Zhiquan Wang, Ph.D.

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SUMMARY

The interests of Mayo Clinic researcher Zhiquan Wang, Ph.D., lie in the chromatin-related mechanisms underlying the initiation and maintenance of hematologic malignancies. Using a combination of biochemical, molecular and bioinformatics approaches, Dr. Wang investigates how chromatin regulators sustain the leukemic processes that contribute to the biological capacity of chronic lymphocytic leukemia (CLL) cells, thereby identifying new therapeutic targets for this disease.

Focus areas

• Bruton's tyrosine kinase inhibitor (BTKi) to treat B cell malignancies. Dr. Wang is exploring the epigenetic determinants of BTKi efficacy and new therapeutic strategies to overcome BTKi efficacy resistance in patients with B cell CLL and other B cell malignancies. To do so, he is analyzing epigenetic profiles of leukemic cells from patients with CLL who are receiving BTKi efficacy (ibrutinib) treatment. The profiles, which Dr. Wang analyzes at baseline, on ibrutinib treatment and at relapse, include:

  • Histone modifications CUT&Tag
  • ATAC-seq
  • Transcription factor CUT&RUN
  • RNA-seq
  • Integrative bioinformatic analyses

  Dr. Wang is working with Mayo Clinic hematologists including Sameer A. Parikh, M.B.B.S., and Neil E. Kay, M.D., to explore the potential translation of these findings for clinical use.

• Epigenetic dependency of genetic mutations in B cell malignancies. With Susan L. Slager, Ph.D., Esteban Braggio, Ph.D., and Huihuang Yan, Ph.D., Dr. Wang is studying the role of mutations of chromatin regulators — for example, CHD2, histone H1 and MED12 — in the epigenetic reprogramming of malignant B cells.
• Maintenance of the epigenetic and malignant signatures of CLL B cells by histone variants.

Significance to patient care

Dr. Wang's research focuses on CLL as a primary model system to better understand how epigenetic programming regulates malignant B cell survival and affects the efficacy of BTKi efficacy therapies. By defining the epigenetic mechanisms of how cancer cells respond to BTKi efficacy therapies, he aims to lay the foundation for epigenetic strategic manipulations that will enhance and improve therapies for B cell malignancies.