Faculty

2008.09-2013.07 doctor, School of chemistry and molecular engineering, Peking University

2004.09-2008.07 bachelor, chemistry and molecular engineering, Peking University

2021.09-now tenure track assistant professor, Shenzhen Graduate School, Peking University

2021.05-now  distinguished researcher of Shenzhen Bay Laboratory

2018.08-2021.05 research scientist, New York University School of medicine, USA

2014.03-2018.08 postdoctoral fellow, New York University School of Medicine (co Supervisor: Eli Rothenberg, associate professor)

2013.07-2014.03 Research Assistant (Supervisor: Professor zhaoxinsheng), School of chemistry and molecular engineering, Peking University

1. development of image mining technology based on high-order correlation function

Multicolor super-resolution microscopic imaging technology provides a powerful tool for in-situ observation of the structure of biomolecular complexes in cells, and its spatial resolution of 15 ~ 40 nm shows the observer more and more fine structural details in cells. However, the presentation of these complex details brings great challenges to the quantitative analysis of images, especially when the observed macromolecular complexes are widely and densely distributed in cells, it is difficult for observers to directly extract effective quantitative information from the images. In view of this, we developed an image mining technology based on the third-order correlation function (TCF) to realize the structural model recognition and related quantitative analysis of biomolecular complexes in complex chaotic images (nat. communs., 2019, first author, CO corresponding author). Using this technology, we 1) quantitatively analyze the monitoring and regulation mechanism of intracellular DNA replication for the first time, and reveal its physical association with the stress response mechanism when DNA replication is inhibited (mol. cell, 2021, first author, CO corresponding author); 2) The transient formation of intracellular g-tetramer at DNA replication forks and its effect on DNA replication were quantitatively analyzed for the first time (nat. communs., 2021, the second author).

2. single molecule tracing in living cells reveals the functional self cleavage mechanism of usp1

Usp1 is one of the important factors that regulate DNA replication by deubiquitination of PCNA. It inactivates itself by auto cleavage, thus ensuring that the ubiquitination deubiquitination of PCNA is in a dynamic balance. However, the functional molecular mechanism by which usp1 self cleavage leads to its own inactivation is unknown. In theory, single-molecule tracing technology of living cells can observe the dynamics of a single usp1 molecule in the cell in real time, so as to analyze its molecular mechanism. However, due to the dense distribution of molecules to be measured in the cell environment, high background noise of self fluorescence, single-molecule tracing in the cell is extremely challenging. To solve this problem, we achieved single-molecule tracking of usp1 molecules with high density distribution in the nucleus by optimizing the lighting and labeling. Combining the advantages of high-resolution quantitative analysis of dual color super-resolution microscopy imaging, we quantitatively analyzed the dynamic characteristics of usp1 spatial distribution and residence time at DNA replication forks, revealing that one of the important physiological significance of usp1 auto cleavage is to promote the dissociation of usp1 from replication forks and ensure the smooth progress of replication forks (nat. communs., 2022, CO first author).

3. development of reduced velocity diffusion fluorescence correlation spectroscopy technology

Fluorescence correlation spectroscopy (FCS) is a single-molecule technology that measures the dynamic process of chemical reaction rate and molecular conformation change in the thermodynamic equilibrium state. Its principle is to count the fluctuations of energy and population of microscopic particles near the ensemble equilibrium state in a very small optical detection volume (such as confocal microscope). However, due to the Brownian motion of the molecule itself, the molecule to be tested cannot stay in the detection area of small light spots for a long time, which limits the detectable time window of FCS to 10 ns - 50 µ s, greatly limiting the potential application range of FCS. In order to overcome the Brownian motion of molecules and ensure that they can stay in the observation area for a long time, we developed the reduced velocity diffusion fluorescence correlation spectroscopy technology (chem. commun., 2012, the first author). This technology weakens the Brownian motion of the molecule by fixing the molecule to be tested on a larger (about 2 µ m in diameter) polystyrene microsphere, prolongs its characteristic residence time in the confocal light point detection area from ~100 µ s to ~1 s, and expands the observable window of FCS dynamics by 2-3 orders of magnitude. Using this method, we quantitatively analyzed the spontaneous turnover of a single mismatched base in double stranded DNA, providing a basic thermodynamic basis for the study of DNA mismatch base repair mechanism (PNAs, 2014, the first author).

1) M Lu, W Yao, Y Li, D Ma, Z Zhang, H Wang, X Tang, Y Wang, C Li, D Cheng, H Lin,Y Yin*,J Zhao*, G Zhong*, Broadly effective ACE2 decoy proteins protect mice from lethal SARS-CoV-2 infection.Microbiol Spectr. 2023, 11, e0110023 (*co-corresponding)

2) SM Christie, T Tada,Y Yin, A, Bhardwaj, NR Landau, E Rothenberg, Single-virus tracking reveals variant SARS-CoV-2 splike proteins induce ACE2-independent membrane interations.Sci. Adv. 2022, 8, eabo3977

3) H Xue, A Bhardwaj,Y Yin, C Fijen, A Ephstein, L Zhang, X Ding, JM Pascal, TL VanArsdale, E Rothenberg, A two-step mechanism governing PARP1-DNA retention by PARP inhibitors.Sci. Adv. 2022, 8, eabp0414

4) KE Coleman#,Y Yin#,SKL Lui, S Keegan, D Fenyo, DJ Smith, E Rothenberg, TT Huang, USP1-trapping lesions as a source of DNA replication stress and genomic instability.Nat. Communs. 2022, 13, 1740 (#co-first contribution)

5) Y Yin*,WTC Lee, D Gupta, H Xue, P Tonzi, JA Borowiec, TT Huang, M Modesti, E Rothenberg*, A basal-level activity of ATR links replication fork surveillance and stress response.Mol. Cell2021, 81, 4243-4257 (*co- corresponding)

6) WTC Lee,Y Yin, M Morton, P Tonzi, PP Gwo, D Odermatt, M Modesti, S Cantor, K Gari, T Huang, E Rothenberg, Single-molecule imaging reveals replication fork coupled formation of G-quadruplex structures hinders local replication stress signaling.Nat. Commun. 2021, 12, 2525

7) DR Whelan, WTC Lee, F Marks, YT Kong,Y Yin, E Rothenberg, Super-resolution visualization of distinct stalled and broken replication fork structures.Plos Genetics2020, 16, e1009256

8) T Trcek, TE Douglas, M Grosch,Y Yin, WVI Eagle, ER Gavis, H Shroff, E Rothenberg, R Lehmann, Sequence-Independent Self-Assembly of Germ Granule mRNAs into Homotypic Clusters.Mol. Cell2020, 78, 941-950

9) H Zhang, CL Christensen, R Dries, MG Oser, J Deng, B Diskin, F Li, Y Pan, X Zhang,Y Yin, …, E Rothenberg, G Miller, NS Gary, KK Wong, CDK7 inhibition potentiates genome instability triggering anti-tumor immunity in small cell lung cancer.Cancer Cell2020, 37, 37-54.e9

10) F Pessina, F Giavazzi,Y Yin, …, E Rothenberg, F d’Adda di Fagagna, Functional transcription promoters at DNA double-strand breaks mediate RNA-driven phase separation of damage-response factors.Nat. Cell. Biol. 2019, 21, 1286-1299

11) JC Kim, M Pérez-Hernández, FJ Alvarado, SR Maurya, J Montnach,Y Yin, …, E Rothenberg, A Lundby, HH Valdivia, M Cerrone, M Delmar, Disruption of Ca2+i homeostasis and connexin 43 hemichannel function in the right ventricle precedes overt Arrhythmogenic Cardiomyopathy in Plakophilin-2-deficient mice.Circulation, 2019, 140, 1015-1030

12) TN Moiseeva,Y Yin, …, E Rothenberg, SC Watkins, CJ Bakkenist, An ATR and CHK1 kinase signaling mechanism that limits origin firing during unperturbed DNA replication.Proc. Natl. Acad. Sci. U. S. A. 2019, 116, 13374-13383

13) Y Yin*,WTC Lee, E Rothenberg*, Ultrafast Data Mining of Molecular Assemblies in Multiplexed High-Density Super-Resolution Images.Nat. Commun.2019, 10, 119 (*co- corresponding)

14) P Tonzi,Y Yin, WTC Lee, E Rothenberg, TT Huang, Translesion polymerase kappa-dependent DNA synthesis underlies replication fork recovery.eLife2018, 7, e41426

15) C Nemoz, V Ropars, P Frit, A Gontier, P Drevet, J Yu, R Guérois, A Pitois, A Comte, C Delteil, N Barboule, P Legrand, S Baconnais,Y Yin, S Tadi, E Barbet-Massin, I Berger, E Le Cam, M Modesti, E Rothenberg, P Calsou, XLF and APLF bind to Ku80 on two remote sites to ensure DNA repair by non-homologous end-joining.Nat. Struct. Mol. Biol. 2018, 25, 971-980

16) D Whelan, WTC Lee,Y Yin, DM Ofri, K Bermudez-Hernandez, S Keegan, D Fenyö, E Rothenberg, Spatiotemporal dynamics of homologous recombination repair at single collapsed replication forks.Nat. Commun.2018, 9, 3882

17) J Wang,Y Yin, S Lau, J Sankaran, E Rothenberg, T Wohland, M Meier-Schellersheim, H Knaut, Anosmin1 Shuttles Fgf to Facilitate Its Diffusion, Increase Its Local Concentration, and Induce Sensory Organs. Dev.Cell2018, 46, 751-766

18) G Rona, D Roberti,Y Yin, JK Pagan, H Homer, E Sassani, A Zeke, L Busino, E Rothenberg, M Pagano, PARP1-dependent recruitment of the FBXL10-RNF68-RNF2 ubiquitin ligase to sites of DNA damage controls H2A.Z loading.eLife2018, 7, e38771

19) K Bermudez-Hernandez, S Keegan, D Whelan, DA Reid, J Zagelbaum,Y Yin, S Ma, E Rothenberg, D Fenyö, A method for quantifying molecular interactions using stochastic modelling and Super-Resolution microscopy.Sci. Rep. 2017, 7, 14882

20) DA Reid, MP Conlin,Y Yin, HH Chang, G Watanabe, MR Lieber, DA Ramsden, E Rothenberg, Bridging of double-stranded breaks by nonhomologous end-joining ligation complex is modulated by DNA end chemistry. Nucl. Acids Res. 2017, 45, 1872-1878

21) Y Yin, E Rothenberg, Probing the spatial orgnization of molecular complexes using triple-pair-correlation.Sci. Rep. 2016, 6, 30819

22) H Bi,Y Yin, B Pan, G Li, XS Zhao, Scanning single-molecule fluorescence correlation spectroscopy enables kinetics study of DNA hairpin folding with a time window from microseconds to seconds.J. Phys. Chem. Lett. 2016, 7, 1865-1871.

23) YH Chen#, MJK Jones#,Y Yin#,SB Crist, L Colnaghi, RJ Sims, E Rothenberg, PV Jallepalli, TT Huang, ATR-mediated phosphorylation of FANCI regulates dormant origin firing in response to replication stress.Mol. Cell2015, 58, 323-338 (# co-first contribution)

24) Y Yin#,L Yang#, G Zheng, C Gu, C Yi, C He, Y Gao, XS Zhao, Dynamics of spontaneous flipping of a mismatched base in DNA duplex.Proc. Natl. Acad. Sci. U. S. A.2014, 111, 8043-8048 (# co-first contribution)

25) Y Yin, R Yuan, XS Zhao, Amplitude of Relaxations in Fluorescence Correlation Spectroscopy for Fluorophores that Diffuse Together.J. Phys. Chem. Lett.2013, 4, 304-309.

26) Y Yin, P Wang, X Yang, X Li, C He, XS Zhao, Panorama of DNA hairpin folding observed via diffusion-decelerated fluorescence correlation spectroscopy.Chem. Commun. 2012, 48, 7413-7415.

27) X Li,Y Yin, X Yang, Z Zhi, XS Zhao, Temperature dependence of interaction between double stranded DNA and Cy3 or Cy5.Chem. Phys. Lett. 2011, 513, 271-275.

28) Y Yin, XS Zhao, Kinetics and Dynamics of DNA Hybridization.Acc. Chem. Res. 2011, 44, 1172-1181 (review).

29) Y Yin, X Zhou, XS Zhao, Maximum Entropy Method for Analyses of Fluorescence Correlation Spectra of Oligonucleotide Intra-Chain Collision.Acta Phys. Chim. Sin. 2010, 26, 1087-1092.