Dr. Xiaotian Zhang earned a B.S. in biological sciences from Fudan University in Shanghai, China followed by a Ph.D. from Baylor College of Medicine in Houston, Texas. As a graduate student in the laboratory of Dr. Margaret Goodell at Baylor, Dr. Zhang contributed significantly to the field’s understanding of leukomogenesis through discoveries that shed light on how DNMT3A and the TET2/IDH1/2 pathway synergize and the development of critical models to study this process. He also conceptualized and designed novel CRISPR/Cas9 tools to aid in epigenetic research. He has won several awards, including a Best of ASH Abstract Selection Award during the 2014 American Society of Hematology Annual Meeting. In March 2017, he joined the laboratory of Dr. Gerd Pfeifer at Van Andel Research Institute as a VARI Fellow.
Targeted modification of DNA methylation
Major breakthroughs in modern molecular biology—restriction enzymes, Taq polymerase and CRISPR—all spring from the utilization of simple bacterial enzymes. Inspired by this, we engineered bacterial DNA methyltransferase as a tethered enzyme with dCas9 to perform targeted CpG DNA methylation in mammalian cells. So far, our tool represents the most specific and efficient tool for locus-specific targeted DNA methylation. Additionally, we aim to utilize other biochemically well-known proteins from Mother Nature that will help us to engineer the epigenome efficiently.
Alteration of high-order chromatin structure and leukemogenesis
Leukemia is marked by frequent mutations in epigenetic modifiers. Besides single-nucleotide variants (SNV), frequent chromosome alterations also lead to leukemogenesis. Interestingly, these translocations always involve the nuclear structure proteins, which result in the oncogenic fusion protein. In this case, the normal function of nuclear protein will be compromised. Thus, when these translocations occur, how high-order chromatin is altered and how it contributes to leukemogenesis is unknown.
We have generated a high-resolution Hi-C map for cord blood hematopoietic stem and progenitor cells (HSPC) and its differentiated red blood cell offspring. By the comparison of cell-state-specific looped domain in the Hi-C map, we have identified the important regulatory elements for HOX gene cluster in HSPC, which is essential for the self-renewal of normal and malignant hematopoiesis.
Houston Gene X Environment Graduate Fellowship, Burroughs Wellcome Fund (July 2013 to January 2015)
American Society of Hematology Annual Meeting Abstract Achievement Award 2014
Best of ASH Abstract Selection (one of 20 chosen from more than 4,000 abstracts), American Society of Hematology Annual Meeting 2014
American Society of Hematology Annual Meeting Abstract Achievement Award 2013
To view a list of selected publications click below. To view Dr. Zhang’s Google Scholar page click here.
Lei Y, Zhang X, Su J, Jeong M, Gundry MC, Huang YH, Zhou Y, Li W, Goodell MA. 2017. Targeted DNA methylation in vivo using an engineered dCas9-MQ1 fusion protein. Nat Comm 8:16026. Article
Karlstaedt A, Zhang X, Vasquez H, Wang J, Goodell MA, Taegtmeyer H. 2016. D-2 hydroxyglutaric acid impairs oxidative decarboxylation by α-ketoglutarate dehydrogenase in rodent heart. Proc Natl Acad Sci U S A 113(37):10436–10441.
Zhang X, Su J, Jeong M, Ko M, Huang Y, Park H, Rao A, Li W, Goodell MA. 2016. Dnmt3a and Tet2 compete and cooperate to repress lineage specific transcriptional factors in hematopoietic stem cells. Nat Gen 48:1014–1023. Article
Yang L, Rodriguez B, Mayle A, Park HJ, Lin X, Luo M, Jeong M, Curry CV, Kim SB, Ruau D, Zhang X, Zhou T, Zhou M, Rebel VI, Challen GA, Göttgens B, Lee JS, Rau R, Li W, Goodell MA. 2016. DNMT3A loss drives enhancer hypomethylation in FLT3-ITD-associated leukemias. Can Cell 29(6):922–934. Article
Luo M, Jeong M, Sun D, Park HJ, Rodriguez BA, Xia Z, Yang L, Zhang X, Sheng K, Darlington GJ, Li W, Goodell MA. 2015. Long non-coding RNAs control hematopoietic stem cell function. Cell Stem Cell 16(4):426–38. Article
Jeong M, Sun D, Luo M, Huang Y, Challen GA, Rodriguez B, Zhang X, Chavez L, Wang H, Hannah R, Kim SB, Yang L, Ko M, Chen R, Göttgens B, Lee JS, Gunaratne P, Godley LA, Darlington GJ, Rao A, Li W, Goodell MA. 2014. Large conserved domains of low DNA methylation maintained by Dnmt3a. Nat Genet 46(1):17–23. Article
Chen X, Cui D, Papusha A, Zhang X, Chu C-D, Tang J, Chen K, Pan X, Ira G (2012). 2012. The Fun30 nucleosome remodeler promotes resection of DNA double-strand break ends. Nature 489(7417):576–580. Article
Wang H, Wu W, Wang HW, Wang S, Chen Y, Zhang X, Yang J, Zhao S, Ding HF, Lu D. 2010. Analysis of specialized DNA polymerases expression in human gliomas: association with prognostic significance. Neuro Oncol 12(7):679–686. Article