Scientific Founders

Dr. Dun Yang, Director

Dr. Dun Yang pursued his graduate study at Columbia University under the mentorship of Dr. James W. Erickson, received his postdoctoral training in cancer cell biology supervised by Dr. J. Michael Bishop at University of California, San Francisco (UCSF) and then worked as an associate specialist at the G. W. Hooper Research Foundation. Dr. Yang has conducted research for more than 20 years, and has a track record of publication in PNAS, Nature Medicine, Nature Cell Biology, Current Biology and MCB. His published studies involve multiple research fields, such as animal cell division, apoptosis, autophagy, mouse tumor models, regulation of gene expression, RNAi and synthetic lethal therapies. His diverse research programs at UCSF were generously supported by the G. W. Hooper Research Foundation, the Susan G. Komen Foundation, and pharmaceutical companies such as Merck, Millennium and Exelixis.

Dr. Yang received Peter Sajovic Memorial Prize from Columbia University for excellence in biomedical research. At Columbia University, Dr. Yang developed a single-embryo transcription translation assay (SETTA) to dissect mechanisms underlying RNAi. His findings provided first evidence that siRNA hydrolyzed from a large double-stranded RNA mediates gene silencing in vivo. In addition, he worked on transcriptional regulation of the Sex-lethal (Sxl), a master regulatory gene of sex determination in Drosophila, revealed that the number, affinity and position of sisB/Da-binding sites in the promoter of Sxl were critical for its female-specific activation, and proposed a reservoir model to explain dosage-sensitive regulation of Sxl. The findings have now been written into some college textbooks of genetics.

世界杯365bet下载365bet滚球注册365bet体育投注正规Together with Dr. Bishop at UCSF, Dr. Yang invented endoribonuclease–prepared siRNA (esiRNA) to silence gene expression in animal cells. The method has become a powerful screening tool for both functional genomic studies and identification of drug targets. Global patent protection of the method held by UCSF and the use of it by many academic and industrial scientists in the literature testify to its utility. Under Dr. Bishop’s supervision, Dr. Yang also discovered a synthetic lethal interaction between overexpression of the Myc oncoprotein and disablement of chromosomal passenger protein complex (CPPC). This finding indicates that expression of Myc is a useful biomarker for sensitivity of tumor cells to inhibition of the CPPC, suggests a therapeutic strategy for killing tumor cells that overexpress Myc, while sparing normal cells, and eliminates the liabilities of both the Myc oncoprotein as a therapeutic target and the mitotic inhibitors as therapeutic agents.

Contact Dr Dun Yang: Dun.Yang ‘at’ mbicr.org

Patents and selected publications:

Co-inventor with Dr. J. Michael Bishop: A method for efficient RNA interference in mammalian cells (United States Patent 20040014113?and?European Patent EP1537227).

Co-inventor with Dr. J. Michael Bishop: The aurora kinase inhibitor, VX-680, is a synthetic lethal agent for tumors that overexpress the MYC proto-oncogene (Invention report, UCSF case number SF2008-017).

Liu H, Radisky DC, Yang D, XuR, Radisky ES, Bissell MJ, Bishop JM.?MYC suppresses cancer metastasis by direct transcriptional silencing of v3 Integrin subunits.?Nature Cell Biology (2012) 14:567-74.

Yang D, Liu H, Goga A, Kim S, Yuneva M, and Bishop JM.?Therapeutic potential of a synthetic lethal interaction between the MYC proto-oncogene and inhibition of aurora-B kinase.?PNAS (2010), 107:13836-41.

Goga A, Yang D, Aaron DT, Morgan DO, and Bishop JM.?Inhibition of Cdk1 as a potential therapy for tumor over-expressing MYC.?Nat Med?(2007), 13:820-827.

Yang?D, Buchholz F, Huang Z, Goga?A, Chen CY, Brodsky FM, and Bishop JM.?Short RNA duplexes produced by hydrolysis with Escherichia coli RNase III mediate effective RNA interference in mammalian cells.?PNAS (2002), 99:9942-7.

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Dr. Jing Zhang, Co-director

Dr. Zhang attended Sichuan University for her undergraduate study and received her Ph.D. training at the University of Nottingham from Prof. Robert G Lloyd, a Royal Society member and world-class expert in the field of DNA repair, recombination and replication. Supported by the Dorothy Hodgkin Postgraduate Award, Dr. Zhang established a synthetic lethal screening assay in E. coli to confirm the known synthetic lethal interaction between RecG and RuvABC, and identified a series of new synthetic lethal mutants of RecG as well as suppressors of RecG-RuvABC synthetic lethality. Characterization of these suppressors allowed Dr. Zhang to cast new light on the interplay between RecG and RuvABC in Holliday junction resolution and uncover previously unknown multifaceted roles for RecG helicase in DNA repair, recombination and replication.

Dr. Zhang worked with Prof. Malcolm F. White for her postdoctoral training at the University of St Andrews from 2009 to 2015. Under Prof. White’s supervision, she investigated the CRISPR-Cas system, an RNA-guided adaptive immune system that protects bacteria and archaea against invading genetic elements. In particular, she investigated two effector complexes, Csm and Cmr, and illustrated how the complexes execute sequence-specific cleavage of nucleic acids. These groundbreaking findings were published at Molecular Cell, Nucleic Acids Research, and PLosOne.

Contact Dr Jing Zhang: Jing.Zhang ‘at’ mbicr.org

Selected publications:

Zhang J, Graham S, Tello A, Liu H and White MF,?Multiple nucleic acid cleavage modes indivergent type III CRISPR systems,?NAR (2016), doi: 10.1093/nar/gkw020.

Rouillon C, Zhou M,?Zhang J?et al,?Structure of the CRISPR interference complex CSM reveals key similarities with Cascade,?Mol Cell (2013), 52(1):124-134.

Zebec Z, Manica A, Zhang J, White MF and Schleper C,?CRISPR-mediated targeted mRNA degradation in the archaeon Sulfolobus solfataricus, NAR (2014), 42(8):5280-8.

Zhang J, Rouillon C, Kerou M et al,?Structure and mechanism of the CMR complex for CRISPR-mediated antiviralimmunity,?Mol Cell (2012), 45(3):303-313.

Zhang J, Kasciukovic T and White MF,?The CRISPR associated protein Cas4 is a 5’to 3’ DNA exonuclease?with an iron-sulfur cluster,?PLoS One (2012), 7(10): e47232.

Zhang J, Mahdi AA, Briggs GS and Lloyd RG,?Promoting and avoiding recombination: contrasting activities of the Escherichia coli RuvABC?Holliday junction resolvaseand RecG?DNA translocase Genetics?(2010), 185(1):23-37.