The Jian Huang Lab

The Huang Lab is investigating the regulation of hematopoietic stem cell (HSC) self-renewal and differentiation as well as drug resistance of hematological malignancies.

Specifically, our research focuses on:

  • Understanding the roles of GSK3 and PPAR-δ/mitophagy signaling in the regulation of HSCs self-renewal, and how defects in the signaling pathways lead to leukemogenesis.
  • Identifying new targets in leukemia therapy with a multiplexed genome editing CRISPR screening platform.
  • Investigating the role of epigenetic regulation especially DNA methylation in HSC function and homeostasis.

Our recent work identified a new connection between GSK3 and PPAR-δ/mitophagy pathway, which will provide new insights into the mechanisms of the regulation of HSC activity and may improve the therapy of many hematopoietic disorders. Currently, we use genetically-engineered mouse models, bone marrow transplantation, single-cell transcriptome profiling and imaging as well as time-lapse tracking assays to investigate the roles of GSK3, PPAR-σ and key regulators of mitophagy in regulating HSC homeostasis and function.

As an effort to understand hematological malignancies, we also developed a new research direction that focuses on drug resistance of Acute Myeloid Leukemia (AML). The drug resistance of AML contributes to the relapse of the disease. We carried out an unbiased CRISPR-based screen for genes whose loss confers drug resistance. In the screen, we identified SPRY3 and GSK3 as the leading hits. SPRY3 and GSK3 are key negative regulators of Ras/MAPK and Wnt signaling, respectively. Accordingly, we discovered that re-activation of these signaling pathways in AML are a major mechanism that confer resistance to Quizartinib (AC220). Remarkably, we also confirmed our findings in primary AML patient samples and discovered that the expression of SPRY3 and GSK3 is dramatically reduced in AC220 resistant AML patient samples. Next, we plan to further explore the detailed molecular mechanisms underlying resistance to Tyrosine kinase inhibitor (TKI) in FLT3ITD+ AML.

Join the Team

The Huang Lab is always looking for talented scientists who share a passion for stem cell biology, signal transduction, epigenetics, or gene engineering. Contact Human Resources if you're a good fit.