Hai Rao

Professor
School of Medicine
raoh@sustech.edu.cn
Department Head of Biochemistry

Our long-term goal is to understand the mechanism and function of ubiquitin/proteasome-mediated proteolysis. Specifically, we aim to determine how key cellular regulators are selected for degradation by the proteasome via an integrated approach (biochemistry, biophysics, genetics, genomics and proteomics). We have used both yeast and  mammalian cells as our experimental systems.  As PI on the American Cancer Society-, NIH- and DOD-funded grants, we have developed unique angles and novel assays to define how proteins (e.g., a telomere regulator Cdc13, the p53 tumor suppressor, prion PrP, a Histone variant Cse4 etc.) are selected and escorted to the proteasome, and also the significance of regulated proteolysis in cancers and prion diseases. Over the years, we have established productive collaborations with other domestic (e.g., U. of Colorado, Ohio State U., St. Jude‘s) or international researchers (e.g., Canada, Japan, China), and published several papers from each project. We have carved out our niches and have a demonstrated record of successful and productive research projects in an area of high relevance for human health and diseases.

 

EDUCATION:

1985 - 1989 Wuhan University BS in Chemistry

1989 - 1991 Boston University MS in Chemistry

1991 - 1996 State University of New York at Stony Brook & Cold Spring Harbor Laboratory, Ph.D

 

WOKRING EXPERIENCE:

1997-2002 Postdoctoral Fellow, California Institute of Technology. (Advisor: Alex Varshavsky) 

2002-2008 Assistant Professor, Department of Molecular Medicine/Institute of Biotechnology, The University of Texas Health, San Antonio 

2008-2019 Associate Professor with tenure, Department of Molecular Medicine, The University of Texas Health, San Antonio 

2019 – 2020.10.09 Professor with tenure, Department of Molecular Medicine, The University of Texas Health, San Antonio 

2020.10.12 - Present Professor with tenure, Department of Biochemistry, School of Medicine, The Southern University of Science and Technology

 

HONORS AND AWARDS:

2006 The American Association for Cancer Research Minority-Serving Institution Faculty Scholar Award in Cancer Research.

1998-2001 Postdoctoral Scholarship, Leukemia & Lymphoma Society of America.

1996 Graduate Research Award, State University of New York at Stony Brook.

 

Research:

2006 The American Association for Cancer Research Minority-Serving Institution Faculty Scholar Award in Cancer Research.

1998-2001 Postdoctoral Scholarship, Leukemia & Lymphoma Society of America.

1996 Graduate Research Award, State University of New York at Stony Brook.

 

MANUSCRIPT REVIEWER AND EDITOR:

Editorial Board: J. Biol. Chem.; Frontiers in Cell and Developmental Biology and Oncology; Adv. In Biol.,; J. Membrane Sci. Tech. 

Journal Reviewer: Nature, Cell, Oncogene, PNAS, EMBO, EMBO Reports, JBC, MCB, MBoC, JCB, BMC Biochemistry, Chemistry & Biology, Yeast etc.

Grant reviews: NIH, Italian Ministry of Health, Qatar National Research Fund, Research Grants Council of Hong Kong, US-Israel Binational Science Foundation, the Wellcome Trust/DBT India Alliance, Canadian Discovery Grant, Taiwan Research Grant 

 

PUBLICATIONS:

1.      Rao, H., Mohr, S.C., Fairhead, H. and Setlow, P. (1992) Synthesis and characterization of a 29-amino acid residue DNA-binding peptide derived from a/b-type small acid soluble spore proteins (SASP) of bacteria. FEBS Ltr. 305: 115-120.

2.      Bell, S.P., Marhrens, Y., Rao, H. and Stillman, B. (1993) The replicon model and eukaryotic chromosomes. Cold Spring Harbor Symp. Quant. Biol. 58: 435-442.

3.      Rao, H., Marhrens, Y. and Stillman, B. (1994) Functional conservation of modular elements in yeast chromosomal replicators. Mol. Cell. Biol. 14: 7643-7651. 

4.      Rao, H. and Stillman, B. (1995) The origin recognition complex (ORC) interacts with a bipartite DNA binding site within yeast replicators. Proc. Natl. Acad. Sci. USA 92: 2224-2228.

5.      Rao, H., Uhlmann, F., Nasmyth, K. and Varshavsky, A. (2001) Degradation of a cohesin subunit by the N-end rule pathway is essential for chromosome stability. Nature 410: 955-959.

6.      Rao, H.* and Sastry, A. (2002) Recognition of specific ubiquitin conjugates is important for the proteolytic functions of the UBA domain proteins Dsk2 and Rad23. J. Biol. Chem. 277: 11691-11695. Kim, I., Mi, K. and Rao, H. (2004) Multiple interactions of Rad23 suggest a mechanism for ubiquitylated substrate delivery important in proteolysis. Mol. Biol. Cell. 15: 3357-3365. PMCID: PMC452589

7.      Apodaca, J., Ahn, J.M., Kim, I. and Rao, H. (2005) Analysis of Ub-binding proteins by yeast two-hybrid. Methods Enzymol. 399: 157-64.

8.      Kim, I., Ahn, J., Liu, C., Tanabe, K., Apodaca, J., Suzuki, T. and Rao H. (2006) The Png1-Rad23 complex regulates glycoprotein turnover. J. Cell Biol. 172: 211-219.

9.      Kim, I. and Rao, H. (2006) What’s Ub chain linkage got to do with it? Science STKE 330: pe18. Apodaca, J., Kim, I. and Rao, H. (2006) Cellular tolerance of prion in yeast requires the unfolded protein response and proteolysis. Biochem. Biophys. Res. Commun. 347: 319-326.

10.   Liu, C., Apodaca, J., Davis, L.E. and Rao, H. (2007) Proteasome inhibition in wild-type yeast Saccharomyces cerevisiae cells. Biotechniques 42: 158-162.

11.   Liu, C., van Dyk, D., Li, Y., Andrews, B. and Rao, H. (2009) A genome-wide synthetic dosage lethality screen reveals multiple pathways that require the functioning of Ub-binding proteins Rad23 and Dsk2. BMC Biol. 7: 75. PMCID: PMC 2777868

12.   Kim, I., Li, Y., Muniz, P. and Rao, H. (2009) Usa1 protein facilitates substrate ubiquitylation through two separate domains. PLos One 4: e7604. PMCID: PMC2764048

13.   Li, Y., Yan, J., Kim, I., Liu, C., Huo, K. and Rao, H. (2010) Rad4 regulates protein turnover at a postubiquitylation step. Mol. Biol. Cell. 21: 177-185. PMCID: PMC2801711

14.   Kim, I., and Rao, H. (2010) Degradation of misfolded secretory and membrane proteins and associated diseases. eLS doi 10.1002/9780470015902.a0022577

15.   Liu, C., van Dyk, D., Xu, P., Choe, V., Pan, H., Peng, J., Andrews, B. and Rao, H. (2010) Ubiquitin chain elongation enzyme Ufd2 regulates a subset of Doa10 substrates. J. Biol. Chem. 285: 10265-10272. PMCID: PMC 2856231

16.   Hosomi, A., Tanabe, K., Hiryama, H., Kim, I., Rao, H. and Suzuki, T. (2010) Identification of an Htm1 (EDEM)- dependent, Mns1-independent Endoplasmic Reticulum-associated Degradation (ERAD) pathway in Saccharomyces cerevisiae: application of a novel assay for glycoprotein ERAD. J. Biol. Chem. 285: 24324-24334. PMCID: PMC2915668

17.   Liu, C., Choe, V. and Rao, H. (2010) Genome-wide approaches to systematically identify substrates of the ubiquitin-proteasome pathway. Trends Biotechnol. 28: 461-467. PMCID: PMC 2926183

18.   Yan, J., Zhang, D., Di, Y., Shi, H., Rao, H. and Huo, K. (2010) A newly identified Pirh2 substrate SCYL-1-BP1 can bind to MDM2 and accelerate MDM2 self-ubiquitination. FEBS Lett. 584: 3275-3278. PMCID: PMC3798065

19.   Yan, J., Di, Y., Shi, H., Rao, H. and Huo K. (2010) Overexpression of SCYL1-BP1 stabilizes functional p53 suppressing MDM2-mediated ubiquitination. FEBS Lett. 584: 4319-4324.

20.   Baek, G.H., Kim, I., and Rao, H. (2011) The Cdc48 ATPase modulates the interaction between two proteolytic factors Ufd2 and Rad23. PNAS 108:13558-63. PMCID: PMC3158229

21.   Liu, C., van Dyk, D., Choe, V., Yan, J., Majumder, S., Costanzo, M., Bao, B., Boone, C., Huo, K. Winey, M., Fisk, H., Andrews, B. and Rao, H. (2011) Ubiquitin ligase Ufd2 is required for efficient degradation of Mps1 kinase. J. Biol. Chem 286: 43660-43667. PMCID: PMC3243506 

22.   Baek, G.H., Cheng, H., Kim, I., and Rao, H. (2012) The Cdc48 and its cofactor Vms1 are involved in Cdc13 protein degradation. J. Biol. Chem 287: 26788-26795. PMCID: PMC3411016 Baek, G.H., Cheng, H., Choe, V., Bao, X., Shao, J., Luo, S., and Rao, H. (2013). Cdc48, a swiss army knife of cell biology. J. Amino Acids 2013, doi 10.1155/2013/183421.

23.   Krzeszinski, J., Choe, V., Shao, J., Bao, X., Cheng, H., Luo, S., Huo, K., and Rao, H. (2014) XPC promotes MDM2-mediated degradation of the p53 tumor suppressor. Mol. Biol. Cell. 25, 213-221. Shao, J., Choe, V., Cheng, H., Tsai, C., Weissman, A., Luo , S. Rao, H. (2014) Ubiquitin ligase gp78 targets unglycosylated prion PrP for ubiquitylation and degradation. PLos One e92290.

24.   Chen, Q., Xu, R., Zeng, C., Lu, Q., Huang, D, Shi, C., Yan, R., Zhang, W., Deng, L., Rao, H., Gao, G., Luo, S. (2014) Down-regulation of Gli transcription factor leads to the inhibition of migration and invasion of ovarian cancer cells via integrin β4-mediated FAK signaling. PLos One e88386.

25.   Xiong, X., Wang, Y., Liu, C., Lu, Q., Liu, T. Chen, G., Rao, H., Luo, S. (2014) Heat shock protein 90 beta stabilizes Focal Adhesion Kinase and enhances cell migration and invasion in breast cancer cells. Exp. Cell Res. 326: 78-89.

26.   Bao, X., Johnson, J., and Rao, H. (2015) Rad25 protein is targeted for degradation by the Ubc4-Ufd4 pathway. J. Biol. Chem 290, 8606-8612. PMCID: PMC4375509

27.   Tang, X., Deng, L., Chen, Q, Wang, Y., Xu, R., Shi, C., Shao, J., Hu, G., Gao, M., Rao, H., Luo, S., Lu, Q. (2015) Inhibition of Hedgehog signaling pathway impedes cancer cell proliferation by promotion of autophagy. Euro. J. Cell Biol., 94:223-233.

28.   Klionsky, A. et al. (2016) Guidelines for the Use and Interpretation of Assays for Monitoring Autophagy Autophagy 12, 1-222. PMID: 26799652

29.   Cheng, H., Bao, X., and Rao, H (2016) The F box protein Rcy1 is involved in the degradation of Histone variant Cse4 and genome maintenance. J. Biol. Chem 291: 10372-10377. 

30.   Wang Y, Li Y, Hu G, Huang X, Rao H, Xiong X, Luo Z, Lu Q, Luo S. (2016) Nek2A phosphorylates and stabilizes SuFu: A new strategy of Gli2/Hedgehog signaling regulatory mechanism. Cellular signaling 28:1304-13. PMID: 27297360.

31.   Zhou F, Huang D, Li Y, Hu G, Rao H, Lu Q, Luo S, Wang Y. (2017) Nek2A/SuFu feedback loop regulates Gli- mediated Hedgehog signaling pathway. Int J Oncol. 50, 373-380.

32.   Shao J., Xu L., Chen L., Lu Q., Xie X., Shi W., Xiong W., Shi C., Huang X., Mei J., Rao H, Lu H., Lu N., Luo S. (2017) The small G-protein Arl13b promotes gastric tumorigenesis by regulating Smoothened trafficking and subsequent Hedgehog signaling pathway activation. Cancer Research 77: 4000-4013. PMID: 28611043

33.   Peng H, Yang J, Li G, You Q, Han W, Li T, Gao D, Xie X, Lee BH, Du J, Hou J, Zhang T, Rao H, Huang Y, Li Q, Zeng R, Hui L, Wang H, Xia Q, Zhang X, He Y, Komatsu M, Dikic I, Finley D, Hu R. (2017) Ubiquitylation of p62/sequestosome1 activates its autophagy receptor function and controls selective autophagy upon ubiquitin stress. Cell Res. 27: 657-674. PMID: 28322253

34.   Cheng, H., Bao, X., Gan, X., Luo, S. and Rao, H (2017) Multiple E3s promote the degradation of Histone variant Cse4. Scientific Reports 7: 8565. PMID: 28819127

35.   Hu, G., Luo, S., Cheng, H., Gan, X., and Rao, H (2018) A simple PCR-based strategy for the introduction of point mutations in the yeast S. cerevisiae via CRISPR/CAS9. Biochem Mol Biol J. 4: 9. DOI: 10.21767/2471-8084.100058

36.   Shanmugasundarum, K., McHardy, S., Luo, T., and Rao, H. (2019) A modular PROTAC design for target destruction using a degradation signal based on single amino acids. J. Biol. Chem 294: 15172 

37.   Yan, Z., Luo, S and Rao, H. (2020) The N-terminal domain of ABL confers protein instability and supresses tumorigenesis. J. Biol. Chem 295: 10.1074/jbc.RA120.012821

38.   Hu, G., Yan, Z., Rios, L., Jasper A., Luo, S. and Rao, H. (2020)  Autophagy regulator Atg9 is degraded by the proteasome. Biochem. Biophys. Res. Commun. 522: 254-8.