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Xiaolu Yang, Ph.D.
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Professor of Cancer Biology
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Member, Abramson Cancer Center
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Member, Center for Molecular Studies in Digestive and Liver Diseases
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Member, Institute for Immunology
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Investigator, Abramson Family Cancer Research Institute
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Department: Cancer Biology
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Graduate Group Affiliations
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Contact information
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654 BRB II/III
1b 421 Curie Boulevard
55 University of Pennsylvania School of Medicine
Philadelphia, PA 19104-6160
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1b 421 Curie Boulevard
55 University of Pennsylvania School of Medicine
Philadelphia, PA 19104-6160
30
Office: (215) 573-6739
34 Fax: (215) 573-6725
24
99
34 Fax: (215) 573-6725
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Email:
xyang@pennmedicine.upenn.edu
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xyang@pennmedicine.upenn.edu
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Publications
23 a
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Links
b5 Search PubMed for articles
41 Immunology graduate group faculty webpage.
3c Abramson Family Cancer Research Institute member webpage.
43 Cell and Molecular Biology graduate group faculty webpage.
6b Primary Work Website
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b5 Search PubMed for articles
41 Immunology graduate group faculty webpage.
3c Abramson Family Cancer Research Institute member webpage.
43 Cell and Molecular Biology graduate group faculty webpage.
6b Primary Work Website
c
13
Education:
21 a B.Sc. 1f (Physical Chemistry) c
3c Tsinghua University, Beijing, China, 1985.
21 9 M.A. 23 (Genetics & Development) c
3b Columbia University, New York, NY , 1990.
21 c M.Phil. 23 (Genetics & Development) c
3a Columbia University, New York, NY, 1992.
21 a Ph.D. 23 (Genetics & Development) c
3a Columbia University, New York, NY, 1994.
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Permanent link21 a B.Sc. 1f (Physical Chemistry) c
3c Tsinghua University, Beijing, China, 1985.
21 9 M.A. 23 (Genetics & Development) c
3b Columbia University, New York, NY , 1990.
21 c M.Phil. 23 (Genetics & Development) c
3a Columbia University, New York, NY, 1992.
21 a Ph.D. 23 (Genetics & Development) c
3a Columbia University, New York, NY, 1994.
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5e
61 The molecular and cellular mechanisms that protect against cancer and neurodegeneration.
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1a Key words:
8c Cancer biology, p53, tumor suppression, metabolism, autophagy, stem cells, protein quality control, aging, neurodegenerative disease
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26 Description of Research
6d Our lab studies cancer and neurodegenerative disease. Our current projects focus on two broad areas:
8
28f (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.
8
2ac (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.
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1e Lab personnel:
2d Lyndsey Makinen - Program Coordinator
3a Kenzo Lacuarta - Research Specialist / Lab Manager
31 Jiale Wu, Ph.D. - Postdoctoral Researcher
37 Zi-Yang Zhang - Ph.D. - Postdoctoral Researcher
35 Yujin Xiang - Ph.D. - Postdoctoral Researcher
35 Jiajia Wang - Ph.D. - Postdoctoral Researcher
36 Ruifang Wang - Ph.D. - Postdoctoral Researcher
34 Sixiang Yu - Ph.D. - Postdoctoral Researcher
33 Kai Huang - Ph.D. - Postdoctoral Researcher
36 Rachel Ou – Undergraduate Student Researcher
36 Steven Su – Undergraduate Student Researcher
38 Megan Zhang – Undergraduate Student Researcher
37 Hong Yu Liu – Undergraduate Student Researcher
26 29
27
Description of Research Expertise
2b Research Interests61 The molecular and cellular mechanisms that protect against cancer and neurodegeneration.
8
1a Key words:
8c Cancer biology, p53, tumor suppression, metabolism, autophagy, stem cells, protein quality control, aging, neurodegenerative disease
8
26 Description of Research
6d Our lab studies cancer and neurodegenerative disease. Our current projects focus on two broad areas:
8
28f (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.
8
2ac (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.
8
9
1e Lab personnel:
2d Lyndsey Makinen - Program Coordinator
3a Kenzo Lacuarta - Research Specialist / Lab Manager
31 Jiale Wu, Ph.D. - Postdoctoral Researcher
37 Zi-Yang Zhang - Ph.D. - Postdoctoral Researcher
35 Yujin Xiang - Ph.D. - Postdoctoral Researcher
35 Jiajia Wang - Ph.D. - Postdoctoral Researcher
36 Ruifang Wang - Ph.D. - Postdoctoral Researcher
34 Sixiang Yu - Ph.D. - Postdoctoral Researcher
33 Kai Huang - Ph.D. - Postdoctoral Researcher
36 Rachel Ou – Undergraduate Student Researcher
36 Steven Su – Undergraduate Student Researcher
38 Megan Zhang – Undergraduate Student Researcher
37 Hong Yu Liu – Undergraduate Student Researcher
26 29
23
12e 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.
e1 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.
139 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.
f6 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.
70 Zhu G., Harischandra D.S., Ghaisas S., Zhang P., Prall W., Huang L., fd 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.
8d Xu Y., Zhang Y., García-Cañaveras J.C., Guo L., Yu S., Blair I.A., Rabinowitz J.D., and Yang X. ba : Chaperone-mediated autophagy regulates the pluripotency of embryonic stem cells. Science 369: 397-403, 2020 Notes: Comment in Science 369: 373-374, 2020.
15b 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
f0 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.
ea 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.
164 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.
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1d
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Selected Publications
125 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 62 Science 381: eadd6696, 2023 Notes: Comment in Science 381: 377-378, 2023.12e 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.
e1 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.
139 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.
f6 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.
70 Zhu G., Harischandra D.S., Ghaisas S., Zhang P., Prall W., Huang L., fd 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.
8d Xu Y., Zhang Y., García-Cañaveras J.C., Guo L., Yu S., Blair I.A., Rabinowitz J.D., and Yang X. ba : Chaperone-mediated autophagy regulates the pluripotency of embryonic stem cells. Science 369: 397-403, 2020 Notes: Comment in Science 369: 373-374, 2020.
15b 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
f0 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.
ea 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.
164 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.
2c