Xiaolu Yang, Ph.D.

faculty photo
Professor of Cancer Biology
Department: Cancer Biology

Contact information
421 Curie Boulevard
University of Pennsylvania School of Medicine
Philadelphia, PA 19104-6160
Office: (215) 573-6739
Fax: (215) 573-6725
B.Sc. (Physical Chemistry)
Tsinghua University, Beijing, China, 1985.
M.Phil. (Genetics & Development)
Columbia University, New York, NY, 1992.
Ph.D. (Genetics & Development)
Columbia University, New York, NY, 1994.
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Description of Research Expertise

Research Interests
The molecular and cellular mechanisms that protect against cancer and neurodegeneration.

Key words:
Cancer biology, p53, tumor suppression, metabolism, autophagy cancer stem cells, embryonic stem cells, neurodegenerative diseases, protein quality control, neuroprotection

Description of Research
Our lab is interested in the biology of cancer and neurodegenerative diseases. Our current projects focus on two areas: (1) tumor suppression, metabolism, and autophagy, and (2) protein quality control systems in animal cells and neurodegenerative diseases.

Cancer encompasses over 100 diseases that occur in most cell types and organs of the human body. The relentless cell proliferation that characterizes malignancy is normally prevented by an intricate tumor suppression network, with its central hub being the preeminent tumor suppressor p53. We are investigating functions and regulation of p53. Our recent results have revealed a role for p53 in modulating metabolic pathways and autophagy that are crucial for cell proliferation. We are examining the function of p53 as both a sentinel and a regulator of metabolism and autophagy. We are also identifying common metabolic alterations that drive initiation and progression of various tumors. A recent extension of this research area is to define the role of metabolism and autophagy in stem cells, including embryonic stem cells and cancer stem cells.

Neurodegenerative diseases are becoming increasingly prevalent as the human population ages; yet they remain incurable. These diseases, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis (Lou Gehrig's disease), and polyglutamine diseases, are associated with misfolding and aggregation of proteins in the central nervous system, which ultimately leads to neuronal cell death. Our lab recently identified a novel protein quality control (PQC) system in animal cells that is mechanistically distinct from canonical PQC systems, and is multifunctional and effective in suppressing protein misfolding and aggregation in neurons and other cells. We are investigating the mechanism of action of this PQC systems and its role in protecting against various neurodegenerative diseases.

Lab personnel:
Lyndsey Makinen, Administrative Coordinator
Shivani Ghaisas, Postdoctoral Researcher
Lianqian Huang, Postdoctoral Researcher
Yi Xu, Postdoctoral Researcher
Hao Zhang, Postdoctoral Researcher
Yang Zhang, Postdoctoral Researcher
Sixiang Yu, Graduate Student
Janet Zhou, Research Specialist
Caitlin Frazee, Undergraduate Researcher
Jacob Huang, Undergraduate Researcher
Kimberly Taing, Undergraduate Researcher
Ivy Wong, Undergraduate Researcher
Steven Wren, Undergraduate Researcher

Selected Publications

Liangqian Huang, Trisha Agrawal, Guixin Zhu, Sixiang Yu, Liming Tao, JiaBei Lin, Ronen Marmorstein, James Shorter, Xiaolu Yang: DAXX represents a new type of protein-folding enabler. Nature 597: 132–137, Aug 2021.

Guixin Zhu, Meenhard Herlyn, Xiaolu Yang: TRIM15 and CYLD regulate ERK activation via lysine-63-linked polyubiquitination. Nature Cell Biology 23: 978-991, Sept 2021 Notes: Online ahead of print.

Yang Zhang, Yi Xu, Wenyun Lu, Jonathan M. Ghergurovich, Lili Guo, Ian A. Blair, Joshua D. Rabinowitz, and Xiaolu Yang* (*Corresponding author): Upregulation of antioxidant capacity and nucleotide precursor availability suffices for oncogenic transformation. Cell Metabolism 33(1): 94-109, January 2021.

Guixin Zhu, Dilshan S. Harischandra, Shivani Ghaisas, Pengfei Zhang, Wil Prall, Liangqian Huang, Chantal Maghames, Lili Guo, Esteban Luna, Korrie L. Mack, Mariana P. Torrente,Kelvin C. Luk, James Shorter, and Xiaolu Yang: TRIM11 Prevents and Reverses Protein Aggregation and Rescues a Mouse Model of Parkinson’s Disease. Cell Reports 33(9): 108418, December 2020.

Xu Y, Zhang Y, García-Cañaveras JC, Guo L, Yu S, Blair IA, Rabinowitz JD, and Yang X.* (*Corresponding author) : Chaperone-mediated autophagy regulates the pluripotency of embryonic stem cells. Science 369(6502): 397-403, July 2020 Notes: commented on in this issue.

Chen L, Zhu G, Johns EM, Yang X: TRIM11 activates the proteasome and promotes overall protein degradation by regulating USP14. Nature Communications 9(1): 1223, March 2018.

Chen L., Brewer M., Guo L., Wang R., Jiang P., Yang X.: Enhanced Degradation of Misfolded Proteins Promotes Tumorigenesis. Cell Reports 18(13): 3143-3154, March 2017.

Guo L., Giasson B.I., Glavis-Bloom A., Brewer M.D., Shorter J., Gitler A.D., and Yang X.: A cellular system that degrades misfolded proteins and protects against neurodegeneration. Mol Cell 55: 15-30, 2014 Notes: Cover story and commented on in this issue.

Du W., Jiang P., Mancuso A., Stonestrom A., Brewer M.D., Minn A.J., Mak T.W., Wu M., and Yang X: TAp73 enhances the pentose phosphate pathway and supports cell proliferation. Nat Cell Bio 15: 991-1000, 2013 Notes: Cover story and commented on in this issue.

Jiang P., Du W., Wang X., Mancuso A., Gao X., Wu M., and Yang X.: p53 regulates biosynthesis through direct inactivation of glucose-6-phosphate dehydrogenase. Nat Cell Biol. 13: 310-18, 2011 Notes: cover story and commented on in this issue.

Jiang P., Du W., Mancuso A., Wellen K. and Yang X.: Reciprocal regulation of p53 and malic enzymes modulates metabolism and senescence. Nature 493: 689-93, 2013.

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Last updated: 09/28/2022
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