Research

My laboratory investigates how genetic and epigenomic alterations converge to drive dysregulation of gene transcription in cancer. Transcriptional misregulation is a critical outcome of oncogenic processes, yet how genetic mutations, change of cis-regulatory elements, and binding of transcription factor activity jointly shape transcriptional programs remains poorly understood. Tumor heterogeneity further complicates this relationship, as bulk analyses can misleadingly associate regulatory events arising from distinct cell populations. The dynamic co-evolution of genetic and epigenomic alterations with the transcriptional outcome remains largely uncaptured, despite its critical implications for cancer diagnosis and treatment. To address these gaps, my laboratory focuses on three interconnected research domains that resolve transcriptional regulation at single-cell resolution:

• Developing high-throughput, cost-effective single-cell technologies that jointly profile multiple modalities from the same cells. These platforms are designed to scale to heterogeneous cancer tissues and to track regulatory and transcriptional evolution across disease stages, such as primary tumors, metastases, and relapse.
  
• Investigating gain of transcriptional silencers. While silencer gain has emerged as a mechanism of tumor suppressor repression, their target genes and regulation by transcription factors and genetic variants remain poorly defined. We integrate high-throughput CRISPR perturbation with novel single-cell readouts to interrogate silencer function at scale.
  
• We collaborate with cancer biologists to understand the epigenetic regulation underlying heterogeneous cancer and immune cell behaviors and variable responses to treatment. Using Paired-TF, a single-cell technology developed by Dr. Xu, we simultaneously assess epigenetic programs and functional transcriptional states in immune cells, with the goal of identifying regulatory programs that can be leveraged to strengthen immune cell states in combating tumors.

My laboratory integrates experimental and computational approaches. By coupling technology development with biological and medical questions, we aim to resolve regulatory mechanisms in heterogeneous tumors and translate these insights into improved cancer diagnosis and therapeutic strategies.