Research we fund

Our research focuses on identifying the molecular mechanism underlying the development of a dominant population of abnormal stem cells in myelodysplastic syndrome (MDS) patients. We will employ mouse genetic models and MDS patient samples to elucidate the role of FOXM1 in the development of a dominant population of abnormal stem cells in vivo. This research program may lead to the identification of new effective therapeutic strategies for the treatment of early stages of MDS patients.

Project Term: July 1, 2018 - June 30, 2023

Cutaneous T-cell lymphoma (CTCL) is a disfiguring, incurable malignancy profoundly affecting patients’ appearances, quality of life, and relationships. Standard treatments only benefit 30% of patients with limited duration. Rather than focusing on the tumor alone, we target the adjacent tumor microenvironment, which nourishes tumor growth. We have begun a clinical trial of durvalumab, which is an inhibitor of the checkpoint protein receptor PD-L1. We are currently investigating how immune checkpoint proteins together with the immune booster lenalidomide affect CTCL growth. This research will benefit not only those with CTCL but many other cancers.

Project Term: July 1, 2018 - June 30, 2023

Acute lymphoblastic leukemia (ALL) represents the most frequent type of cancer in children and displays high rates of relapse. In this context, mutations in NT5C2 act as major drivers of resistance to chemotherapy with 6-mercaptopurine and are associated with early relapse and progression. Our project aims to investigate the regulation of this protein and design NT5C2 inhibitors that would prevent and improve the treatment of relapsed leukemia patients.

Project Term: October 1, 2021 - September 30, 2023

Short telomeres, the protective caps at the ends of DNA, are associated with increased risk of fatal toxicity among stem cell transplant recipients. We will determine 1) the relationship between recipient telomere length and intestinal injury after transplant and 2) how telomere length influences intestinal healing in a transplant mouse model. The goal of this work is to identify transplant patients at increased risk of toxicity and design therapies to improve patient survival.

Project Term: October 1, 2021 - September 30, 2023

Our research focuses on the study of a novel therapeutic target, named Plek2, in the development of myeloproliferative neoplasms (MPNs). MPNs can progress to leukemia and there are currently no cures. We use animal models and patient samples to study how elevated levels of Plek2 causes the disease and identify approaches to suppress the function of Plek2. Our goal is to use the knowledge from this study to develop novel therapies to treat MPNs.

Project Term: July 1, 2017 - June 30, 2022

CAR T-cells are highly effective in lymphoma but limited by a profound and potentially fatal toxicity involving the central nervous system (CNS). Little is known about how CAR T-cells eliminate lymphoma cells in the CNS nor how this therapy causes toxicity. I will study CAR T-cells in patients with CNS lymphomas with the goal of expanding CAR T-cell indications. I will also examine serial blood and CNS samples to understand neurologic toxicity to inform new therapies to control this toxicity.

Project Term: October 1, 2021 - September 30, 2026

Ibrutinib is a targeted oral treatment for CLL that is safe and highly effective, however it must be given indefinitely which leads to chronic side effects and allows resistance to develop. We are conducting two clinical trials that add a second drug to ibrutinib to eliminate the remaining leukemia or ibrutinib-resistant leukemia cells. If these trials are successful, people taking CLL with or without resistance may be able to stop treatment in remission after taking an ibrutinib combination.

Project Term: July 1, 2019 - June 30, 2024

Enhancing the commitment of leukemia stem cells (LSCs) is a promising therapeutic strategy against blood cancer, but tracking the division pattern of individual cells has proved difficult. We have established a novel technical regimen to assess the behavior of individual LSCs and their cell fate in vivo. Genetic mouse models and mouse models engrafted with leukemia patient samples are also used. Our project seeks to elucidate the role of mitophagy in the control of LSC division balance, which may facilitate new therapy targeting these cells.

Project Term: July 1, 2018 - June 30, 2023

Coming soon.

Project Term: July 1, 2021 - June 30, 2026

Apoptosis is a normal cellular process of getting rid of extra cells that is co-opted by cancer cells to enhance their own survival, and we aim to better understand this process in myelodysplastic syndromes (MDS). Pevonedistat (PEV) is a novel therapy presumed to function, in part, through its effects on apoptosis. Our clinical trial will combine PEV with the standard of care therapy for MDS, azacitidine, in order to keep cancer cells from hijacking apoptosis, and we will study patient samples to match responses with molecular changes in the cancer cells. We seek to determine the suitability of this approach for MDS, and the ability to predict which patients may respond to PEV-based therapy.

Project Term: July 1, 2018 - June 30, 2023

New, non-chemotherapy treatments that use a patient’s own immune system have transformed the treatment of Hodgkin lymphoma (cHL). Typically used in patients with cHL that is resistant to standard treatment, these immune therapies can control the disease for months to years. However, in the long run, most patients will not be cured and will have immunotherapy-resistant cHL. My research evaluates strategies for reversing resistance to brentuximab vedotin (BV) immunotherapy for cHL by combining BV with other treatments in clinical trials.

Project Term: July 1, 2018 - June 30, 2023

We seek to understand the genetic and epigenetic etiology of B-cell lymphoma and how deregulation of normal epigenetic programs perturb developmental programs and immune interactions. We approach this using a variety of genomic technologies to interrogate primary human tumors, CRISPR-engineered cell lines, patient-derived xenograft models and transgenic mouse models with different genetic lesions. We hope to understand how genetic and epigenetic changes associated with B-cell lymphoma create dependencies or characteristics that can be targeted through rational therapeutic interventions to improve patient outcomes.

Project Term: October 1, 2020 - September 30, 2025