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.A. (Genetics & Development)
Columbia University, New York, NY , 1990.
M.Phil. (Genetics & Development)
Columbia University, New York, NY, 1992.
Ph.D. (Genetics & Development)
Columbia University, New York, NY, 1994.
Permanent link

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, stem cells, protein quality control, aging, neurodegenerative disease

Description of Research
Our lab studies cancer and neurodegenerative disease. Our current projects focus on two broad areas:

(1) The tumor suppressor p53, metabolism, and autophagy. We are interested in the regulation and functions of the preeminent tumor suppressor p53. Our results have revealed a role for p53 in modulating metabolic pathways that are critical for biosynthesis and redox balance. We are investigating the function of p53 as both a sentinel and a regulator for metabolic activities. We are also identifying and characterizing metabolic alterations that drive tumor initiation and progression. 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.

(2) Protein quality control, aging, and neurodegeneration. Our lab recently identified two protein quality control (PQC) systems, which consist of tripartite motif (TRIM) proteins and poly-Asp/Glu (polyD/E) proteins, respectively. Unlike canonical PQC systems, these new systems are independent of ATP and are unique for animals (the TRIM system) or eukaryotes (the polyD/E system). Both systems are multifunctional and highly effective. We are investigating their mechanisms of action; their roles in aging and neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis; and their utility in treating these diseases.

Lab personnel:
Lyndsey Makinen - Program Coordinator
Kenzo Lacuarta - Research Specialist / Lab Manager
Jiale Wu, Ph.D. - Postdoctoral Researcher
Zi-Yang Zhang - Ph.D. - Postdoctoral Researcher
Yujin Xiang - Ph.D. - Postdoctoral Researcher
Jiajia Wang - Ph.D. - Postdoctoral Researcher
Ruifang Wang - Ph.D. - Postdoctoral Researcher
Sixiang Yu - Ph.D. - Postdoctoral Researcher
Kai Huang - Ph.D. - Postdoctoral Researcher
Rachel Ou – Undergraduate Student Researcher
Steven Su – Undergraduate Student Researcher
Megan Zhang – Undergraduate Student Researcher
Hong Yu Liu – Undergraduate Student Researcher

Selected Publications

Zhang Z.-Y., Harischandra D.S., Wang R., Ghaisas S., Zhao J.Y., McMonagle T.P., Zhu G., Lacuarta K.D., Song J., Trojanowski J.Q., Xu H., Lee V. M.-Y., Yang X.: TRIM11 protects against tauopathies and is down-regulated in Alzheimer’s disease Science 381: eadd6696, 2023 Notes: Comment in Science 381: 377-378, 2023.

Zhang Y., Xu Y., Lu W., Li J., Yu S., Brown E.J., Stanger B.Z., Rabinowitz J.D., Yang X.: G6PD-mediated increase in de novo NADP+ biosynthesis promotes antioxidant defense and tumor metastasis. Science Advances 8: eabo0404, 2022.

Zhu, G., Herlyn M., and Yang X.: TRIM15 and CYLD regulate ERK activation via lysine-63-linked polyubiquitination. Nature Cell Biology 23: 978-991, 2021.

Zhang Y., Xu Y., Lu W., Ghergurovich J.M., Guo L., Blair I.A., Rabinowitz J.D., and Yang X.: Upregulation of antioxidant capacity and nucleotide precursor availability suffices for oncogenic transformation. Cell Metabolism 33: 94-109, 2021.

Huang L., Agrawal T., Zhu G., Yu S., Tao L., Lin J., Marmorstein R., Shorter J., Yang X.: DAXX represents a new type of protein-folding enabler. Nature 597: 132–137, 2021.

Zhu G., Harischandra D.S., Ghaisas S., Zhang P., Prall W., Huang L., Maghames C., Guo L., Luna E., Mack K.L., Torrente M.P., Luk K.C., Shorter J., and Yang X.: TRIM11 Prevents and Reverses Protein Aggregation and Rescues a Mouse Model of Parkinson’s Disease. Cell Reports 33: 108418, 2020.

Xu Y., Zhang Y., García-Cañaveras J.C., Guo L., Yu S., Blair I.A., Rabinowitz J.D., and Yang X. : Chaperone-mediated autophagy regulates the pluripotency of embryonic stem cells. Science 369: 397-403, 2020 Notes: Comment in Science 369: 373-374, 2020.

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. Molecular Cell 55: 15-30, 2014 Notes: Cover story and comment in Molecular Cell 55:1-3, 2014

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

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.

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. Nature Cell Biology 15: 991-1000, 2013 Notes: Cover story and comment in Nature Cell Biology 15:891-3, 2013.

back to top
Last updated: 02/12/2024
The Trustees of the University of Pennsylvania