Research we fund

Dana-Farber Cancer Institute

AML recurrence is a devastating event after allo-HCT. I hypothesize that it could be counteracted through targeting of leukemia-restricted mHAgs via TCR-like CARs. I will identify scFVs recognizing mHAg:HLA complexes using a cell-free nanobody screening platform, and test the anti-leukemia activity and safety of CAR-Ts bearing such scFVs in vitro and in vivo. Through this approach, I will build a library of CAR constructs able to provide population-scale coverage for at-risk allo-HCT patients.

Program Name(s)

Career Development Program

University of Colorado Denver, Anschutz Medical Campus

Relapsed and/or refractory acute myeloid leukemia (AML) display resistance to Venetoclax and Azacitidine (Ven/Aza) with approximately one third of patients demonstrating upregulated protein synthesis. This proposal will investigate the mechanism(s) underlying the dependence of Ven/Aza-resistant AML on protein synthesis as well as the functional consequences of targeting this pathway. Successful completion of these studies will provide novel insights into Ven/Aza resistance mechanisms.

Program Name(s)

Career Development Program

Weill Cornell Medicine

Richter’s syndrome (RS) is a critical complication of chronic lymphocytic leukemia. RS patients are refractory to most existing therapies and show a median survival of ~12 months. I aim to dissect the function of a frequently mutated gene in RS (i.e., MGA) through cutting-edge single-cell analyses of patient samples and mouse models. The objective of these studies is to understand transformation biology, unravel novel therapeutic vulnerabilities, and provide the basis for personalized therapy.

Program Name(s)

Career Development Program

University of Cincinnati

Based on our preliminary data, we hypothesize that IRAK4 inhibition leads to LSPC reprogramming in MDS and AML. Aim 1 will evaluate the mechanism by which IRAK4 inhibition leads to LSPC reprogramming in cell lines, mice, and PDX samples. Aim 2 will concentrate on understanding of how IRAK4 inhibition creates synthetic lethal dependencies with the CELMoD CC-885 and how neosubstrates of CC-885 mediate the synergy upon IRAK4 inhibition in leukemic cells.

Program Name(s)

Career Development Program

Memorial Sloan Kettering Cancer Center

A major limitation of immunotherapy approaches for AML has been the lack of known targetable cell surface antigens specific to AML cells. This project characterizes the pathologic and biologic effects of a novel cell surface antigen complex uniquely present on AML cells but not normal hematopoietic precursors, known as the U5 snRNP complex. Furthermore, we will interrogates U5 snRNP complex components as novel AML-associated antigens and CAR T cells targets for AML treatment.

Program Name(s)

Career Development Program

Versiti Blood Center of Wisconsin

p>SIRT5 is a master regulator of central energy metabolism. The survival and growth of Acute Myeloid Leukemia (AML) cells depend on SIRT5. I will employ genetic SIRT5 disruption and small molecule inhibitors to target SIRT5 in Acute Lymphoblastic Leukemia (ALL) cells and primary samples. This study aims to 1) determine the effects of SIRT5 inhibition on ALL in vitro and in vivo, and 2) identify SIRT5-regulated pathways and mechanisms underlying SIRT5 dependency in T-ALL. 

Program Name(s)

Career Development Program

Cincinnati Children's Hospital

AML risk stratification established by previous studies do not reflect survival outcomes observed in Black patients. Exome sequencing of 100 Black AML patients revealed the novel variants previously not affiliated with AML, including PHIP. Using multiomic patient sample captures and GEMMs, we will functionalize variants in PHIP and assess if they drive leukemogenesis and/or therapy resistance. The overall goal of this work is to implement inclusive genetic assessment tools for AML diagnosis.

Program Name(s)

Career Development Program

The Brigham and Women’s Hospital

The focus of my research is to evaluate the efficacy of and to unravel the molecular mechanisms underpinning a novel drug combination in AML targeting oncogenic protein translation and apoptosis. We will utilize genetic perturbation and other orthogonal approaches, including in vitro and ex vivo assays, and in vivo AML PDX models. The goal of my research is to transform the clinical management of AML patients, particularly for relapsed and difficult-to-treat subgroups.

Program Name(s)

Career Development Program

Dana-Farber Cancer Institute

NPM1-mutated leukemia is the most common AML in adult and characterized by upregulations of HOXA/B genes and MEIS1. Given the importance of oncogenic transcriptional program, I will determine regulatory molecules that cooperate with mutant NPM1 on chromatin by combining CRISPR/Cas9 screening approach in an innovative model system of endogenous transcription reporters with proteomics approach. This will facilitate identification of novel therapeutic targets specific for NPM1-mutated AML.

Program Name(s)

Career Development Program

Duke University Medical Center

Altered B cell homeostasis plays a key role in the development of chronic graft-vs-host-disease (cGVHD) after hematopoietic stem cell transplantation (HCT). We hypothesize that the DNA sensor AIM2 plays a critical role in the fate of BCR-activated B cells after HCT. We will utilize novel mouse models to investigate AIM2-BCR modulation with clear translational implications in autoreactivity perpetuating cGVHD as well as functional humoral deficiency and vaccine hyporesponsiveness after HCT.

Program Name(s)

Career Development Program

Nodular lymphocyte-predominant Hodgkin lymphoma is recognized as a disease entity in a spectrum of related diseases, including T-cell rich B-cell lymphoma. Although treatments are generally effective, a subset of patients suffers from lymphoma progression and aggressive disease transformations. Here, we propose to analyze clonal evolution of tumor cells and describe the spatial architecture of tissues with the goal to improve molecular classification and develop novel therapeutic approaches.

Program Name(s)

Career Development Program

Yale

I want to understand how the t(1;22) translocation that involves a member of the m6A writer complex drives acute megakaryoblastic leukemia (AMKL). To identify culprit genes and pathways I will use multi-omics, including RNA, eCLIP, and TimeLapse Seq and proteomics. I will dissect the RBM15-MKL specific effects of a novel METTL3 inhibitor in primary murine and human AMKL in vitro and in vivo. My ultimate goal is to cure this rare infant leukemia by harnessing METTL3 inhibition.

Program Name(s)

Career Development Program