Our Research

Our primary goals are to identify the mechanism of relapse to targeted therapy by studying tumor intrinsic and tumor extrinsic mechanisms.

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In the long run, we envision that understanding the emergence of drug resistance mechanisms in-vivo by combining unique functional and genomic technologies will guide us towards clinically-relevant precision target identification for treating relapsed cancers.

Methodologies and Experimental Platforms

Functional Genomics

We preform functional genomic screens to identify relapse specific dependencies that results in druggable vulnerabilities

Multi-Dimensional
Multi-Omics

We perform multi-dimensional studies involving mitochondrial outer membrane potential measurements, targeted exome sequencing, transcriptomics and DNA barcoding.

Translational Tumor Models

We exploit human blood cancer cell lines, patient-derived xenograft models and primary tumor specimens to address our hypotheses.

Mitochondrial Priming Platform

By using mitochondrial priming as a platform, we can identify changes in mitochondrial signaling in PDX models and patient tumors.

Overcoming resistance to acute myeloid leukemia therapy

While it has been realized that there is no one-size-fits-all solution, selecting the right patient population that can benefit from therapy and yet not develop drug resistance remains a major challenge. The need to personalize therapy in relapse settings is more dire as the relapsed tumor is more heterogeneous and responsive to a smaller handful of treatments. We seek to understand the process by which resistant cells evolve during therapy as a basis to develop improved and personalized therapy.

Identifying mechanism of resistance to venetoclax based therapy in myeloid malignancies

Combination therapy of hypomethylating agent with the BCL2 antagonist venetoclax has emerged as an effective treatment option for patients with AML (73% response in patients >75 years or patients unfit for intensive chemotherapy).

However, mutations in TP53 are associated with low response rates (40%) and poor outcomes in venetoclax-based combination therapy. We aim to elucidate mechanisms behind the resistance towards venetoclax-based combination therapy and seek potential treatments to overcome this resistance.

Characterizing

mechanisms of immune dysfunction in acute myeloid leukemia

Growing evidence suggests that immune dysfunction plays a central role in tumor development, progression, and drug resistance in both hematopoietic and solid tumors. However, despite the progress in this field, patients with AML remain devoid of benefits from immunotherapy. Our group aims to study the relationship between immune dysfunction and therapy resistance in AML.