Research we fund

Stanford University

I aim to develop an accurate disease monitoring system and identify immunologic determinants of development and progression in T-cell lymphoma (TCL). I will integrate noninvasive liquid biopsy methods by high-throughput sequencing. I will study blood samples at various milestones, including pre-diagnostic, diagnostic/baseline, and post-treatment specimens during the natural history of TCL. Using these novel tools and unique specimens, my goal is the development of effective therapies for TCL.

Program Name(s)

Career Development Program

St. Jude Children's Research Hospital

Lineage-ambiguous leukemias are high-risk blood cancers with unclear biologic basis and suboptimal treatment options. Here, I will identify the cell of origin of lineage ambiguous leukemia and investigate new therapeutic strategies through in vitro and in vivo experimental modeling approaches and preclinical drug studies in patient-derived xenografts. These studies will clarify the cellular and molecular alterations driving lineage ambiguity and advance a new, rational therapeutic approach.

Program Name(s)

Career Development Program

Washington University in St. Louis

NPM1c and TP53 mutations are exclusive in acute myeloid leukemia (AML) despite both being commonly present in patients, suggesting a fitness disadvantage for cells with co-occurring mutations. However, the mechanisms underlying this exclusivity have not been explored. This project will utilize novel models to dissect the importance of TP53 signaling in NPM1c+ (pre)-leukemic stem cells. Generated results may highlight therapeutic opportunities for improved risk management of NPM1c+ AML patients.

Program Name(s)

Career Development Program

Perelman School of Medicine at the University of Pennsylvania

The goal of this proposal is to investigate the consequence of the chromatin reader eleven-nineteen-leukemia (ENL) gain-of-function mutations in the pathogenesis of leukemia. Our studies leverage the expertise in the molecular and chromatin biology of chromatin reader in leukemia utilizing mouse model, high resolution image, epigenomic and transcriptomic approaches. Our goal is to understand how chromatin reader contributes to cancer development, progression, and therapeutic outcome.

Program Name(s)

Career Development Program

Weill Cornell Medicine

We aim to clarify the role of EZH2 mutations in the development of double hit lymphoma (DHL) and acquisition of chemo-resistance. We confirmed that Ezh2 mutation is essential to develop aggressive murine GCB lymphoma and deplete T cells from tumor in combination with BCL2 and MYC. The mice showed resistance to chemotherapy and the combination with EZH2 inhibitors improve the outcome in vivo. Our goal is to show the synergy and propose a new mechanism-based therapeutic approach for DHL.

Stanford University

The development of acute myeloid leukemia (AML) is preceded by a “preleukemic” phase in which mutated hematopoietic stem cells expand due to a fitness advantage. Our work uses prospective models and analysis of patient samples to study how the duration of preleukemia and how the preleukemic clonal burden affect progression to AML. Results of our studies will shed new light on AML pathogenesis and help guide clinical management of preleukemic conditions such as clonal hematopoiesis.

Program Name(s)

Career Development Program

MD Anderson Cancer Center

Most patients respond well to drugs that inhibit an important MCL target named BTK. However, almost all of them will eventually relapse and then do very poorly. Inhibition of MALT1, a target which is biochemically downstream of BTK, may rescue many of these patients, and inhibiting both BTK and MALT1 may be better still. Developing a drug that inhibits both targets at the same time, from the beginning of treatment, will avoid some complications and likely be best of all; we will find out.

Program Name(s)

Mantle Cell Lymphoma Research Initiative

Albert Einstein College of Medicine

Our research program’s goal is to identify therapeutically actionable pathways in pre-leukemic and leukemic stem cells in myeloid malignancies. We specifically dissect molecular circuits governing stem cell self-renewal and differentiation, how these change during aging, and contribute to leukemic stem cell evolution and maintenance. Accomplishing this work will enable the rational design of curative intervention and perhaps even prevention strategies for patients with myeloid malignancies.

Program Name(s)

Career Development Program

Perelman School of Medicine at the University of Pennsylvania

The goal of this project is to investigate the role of the epigenetic regulator Eleven-Nineteen-Leukemia (ENL) and its cancer mutations in acute myeloid leukemia (AML). Our studies leverage the expertise in chromatin biology, functional genomics, and AML modeling, as well as unique chemical compounds and mouse models. Results from this project will provide novel biological insights into our understanding of AML pathogenesis and facilitate the development of novel epigenetic therapies.

Program Name(s)

Career Development Program

University of Colorado Denver, Anschutz Medical Campus

My lab is focused on understanding the pathogenic interplay between oncogenic mutations, chronic inflammation and aberrant metabolism as a driver of the evolutionary processes that culminate in lethal myeloid malignancies. We leverage mouse models and human patient samples to establish modalities for targeting this interplay throughout disease pathogenesis. My long-term goal is to improve patient outcomes by establishing therapies that prevent and/or delay evolution to acute leukemia.

Program Name(s)

Career Development Program

Columbia University Medical Center

Our research seeks to understand how ordered acquisition of oncogenic mutations transforms human hematopoietic stem cells into myeloid malignancies. We leverage patient-derived induced pluripotent stem cells and primary normal and malignant stem cells to study how mutation cooperation drives leukemic progression in vitro and in vivo. Our long-term goal is to identify disease mechanisms and develop targeted therapies to eradicate malignant stem cells.

Program Name(s)

Career Development Program

University of Southern California

The focus of my research is to understand the causes and early-life origins of acute lymphoblastic leukemia (ALL). We use a two-pronged approach: 1) conducting epidemiological studies of ALL in susceptible populations to understand genetic predisposition, and 2) investigating the in utero origins of ALL across subtypes. Our goals are to identify children at the highest risk of developing ALL through genetic screening and to lay the groundwork for precision prevention strategies.

Program Name(s)

Career Development Program