1e
19
1
49
2
2
18
1b
1d
18
34
5e
1d
2 29
1d
25
Chengyu Liang, MD, PhD
88
5e
Wistar Institute Professor of Biochemistry and Biophysics
7
72
Department: Biochemistry and Biophysics
4
1
23
1f
Graduate Group Affiliations
8
a
b
1d
46
Contact information
42
4
3
3
3
2
4
b
1f
42
The Wistar Institute
1a 3601 Spruce Street
35 Office 231 - Tower
Philadelphia, PA 19104
26
1a 3601 Spruce Street
35 Office 231 - Tower
Philadelphia, PA 19104
2e
Office: 215-898-3862
3e Lab: 215-898-3860
18
83
3e Lab: 215-898-3860
18
Email:
cliang@wistar.org
12
cliang@wistar.org
13
Education:
21 7 MD 15 (Medicine) c
4e Qingdao University School of Medicine, Qingdao, China, 1995.
21 7 MS 15 (Genetics) c
5b Peking Union Medical College& Chinese Academy of Medical Sciences , 1998.
21 7 MS 1d (Computer Science) c
55 State University of New York (SUNY) at Stony Brook, New York, 2004.
21 8 PhD 1f (Molecular Genetics) c
55 State University of New York (SUNY) at Stony Brook, New York, 2004.
c
3
3
3
3
8d
Permanent link21 7 MD 15 (Medicine) c
4e Qingdao University School of Medicine, Qingdao, China, 1995.
21 7 MS 15 (Genetics) c
5b Peking Union Medical College& Chinese Academy of Medical Sciences , 1998.
21 7 MS 1d (Computer Science) c
55 State University of New York (SUNY) at Stony Brook, New York, 2004.
21 8 PhD 1f (Molecular Genetics) c
55 State University of New York (SUNY) at Stony Brook, New York, 2004.
c
2 29
21
1e
1d
24
76
4c2 The homeostasis of all eukaryotic cells depends on their “greening” ability to use a lysosomal pathway known as autophagy to degrade and recycle self-components. Liang lab has identified and studied the mammalian essential autophagy protein, UV irradiation resistance associated gene (UVRAG), which functions in and beyond autophagy and has emerging significance in cancer research. Using a series of genetic, biochemical, molecular and cell biological, and computational approaches in model organisms from Drosophila to Zebrafish to mice, we have defined both canonical and non-degradative functions of UVRAG and the autophagy pathway in multiple endomembrane trafficking (Nat Cell Bio. 2006, 2008, 2013; PNAS 2018), in cell death control, in DNA damage repair, and in organelle homeostasis, and has linked a fundamental process to disease-causing pathological mechanisms. They have shown that UVRAG function and autophagy are inactivated by oncogenes such as cellular Bcl-2 and oncogenic γ-herpesvirus-encoded Bcl-2 proteins, by the oncogenic BRAF kinase, and by genetic mutations that increase inflammation and cancer susceptibility and can also be hitchhiked by viruses for their efficient infection.
38 Liang lab currently have several areas of focus:
37 •UVRAG in autophagy, inflammation, and cancer
56 •Autophagy-lysosomal activation in melanoma pathogenesis and drug resistance
49 •Molecular mechanisms of UV-indued mutagenesis in skin melanoma
19 •UV and tanning
44 •Chromosomal instability and cancer progression/recurrence
62 •Bcl-2 protein family in autophagy inhibition, cancer progression, and viral persistency
51 •Molecular mechanism of autophagy and intracellular membrane trafficking
e 29
27
Description of Research Expertise
29 14. Expertise statements4c2 The homeostasis of all eukaryotic cells depends on their “greening” ability to use a lysosomal pathway known as autophagy to degrade and recycle self-components. Liang lab has identified and studied the mammalian essential autophagy protein, UV irradiation resistance associated gene (UVRAG), which functions in and beyond autophagy and has emerging significance in cancer research. Using a series of genetic, biochemical, molecular and cell biological, and computational approaches in model organisms from Drosophila to Zebrafish to mice, we have defined both canonical and non-degradative functions of UVRAG and the autophagy pathway in multiple endomembrane trafficking (Nat Cell Bio. 2006, 2008, 2013; PNAS 2018), in cell death control, in DNA damage repair, and in organelle homeostasis, and has linked a fundamental process to disease-causing pathological mechanisms. They have shown that UVRAG function and autophagy are inactivated by oncogenes such as cellular Bcl-2 and oncogenic γ-herpesvirus-encoded Bcl-2 proteins, by the oncogenic BRAF kinase, and by genetic mutations that increase inflammation and cancer susceptibility and can also be hitchhiked by viruses for their efficient infection.
38 Liang lab currently have several areas of focus:
37 •UVRAG in autophagy, inflammation, and cancer
56 •Autophagy-lysosomal activation in melanoma pathogenesis and drug resistance
49 •Molecular mechanisms of UV-indued mutagenesis in skin melanoma
19 •UV and tanning
44 •Chromosomal instability and cancer progression/recurrence
62 •Bcl-2 protein family in autophagy inhibition, cancer progression, and viral persistency
51 •Molecular mechanism of autophagy and intracellular membrane trafficking
e 29
23
1b7 Li, S., Song, Y., Quach, C., Guo, H., Jang, G., Maazi, H., Zhao, S., Sands, N., Liu, Q., In, G., Peng, D., Yuan, W., Machida, K., Yu, M., Akbari, O., Hagiya, A., Yang, Y., Punj, V., Tang, L., and Liang, C*. : Transcriptional regulation of autophagy-lysosomal function in BRAF-driven melanoma progression and chemoresistance. Nature Communications 10(1):1693, 2019.
f1 Guo, J., Jayaprakash, P., Dan, J., Wise, P., Jang, G., Liang, C., Chen, M., Woodley, D., Fabbri, M., and Li, W: PMC4519330. Molecular and Cellular Biology 37(19), 2017.
144 Minassian, A., Zhang, J, He, S., Zhao, J., Zandi, E., Saito, T., Liang, C., and Feng, P: An internally translated variant of MAVS exposes its amino-terminal TRAF-binding motifs to deregulate interferon induction. PLoS Pathogens 11(7): 110-120, 2015.
165 Pirooz, DS., He, S., Zhang, T., Zhao, Z., Oh, S., Amini-Bavil-Olyaee, S., Zhang, XW., Farzan, M., Huang, I-C., Liang, C*. : UVRAG is essential for endocytic virus entry through combinatorial interaction with the class C Vps complex and SNAREs. Proc Natl Acad Sci U S A 111 (7) , 2014.
1e6 He, S., Ni, D., Ma, B., Lee, JH., Zhang, T., Ghozalli, I., Pirooz, SD., Zhao, Z., Bharatham, N., Li, B., Oh, S., Lee, W-H., Takahashi, Y., Wang, H-G., Minassian, A., Feng, P., Deretic, V., Pepperkok, R., Tagaya, M., Yoon, HS., and Liang, C*: P-bound UVRAG coordinates Golgi-ER retrograde and Atg9 transport by differential interactions with the ER tether and the Beclin1 complex. Nature Cell Biology 15(10), 2013.
134 Zhao, Z., Oh, S., Ni, D., Pirooz, S., Li, D, Lee, JY, Lee, JH, Yang, S, Costanzo V, Stark, J, and Liang, C*: A dual role for UVRAG in maintaining chromosomal stability independent of autophagy. Developmental Cell 22(5): 1001-16, 2012.
e5 Kliionsky DJ… Liang, C: Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes. Autophagy 8(9), 1392-1393 2012.
dc Pirooz, S., Lee, JH., Zhen, Z., Ni, D, Oh, S., and Liang, C: Measurement of γ-HV68 infection in mice. Cell Host and Microbe 11(2): 101-103, 2011.
117 Lee, G., Liang, C., Jang, C., Ohashi, H., Jung, JU and Chung, JK: Drosophila UVRAG mediates left-right axis rotation by regulating Notch endocytic degradation. Developmental Biology 356(2): 588-597, 2011.
2c
7
1d
1f
Selected Publications
1ae Choi, HY., Siddique. H., Zheng, M., Kou, Y., Yeh, DW., Machida, T., Chen, CL., Kumar, D., Punj, V., Winder, P., Pita, A., Sher, L., Tahara, S., Ray, RB., Liang, C., Chen, L., Tsukamoto, H., and Machida, K: destabilizing protein skews asymmetric division and enhances Notch activation to direct self-renewal of TICs. Nature Communications 11(1):3084, 2020.1b7 Li, S., Song, Y., Quach, C., Guo, H., Jang, G., Maazi, H., Zhao, S., Sands, N., Liu, Q., In, G., Peng, D., Yuan, W., Machida, K., Yu, M., Akbari, O., Hagiya, A., Yang, Y., Punj, V., Tang, L., and Liang, C*. : Transcriptional regulation of autophagy-lysosomal function in BRAF-driven melanoma progression and chemoresistance. Nature Communications 10(1):1693, 2019.
f1 Guo, J., Jayaprakash, P., Dan, J., Wise, P., Jang, G., Liang, C., Chen, M., Woodley, D., Fabbri, M., and Li, W: PMC4519330. Molecular and Cellular Biology 37(19), 2017.
144 Minassian, A., Zhang, J, He, S., Zhao, J., Zandi, E., Saito, T., Liang, C., and Feng, P: An internally translated variant of MAVS exposes its amino-terminal TRAF-binding motifs to deregulate interferon induction. PLoS Pathogens 11(7): 110-120, 2015.
165 Pirooz, DS., He, S., Zhang, T., Zhao, Z., Oh, S., Amini-Bavil-Olyaee, S., Zhang, XW., Farzan, M., Huang, I-C., Liang, C*. : UVRAG is essential for endocytic virus entry through combinatorial interaction with the class C Vps complex and SNAREs. Proc Natl Acad Sci U S A 111 (7) , 2014.
1e6 He, S., Ni, D., Ma, B., Lee, JH., Zhang, T., Ghozalli, I., Pirooz, SD., Zhao, Z., Bharatham, N., Li, B., Oh, S., Lee, W-H., Takahashi, Y., Wang, H-G., Minassian, A., Feng, P., Deretic, V., Pepperkok, R., Tagaya, M., Yoon, HS., and Liang, C*: P-bound UVRAG coordinates Golgi-ER retrograde and Atg9 transport by differential interactions with the ER tether and the Beclin1 complex. Nature Cell Biology 15(10), 2013.
134 Zhao, Z., Oh, S., Ni, D., Pirooz, S., Li, D, Lee, JY, Lee, JH, Yang, S, Costanzo V, Stark, J, and Liang, C*: A dual role for UVRAG in maintaining chromosomal stability independent of autophagy. Developmental Cell 22(5): 1001-16, 2012.
e5 Kliionsky DJ… Liang, C: Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes. Autophagy 8(9), 1392-1393 2012.
dc Pirooz, S., Lee, JH., Zhen, Z., Ni, D, Oh, S., and Liang, C: Measurement of γ-HV68 infection in mice. Cell Host and Microbe 11(2): 101-103, 2011.
117 Lee, G., Liang, C., Jang, C., Ohashi, H., Jung, JU and Chung, JK: Drosophila UVRAG mediates left-right axis rotation by regulating Notch endocytic degradation. Developmental Biology 356(2): 588-597, 2011.
2c