malignancies.

Project Term: July 1, 2022 - June 30, 2027

Our central goal is to improve clinical outcomes in patients with myeloid malignancies through developing an enhanced mechanistic understanding of disease. We use multiomic analyses of primary patient samples combined with complementary laboratory models using mice and cell lines to generate and test our hypotheses. The results of our studies will help improve patient outcomes by identifying strategies to mitigate risk of disease progression/relapse and treatment toxicity.

Project Term: July 1, 2022 - June 30, 2027

The goal of this proposal is to investigate the significance of genes of the ubiquitin proteasome system (UPS) that are mutated in Diffuse Large B-cell Lymphoma (DLBCL). Our studies leverage the expertise in the molecular modeling of the UPS in the pathogenesis of DLBCL utilizing mouse models, patient derived xenotransplant (PDX) and cell lines. Our goal is the understanding of how genetic mutations contribute to disease development, progression and therapeutic outcome.

Project Term: July 1, 2022 - June 30, 2027

The overarching focus of my research is to understand the clonal origin, evolution, and progression of myeloid malignancies and biological and clinical factors that influence the process. We tackle this question by analyzing patient samples with integrated approach combining single-cell omics, evolutionary genetics, and computational analytics. The ultimate goal of our research is to develop clinical strategies for early detection, prevention, and treatments of myeloid malignancies.

Project Term: July 1, 2022 - June 30, 2027