西雅图系统生物学所 HuangLab欢迎你 系统生物学的研究源远流长,主要有两个分支:一个是对近十来年蓬勃发展 -omics 数据的分析来了解生物现象。比如研究一种新的传染病,可以对致病微生物测序,以及对传染前,传染后和药物治疗后微生物的基因表达做基因表达芯片, RNAseq 和蛋白质组测定等,来了解其控制重要生命过程的调控基因网络和引发疾病的机理,从而发现治疗这种传染病的药物。另一个分支是针对生物基因,蛋白和代谢物等相互作用的小系统建立一个由下到上基于已知机理的详细数学模型,结合实验做比较深入的研究,比如了解细胞分化,转分化等复杂功能。 我们小组的工作主要是第二个分支的工作,研究人体细胞如何分化, iPS 细胞如何被定向分化,癌症干细胞和一般癌细胞的相互转化以及和癌症抗药性的关系。小组的 PI Sui Huang 在应用动力系统吸引子来解释细胞分化和癌症研究方面做了开创性的工作。这个领域最早的推断细胞吸引子存在的实验论文投遍了生物杂志没人接受,最后在物理学杂志 PRL 上发表了。他也是最早提出细胞基因表达的涨落不仅仅是噪声,而直接与干细胞的更新和分化( stem cell renewing anddifferentiation) ,细胞重定向 (cell reprogramming ),以及癌症干细胞转化有直接关系。最有趣的是,他阐发了 Kauffman 的癌症吸引子的观点,认为癌细胞是预先进化然后封存的 “ 救生艇 ” 程序,通常不会产生作用。当特定的基因发生变异或外界刺激以后,这段程序被激活后引发癌细胞大量繁殖求生,却危及了宿主的生命。小组的部分论文见后。 我们欢迎对系统生物学和计算生物学感兴趣的 暑期实习生(本科或硕士)、 访问学者和访问博士后来西雅图系统生物所来做学术交流。请联系 j zhou @systemsbiology.org (请附上简历和论文列表和两封介绍信)。 小组介绍: https://www.systemsbiology.org/ sui - huang -group Selected Peer-Reviewed Publications (most relevant, recent and requested) 1. Cancer JX Zhou, Z Isik, C Xiao, I Rubin, SA Kauffman, M Schroeder, S Huang, Systematic drug perturbations on cancer cells reveal diverse exit paths from proliferative state. Oncotarget, (2016) Anne Grosse-Wilde, Aymeric Fouquier d’Hérouël, Ellie McIntosh, Gökhan Ertaylan, Alexander Skupin, Rolf E Kuestner, Antonio del Sol, Kathie-Anne Walters, Sui Huang, Stemness of the hybrid epithelial/mesenchymal state in breast cancer and its association with poor survival, PloS one 10 (5), e0126522 (2015) S Huang, Genetic and non-genetic instability in tumor progression: link between the fitness landscape and the epigenetic landscape of cancer cells, Cancer and Metastasis Reviews 32 (3-4), 423-448 (2013) AO Pisco, A Brock, J Zhou, A Moor, M Mojtahedi, D Jackson, S Huang, Non-Darwinian dynamics in therapy-induced cancer drug resistance, Nature communications 4, (2013) S Huang, S Kauffman, How to escape the cancer attractor: rationale and limitations of multi-target drugs, Seminars in cancer biology 23 (4), 270-278 (2013) Dipak Panigrahy, Brian T Kalish, Sui Huang, et. al., Epoxyeicosanoids promote organ and tissue regeneration, Proceedings of the National Academy of Sciences 110 (33), 13528-13533 (2013) Huang, S. Tumor progression: chance and necessity in Darwinian and Lamarckian somatic (mutationless) evolution, Progress in biophysics and molecular biology 110 (1), 69-86 (2012) · Huang, S. On the intrinsicinevitability of cancer: From foetal to fatal attraction. Semin CancerBiol 21: 183-199 (2011). · Bracha AL, Ramanathan A,Huang S, Ingber DE, Schreiber SL. Carbon metabolism-mediated myogenicdifferentiation. Nat Chem Biol. 6:202-204 (2010) · Huang S, Ernberg I,Kauffman S. Cancer attractors: a systems view of tumors from a gene networkdynamics and developmental perspective. Semin Cell Dev Biol .20:869-876 (2009) · Brock A, Chang H, Huang S.Non-genetic heterogeneity - a mutation-independent driving force for thesomatic evolution of tumours. Nat Rev Genet . 10: 336-42. (2009) · Panigrahy D, Kaipainen A,Huang S, Butterfield KE, Barnes CM, Fannon M, Laforme AM, Folkman J, Kieran MW.The PPARα agonist fenofibrate suppresses tumor growth through direct andindirect angiogenesis inhibition. Proc Natl Acad Sc i U S A. 105:985-990 (2008). · Huang S, Ingber DE. Anon-genetic basis for cancer progression and metastasis: self-organizingattractors in cell regulatory networks. Breast Disease 26:27-54(2006-2007) · Huang S and Ingber DE. Celltension, matrix mechanics and cancer development. Cancer Cell 8:175-176(2005) 2. Gene networks, Systemsbiology SH Carsten Marr, Joseph X Zhou, S. Huang, Single-cell gene expression profiling and cell state dynamics: collecting data, correlating data points and connecting the dots, Current Opinion in Biotechnology 39, 207-214 (2016) JX Zhou, A Samal, AF d’Hérouël, ND Price, S Huang, Relative stability of network states in Boolean network models of gene regulation in development, Biosystems 142, 15-24 (2016) Joseph Xu Zhou, MDS Aliyu, Erik Aurell, Sui Huang, Quasi-potential landscape in complex multi-stable systems, Journal of The Royal Society Interface 9 (77), 3539-3553 (2012) C Torres-Sosa, S Huang, M Aldana, Criticality is an emergent property of genetic networks that exhibit evolvability, PLoS computational biology 8 (9), e1002669 (2012) S Huang, The molecular and mathematical basis of Waddington's epigenetic landscape: A framework for post‐Darwinian biology?, Bioessays 34 (2), 149-157 (2012) S Huang, SA Kauffman, Complex GRN complex Gene Complex GRN Regulatory Networks–from Structure to Biological Observables: Cell Fate Determination Gene regulation, cell fate determination, book, Computational Complexity: Theory, Techniques, and Applications (2012) · Guo, Y, Feng Y, Trivedi,NS, Huang S. Medusa structure of the gene regulatory network: dominance oftranscription factors in cancer subtype classification. Exp BiolMed 236: 628-636 (2011). · Wang, J., Xu, L., Wang, E.K. Huang, S. The potential landscape of genetic circuitsimposes the arrow of time in stem cell differentiation. BiophysJ 99:29-39 (2010). · Huang S. and Kauffman S.Gene Regulatory Networks - From Structure to Biological Observable: Cell fateDetermination. Encyclopedia of Complexity, Springer (2009) · Huang S, Wikswo PJ. Fivedimensions of systems biology. Reviews of Physiology, Biochemistry, andPharmacology 157: 81-104 (2006) 3.Differentiation, cell fate control Merja Heinäniemi, Matti Nykter, Roger Kramer, Anke Wienecke-Baldacchino, Lasse Sinkkonen, Joseph Xu Zhou, Richard Kreisberg, Stuart A Kauffman, Sui Huang, Ilya Shmulevich, Gene-pair expression signatures reveal lineage control, Nature methods 10 (6), 577-583 (2013) · Huang S. Systems biology ofstem cells: three useful perspectives to help overcome the paradigm of linearpathways. Philos Trans R Soc Lond B Biol Sci 366:2247-2259 (2011). · Zhou, JX and Huang S.Understanding gene circuits at cell-fate branch points for rational cellreprogramming. Trends Genet Dec 10 (2010). · Huang S. Cell lineagedetermination in state space: a systems view brings flexibility to dogmaticcanonical rules. PLoS Biol 8: e1000380. (2010) · Huang S. Non-geneticheterogeneity of cells in development: More than just noise. Development 136:3853-62(2009). · Huang S. Reprogramming cellfates: reconciling rarity with robustness. BioEssays .31:546-60 (2009) · Chang H, Hemberg M,Barahona B, Ingber D and Huang S. Transcriptome-wide noise controls lineagechoice in mammalian progenitor cells. Nature , 453:544-547 (2008). · Huang S, Guo YP, May G,Enver T. Bifurcation dynamics in lineage-commitment in bipotent progenitor cells. Dev.Biol . 305:695-713 (2007). · Huang S, Eichler G, Bar-YamY, Ingber D. Cell fate as a high-dimensional attractor of a complex generegulatory network. Phys. Rev. Lett. 94:128701 (2005).
2000 年西雅图开过一次会,那个 view 很像这个,更宽广 巨大的床对着长长的转角窗户,躺在床上像是看 live 立体宽荧幕一样,有如仙境。我好几夜不怎么睡觉,就这么傻傻地看着近处的港湾和远处的雪山,感受天然美景的极致。 那一年正是 dot com 最火的大跃进年代,ACL ( Association for Computational Linguistics )非常容易得到工业界的大笔赞助,大概是我们这行年会中最奢侈的一次。我们沾光就住进了豪华旅馆的豪华间。记得报告的是问答系统,当时最热的话题。 不由得怀念美国大跃进。 但肥皂泡总是要破灭的。
在西雅图熊猫快餐店( Panda Express )就餐 黄安年文 黄安年的博客 /2011 年 9 月 8 日发布 美国的熊猫快餐店颇有点蒸蒸日上的味道,有资料称“ Panda Express has 1,321 restaurants covering 38 states and Puerto Rico. ”根据 2011 年 8 月的资料美国已经有 1372 家熊猫快餐店 , 而总部设在 Rosemead, California , U.S. 的创始店仅建立于 1983 年。 27 日傍晚,我们本想在西雅图找家 PAZZA 店 , 但是看了三家均是没有座位只能带走的服务 , 于是来到这家熊猫快餐店 ,` 快餐店具有浓厚的中国风情,只是加入了在美国发展的新元素。 照片 17 张为即时拍摄的。 ****************** Panda Express From Wikipedia, the free encyclopedia Jump to: navigation , search Panda Express Type Private Industry Foodservice Founded 1983 Founder(s) Andrew Cherng Peggy Cherng Ming Tsai Cherng Headquarters Rosemead, California , U.S. Number of locations 1,372 (August 2011) Area served United States and Puerto Rico Products American Chinese cuisine Revenue $1 billion (2007) Employees 13,000 (2007) Parent Panda Restaurant Group Inc. Website pandaexpress.com A stand-alone Panda Express restaurant in Oakland, California with drive-through window A mall food court Panda Express at Ala Moana Center Panda Express is a fast casual restaurant chain serving American Chinese cuisine . It operates mainly inside the United States , in casinos , shopping malls , supermarkets , airports , train stations , strip plazas , theme parks , stadiums , college campuses and The Pentagon . It is the largest chain of Chinese fast food restaurants in the United States. In 2004, the company began opening stand-alone restaurants with drive-through windows. Panda Express has 1,321 restaurants covering 38 states and Puerto Rico. There used to be Panda Express locations in Japan. The chain offers a variety of food such as Orange Chicken , Beijing Beef, Mandarin Chicken, and Kung Pao Chicken . Combo meals are served with fried rice , steamed rice, chow mein , or mixed vegetables. No MSG is added to any of the items at Panda Express after it has been delivered to the restaurant, nor does Panda Express purchase from any suppliers who add MSG prior to delivery. Panda Express has its headquarters in Rosemead , California . It is a faster, casual representation of the more upscale Panda Inn , from which the chain concept was derived. Contents · 1 History · 2 Overview · 3 References · 4 Further reading · 5 External links History The Panda Restaurant Group , parent company of Panda Inn, Panda Express Hibachi-San, was founded by Andrew and Peggy Cherng and Andrew's father, Master Chef Ming Tsai Cherng, all of whom used to live in the Yangzhou region of China 's Jiangsu province. They started their first Panda Inn restaurant in 1973 in Pasadena, California . In 1983, Donahue Schriber Real Estate, the manager of the Glendale Galleria , invited the Cherngs to develop a fast-food version of Panda Inn for the Galleria's food court, and Panda Express was born. The chain has steadily expanded across the United States since then. In 2007, The Panda Restaurant Group had annual sales of over $1 billion and over 13,000 employees. In 2008, Andrew Cherng and his wife, Peggy, were the recipients of the 2008 City of Angels Award, given by the LAX Coastal Area Chamber of Commerce, for their contributions to the greater Los Angeles area. Andrew Cherng '70 and his wife Peggy Tsiang Cherng '68 are alumni of Baker University in Baldwin City, Kansas . Peggy Cherng also received her B.S. degree in applied mathematics from Oregon State University in 1971, and her M.S. in Computer Science and doctoral degree in electrical engineering from the University of Missouri-Columbia . Andrew Cherng also received his M.S. in Mathematics from the University of Missouri. On November 23, 2009, it was announced that Panda Express had selected Trusonic to provide Asian themed background music to its store locations. On the ABC News TV program Nightline , April 18, 2011, there was a feature segment on Panda Express and its success. The segment described how Andrew Cherng encourages his workers and management to go through various life-changing motivational programs, especially emphasizing Landmark Education . Overview With approximately 1,372 locations, it is the largest Chinese fast food restaurant chain in the United States . Andrew Cherng feels that Panda Express food needs more care and concern than other fast food restaurants. Panda Express tries to pay employees $1-2 more per hour than other nearby fast-food restaurants to get employees to put the extra care and concern into the food. The company's highest revenue location, bringing in over US$ 4 million annually, is located at the Ala Moana Center food court in Honolulu, Hawaii . References 1. ^ "Panda Express Restaurant Locations" . http://www.pandaexpress.com/locations/locator.aspx . Retrieved 2011-08-13 . 2. ^ Bruce Haring, "Panda gains higher visibility for chain amid shift from malls, food courts," Nation's Restaurant News , 9 August 2004, 6. 3. ^ Panda Express Location Finder . "Panda Restaurant Group has 1333 restaurants covering 38 states and Puerto Rico. (1279 Panda Express, 28 Hibachi-San, 7 Panda Inn)" 4. ^ "Building Panda" . Archived in 2000. 5. ^ Panda Express FAQ - "Panda Express does not add MSG to any of our entrees or sides and we do not purchase products from suppliers who add MSG. However, glutamate is found naturally in some ingredients." 6. ^ " Contact Us ." Panda Express. Retrieved on February 26, 2010. 7. ^ Panda Restaurant Group History 8. ^ James Flanigan, "Cooking Up a Powerhouse of Chinese Fast Food," Los Angeles Times , 8 October 2001, C1. 9. ^ Panda Restaurant Group information page 10. ^ LAX Coastal Area Chamber of Commerce website 11. ^ "Andrew and Peggy Cherng of Panda Restaurant Group Receive City of Angels Award Honoring Contributions to the Los Angeles Area" , Business Wire, February 8, 2008. 12. ^ "Cherngs honored for contributions in L.A. area" , Baker Pride alumni magazine, Baker University, Baldwin City, Kansas, Spring 2008 issue. 13. ^ "OSU ALUMNI FELLOWS 2000: OSU honors veterinarian, animal nutrition researcher and president of Panda Management , Oregon Stater Association News , Oregon State University, 2000 14. ^ "Profile: Andrew Cherng" , Fremont College , Board of Advisors. 15. ^ "Panda Express Selects Trusonic(R) to Provide In-Store Background Music" , PR Newswire Association , November 23, 2009 16. ^ Berman, John; Rosenberg, Sarah, "Panda Express: Self-Help Courses and Zumba Are Recipe for Success? CEO Says Motivational Forums, Not Orange Chicken, Make His Business Successful" , ABC News Nightline , April 18, 2011 17. ^ Bartiromo, Maria (November 2007). "Positive Thinkers" . http://www.rd.com/content/the-success-story-of-panda-express/ . 18. ^ Krantz, Matt (2006-09-13). "Panda Express spreads Chinese food across USA" . USA Today . http://www.usatoday.com/money/companies/management/2006-09-10-entrepreneur-panda-express_x.htm . Retrieved 2010-11-10 . 19. ^ Shimabukuro, Betty (2007-01-17). "Orange Chicken on the house" . Honolulu Star-Bulletin . http://starbulletin.com/2007/01/17/features/story01.html . Retrieved 2007-01-17 . Further reading · Flanigan, James, "Fast Food Powerhouse" , Asian Week , Nov. 30 - Dec. 6, 2001 issue. Associated Press story. · Foodservice Equipment Supplies (FES) magazine, Panda Express Profile · Andrew Cherng Profile - Asia Society , Southern California. · Andrew Cherng interview , The Tavis Smiley Show , original airdate November 14, 2006. · Jennings, Lisa, "Having words with Peggy Tsiang Cherng: chief executive and co-chair, Panda Restaurant Group" , Nation's Restaurant News, August 1, 2005. · "Panda Express is Alumni Brainchild" , @Mizzou, University of Missouri , Alumni Association magazine, January 2004. · Panda Restaurant Group Corporate Data - from Panda Restaurant Group website · Hirsch, Jerry, "Chinese fast-food chain Panda Express thrives on a diet of orange chicken Now celebrating its 25th year" , Los Angeles Times, August 13, 2008 · Bernstein, Charles, 'Manchu Leads the Working Race,' Restaurants Institutions, August 1, 1994, p. 30. · Cebrzynski, Gregg, 'Panda Express Breaks TV Ad Campaign as Test to Raise Brand Awareness,' Nation's Restaurant News, August 9, 1999, p. 11. · Farkas, David, 'Fast and Friendly,' Chain Leader, March 2000, p. 72. · Glover, Kara, 'Success on Oriental (Food) Express,' Los Angeles Business Journal, September 25, 1995, p. 21. · Krantz, Matt, "Panda Express Spreads Chinese Food Across USA" , USA Today , September 11, 2006 · Marchetti, Michele, and Alisson, Lucas, 'Creating Panda-monium,' Sales Marketing Management, January 1996, p. 14. · Martin, Richard, 'Panda Express: Bullish about the Bear,' Nation's Restaurant News, May 16, 1994, p. 86. · ------, 'Top Chi-Chi's, El Torito Execs Tackle Panda Push,' Nation's Restaurant News, August 7, 1995, p. 18 · Walkup, Carolyn, 'Panda Express Promo Targets Takeout Business,' Nation's Restaurant News, February 28, 1994, p. 7. · "Panda Restaurant Group Founders Pledge $2.5 Million to Collins College" , Polycentric , Cal Poly Pomona , February 28, 2011 http://en.wikipedia.org/wiki/Panda_Express
回头翻看以前的博客,算算我做免疫组库方面的工作已经有四个年头了。 这篇从苹果网搬过来的博客 记录了最早开始为免疫组库项目设计引物时候的情景。时间是07年十二月。而决定去用高通量测序方法做免疫组库研究是在07年的十月份,那是我刚刚离开Qiagen,加入HudsonAlpha研究院。 这篇08年七月的博客 记录了我和太太去斯坦福大学访问,那时我们刚刚完成了第一次用454测序免疫组库的工作,得到了很好的结果。在那以前,有关免疫组库方法学的专利已经申请进去了。 首次向外界披露我们的技术是在09年西雅图召开的 免疫年会 上。 论文 也是大概那个时候开始投稿的,不过一直到2010年年初 我们的论文 才在PNAS上发表。 免疫组库测序是个全新的领域,与其它“学院派”科学家不同,我们在做这个项目的时候不是把注意力集中在抢先发表论文上,而是努力把技术做得比别人好:更简 单,更好用,全自动,产品更全,软件更快更好。所以在他人不断发表论文的时候,我们却默默地做了大量技术研发的工作,也抢先申请了 一系列的专利 。 说道专利,我们最近还申请了另一个专利。这个专利的内容在 这篇博客 里面已经透露了一些。这个新专利是一个诊断产品。不过 我们要诊断的不是一个特定的病,而是一个正常指标 ! 事情是这样的,早在09年西雅图免疫年会上,我们就报告了免疫组库在肿瘤病人中有明显的多样性缺失的现象: 如上面的幻灯片所示,正常人的免疫组库(T细胞beta受体)多样性很好,在三维图像上看起来丛林密布;而结肠癌病人或系统性红斑狼疮病人的免疫组库则多 样性缺失,三维图像看上去就是几棵树。这些病人T细胞总数是正常的,可是他们的T细胞功能太专一,缺乏健康人应有的多样性。我们随后做了许多病人,都是如此。 开始,我们也和其它科学家一样,试图通过多做一些病人标本找到 更特异性 的免疫组库变化:某个特定的VDJ重组总是和某个肿瘤相关。可是,免疫系统潜在的多样性(人可以有10的20次方那么多不同的T细胞)实在太大,找到病人之间共有的特异性VDJ (或者CDR3)可能性很小。那么,免疫组库研究的诊断意义到底在哪里? 受中医思维影响,我对“上医医未病之病”一直感兴趣。可是医未病之病的前提条件就是能够诊断正常:只有能诊断正常,医生才能在病人稍微偏离正常状态时就能知道,及时加以纠正。引申开来,免疫组库技术在能诊断各种特异性疾病的同时,它的一个最好的应用可能就是去 诊断正常 。 如何评估一个人的免疫组库是否正常? 那就看他(她)的免疫组库多样性是否完好。可是作为一个临床诊断,最好要有一个定量的描述。这,就是我们新专利的一个特点和诉求。我们称之为D50(Diversity 50)。下面是专利里面对D50的描述: Aspects of the invention include arm-PCR amplification of CDR3 from T cells, B cells, and/or subsets of T or B cells. Large numbers of amplified products may then be efficiently sequenced using next-generation sequencers. If the significant percentage that is chosen is 50%, the number may be referred to as the “D50.” D50 may then be the p ercent of dominant and unique T or B cell clones that account for fifty percent (50%) of the total T or B cells counted in that sample. For high-throughput sequencing, for example, the D50 may be the number of the most dominant CDR3s, among all unique CDR3s, that make up 50% of the total effective reads, where total effective reads is defined as the number of sequences with identifiable V and J gene segments which have been successfully screened through a series of error filters. 所谓D50,就是通过arm-PCR技术扩增免疫组库然后测序。把半定量扩增出的免疫组库和测序结果做sorting, 表达量最高到表达量最低排列,然后从高到低地相加。加到50%(reads)的时候看看一共包括多少个克隆,克隆数占总数的百分比就是D50值。一个健康 人,因为免疫组库多样性好,免疫细胞总数的50%就会由许多不同的细胞组成,D50值就会偏高;相反,病人常常会有克隆性扩增,免疫多样性差,所以几个克 隆就占据了免疫细胞的50%了,因此D50值就偏低。 专利诉求中除了可以用测序方法做D50计算以外,还提到可以用iCubate仪器通过杂交的方法对D50进行评估。这样就有快速,便宜的方法来“诊断正常”了。