investigate cellular responses for environmental cues qian wang department of chemistry and...
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Investigate Cellular Responses for Investigate Cellular Responses for Environmental CuesEnvironmental Cues
Qian Wang
Department of Chemistry and Biochemistry, and NanocenterUniversity of South Carolina, SC, USA
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Cell shape determines fate of stem cellsCell shape determines fate of stem cells
Mrksich M., et al. PNAS, 2010, 16, 4872-4877
Star shape and flower shape expressed different differentiation profile
Flower shape promoted adipogenesisStar shape promoted osteogenesis
Flower
Star
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ECM Mimetic SubstratesECM Mimetic Substrates
Abrams, G. A., et al., Cell Tissue Res , 2000, 299, 39-46 Kim, D. H. et al., PNAS , 2010, 107,565-570Roohani-Esfahani, S.I., et al., Biomaterials , 2010, 31, 5498-5509 Pham, Q. P. et al., Tissue Eng , 2006, 12, 1197-211
50um
Natural ECM architecture
ECM mimetic substrates
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Nature 414:105, 2001
Models of Tumor HeterogeneityModels of Tumor Heterogeneity
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Are We Targeting the Right Cancer Cells?Are We Targeting the Right Cancer Cells?
Sarkar, B. ; Dosch, J., et al. Chem. Rev. 2009, 109, 3200–3208
Major Challenges:•Lack of universal biomarker•Lack of In vitro cell culture model
Major Challenges:•Lack of universal biomarker•Lack of In vitro cell culture model
Nature 414:105, 2001
Dr. Hexin ChenBiologist
Dr. Xinfeng LiuMathematician
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A Novel Breast Cancer Stem Cell Model - A Novel Breast Cancer Stem Cell Model - H6O5 CellsH6O5 Cells
Lo, P. K., et al., Oncogene 2012, (doi: 10.1038/onc.2011.439)
Her2/neu induced mouse mammary tumor
Consists of a highly tumorigenic population (CSCs)
Isolated based on two integrin markers CD49f and CD61
Confirmed by its in vivo tumorigenicity
NMuMG H6O5
CD61
CD
49
f G1G2
G3
G1: CD49fhighCD61high
G2: CD49fhighCD61low
G3: CD49flowCD61low
1.2 89.9
6.2 2.7
CD49fhighCD61high
2.7 74.0
8.0 15.2
CD49fhighCD61low
2.0 25.4
35.3 37.3
CD49flowCD61low
CD24
ES
A
CD
49f
CD61
Fluorescence assisted cell sorting
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H6O5
Aligned fiber substrate
Tissue culture well
H6O5 Cells on Fiber SubstrateH6O5 Cells on Fiber Substrate
• Morphology
• EMT- associated gene expression
Culture for 3- 5 days
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Morphology of Electrospun Fiber Morphology of Electrospun Fiber SubstrateSubstrate
SEM images of aligned (d = 1.8 ± 0.46 μm) and random (d = 2.0 ± 0.65 μm) Scale bar = 20 μm
Poly-Caprolactone
BiodegradableCytocompatible
AAligned Fiber Random Fiber
Saha. S et al.,Langmuir, 2012, 28, 2028-2034
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Morphology of H6O5 Cells on Aligned Morphology of H6O5 Cells on Aligned Fiber SubstrateFiber Substrate
10x
10x
• Cell attach to fiber• Elongated morphology
• Growth, • Proliferation • Maintain elongated morphology
10x
Green: actin cytoskeletonBlue: nucleiWhite arrows: underlying fiber direction,Scale bar = 40 µm
a b
S. Saha et al. Langmuir, 2012, 28, 2028-2034
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Enrichment of Cancer Stem Cells Using Enrichment of Cancer Stem Cells Using Nano-fibrous ScaffoldsNano-fibrous Scaffolds
S. Saha et al. Langmuir, 2012, 28, 2028-2034
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Gene expression by qRT-PCR
S. Saha et al. Langmuir, 2012, 28, 2028-2034
Enhanced Expression of EMT Markers of Enhanced Expression of EMT Markers of MCF-7 CellsMCF-7 Cells
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ALDH (Aldehyde DALDH (Aldehyde Dehydrogenaseehydrogenase) Activity ) Activity of MCF-7 Cellsof MCF-7 Cells
AAligned Fiber Random Fiber
Sheng Feng
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Increased Mammosphere-Forming Increased Mammosphere-Forming CapabilityCapability
AAligned Fiber Random Fiber
Sheng Feng
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Increased Invasion Property of Epithelial Increased Invasion Property of Epithelial Breast Cancers Cells Cultured On PCL FiberBreast Cancers Cells Cultured On PCL Fiber
AAligned Fiber Random Fiber
Sheng Feng
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Results of MDA-MB-231 Cells Cultured Results of MDA-MB-231 Cells Cultured from PCL Fiberfrom PCL Fiber
AAligned Fiber Random Fiber
Sheng Feng
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A Hypothesis of the Double-Feedback to A Hypothesis of the Double-Feedback to Control the CSCs Fate Control the CSCs Fate
A
Dr. Xinfeng Liu, Hexin Chen
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Zhongwei, Jianhua, Mike Bruckman O. D. Velev et al, Small 2006, 2, 1462
Alignment of Rod Like NanoparticlesAlignment of Rod Like Nanoparticles
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2D Alignment of Colloidal Particles2D Alignment of Colloidal Particles
Dimitrov and Nagayama, Langmuir 1996, 12, 1303
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2D Alignment of Protein Nanoparticles2D Alignment of Protein Nanoparticles
Mike Bruckman, Zhongwei Niu O. D. Velev et al, Small 2006, 2, 1462
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Jianhua Rong, Zhongwei Niu, in collaboration with Dr. Charlene Mello
Controlled Alignment of Cell GrowthControlled Alignment of Cell Growth
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Rosamond W et al., Circulation 2008, 117 (4): e25-146Rosamond W et al., Circulation 2008, 117 (4): e25-146
United States, 2004. Source: NCHS and NHLBI
Cardiovascular Disease in USACardiovascular Disease in USA
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Vascular Disorders and Vascular Disorders and Pathogenesis of Atherosclerosis Pathogenesis of Atherosclerosis
Osterud & Bjorklid; Physiol Rev. 2003, 83, 1069-112
VSMC Proliferative formVSMC Proliferative formVSMC Normal formVSMC Normal form
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Smooth Muscle Cells: Different MorphologiesSmooth Muscle Cells: Different Morphologies
Lilly
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Control
AlignedScaffold
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Significance of the Alignment of Significance of the Alignment of Smooth Muscle CellsSmooth Muscle Cells
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Are There a Good Model to Predict/Explain Are There a Good Model to Predict/Explain The Cellular Responses to Contact Cues??The Cellular Responses to Contact Cues??
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Are There a Good Model to Predict/Explain Are There a Good Model to Predict/Explain The Cellular Responses to Contact Cues??The Cellular Responses to Contact Cues??
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AcknowledgmentsAcknowledgments
BNP Assembly:Tom Russell (UMass)Yao Lin (UConn)Alex Böker (MPI)P. Thiyagarajan (DOE)Byeongdu Lee (ANL)Lin Yang (BNL)Z. Su (CIAC, CAS)C. Xiaodong Li (USC)Wenke Zhang (Jilin U)
Cell StudyHexin Chen (USC)Tara Soto-Atwood (UF)J. Potts (USC)
Protein Binding StudyLukasz Lebioda (USC)Frank Berger (USC)
Virus:Theo Dreher (OSU)Rick Nelson (Noble)Charlene Mello (ARL)Peter E. Prevelige (UAB)
Polymeric Assembly:Mihaela Stephan (UTD)Yuan Lin (CIAC, CAS)
$$$NSF-CAREER/NSF-DMRNIH-COBRESloan/Camille DreyfusDOD-ARODOE-BESW. M. Keck FoundationSC EPSCoR Office & SCCC
Wang Group:L. Andrew Lee (Postdoc)Xinrui Duan (Postdoc)Honglin Liu (Postdoc)Jun Hu (Postdoc)Pan He (Research Ass.)
Dan MenascoNikki Sitasuwan Matsepo RamaboliAmie J. Luckanagul
Wang Group Alumni:Yi Chen (Res. Professor)Gary Horvath (S. Scientist)
Postdoc:K. SivakumarS. ChittaboinaV.S. KotakadiZhongwei NiuQingbing ZengCéline le DroumaguetJianhua RongYuan LinJiangli FanXingjie Zan
Undergraduate Student:Lisa AlexanderGiang Nguyen……
Sheng FengHong GuanClorissa WashingtonYixing ChengEnoch AdoglaIin LvGift MetavarayuthPeiyi WangFang Zhou (CIAC)Xia Zhao (CIAC)Limin Chen (CIAC)
Many talent undergrad.
Graduate Student:Hannah BarnhillFang XieSu LongBrandon CashSaswat KabisatpathySiqi LiMike BruckmanGagandeep KaurTao LiKai LiChao WangJerry OxsherLaying WuEve Suthiwangcharoen Sharmi SahaLilly Balizan
SimulationQi Wang (USC)Xinfeng Liu (USC)