M.P. (Miao-Ping) Chien, PhD

Miao-Ping Chien joined the Department of Molecular Genetics at Erasmus Medical Center in June 2017. Chien was born and raised in Taiwan, where she studied Molecular Biology at National Yang-Ming University. She obtained her PhD in Chemistry and Biochemistry at the University of California, San Diego, and went to Harvard University for postdoctoral research, focusing on technology development for biology using multidisciplinary approaches. 

Visit Chien Lab

• Single cell technology
• Functional single cell selection technology (FUNsice)
• Advanced (custom-built) optical microscopy
• Quantitative image analysis
• Bioinformatics (single cell sequencing and proteomic profiling)
• Photochemistry
• Cancer biology
  
   

Why are certain specific, aggressive cancer cells able to resist traditional therapies? Finding the answer to that question drives Miao-Ping Chien’s research: “Resistant cancer cells are extremely elusive. They are able to quickly mutate in unexpected directions, which enables them to withstand chemotherapy or radiation. These cells are rare, difficult to identify, and, therefore, extremely challenging to isolate and analyze. We address this problem in our lab by developing multidisciplinary technologies.”

"Optochemistry" for single cell selection and isolation

Isolation of target cells from a heterogeneous pool is technically difficult when the selection criterion is complex, such as dynamic response over time or morphological features. The majority of technologies for single-cell separation highly rely on static fluorescence or snapshot fluorescent signals, which limits the chance to identify functional and rare single cells. Cancer stem-like or driving cells, as an example, are constantly changing their genetic, transcriptomic and proteomic expression over time, which makes them extremely difficult to isolate via traditional cell separation methods. We address this problem in our lab by improving and developing photoselection tools to isolate desired cells from cultures or tissue based on complex cellular dynamics with a combination of optical and chemical tools.

Quantitative Imaging

To accurately monitor aberrant cellular dynamics in real-time, a fast and accurate cell tracking algorithm is critical. We develop image processing algorithms, through which desired cellular dynamics can be analyzed and identified.

Cancer Bioinformatics

State-of-the-art single cell sequencing methods allow profiling whole genomes or transcriptomes of individual cells. However, current methods lack the capability to link aberrant functional cellular characteristics (i.e. aggressive migration) to genomic or transcriptomic profiles; cannot profile sparse subsets of cancer cells (i.e., cancer stem-like cells); and cannot differentiate populations with mildly differing gene expression profiles. We develop functionally annotated single cell sequencing methods to identify variant genes associated with phenotypic traits of interest and to identify genes and pathways that would be otherwise invisible.

DNA-damage Response and Cancer Biology

Understanding the complexity of cancer highly depends on an elucidation of the changes in the underlying regulatory signaling networks. As an example, resistant breast cancer cells have a superior ability to repair DNA damage upon radiotherapy. This ability involves DNA-damage response (DDR) signaling pathways.
We use optogenetics and optical tools that enable temporal and spatial light patterning to investigate genes associated with carcinogenesis. Modulating upstream signals will lead to downstream changes of cancer hallmarks. These experiments, combined with rapid and sensitive read-outs of cell signaling and behavior, can lead to a new understanding of key events underlying cancer in real-time and with high spatial resolution.

Miao-Ping Chien studied Molecular Biology at National Yang-Ming University in Taiwan in 2006. During 2006-2008, she was a research assistant in Prof. Ding-Kwo Chang’s Lab in the Institute of Chemistry at Academia Sinica in Taiwan, applying biophysical tools to study HIV and influenza viral infection mechanisms.

PhD in Chemistry and Biochemistry

She obtained her PhD with Prof. Nathan Gianneschi in Chemistry and Biochemistry at the University of California, San Diego (UCSD) in 2013, developing a new method to detect and treat tumors with programmable enzyme-responsive nanomaterials.

Postdoc at Harvard University

Miao-Ping Chien then joined Prof. Adam Cohen’s group for her postdoc research in Chemistry and Chemical Biology and Physics at Harvard University, combining advanced optics and photochemistry to develop methods for live single cell isolation based on functional analysis.

Publications

1. Brinks, D., Chien, M.P. "Functional single-cell sequencing links dynamic phenotypes to their genotypes". Nature Biomedical Engineering (research briefing), 2022. (https://rdcu.be/cJr8o) (https://doi.org/10.1038/s41551-022-00877-3)
2. Smit M., Feller K., You L., Storeteboom J., Begce Y., Beerens C. Chien M.P. "Spatially annotated single cell sequencing for unraveling intratumor heterogeneity”, Frontiers in Bioengineering and Biotechnology, 2022 (https://doi.org/10.3389/fbioe.2022.829509).
3. You L.*, Su P.R.*, Betjes M*. Ghadiri Rad, R., Chou, T.C., Beerens, C., van Oosten, E., Leufkens, F., Gasecka, P., Muraro, M., van Tol, R., van Steenderen, D., Farooq, S., Hardillo, J., Baatenburg de Jong, R., Brinks, D., Chien, M.P. “Linking the genotypes and phenotypes of cancer cells in heterogenous populations via real-time optical tagging and image analysis”, Nature Biomedical Engineering, 2022 (https://doi.org/10.1038/s41551-022-00853-x)
4. Su, P.R., You, L., Beerens, C., Bezstarosti, K., Demmers, J., Pabst, M., Kanaar, R., Hsu, C.C., Chien, M.P., “Functional single cell proteomic profiling of cells with abnormal DNA damage response dynamics”. (doi: https://doi.org/10.1101/2021.10.13.464241)
5. Li L., Ugalde A. P., Scheele C. LGJ, Dieter S. M., Nagel R., Ma J., Pataskar, A., Korkmaz, G., Elkon R., Chien M.P., You L., Su P. R., Bleijerveld O. B., Altelaar, M., Momchev L., Manber Z., Han R., van Breugel P. C., Lopes R., ten Dijke P., van Rheenen J., Agami R. "A Comprehensive enhancer screen identifies TRAM2 as a key and novel mediator of YAP oncogenesis." Genome Biology, 2021, 22, 54 (https://doi.org/10.1186/s13059-021-02272-8).
6. Chien M.P.*, Brinks D.*, Adam, Y., Bloxham, W., Kheifets, S., Cohen A.E. “Photoactivated voltage imaging in tissue with an archaerhodopsin-derived reporter.” Science Advances, 2021, 7(19):eabe3216. doi: 10.1126/sciadv.abe3216.
7. Werley C.A., Chien M.P., Cohen A.E. “An ultrawidefield microscope for high-speed fluorescence imaging and targeted optogenetic stimulation.” Biomedical Optics Express. 2017, 8(12), 5794-5813.
8. Werley C.A.*, Chien M.P.*, Gaublomme J, Shekhar K., Yi A., Bloxham W., Regev A., Cohen A. “Geometry-dependent maturation of iPSC-derived cardiomyocytes probed by simultaneous voltage and calcium imaging with genetically encoded fluorescent sensors.” PLOS One, 2017, 12(3):e0172671.
9. Chien M.P., Werley C.A., Farhi S.L., Cohen A. E. “Photostick: a method for selective isolation of target cells from culture.” Chemical Science, 2015; 6: 1701-1705.
10. Nguyen M.M., Carlini A.S., Chien M.P., Sonnenberg S., Luo C., Braden R.L., Osborn K.G., Li Y, Gianneschi N.C., Christman K.L. “Enzyme-Responsive Nanoparticles for Targeted Accumulation and Prolonged Retention in Heart Tissue after Myocardial Infarction.” Advanced Materials. 2015, 37: 5547-52.
11. Proetto M.T., Rush A.M., Chien M.P., Baeza P.A., Thompson M.P., Olson N.H., Andolina C., Millstone J., Moore C.E., Rheingold A.L., Howell S.B., Browning N.D., Evans J.E., Gianneschi N.C. “Dynamics of soft nanomaterials captured by transmission electron microscopy in liquid water.” J Am Chem Soc. 2014 Jan 29;136(4):1162-5.
12. Chien M.P., Hu D., Barback C.V., Rush A.M., Orr G., Hall D.J., and Gianneschi N. C. “Enzyme-Directed Assembly of Nanoparticles in Tumors Monitored by In Vivo Whole Animal and Ex Vivo Super Resolution Fluorescence Imaging.” J Am Chem Soc. 2013 Dec 18;135(50):18710-3.
13. Chien M.P., Thompson M.P., Ku T.H., Barback C. and Gianneschi N. C. “Enzyme-Directed Assembly of a Nanoparticle Probe in Tumor Tissue.” Advanced Materials. 2013, July 12 (25): 3599-3604.
14. Chien M.P., Thompson M.P., Eugene C. Lin, and Gianneschi N.C. “Fluorogenic Enzyme-Responsive Micellar Nanoparticles.”  Chemical Science. 2012, 3: 2690-2694. (Cover Art)
15. Randolph L.M.*, Chien M.P.*, and Gianneschi N.C. “Biological Stimuli and Biomolecules in the Assembly and Manipulation of Nanoscale Polymeric Particles.” Chemical Science. 2012, 3(5). doi: 10.1039/C2SC00857B.
16. Chien M.P. and Gianneschi N.C. “A morphology-dependent bio-organic template for inorganic nanowire synthesis.” Small. 2011 Jul 18;7(14):2041-6.
17. Ku T.H.*, Chien M.P.*, Thompson M.P., Sinkovits R.S., Olson N.H., Baker T.S. and Gianneschi N.C. “Controlling and Switching the Morphology of Micellar Nanoparticles with Enzymes.” J Am Chem Soc. 2011 Jun 8;133(22):8392-5. (Cover Art)
18. Kinsella J.M., Ananda S., Andrew J.S., Grondek J.F., Chien M.P., Scadeng M., Gianneschi N.C., Ruoslahti E., Sailor M.J. “Enhanced magnetic resonance contrast of fe(3)o(4) nanoparticles trapped in a porous silicon nanoparticle host.” Advanced Materials. 2011 Sep 22;23(36):H248-53.
19. Chien M.P., Thompson M.P., Gianneschi N.C. “DNA-nanoparticle micelles as supramolecular fluorogenic substrates enabling catalytic signal amplification and detection by DNAzyme probes.” Chem. Commun. 2011. (Cover Art)
20. Chien M.P., Rush A.M., Thompson M.P., and Gianneschi N.C.  “Programmable phase shifting micelles.” Angew. Chem. Int. Ed. Engl. 2010 Jul 12;49(30):5076-80. (Cover Art). Selected for Faculty of 1000 Biology.
21. Thompson M.P.*, Chien M.P.*, Ku T.H., Rush A.M., Gianneschi N.C. “Smart lipids for programmable nanomaterials.” Nano Lett. 2010 Jul 14;10(7):2690-3.
22. Jiang S., Chien M.P. and Chang D.K. “The fusion peptide domain is the primary membrane-inserted region and enhances membrane interaction of the ectodomain of HIV-1 gp41.” Mol. Membr. Biol. 2010 Jan;27(1):32-49.
23. Chien M.P., Lin C.H. and Chang D.K. “Recruitment of HIV-1 envelope occurs subsequent to lipid mixing: a fluorescence microscopic evidence.” Retrovirology, 2009 Mar 2;6:20.
24. Chien M.P., Jiang S. and Chang D.K. “The function of coreceptor as a basis for the kinetic dissection of human immunodeficiency virus type 1 Env-mediated cell fusion.” FASEB Journal, 2008 Apr;22(4):1179-92.

Scholarships, grants and awards

Prior to appointment as a Principal Investigator

Single Cell Technology for Cancer Biology

Our lab applies the power of single cell sequencing and analysis to cancer research. We focus on the robust identification and accurate isolation of rare, heterogeneous and dynamically changing tumor-driving cancer cells and apply optogenetics and single cell sequencing to investigate tumorigenesis at the single cell level.

My Group

• Postdoc: Li You, Jelle Storteboom, Mayte Lopez-Cascales
• Technician: Cecile Beerens, Pierangela Chiafele
• PhDs: Pin-Rui (Ray) Su, Reza Ghadiri Rad, Ting-Chung Chou, Kate Feller, Tsai-Ying Chen, Lars van Roemburg, Junfeng Huang