Assistant Professor
Liu Lab: The mechanisms that fold and regulate the genome
1. Molecular basis of genome folding, function and regulation
2. Interplays between genome folding and epigenetic modifications
3. 3D nuclear dynamics in cancer
At the Liu Lab, our focus is on advancing our understanding of the mechanistic aspects of the human 3D genome and its implications in cancer. Through a combination of biochemical, molecular, and cell biology techniques, along with state-of-the-art genomic and computational analyses, we aim to address three fundamental questions:
1. How do cancer-associated mutations in architectural proteins impact genome folding and function?
2. How does the genome folding machinery process epigenetic codes?
3. What is the biological and clinical relevance of 3D genome folding?
Mechanistic Studies of Genome ArchitectureMechanistic Studies of Genome Architecture
1. Liu Y and Dekker J. CTCF-CTCF loops and intra-TAD interactions show differential dependence on cohesin ring integrity. Nature Cell Biology, 2022, 24:1516-1527.
2. Hildebrand EM, Polovnikov K, Dekker B, Liu Y, Lafontaine DL, Fox AN, Li Y, Venev SV, Mirny L and Dekker J. Chromosome decompaction and cohesin direct Topoisomerase II activity to establish and maintain an unentangled interphase genome. Cell, in revision, 2022.
BioRxiv (https://doi.org/10.1101/2022.10.15.511838).
3. Tavares-Cadete F*, Norouzi D*, Dekker B, Liu Y and Dekker J. Multi-contact 3C data reveal that the human genome is largely unentangled. Nature Structural & Molecular Biology, 2020, 12: 1105-1114. *Co-first.
4. Oomen ME, Hansen A, Liu Y, Darzacq X and Dekker J. CTCF sites display cell cycle dependent dynamics in factor binding and nucleosome positioning. Genome Research, 2019, 29: 236-249.
5. Oudelaar AM, Davies JOJ, Hanssen LLP, Telenius JM, Schwessinger R, Liu Y, Brown JM, Downes DJ, Chiariello AM, Bianco S, Nicodemi M, Buckle VJ, Dekker J, Higgs DR, and Hughes JR. Single-allele chromatin interactions identify regulatory hubs in dynamic compartmentalized domains. Nature Genetics, 2018, 50:1744-1751.
Genome Folding and Human Diseases
6. Zhang BN*, Liu Y*, Yang Q, Leung PY, Wang C, Wong TCB, Tham CC, Chan SO, Pang CP, Chen LJ, Dekker J, Zhao H and Chu WK. rad21 is involved in corneal stroma development by regulating neural crest migration. 2020. International Journal of Molecular Sciences, 2020. 21(20), 7807. *Co-first.
7. Viny AD, Bowman RL, Liu Y, Durham B, Eisman S, Navitski A, Witkin M, Baslan T, Lowe S, Ott CJ, Dekker J, Koche R and Levine RL. Cohesin members Stag1 and Stag2 display distinct roles in chromatin accessibility and topological control of HSC self-renewal and differentiation. Cell Stem Cell, 2019, 25: 682-696
8. Zhang BN*, Chan TCY*, Tam POS, Liu Y, Pang CP, Jhanji V, Chen LJ and Chu WK. A cohesin subunit variant identified from a peripheral sclerocornea pedigree. Disease Markers, 2019, 8781524. *Co-first.
Transcriptome Dynamics and Regulation in Human Diseases and Evolution
9. Liu Y, Noon A, Aguiar Cabeza E, Shen J, Cynthia Kuk C, Ilczynski C, Huang K, Ni R, Balram S, Chan K, Barbosa-Morais NL, Hermanns T, Blencowe BJ, Azad A, van der Kwast TH, Zlotta AR, and Wrana JL. Next-generation RNA sequencing of Archival Formalin-fixed Paraffin-embedded Urothelial Bladder Cancer. European Urology, 2014 Dec, 66(6):982-986.
10. Li JJ*, Liu Y*, Xin XF, Kim TH, Aguiar Cabeza E, Ren J, Wrana JL, and Zhang Z. Evidence for positive selection on a number of microRNA regulatory interactions during recent human evolution. PLoS Genetics, 2012 Mar, 8:e1002578. *Co-first.
11. Gregorieff A, Liu Y, Inanlou MR, Khomchuk, Y, and Wrana JL. Yap dependent reprogramming of Lgr5+ stem cells drives intestinal regeneration and cancer. Nature, 2015, Oct, 526: 715-718.
12. Golipour A*, David L*, Liu Y, Jayakumaran G, Hirsch CL, Trcka D, Wrana JL. A late transition in somatic cell reprogramming requires regulators distinct from the pluripotency network. Cell Stem Cell, 2012 Dec, 11(6):769-82. *Co-first.
13. Campbell JE, Ussher JR, Mulvihill EE, Kolic J, Baggio LL, Cao X, Liu Y, Lamont BJ, Morii T, Streutker C, Tamarina N, Philipson LH, Wrana JL, MacDonald PE and Drucker DJ. TCF1 links GIPR signaling to the control of beta cell function and survival. Nature Medicine, 2016, Jan, 22: 84-90.
14. Ma F, Arai S, Wang K, Calagua C, Yuan A, Poluben L, Gu Z, Russo JW, Einstein DJ, Ye H, He MX, Liu Y, Allen EV, Sowalsky AG, Bhasin MK, Yuan X and Balk SP. Autocrine Wntless-dependent Wnt signaling drives distinct pathways in primary and metastatic castration-resistant prostate cancer. Cancer Research, 2022, 82(8): 1518-1533.
15. Zheng S, Xiao L, Liu Y, Wang Y, Cheng L, Zhang J, Yan N, Chen D. DZNep inhibits H3K27me3 deposition and delays retinal degeneration in the rd1 mice. Cell Death and Disease, 2018, 9:310.
16. El Hassan MA*, Huang K*, Eswara MBK*, Zhao M, Song L, Yu T, Liu Y, Liu CJ, McCurdy S, Ma A, Wither J, Jin J, Zacksenhaus E, Wrana JL, and Bremner R. Cancer cells hijack PRC2 to modify multiple immune pathways. PLoS ONE, 2015 Jun, 10(6): e0126466. *Co-first.
Mechanistic Studies of Electron Transfer and Proton Pumping
17. Liu Y, and Hill BC. Formamide probes a role for water in the catalytic cycle of cytochrome c oxidase. Biochim Biophys Acta, 2007 Jan, 1767 (1): 45-55.
ABOUT THE POSITION
The laboratory of Dr. Yu (Sunny) Liu at the Cancer Epigenetics Institute, based at Fox Chase Cancer Center in Philadelphia, PA, USA, is seeking skilled and self-motivated individuals to join our dynamic research team. The Liu lab focuses on mechanistical studies of human 3D genome and its connection to cancer. Current ongoing projects include: 1) elucidate the mechanism of genome folding using both synthetic and cancer-associated variants of architectural proteins, including cohesin and CTCF; 2) study the interplay between genome folding and histone modifications; 3) establish a semi-in vitro system to examine 3D nuclear dynamics in cancer. We are actively publishing high-impact papers, including Nature, Nature Genetics, Nature Cell Biology and Genome Research. Additional details about the lab can be found at www.3dliulab.org.
ABOUT THE TRAINING ENVIRONMENT
As one of the four original cancer centers to receive comprehensive designation from the National Cancer Institute, Fox Chase Cancer Center has been at the forefront of cancer research for almost 90 years. We are home to excellent research facilities, top clinicians and scientists, and outstanding patient care. Our singular focus on cancer, which couples discovery science with state of the art clinical care and population health, remains the foundation of our work.
The scientist training programs at Fox Chase Cancer Center provide professional development opportunities in four core areas identified as crucial for successful careers in science, research, and health care including communication, leadership, teaching, and mentorship. Upon joining the program, graduate students and postdocs develop individual development plans to help guide their growth. Training throughout the year is supplemented with free professional development opportunities, including a robust ‘How To’ series, writing courses, networking, mentorship, and teaching opportunities, a trainee-led seminar series, a trainee-led annual Research Conference, and more. Postdocs at Fox Chase Cancer Center are supported by the Temple University Postdoc Association and the Office of Academic Affairs at Fox Chase, and are compensated with competitive pay and benefits.
In addition to the robust training program, scientists at Fox Chase Cancer Center benefit from being part of the rich scientific and biotech environment in the Philadelphia region. Many of our former trainees are now employees (and contacts) at nearby institutions and companies, including The Wistar Institute, Merck, GSK, AACR, and numerous others.
TO APPLY
Email a CV, cover letter with research interest(s) and goals, and the name of at least three references to [email protected]. Qualified candidates will then be invited to complete a job application.
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