# Biography I obtained my Bachelor’s degree from National Taiwan University (Taipei, Taiwan) in 2000 and subsequently pursued a PhD at Stanford University (Stanford, California, USA), which I completed in 2012. During my doctoral studies, I was honored with the Department of Defense Breast Cancer Research Program Traineeship Award in 2009. My PhD research resulted in several seminal publications on DNA damage response and cell cycle regulation in Molecular Cell, a leading journal in the field of cell and molecular biology. Following my graduation, I served as a Postdoctoral Researcher in Dr. Cimprich’s laboratory at Stanford University. In 2013, I transitioned to Harvard Medical School, joining the Laboratory of Systems Pharmacology as a Postdoctoral Fellow. Currently, I am engaged in postdoctoral research at the Laboratory of Systems Pharmacology. My work involves leveraging contemporary computational and experimental methodologies to explore drug-gene interactions in cancer. This includes a particular emphasis on developing novel imaging techniques for both high-content/live-cell imaging in research environments and multiplexed methods for clinical specimens. My primary objective is to understand how genetic variations influence the diverse responses within signaling networks, with the aim of using this knowledge to devise more effective therapeutic strategies - #### **Positions and Honors** ***Position and Employment*** Sort2020 - **Technical Director of Tissue Imaging.** Laboratory of Systems Pharmacology, Harvard Medical School 2017 - 2020 **Research Fellow.** Laboratory of Systems Pharmacology, Harvard Medical School 2013 - 2017 **Postdoctoral Fellow.** Laboratory of Systems Pharmacology, Harvard Medical School 2012 - 2013 **Postdoctoral Fellow.** Chemical and Systems biology, Stanford University 2004 – 2005 **Research Assistant.** National Taiwan University, Institute of Molecular Medicine, Taiwan . ***Honors*** Sort2009-2011 **DOD Breast Cancer Research Program Predoctoral Traineeship Award,** sponsored by Department of Defense 2006-2008 **Quantitative Chemical Biology Training Program,** sponsored by Molecular Pharmacology, Stanford University 2006, 2007,2008 **Outstanding Student Poster Presentation**. Department of Chemical and Systems Biology Retreat, Stanford. 1999 – 2000 **Undergraduate Research Fellowship** sponsored by National Science Council, Taiwan - #### **Contribution to Science** **1.** **I developed a method to achieve high multiplexed single-cell imaging with cyclic immunofluorescence (**[**I developed a method to achieve high multiplexed single-cell imaging with cyclic immunofluorescence (**](https://www.cycif.org/)**), a simple and versatile procedure in which four-color staining alternates with chemical inactivation of fluorphores to progressively build a multi-channel image.** I also demonstrate that live and fixed-cell imaging can be combined to exploit the advantages of both. In addition, CycIF data can be analyzed using conventional imaging software or the algorithms recently developed for high-dimensional data analysis & visualization. Altogether, this method will leads to many new venues for different research fields. - **Jia-Ren Lin**, Mohammad Fallahi-Sichani, and Peter K Sorger. Highly multiplexed high-throughput imaging of single-cell using CycIF cyclic immunofluorescence, *Nat. Comm.* **2015,** vol 6 8390 - **Jia-Ren Lin**, Mohammad Fallahi-Sichani, Jia-Yun Chen and Peter K Sorger. Cyclic Immunofluorescence (CycIF), A highly Multiplexed Method for Single-Cell Imaging, *Cuurent Protocols in Chemical Biology* **2016** *in press* 2\. During my PhD and postdoc at Stanford, I study of the regulations of mutagenesis during damaged DNA replication, specifically focusing on the functions of post-replication repair (PRR) pathway. My research reveals a novel mechanism that cells differentially utilize HLTF and SHPRH for different forms of DNA damage through coordinating the two main branches of PRR to choose the proper bypass mechanism for minimizing mutagenesis. Furthermore, I also identified a new role for monoubiquitination in controlling Rad18 function and suggest that damage-specific deubiquitination promotes a switch from Rad18•Ub-Rad18 complexes to the Rad18-SHPRH complexes necessary for error-free lesion bypass in cells. - **Jia-Ren Lin**, **Zeman MK**, Freire R, Cimprich KA. DNA Damage Alters the Ubiquitination State of Rad18 to Regulate Its Function and Its Assembly into DNA Damage Tolerance Complexes, *J Cell biol.* **2014** 206(2): 183-197. - **Jia-Ren Lin**, Zeman MK, Chen JY, Yee MC, Cimprich KA. SHPRH and HLTF act in a damage-specific manner to coordinate different forms of postreplication repair and prevent mutagenesis. *Mol. Cell.* **2011** 42(2):237-49. 3\. The other part of my PhD project was to study the process of oncogene-induced senescence with a focus on how cell-to-cell variability in oncogenic activity is linked to different cellular fates via time-lapse imaging and single-cell quantification. I helped to discover the roles of two disease-related genes, DyrK1a and Nek8 in regulating cell cyle length and DNA damage response during S-phase. - Chen JY, **Jia-Ren Lin**, Tsai FC, and Meyer T. Dosage of Dyrk1a controls a decision for cell cycle exit by co-regulation of cyclin D1 and p21 levels. *Mol. Cell.* **2013** 52(1):87-100. - Choi HJ, **Jia-Ren Lin**, Vannier J, Saats GG, Kile AC, Paulsen RD, Manning DK, Beier DR, Giles RH, Boulton SJ, Cimprich KA. The ciliopathy-associated protein Nek8/NPHP9 acts with ATR to regulate the replication stress response. *Mol. Cell.* **2013** 51(4):423-439. - Chen JY, **Jia-Ren Lin**, Cimprich KA, Meyer T. A two dimensional ERK-AKT signaling code for an NGF-triggered cell fate decision. *Mol. Cell.* **2012** 45(2):196-209. 4\. My works in National Taiwan University was to investigations of the cellular function of two cytoskeleton associated genes, DAP kinase and a novel gene eIF3k. I identified that myosin regulatory light chain II as the in vitro and in vivo kinase substrate for DAP kinase. I also helped to reveals the function of eIF3k to relieve the caspase-sequestration effect of K8/K18, thereby increasing the availability of caspases to their non-keratin-residing substrates. - Lin YM, Chen YR, **Jia-Ren Lin**, Wang WJ, Inoko A, Inagaki M, Wu YC, Chen RH. eIF3k regulates apoptosis in epithelial cells by releasing caspase 3 from keratin-containing inclusions. *J Cell Sci*. **2008** 121(14):2382-93*.* - Chen CH, Wang WJ, Kuo JC, Tsai HC, **Jia-Ren Lin**, and Chen RH. Bi-directional signals transduced by DAPK-ERK interaction promote the apoptotic effect of DAPK. *EMBO J*. **2005** 24, 294-304. - Kuo JC, **Jia-Ren Lin**, Staddon JM, Hosoya H, Chen RH. Uncoordinated regulation of stress fibers and focal adhesions by DAP kinase. J. Cell Sci. 2003 116, 4777-90