Research we fund

TP53-mutant clonal hematopoiesis (CH) is prevalent in populations that received genotoxic cancer therapy and is associated with elevated risk for therapy-related myeloid neoplasms (t-MNs). Here, I developed a human model of TP53-mutant CH that exhibits clonal expansion upon exposure to olaparib or paclitaxel treatment and identified a targetable synthetic lethality target DOCK1 that might prevent this clonal expansion. I aim to develop targeted therapies of high-risk TP53-mutant CH and t-MNs.

Relapse after allogeneic hematopoietic cell transplantation (HCT) in acute myeloid leukemia (AML) remains a leading cause of mortality. Our studies reveal that AML drives Wilms’ Tumor 1-specific CD8⁺ T cells into a senescent, natural killer-like state that impairs function and persistence. We will target this pathway and engineer costimulatory switch receptors to rejuvenate T-cell receptor–engineered T cells, enabling durable leukemia control and preventing post-HCT relapse.

My program includes three investigator-initiated studies focusing on large B-cell lymphoma (LBCL), including those with central nervous system involvement. These studies incorporate novel agents in untreated and relapsed/refractory LBCL, tailoring treatment based on genomic signatures and the clearance of minimal residual disease. My goal is to conduct practice-changing research that will positively impact patient outcomes, incorporating biomarkers into the decision-making process.

Patients with T-cell lymphomas (TCL) face poor outcomes due to ineffective therapies and lack of validated biologic targets. My proposal evaluates 3 clinical trials: JAK1 inhibition in untreated peripheral TCL, JAK2/PD-1 blockade in relapsed/refractory peripheral and cutaneous TCL, and chemotherapy optimization in HTLV-1-associated TCL. My overall goal is to generate evidence that redefines therapeutic standards and informs the design of future biomarker-driven clinical trials in TCL.

My research aims to understand the genetic drivers of leukemia to develop safer, more effective therapies. I lead the clinical studies of menin inhibitors which resulted in the first FDA approval of this class. I have also established a precision medicine program centered on biomarkers, resistance, and rational combination strategies with menin inhibitors, including advancement of next-generation epigenetic therapies that target aberrant transcription in leukemia.

This program leverages the accessibility of cutaneous T-cell lymphoma (CTCL) to define how interactions among tumor cells, host immunity, and microbes shape disease progression and treatment response. Through integrated clinical trials, multi-omic mapping, and biomarker discovery, it aims to advance precision diagnosis and therapy for patients with CTCL.

My research focuses on dissecting the epigenetic and transcriptional mechanisms in acute myeloid leukemia. Using tools from molecular and structural biology, chemical biology, genomics, bioinformatics, and preclinical models, I aim to decode chromatin dynamics and regulatory landscapes that drive disease progression and therapy resistance. The ultimate goal of my work is to facilitate the development of more effective, targeted treatments to improve patient outcomes.

I will advance precision combination therapy for blood cancers by computational and experimental pharmacology. In large B-cell lymphoma we will analyze and model subtype-guided pola-vedotin, genome-guided targeted therapy trials, and MRD-based care. In T-cell lymphomas, drug profiling and CRISPR screens will identify response predictors for subtype-specific regimens. In multiple myeloma we will analyze trials to resolve when intensified first-line regimens are superior to sequential therapy.

Our research aims to identify and exploit vulnerabilities that distinguish acute myeloid leukemia (AML) cells from healthy blood cells. We found that targeting protein translation can selectively induce apoptosis in AML cells and are working to translate this into new therapies. Using advanced single-cell sequencing, we track malignant cells across disease evolution to eliminate those that drive relapse. Our overall goal is to develop more effective treatments for patients with AML.

A ketogenic diet, implemented by use of a beta-hydroxybutyrate energy drink (BHB), improves the ability of CAR T cells to fight cancer in laboratory experiments. We now apply this discovery to patients with large B-cell lymphomas who need CAR T cell treatment (CART). The main goals of this clinical trial are to show that BHB, a dietary supplement, in combination with CART improves CART function, is safe for lymphoma patients, and increases the number of patients who are cured.