Research we fund

Improving survival for patients with diffuse large B-cell lymphoma requires tailoring treatment to lymphoma genetic heterogeneity, addressing minimal residual disease (MRD), and bringing safer, effective therapies for frail patients who cannot tolerate aggressive regimens. I address these challenges with genomic subtype targeted treatment, bispecific antibody to eliminate MRD, and novel treatment for frail patients. My goal is to improve outcomes by bringing biomarkers to standard of care.

I focus on developing bispecific antibodies (BsAb) for the treatment of B-cell non-Hodgkin lymphoma (B-NHL). We are testing chemo-free epcoritamab or mosunetuzumab combinations in follicular lymphoma, incorporating glofitamab or epcoritamab in the treatment of aggressive lymphomas, studying resistance mechanisms in patient samples from our trials, analyzing our experience to increase BsAb safety. Our goal is to leverage BsAb to improve upon current standards and shift B-NHL treatment paradigms.

The overall focus of my research is improving outcomes with immunotherapy in multiple myeloma.  I will accomplish this through 1) novel clinical trials of bispecific antibodies and CAR-T therapy; 2) outcomes research including real world evidence and patient reported outcomes to understand the safety, efficacy and areas of unmet need with standard of care immunotherapy; and 3) correlative studies focused on understanding factors impacting the efficacy and toxicity of these therapies.

My group studies the mechanisms of relapse and toxicity after chimeric antigen receptor T cell (CART) immunotherapy to rationally design innovative next-generation immunotherapies for relapsed/refractory lymphomas. To achieve this goal, we use patient-derived samples, cutting-edge technologies, and translational models. The ultimate objective of my research is to establish novel clinical strategies to overcome relapses and improve the safety of our patients.

We investigate the biology, genetics and treatment of myeloid malignancies, including CHIP, MDS and AML. Our goal is to improve our understanding of the effect of chromatin organization on hematopoietic stem cell transformation in the context of mutations in cohesin genes and other recurrently mutated epigenetic modulators. We employ a combination of genomic, mouse modeling, biochemistry and molecular biology approaches to answer disease relevant questions to identify novel therapeutic targets.

Hematopoiesis is tightly regulated by intrinsic and extrinsic signals, alterations of which can affect hematopoietic stem cell (HSC) function and lead to leukemia. We will employ novel preclinical mouse models to investigate the mechanisms that promote leukemogenesis, with the focus on interplay between DNA damage and immune response; stem cell-niche interaction; aging; oncogenic stress-induced complex formation; thereby develop new approaches to improve HSC function and for leukemia therapy.

This study will evaluate the effectiveness of two integrated initiatives aimed at enhancing enrollment of minoritized patients in blood cancer clinical trials. The first initiative aims to increase access to trials by utilizing procedures and technology that facilitate referral of patients from community sites of care to an academic cancer center, fostering physician collaboration, and supporting patient navigation. The second initiative seeks to lower trial design-related barriers at the cancer center through equity-focused alterations to the trial development infrastructure and processes combined with a comprehensive staff engagement strategy.

Cancer clinical trials (CTs) provide high-quality care and are important for advancing treatment options, yet most Veterans Administration (VA) facilities do not have CTs available for veterans with blood cancer and face challenges in enrolling veterans on the CTs that do exist. With an innovative, multi-faceted approach to supporting VA research teams as well as educating and assisting veterans, this study will address barriers at the institutional, clinician, and patient levels to increase enrollment of veterans with blood cancer on CTs.

Posttransplant lymphoproliferative disorders (PTLD) are a group of lymphomas that arise during immunosuppression following organ transplantation and are a significant source of morbidity and mortality. PTLD remains challenging to treat due to disease heterogeneity, patient comorbidities, the risk of infectious complications, and organ rejection. The goals of this proposal are to (1) study the therapeutic efficacy and safety of dose modified R-EPOCH in High-Risk PTLD patients; (2) determine the utility of ctDNA defined molecular response as a novel risk-stratification biomarker in PTLD; (3) understand the impact of immune-suppression on T cell function, T cell receptor diversity, and the detection of oncoviruses. The overall goal is to reduce morbidity and identify novel biomarkers for personalized precision treatment decisions to improve survival in this devastating disease.

AMKL is a rare leukemia that largely affects infants and toddlers. Of the various subtypes of this disease, CBAF2T3-GLIS2 positive AMKL has proven particularly difficult to treat with traditional cytotoxic chemotherapies and bone marrow transplantation with dismal outcomes. The objective of this study is to investigate protein dependencies in CBAFT2T3-GLIS2 fusion positive AMKL to identify new, and desperately needed, drug targets.

We will conduct a decentralized randomized controlled trial of a high-fiber plant-based dietary intervention among patients with multiple myeloma undergoing induction chemoimmunotherapy. The study will assess whether the intervention (meals and virtual coaching) leads to improved rates of complete response, and quality of life mediated by improvements in weight and insulin resistance. The study is expected to provide rigorous evidence of the effectiveness of this intervention in patients with newly diagnosed multiple myeloma and support the development of low-cost, minimal-risk nutrition as a strategy to improve cancer treatment outcomes.

To improve the cure rate of patients suffering from acute myeloid leukemia (AML), our study aims to target resistant leukemia stem cells by developing an 'antibody-drug conjugate' (ADC) against CD99, a protein expressed on these cells. Initial tests of two ADC versions have shown promise in combating AML. Our next steps involve refining the anti-CD99 antibody, identifying the optimal drug for conjugation, and testing the ADC on patient-derived leukemia models. Completing these objectives will pave the way for a phase 1 clinical trial, offering a potentially transformative treatment for AML.