Research we fund

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’.

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.

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.

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.

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.

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.

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.

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.

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.

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.