Jian Xu received his Ph.D. with Dr. Stephen Smale from UCLA, where he studied epigenetic regulation of stem cell pluripotency. In 2008, he joined Dr. Stuart Orkin’s laboratory at Boston Children’s Hospital as a Helen Hay Whitney-HHMI postdoctoral fellow and studied the developmental control of fetal-to-adult hemoglobin switching. In 2012, he became an instructor in Pediatric Hematology-Oncology at Harvard Medical School. His studies with Dr. Orkin provide the first in vivo evidence that genetic inactivation of the zinc finger protein BCL11A is sufficient to ameliorate sickle cell disease in preclinical models, and lay the groundwork for ongoing development of gene therapies to target BCL11A for treating patients with inherited hemoglobin disorders. In 2014, Dr. Xu received a first-time investigator award from the Cancer Prevention and Research Institute of Texas (CPRIT) and joined the faculty of the Children’s Medical Center Research Institute at UT Southwestern.
One of the fundamental questions in biology is how gene expression programs are established and maintained to control cell identity. Although we know diseases such as cancer and inherited blood disorders are the results of malfunctions in gene regulation, pinpointing the disease-causing genes and genetic regulatory elements remains difficult. Further complicating this is the epigenetic control of gene function which often contributes to disease pathophysiology.
Our goal is to better understand the gene regulatory processes that control stem cell development and cancers. We employ interdisciplinary approaches including molecular biology, genome engineering, disease modeling, single cell technology and computational biology to discover new mechanisms in gene regulation and genome sciences. By elucidating the basic principles of gene regulation in normal and neoplastic blood cell development, we seek to develop innovative strategies to precisely control gene function and advance diagnosis, prognosis and treatment of human disorders.
- Fudan University (2000), Biochemistry
- Graduate School
- Uni of California (UCLA) (2008), Molecular Biology
- Epigenetic Regulation of Stem Cells and Cancers
- Erythropoiesis and Hematopoiesis
- Functional Genomics and Computational Biology
- Gene Expression and Regulation
- Metabolic Control of Hematopoiesis and Leukemia
- Non-Coding Regulatory Genome
- Silencing of LINE-1 retrotransposons is a selective dependency of myeloid leukemia.
- Gu Z, Liu Y, Zhang Y, Cao H, Lyu J, Wang X, Wylie A, Newkirk SJ, Jones AE, Lee M, Botten GA, Deng M, Dickerson KE, Zhang CC, An W, Abrams JM, Xu J, Nat Genet 2021 Apr
- Multiplexed capture of spatial configuration and temporal dynamics of locus-specific 3D chromatin by biotinylated dCas9.
- Liu X, Chen Y, Zhang Y, Liu Y, Liu N, Botten GA, Cao H, Orkin SH, Zhang MQ, Xu J, Genome Biol. 2020 Mar 21 1 59
- Non-Coding Variants Connect Enhancer Dysregulation with Nuclear Receptor Signaling in Hematopoietic Malignancies.
- Li K, Zhang Y, Liu X, Liu Y, Gu Z, Cao H, Dickerson KE, Chen M, Chen W, Shao Z, Ni M, Xu J, Cancer Discov 2020 Mar
- Interrogation of enhancer function by enhancer-targeting CRISPR epigenetic editing.
- Li K, Liu Y, Cao H, Zhang Y, Gu Z, Liu X, Yu A, Kaphle P, Dickerson KE, Ni M, Xu J, Nat Commun 2020 Jan 11 1 485
- Loss of EZH2 Reprograms BCAA Metabolism to Drive Leukemic Transformation.
- Gu Z, Liu Y, Cai F, Patrick M, Zmajkovic J, Cao H, Zhang Y, Tasdogan A, Chen M, Qi L, Liu X, Li K, Lyu J, Dickerson KE, Chen W, Ni M, Merritt ME, Morrison SJ, Skoda RC, DeBerardinis RJ, Xu J, Cancer Discov 2019 Jun
- In Situ Capture of Chromatin Interactions by Biotinylated dCas9.
- Liu X, Zhang Y, Chen Y, Li M, Zhou F, Li K, Cao H, Ni M, Liu Y, Gu Z, Dickerson KE, Xie S, Hon GC, Xuan Z, Zhang MQ, Shao Z, Xu J Cell 2017 Aug 170 5 1028-1043.e19
- Regulation of mitochondrial biogenesis in erythropoiesis by mTORC1-mediated protein translation.
- Liu X, Zhang Y, Ni M, Cao H, Signer RAJ, Li D, Li M, Gu Z, Hu Z, Dickerson KE, Weinberg SE, Chandel NS, DeBerardinis RJ, Zhou F, Shao Z, Xu J Nat. Cell Biol. 2017 May
- Dynamic Control of Enhancer Repertoires Drives Lineage and Stage-Specific Transcription during Hematopoiesis.
- Huang J, Liu X, Li D, Shao Z, Cao H, Zhang Y, Trompouki E, Bowman TV, Zon LI, Yuan GC, Orkin SH, Xu J Dev. Cell 2016 Jan 36 1 9-23
- Designing an enhancer landscape.
- Xu J, Smale ST Cell 2012 Nov 151 5 929-31
- Correction of sickle cell disease in adult mice by interference with fetal hemoglobin silencing.
- Xu J, Peng C, Sankaran VG, Shao Z, Esrick EB, Chong BG, Ippolito GC, Fujiwara Y, Ebert BL, Tucker PW, Orkin SH Science 2011 Nov 334 6058 993-6
Honors & Awards
- Leukemia and Lymphoma Society Scholar
- American Society of Hematology Scholar Award
- CPRIT Scholar in Cancer Research
- New Investigator Award, American Cancer Society/UT Southwestern
- NIH/NIDDK Career Development Award (K01)
- American Society of Hematology (ASH) Merit Award
- American Society of Hematology (ASH) Merit Award
- Helen Hay Whitney Foundation-HHMI Post-Doctoral Fellowship
- California Institute for Regenerative Medicine (CIRM) Pre-Doctoral Fellowship
- International Society of Experimental Hematology (2017)
- International Society for Stem Cell Research (2014)
- American Society of Hematology (2008)