Cells integrate signals in space and time to commit to particular fates such as growth, death and differentiation. During this period, distinct patterns of signaling molecules emerge, resembling the "thinking process" of the cells before final commitment. We seek to understand the nature of cellular decision by characterizing these emergent patterns of signaling molecules and the underlying regulatory principles using systems and synthetic biology approaches. To this end, we are taking quantitative methods including long-term single-cell imaging, genomics and proteomics, mathematical modeling and big data analysis. Our ultimate goal is to gain a systems understanding of cell fate commitment in order to predict and control cellular behavior for better design of therapeutic strategies toward cancers and neurodegenerative diseases.
What are cells pondering upon?
Single-cell systems biology
How cells make a decision is a fundamental and unanswered question. We hypothesize that temporal dynamics of signaling molecules represent cell's "thinking process“. To test this hypothesis, we use long-term time-lapse imaging to quantitatively characterize single-cell behavior (growth, division, death and differentiation) and the corresponding dynamics of signaling molecules. We aim to decode the thinking process of cells in order to control their behavior. Click here to see the behavior of actively growing RPE cells.
How do biological patterns emerge?
Emergent properties of biological systems
Signaling molecules and individual cells exhibit diverse temporal and spatial dynamics (click here to see p53 oscillations after gamma-irradiation in a single cell). How do signaling dynamics emerge from interactions among signaling molecules? For a population of cells, how do tissue patterns emerge via cell-cell interactions? What are the functions of these biological patterns? We aim to understand the mechanisms and functions of biological patterns using in-silico modeling and single-cell measurements.
How does metabolic stress influence cancer cells?
Compared to normal cells, cancer cells can be particularly sensitive to certain metabolic stresses e.g. amino acid and serum starvation. We are interested in investigating how cancer cells respond to different nutrient starvation conditions and how nutrient status of human body can alter immune response toward cancer cells. Click here to see the kinetics of breast cancer cell killing by NK cells.
How to design personalized cancer therapies?
Cells are not static and can change their state after drug treatments. We aim to incorporate cell dynamics into the design of cancer therapies by
1. using targeted drugs to identify temporal combinations that yield synergistic effects; 2. developing systematic screening platform to identify targets that function in order and time to kill cancer cells; and 3. integrating system-level information i.e. genomics, proteomics and transcriptomics to identify novel drug targets and potential effective drug combinations. Click here to see temporal changes in drug synergy between two p53-activating drugs.
Principal Investigator (Zoology/Artificial Intelligence) firstname.lastname@example.org
Sheng-hong (Sheng) Chen was born and raised in Taipei, Taiwan. He was an undergraduate at National Taiwan University, where he majored in Zoology and worked with Alex Yu on the population genetics of Mus musculus. After graduation, he went to University of Sussex to do his M.Sc. in Artificial Intelligence. For his thesis project, he worked with Inman Harvey to build an agent-based model to simulate the epidemic dynamics and evolution of the Foot-and-Mouth virus in a small-world network. He then did his Ph.D. at UC San Diego with Huilin Zhou, working on enzymology and quantitative proteomics of the DNA damage checkpoint. He received his Ph.D. in Biological Sciences in 2008 and moved to UC San Francisco and Harvard Medical School for postdoctoral training with Keith Yamamoto and Galit Lahav respectively. During this period, he worked on transcriptional dynamics of glucocorticoid receptor and p53 dynamics in single cells. He began his independent career in the Institute of Molecular Biology at Academia Sinica in 2016.
Ph.D. Scientist (Cancer biology/Epigenetics) email@example.com
Science should be ‘show me’, not ‘trust me’; it should be ‘help me if you can’, not ‘catch me if you can’. — Philip B. Stark
Feng-Shu Hsieh was born and raised in Taipei, Taiwan. She received a B.S. degree (2007) in Agricultural Chemistry from National Taiwan University, and pursued her Ph.D. at Dr. Wen-Ming Yang’s lab in the Institute of Molecular Biology, National Chung-Hsing University (2014). She worked with Dr. Yang on molecular mechanism of transcriptional repression. In Dr. Yang’s lab, she found her career passion in scientific research. After graduation, she moved back to Taipei and started her postdoctoral training with Dr. Kuen-Feng Chen in National Taiwan University Hospital. She participated in the basic science team to uncover potential targets of anti-cancer drugs. Now, she is eager to upgrade her knowledge in better understanding of cell behaviors and gain more insights in the better design of therapeutic strategies against cancer.
Ph.D. Scientist (Biology/Electrical Engineering) firstname.lastname@example.org
Chia-Chou Wu received the B.S. degree in life science (2006), the M.S. degree in biotechnology (2008) and the Ph.D. degree in electrical engineering (2016) from National Tsing Hua University, Hsinchu, Taiwan. During his Ph.D., he focused on a variety of biological datasets to understand the underlying mechanisms of various biological behaviors and to develop corresponding analyses for measuring information flow and systematic characteristics of biological systems. After that, he was funded by the Ministry of Science of Technology, Taiwan to conduct his postdoctoral research with Prof. Tom Freeman at the Roslin Institute in the University of Edinburgh. He worked on the melanoma classification based on the gene expression profiles and survival analysis. Now, he is funded by the Academia Sinica to conduct his postdoctoral research with Dr. Sheng-hong Chen. His current research interest is in modeling dynamic systems in cancer cells.
Ann Mikaela Lynne Ong Co
TIGP Molecular & Cellular Biology PhD student
Mika was born and raised in Manila, Philippines. She recently graduated from the University of the Philippines with a Bachelor’s degree in Molecular Biology and Biotechnology. She is immensely interested in the workings of the immune system, and for her undergraduate research, she studied the T cell response against a candidate vaccine antigen against malaria. Currently, she is looking into how key players in the immune response, metabolism, and DNA damage response interact upon exposure of normal and cancer cells to genotoxic compounds.
MOST undergraduate fellow
Hao-Kuen is currently studying at NTU medical school. He is intrigued by the unsolved questions in science and wishes to know it better through bioinformatics. He now focuses on modeling cancer metabolism to identify interesting properties!
Hannah Katrina Co
TIGP Molecular & Cellular Biology PhD student
"...the scope of things I didn’t know wasn’t merely vast; it was, for all practical purposes, infinite. If our ignorance is infinite, the only possible course of action is to muddle through as best we can.” — Martin A. SchwartzHannah was born and raised in Manila, Philippines. She received her Bachelor's degree in Biochemistry from the University of the Philippines. During her undergraduate study, she found her love for understanding the intricate metabolic pathways involved in the complex interplay among biological processes. In LCD, she is drawn and amazed (!!) by cellular properties emerged from metabolic dynamics. Currently, she is investigating how cells talk with each other, and their language for communication. She hopes to learn their language, participate in their conversations to know them better, and finally decode their thinking processes that give rise to functional consequences.
NTU/AS Genomics & Systems Biology PhD student
Before I came here I was confused about this subject. Having listened to your lecture I am still confused. But on a higher level. — Enrico Fermi
Jen-Hao Cheng grew up in various places in Asia and the US. He studied Biology at Macalester College and Computational Biology at Carnegie Mellon University. Upon graduation, he returned to Taiwan and studied transcriptional regulation and molecular evolution at Huai-Kuang Tsai's lab in Academia Sinica. He then worked as a Bioinformatics Engineer at ACT Genomics, where he analyzes NGS data to improve cancer precision medicine. Jen-Hao is currently pursuing for a Ph.D. degree at LCD while simultaneously working at ACT Genomics. Jen-Hao is interested in using computational approaches to study cancer systems biology and aiming to discover potential combinatorial therapuetic strategies.
Yi-Chen (Vivian) Lee
Junior Scientist（Biomedical Science/Cancer Biology）email@example.com
Vivian was born and raised in Taipei, Taiwan, and received a B.S. degree in Biomedical Science from Chang-Gung University. During university, she worked on figuring out how compounds would affect the human immune system. After graduation, she focused on how cancer cells acquire drug resistance after short/long term therapy. Currently, she is trying to understand how cells communicate with each other through metabolism. She has been trying to explore more about science in any way to express her enthusiasm for it and she will continue to do so.
Duy Pham Minh Nguyen
Junior Scientist（Biotechnology/Systems Biology）firstname.lastname@example.org
"I am just a child who has never grown up. I still keep asking these ‘how’ and ‘why’ questions. Occasionally, I find an answer." — Stephen Hawking
Duy was born and raised in Ho Chi Minh city, Vietnam and went to the UK for high school and university. He graduated with a Bachelor's degree in Biotechnology at Imperial College London
For his final-year project, he developed a tool that automatically analyzes mouse brain and muscle waves to study sleep patterns. This project sparked his interest in studying biological dynamics. At the LCD, he is looking into the behaviors of single-cell p53/mdm2 oscillatory dynamics in response to DNA damage. By using statistical analysis and mathematical modelling, he hopes to understand how human cells can give rise to such a seemingly chaotic, yet robust biomolecular system to protect ourselves from cancer.
Eclipse Ti LCD
Single-cell observer (Optics)
Elipse Ti LCD was born in Japan and raised in Taiwan. She joined LCD in December 2016 and has been spending all of her time observing dynamics of signaling molecules and single-cell behavior. Her current research interest is to find what dynamics encode cellular thoughts after metabolic and anti-cancer drug stresses by direct observation.
Inferring leading interactions in the p53/Mdm2/Mdmx circuit through live-cell imaging and modeling. Cell Syst. 2019 Dec 18;9(6):548-558
Biological oscillator: p53/Mdm2 acts as an autonomous oscillator that is suppressed by Mdmx in proliferating cells.
Two is better than one; toward a rational design of combinatorial therapy. Curr Opin Struct Biol, 2016 Aug 10;41:145-150.
Drug combinations: A review paper on the emerging trend of using the dynamics of biological systems for the rational design of combinatorial therapy. Specifically, we focus how to leverage three properties of signaling networks including 1. single-cell signaling dynamics; 2. signal adaptation and 3. crosstalk among signaling pathways for the rational design of drug combinations.
Schedule-dependent interaction between anticancer treatments. Science 2016 Mar 11;351(6278):1204-8.
Incoherent feed-forward regulatory logic underpinning glucocorticoid receptor action. Proc. Natl Acad Sci U S A. 2013 Jan 29;110(5):1964-9.
Transcriptional dynamics: Here we identified the regulatory logic underlying a pulsatile transcriptional activity of glucocorticoid receptor (GR) using systematic and quantitative perturbations of the GR transcriptional system.
A proteome-wide analysis of kinase-substrate network in the DNA damage response. J Biol Chem. 2010 Apr 23;285(17):12803-12.
Phospho-proteomics: Kinase-substrate network of the DNA damage checkpoint was mapped using quantitative phospho-proteomics.
Reconstitution of Rad53 activation by Mec1 through adaptor protein Mrc1. J Biol Chem. 2009 Jul 10;284(28):18593-604.
Enzyme kinetics: The DNA damage checkpoint signaling cascade was firstly reconstituted for identifying molecular mechanisms for checkpoint kinase activation.
We are always interested in hearing from motivated junior scientists. Please see the following for potential positions. Most of our projects involve a combination of computational and experimental approaches. They can be carried out by collaborating with people in the lab or by yourself (through reading, thinking and trying!). Passionate scientists with only computational or experimental experience are encouraged to apply. For further information, please contact Sheng!
There are internship opportunities for high school/undergraduate students all year round (Summer Internship Fellowship available at IMB and NPAS, and TIGP IIP, Winter Internship Fellowship available at LCD). Students interested in quantitative/systems/cancer biology are welcome to contact us for more information about our research projects.
Graduate Student (Master/PhD)
We have openings for master and doctoral students. For master students, you can apply through the Genome and Systems Biology at National Taiwan University. For doctoral students, we are part of the Molecular and Cellular Biology, Neuroscience, Bioinformatics and Nano Science and Technology program in the Taiwan International Graduate Program in Academia Sinica. In addition, you can also apply the joint Ph.D. program with National Taiwan University in Genome and Systems Biology.
We have openings for bachelor/master degree level scientists in biology and physics. To apply, send a description of your research experience, and a CV including names of 1-3 references by email with the title “RA Application for LCD” to email@example.com.
We are interested in candidates who are
Applications for postdoctoral positions will be considered on a case-by-case basis. To apply, e-mail a statement of your research accomplishments and interests, and a CV including names of 1-3 references to firstname.lastname@example.org with the header “Postdoctoral Application for LCD”.
Postdoctoral Fellowship at Academia Sinica: http://daais.sinica.edu.tw/english/pro_pfp.php
“I do not know what I may appear to the world, but to myself I seem to
have been only like a boy playing on the seashore, and diverting
myself in now and then finding a smoother pebble or a prettier
shell than ordinary, whilst the great ocean of truth lay all
undiscovered before me.” --- Isaac Newton, 1642-1727
Chih-Yao Chung, 2016-2017 Scientist, (Veterinary/Bioengineering), email@example.com
Current: Ph.D. student at University College London
Jeffrey Shu, 2017 LCD Intern, (Molecular and Cell Biology), firstname.lastname@example.org
Current: Erasmus Mundus Scholar, International Master in Innovative Medicine
Qing Chang, 2017/2018 LCD Intern, (Medicine), email@example.com
Current: M.D. student at China Medical School, Taiwan
Zhibek Keneskhanova, 2017 LCD Intern, (Biology), firstname.lastname@example.org
Current: M.Sc. Student at Kazakhstan
Hsuan-Wu (Patty) Hou, 2017-2018 Scientist, (Biochemistry), email@example.com
Current: Ph.D. student in Germany
Gaurav Agarwal, 2018 LCD Intern, (Chemical Engineering), firstname.lastname@example.org
Current: B.Sc. student at Indian Institute of Technology, Kharagpur
Cheng-Xue Lee, 2018 LCD Intern, (Biology & Engineering), email@example.com
Current: M.Sc. student at National Cheng Kung University
Hao-Kuen Lin, 2018 LCD Intern, (Medicine), firstname.lastname@example.org
Current: M.D. student at National Taiwan University
Jose Sandino Bandonil, 2018 LCD Scientist, (Immunology/Biology), email@example.com
Current: Research Assistant at Institute of Molecular Biology, Academia Sinica
Jo-Hsi Huang, 2018-2019 LCD Scientist, (Biology/Dynamics Systems), firstname.lastname@example.org
Current: Ph.D. student at Stanford (Chemical and Systems Biology graduate program)
Carolyn Dunlap, 2018-2020 LCD Scientist, (Molecular and Cell Biology) email@example.com
Current: Research Scientist at ChemoCentryx