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
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
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
Nature 414:105, 2001
Models of Tumor HeterogeneityModels of Tumor Heterogeneity
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
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
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
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
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
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
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
ALDH (Aldehyde DALDH (Aldehyde Dehydrogenaseehydrogenase) Activity ) Activity of MCF-7 Cellsof MCF-7 Cells
AAligned Fiber Random Fiber
Sheng Feng
Increased Mammosphere-Forming Increased Mammosphere-Forming CapabilityCapability
AAligned Fiber Random Fiber
Sheng Feng
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
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
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
Zhongwei, Jianhua, Mike Bruckman O. D. Velev et al, Small 2006, 2, 1462
Alignment of Rod Like NanoparticlesAlignment of Rod Like Nanoparticles
2D Alignment of Colloidal Particles2D Alignment of Colloidal Particles
Dimitrov and Nagayama, Langmuir 1996, 12, 1303
2D Alignment of Protein Nanoparticles2D Alignment of Protein Nanoparticles
Mike Bruckman, Zhongwei Niu O. D. Velev et al, Small 2006, 2, 1462
Jianhua Rong, Zhongwei Niu, in collaboration with Dr. Charlene Mello
Controlled Alignment of Cell GrowthControlled Alignment of Cell Growth
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
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
Smooth Muscle Cells: Different MorphologiesSmooth Muscle Cells: Different Morphologies
Lilly
Control
AlignedScaffold
Significance of the Alignment of Significance of the Alignment of Smooth Muscle CellsSmooth Muscle Cells
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??
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??
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)