Research we fund

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.

In June 2025, LLS made an equity investment in Auron Therapeutics to "Support Clinical Development of AUTX-703 in Relapsed/Refractory AML and MDS."

Auron Therapeutics is a platform-powered company targeting cell-state plasticity to improve patient outcomes in oncology and inflammatory disease. Auron pioneered its AURIGIN platform, which uses AI and machine learning to compare cell states and identify novel drug targets, optimal development models, and biomarkers to facilitate proper patient selection, ultimately accelerating the development of effective and durable therapies.  

Leveraging its AURIGIN platform, KAT2A/B was identified as a key driver of cell plasticity and disease. AUTX-703 is a first-in-class, oral KAT2A/B degrader and is being evaluated in a Phase 1 dose escalation and dose optimization study in patients with relapsed/refractory AML or MDS (NCT06846606). 

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.

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.

In October 2023, LLS made an equity investment in Vittoria to "Support Clinical Development of VIPER-101, a CAR-T Cell Therapy for T-cell lymphomas."

Vittoria Biotherapeutics is developing novel CAR-T cell therapies that transcend the limitations of current cell therapies. Based on technology exclusively licensed from the University of Pennsylvania, Vittoria's proprietary Senza5 platform unlocks the antitumor potential of engineered T cells and utilizes a five-day manufacturing process to maximize stemness, durability, and target cell cytotoxicity. By acting on the fundamental biology of T cells, Senza5 can be used to improve the efficacy of engineered T cell therapies with pipeline applications in oncology and autoimmune diseases.

Vittoria aims to conduct a Phase 1 dose escalation clinical trial for its lead program VIPER-101, an autologous, dual population CD5-knockout CAR-T cell therapy for T-cell Lymphoma featuring the novel Senza5 platform technology. The Phase 1 trial is ongoing to assess the safety and efficacy of VIPER-101 in patients with T-cell lymphomas (NCT06420089).