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 jzhou@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 CancerBiol21: 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 Sci 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).