Saturday, February 1, 2014
The members of the Leung Lab gathered to celebrate the Christmas and New Year holidays on 12/6/2013. Here are some pictures (Courtesy of Lue Xiang).
you may get a pleasant surprise when you come back!
It looks like that a Christmas/New Year ritual has been established in the lab….

Thursday, January 30, 2014
Stem cells
A young scientist in Japan has found a simple approach to make totipotent stem cells by lowering the pH.
Stimulus-triggered fate conversion of somatic cells into pluripotency. Nature
Bidirectional developmental potential in reprogrammed cells with acquired pluripotency. Nature
Retina
- Raymond PA, Colvin SM, Jabeen Z, Nagashima M, Barthel LK, Hadidjojo J, Popova L, Pejaver VR, Lubensky DK. Patterning the cone mosaic array in zebrafish retina requires specification of ultraviolet-sensitive cones. PLoS One. 2014 Jan 21;9(1):e85325. doi: 10.1371/journal.pone.0085325. eCollection 2014 Jan 21. PubMed PMID: 24465536.
- Centanin L, Wittbrodt J. Retinal neurogenesis. Development. 2014 Jan;141(2):241-4. doi: 10.1242/dev.083642. PubMed PMID: 24381194.
- Lenkowski JR, Raymond PA. Müller glia: Stem cells for generation and regeneration of retinal neurons in teleost fish. Prog Retin Eye Res. 2014 Jan 8. pii: S1350-9462(14)00002-0. doi: 10.1016/j.preteyeres.2013.12.007. [Epub ahead of
print] PubMed PMID: 24412518.
Genome-editing
- Hruscha A, Krawitz P, Rechenberg A, Heinrich V, Hecht J, Haass C, Schmid B. Efficient CRISPR/Cas9 genome editing with low off-target effects in zebrafish. Development. 2013 Dec;140(24):4982-7. doi: 10.1242/dev.099085. Epub 2013 Nov 20. PubMed PMID: 24257628.
- Roberts JA, Miguel-Escalada I, Slovik KJ, Walsh KT, Hadzhiev Y, Sanges R, Stupka E, Marsh EK, Balciuniene J, Balciunas D, Müller F. Targeted transgene integration overcomes variability of position effects in zebrafish. Development. 2014 Feb;141(3):715-24. doi: 10.1242/dev.100347. PubMed PMID: 24449846.
- Wang T, Wei JJ, Sabatini DM, Lander ES. Genetic screens in human cells using the CRISPR-Cas9 system. Science. 2014 Jan 3;343(6166):80-4. doi: 10.1126/science.1246981. Epub 2013 Dec 12. PubMed PMID: 24336569.
- Shalem O, Sanjana NE, Hartenian E, Shi X, Scott DA, Mikkelsen TS, Heckl D, Ebert BL, Root DE, Doench JG, Zhang F. Genome-scale CRISPR-Cas9 knockout screening in human cells. Science. 2014 Jan 3;343(6166):84-7. doi: 10.1126/science.1247005. Epub 2013 Dec 12. PubMed PMID: 24336571.
- Wu Y, Liang D, Wang Y, Bai M, Tang W, Bao S, Yan Z, Li D, Li J. Correction of a genetic disease in mouse via use of CRISPR-Cas9. Cell Stem Cell. 2013 Dec 5;13(6):659-62. doi: 10.1016/j.stem.2013.10.016. PubMed PMID: 24315440.
Neuroscience
- Dias BG, Ressler KJ. Parental olfactory experience influences behavior and neural structure in subsequent generations. Nat Neurosci. 2014 Jan;17(1):89-96. doi: 10.1038/nn.3594. Epub 2013 Dec 1. PubMed PMID: 24292232.
Gene therapy
- Maclaren RE, Groppe M, Barnard AR, Cottriall CL, Tolmachova T, Seymour L, Clark KR, During MJ, Cremers FP, Black GC, Lotery AJ, Downes SM, Webster AR, Seabra MC. Retinal gene therapy in patients with choroideremia: initial findings from a phase 1/2 clinical trial. Lancet. 2014 Jan 15. pii: S0140-6736(13)62117-0. doi: 10.1016/S0140-6736(13)62117-0. [Epub ahead of print] PubMed PMID: 24439297.
Sunday, December 29, 2013

Image courtesy: Lue Xiang @ Leung lab
We have been hoping to set up the zebrafish electroretinography in the lab to facilitate our drug discovery program for a while. When Prof. Kwoon Wong from the Kellogg Eye Center at the University of Michigan visited our department in early December, we seized the opportunity to learn from him and asked for his help to put the components together.

Image courtesy: Lue Xiang @ Leung lab
Dr. Don Ready kindly let us used his fly ERG setup for our test. Dr. Wong spent an afternoon trying different parameters and finally we have obtained a very decent ERG trace. Many more friends and colleagues contributed to this endeavour, including Dr. Woody Walls who gathered a number of components and laid down the foundation over a period of time, lab members Prahatha Venkatraman and Lue Xiang who collected ample healthy embryos for the test, and Lue Xiang as the assistant of Dr. Wong during the course of experimentation. We would like to optimize this system further and are seeking highly motivated students with physiology and/or engineering background. We are particularly interested in the talents who like electrophysiology and would like to contribute their effort to identify new drugs for patients.

Left: Dr. Wong explained various ERG concepts to the lab members. Top right: lab members shared their research with Dr. Wong over lunch. Middle right: Dr. Wong worked on the ERG setup. Bottom right: Dr. Wong and Fai learned from Dr. Ready on several critical components of the ERG setup. Image courtesy: Lue Xiang @ Leung lab

Dr. Woody Walls instructed us on using LabChart for data collection. Image courtesy: Lue Xiang @ Leung lab
Tuesday, September 3, 2013
Genetics
- Xiao A, Wang Z, Hu Y, Wu Y, Luo Z, Yang Z, Zu Y, Li W, Huang P, Tong X, Zhu Z, Lin S, Zhang B. Chromosomal deletions and inversions mediated by TALENs and CRISPR/Cas in zebrafish. Nucleic Acids Res. 2013 Aug 1;41(14):e141.doi: 10.1093/nar/gkt464. Epub 2013 Jun 6. PubMed PMID: 23748566; PubMed Central PMCID: PMC3737551.
- Wei C, Liu J, Yu Z, Zhang B, Gao G, Jiao R. TALEN or Cas9 – rapid, efficient and specific choices for genome modifications. J Genet Genomics. 2013 Jun 20;40(6):281-9. doi: 10.1016/j.jgg.2013.03.013. Epub 2013 Apr 12. PubMed PMID: 23790627.
- Gaj T, Gersbach CA, Barbas CF 3rd. ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. Trends Biotechnol. 2013 Jul;31(7):397-405. doi: 10.1016/j.tibtech.2013.04.004. Epub 2013 May 9. PubMed PMID: 23664777; PubMed Central PMCID: PMC3694601.
- Ochiai H, Fujita K, Suzuki K, Nishikawa M, Shibata T, Sakamoto N, Yamamoto T. Targeted mutagenesis in the sea urchin embryo using zinc-finger nucleases. Genes Cells. 2010 Aug;15(8):875-85. doi: 10.1111/j.1365-2443.2010.01425.x. Epub 2010 Jul 2. PubMed PMID: 20604805.
- Pattanayak V, Lin S, Guilinger JP, Ma E, Doudna JA, Liu DR. High-throughput profiling of off-target DNA cleavage reveals RNA-programmed Cas9 nuclease specificity. Nat Biotechnol. 2013 Aug 11. doi: 10.1038/nbt.2673. [Epub ahead of print] PubMed PMID: 23934178.
- Bruder CE, Piotrowski A, Gijsbers AA, Andersson R, Erickson S, Diaz de Ståhl T, Menzel U, Sandgren J, von Tell D, Poplawski A, Crowley M, Crasto C, Partridge EC, Tiwari H, Allison DB, Komorowski J, van Ommen GJ, Boomsma DI, Pedersen NL, den Dunnen JT, Wirdefeldt K, Dumanski JP. Phenotypically concordant and discordant monozygotic twins display different DNA copy-number-variation profiles. Am J Hum Genet. 2008 Mar;82(3):763-71. doi: 10.1016/j.ajhg.2007.12.011. Epub 2008 Feb 14. PubMed PMID: 18304490; PubMed Central PMCID: PMC2427204.
- Narlikar GJ, Sundaramoorthy R, Owen-Hughes T. Mechanisms and Functions of ATP-Dependent Chromatin-Remodeling Enzymes. Cell. 2013 Aug 1;154(3):490-503. doi: 10.1016/j.cell.2013.07.011. PubMed PMID: 23911317.
Cell cycle
- Jonas K, Liu J, Chien P, Laub MT. Proteotoxic Stress Induces a Cell-Cycle Arrest by Stimulating Lon to Degrade the Replication Initiator DnaA. Cell. 2013 Aug 1;154(3):623-36. doi: 10.1016/j.cell.2013.06.034. PubMed PMID: 23911325; PubMed Central PMCID: PMC3749246.
Disease gene mapping and sequencing
- Brunham LR, Hayden MR. Hunting human disease genes: lessons from the past, challenges for the future. Hum Genet. 2013 Jun;132(6):603-17. doi: 10.1007/s00439-013-1286-3. Epub 2013 Mar 17. Review. PubMed PMID: 23504071; PubMed Central PMCID: PMC3654184.
- Shendure J, Lieberman Aiden E. The expanding scope of DNA sequencing. Nat Biotechnol. 2012 Nov;30(11):1084-94. doi: 10.1038/nbt.2421. Epub 2012 Nov 8. Review. PubMed PMID: 23138308.
- Gilissen C, Hoischen A, Brunner HG, Veltman JA. Disease gene identification strategies for exome sequencing. Eur J Hum Genet. 2012 May;20(5):490-7. doi: 10.1038/ejhg.2011.258. Epub 2012 Jan 18. Review. PubMed PMID: 22258526; PubMed Central PMCID: PMC3330229.
- Ku CS, Cooper DN, Polychronakos C, Naidoo N, Wu M, Soong R. Exome sequencing: dual role as a discovery and diagnostic tool. Ann Neurol. 2012 Jan;71(1):5-14. doi: 10.1002/ana.22647. Review. PubMed PMID: 22275248.
- Goldstein DB, Allen A, Keebler J, Margulies EH, Petrou S, Petrovski S, Sunyaev S. Sequencing studies in human genetics: design and interpretation. Nat Rev Genet. 2013 Jul;14(7):460-70. doi: 10.1038/nrg3455. Epub 2013 Jun 11. PubMed PMID: 23752795.
- Cirulli ET, Goldstein DB. Uncovering the roles of rare variants in common disease through whole-genome sequencing. Nat Rev Genet. 2010 Jun;11(6):415-25. doi: 10.1038/nrg2779. Review. PubMed PMID: 20479773.
- Rehm HL. Disease-targeted sequencing: a cornerstone in the clinic. Nat Rev Genet. 2013 Apr;14(4):295-300. doi: 10.1038/nrg3463. Epub 2013 Mar 12. PubMed PMID: 23478348.
- Gulsuner S, Walsh T, Watts AC, Lee MK, Thornton AM, Casadei S, Rippey C, Shahin H; Consortium on the Genetics of Schizophrenia (COGS); PAARTNERS Study Group, Nimgaonkar VL, Go RC, Savage RM, Swerdlow NR, Gur RE, Braff DL, King MC, McClellan JM. Spatial and temporal mapping of de novo mutations in schizophrenia to a fetal prefrontal cortical network. Cell. 2013 Aug 1;154(3):518-29. doi: 10.1016/j.cell.2013.06.049. PubMed PMID: 23911319.
Alzheimer’s Disease
- Mullard A. Sting of Alzheimer’s failures offset by upcoming prevention trials. Nat Rev Drug Discov. 2012 Sep;11(9):657-60. doi: 10.1038/nrd3842. PubMed PMID: 22935790.
- Aisen PS, Vellas B, Hampel H. Moving towards early clinical trials for amyloid-targeted therapy in Alzheimer’s disease. Nat Rev Drug Discov. 2013 Apr;12(4):324. doi: 10.1038/nrd3842-c1. Epub 2013 Mar 15. PubMed PMID: 23493086.
- Doody RS, Raman R, Farlow M, Iwatsubo T, Vellas B, Joffe S, Kieburtz K, He F, Sun X, Thomas RG, Aisen PS; Alzheimer’s Disease Cooperative Study SteeringCommittee, Siemers E, Sethuraman G, Mohs R; Semagacestat Study Group. A phase 3 trial of semagacestat for treatment of Alzheimer’s disease. N Engl J Med. 2013 Jul 25;369(4):341-50. doi: 10.1056/NEJMoa1210951. PubMed PMID: 23883379.
- Mullard A. Sting of Alzheimer’s failures offset by upcoming prevention trials. Nat Rev Drug Discov. 2012 Sep;11(9):657-60. doi: 10.1038/nrd3842. PubMed PMID: 22935790.
- Jonsson T, Atwal JK, Steinberg S, Snaedal J, Jonsson PV, Bjornsson S, Stefansson H, Sulem P, Gudbjartsson D, Maloney J, Hoyte K, Gustafson A, Liu Y, Lu Y, Bhangale T, Graham RR, Huttenlocher J, Bjornsdottir G, Andreassen OA, Jönsson EG, Palotie A, Behrens TW, Magnusson OT, Kong A, Thorsteinsdottir U, Watts RJ, Stefansson K. A mutation in APP protects against Alzheimer’s disease and age-related cognitive decline. Nature. 2012 Aug 2;488(7409):96-9. doi: 10.1038/nature11283. PubMed PMID: 22801501.
Retinal development
- Suzuki SC, Bleckert A, Williams PR, Takechi M, Kawamura S, Wong RO. Cone photoreceptor types in zebrafish are generated by symmetric terminal divisions of dedicated precursors. Proc Natl Acad Sci U S A. 2013 Aug 26. [Epub ahead of print] PubMed PMID: 23980162.
Zebrafish
- Vignet C, Bégout ML, Péan S, Lyphout L, Leguay D, Cousin X. Systematic Screening of Behavioral Responses in Two Zebrafish Strains. Zebrafish. 2013 Jun 5. [Epub ahead of print] PubMed PMID: 23738739.