xinyang zhaoAssistant Professor

Research Areas
Hematopoiesis and hematological malignancies


Research Interests

My research interestis focused on understanding the molecular mechanisms involved in normal hematopoiesis as well as hematological malignancies including leukemia and pre-leukemia diseases such as myeloid proliferative neoplasm and myelodysplasia syndrome (MDS). Right now my research is funded by NIH and leukemia research foundation.

1. To understand PRMT1-mediated metabolic reprogramming in leukemogenesis.
We elucidate that protein arginine methyltransferases 1 (PRMT1) methylates an RNA binding protein called RBM15 and thus controls the RBM15 protein stability. RBM15 is required for the metabolic stress response of hematopoietic stem cell for self-renewal, and is involved in chromosome translocation with MKL1 in acute megakaryocytic leukemia (AMKL). In this project, I will address how the PRMT1-RBM15 axis regulates metabolic pathways, which are criticalfor AMKL progression.

2. To understand PRMT1-mediated RNA splicing pathways in MDS.
We have demonstrated that alternative RNA splicing of a few key transcription factors pivotal for hematopoiesis is regulated by the PRMT1-RBM15 axis. Enhanced interaction between RBM15 and SF3B1 K700E mutant found in MDS patients dysregulates alternative RNA splicing of transcription factors. Given that more than 70% of MDS have mutations in splicing factors, understanding the RNA splicing codes recognized by RBM15 will hold a key to design precision medicine for MDS.

3. To understand PRMT1-controled signaling pathways in hematopoiesis and leukemogenesis.
My lab has discovered that PRMT1 methylates a dual specific phosphatase called DUSP4. DUSP4 is a chromatin-associated phosphatase which can directly relay mitogen-activated protein (MAP)kinase signals to cause epigenetic changes. Methylation of DUSP4 by PRMT1 leads to its degradation and blockage of megakaryocyte differentiation. In collaboration with scientists at Memorial Sloan Kettering Cancer Center and Cold Spring Harbor Lab, my lab is using single cell RNA-seq technology and CRSPR-Cas technology to analyze pathways regulated by the PRMT1-DUSP4 axis. We are attempting to purify the E3 ligase which is responsible for recognizing the methylated DUSP4 using biochemical approaches. The role this PRMT1-DUSP4 pathway in leukemogenesis is being studied with PRMT1 transgenic mouse models.

4. To understand the role of long non-coding RNA genes in hematopoiesis.
My lab has reported how RBM15 protein translation is regulated by along noncoding RNA (AS-RBM15). Given that little is known about the biological roles of long noncoding RNAs in hematology, the endeavor in my lab will open up new frontiers to understand hematopoiesis and cancer.

5. To develop therapeutic approaches by inhibiting PRMT activities for cancer and cardiovascular diseases.
We have been developing methods to target PRMT1, 4 and 5 for leukemia treatment for many years. In collaboration with biological chemists at Memorial Sloan Kettering Cancer Center and University of Georgia, we have a few potent and specific PRMT1, PRMT4 and PRMT5 inhibitors. Preliminary studies of using these inhibitors have yielded promising data on treating acute myeloid leukemia and cardiovascular diseases. We are now using patient xenograft models to test these inhibitors.

Education

Graduate School
Ph.D., SUNY at Buffalo, New York

Postdoctoral Fellowship
Cold Spring Harbor Lab, and Memorial Sloan-Kettering Cancer Center

Contact

Office
Shelby Biomedical Research Building
Room 703
1825 University Blvd.
Birmingham, AL 35294-2182

Phone
(205) 975-5016

Email
zhaox88@uab.edu

Committed to exploring new frontiers in basic and translational research.

The Department of Biochemistry and Molecular Genetics is an integral part of the vibrant biomedical research community at the University of Alabama at Birmingham (UAB). UAB ranks among the top public institutions of higher education in terms of research and training awards. Research conducted by the faculty, staff, and students of the Department of Biochemistry and Molecular Genetics is currently supported by more than $4.3 million per year in extramural, investigator-initiated grants.

Research

The Department of Biochemistry and Molecular Genetics carries out cutting-edge basic and translational research. Research strengths in the department includes cancer biology, chromatin and epigenetic signaling, metabolism and signaling, regulation of gene expression, structural biology, DNA synthesis and repair, and disease mechanisms.

Education

Graduate students and postdoctoral fellows in the Department of Biochemistry and Molecular Genetics are trained to carry out hypothesis-driven research using advanced research techniques. This training will prepare our graduates for a career in not just biomedical research, but also in other diverse fields that require critical thinking. Our faculty also proudly trains professional (MD, DDS, & DO) students, as well as undergraduate students at UAB.

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