faculty portrait if available
Yong-Yu Liu
Professor
School Basic Pharm & Toxicol Sci
PHAR 368
318-342-1709
ULM logo

Yong-Yu Liu, PhD
Professor, Pharmacy

Education

Ph D

1989, Biochemistry
Shanghai University of Traditional Chinese Medicine

MEd

1984, Medicine
Soochow University School of Medicine

faculty feature photo

Biographical Sketch

Education:

1986 – 1989        Ph.D., Biochemistry

                            Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China

1984 – 1985        Intern, Medicine and Surgery

                            Soochow University School of Medicine Hospital, Suzhou, P. R. China

1979 – 1984        M.D., Medicine & Surgery

                            Soochow University School of Medicine, Suzhou, P. R. China

Professional training:

1997 – 1999        Postdoctoral Fellow, Molecular Oncology

                             John Wayne Cancer Institute, Santa Monica, California, USA

1996 – 1997        Postdoctoral Fellow, Molecular Endocrinology

                            Department of Physiology and Department of Internal Medicine

                            University of Manitoba, Canada 

1993 – 1996        Postdoctoral Fellow, Molecular Endocrinology

                            Laboratory of Molecular Medicine, Dept. of Internal Medicine,

                             University of Rome-Tor Vergata, Rome, Italy

Professional Experience

Professional Appointments: 

2016 –                  Professor of Pharmacology (tenured)

                             Department of Basic Pharmaceutical Sciences

                             University of Louisiana at Monroe, Monroe, LA

2012 – 2016         Associate Professor of Pharmacology (tenured)

                             Department of Basic Pharmaceutical Sciences

                             University of Louisiana at Monroe, Monroe, LA

2006 – 2012         Assistant Professor of Pharmacology (tenure track)

                             Department of Basic Pharmaceutical Sciences

                             University of Louisiana at Monroe, Monroe, LA

2007 – present     Adjunct Professor

                             Department of Medicine

                             Tulane University School of Medicine, New Orleans, Louisiana

2008 – present     Adjunct Professor

                             Division of Biotechnology and Molecular Medicine

                             LSU School of Veterinary Medicine, Baton Rouge, Louisiana

2005 – 2006         Assistant Researcher of Molecular Biology

                             Department of Molecular Cell & Developmental Biology

                             University of California at Los Angeles, Los Angeles, California

2002 – 2005         Assistant Member, Assistant Director, Experimental Therapeutics

                             John Wayne Cancer Institute, Santa Monica, California

1999 – 2002         Junior Member, Breast Cancer Research Program

                             John Wayne Cancer Institute, Santa Monica, California

1989 – 1992         Assistant Professor of Biochemistry

                             Department Biochemistry and Department of Endocrinology

                            Soochow University School of Medicine, Suzhou, P. R. China

2006-pre          Reviewer for Stem Cells; Biochem Pharm; J Med Chem; J Pharm Exp Ther; J Clin Invest; EMBO Mol Medicine; J. Biol. Chem.; Int. J. Cancer.; Cancer Res.; Clin. Cancer Res.; Oncotarget; FEBS Lett.; J Pharmacol Exp Ther; Cancer Chem. Pharm.; Mol Cell Biochem.; Biochim Biophys Acta; Endocrinol; J Surg Oncol; Lipids; Chemi. Res. Toxicol

2011-pre          Editorial Board ISRN Oncology, Cell Biology, OMISC Biochemistry Pharmacology, J. Cancer Res. Updates

2012-pre          Grant Reviewer for Word Cancer Research Fund, UK; Changjiang Scholars Program, China Program of Global Experts (1000plan); The Pennsylvania Department of Health (PA DOH/Oak Ridge Associated Universities); Kentucky Science & Engineering Foundation (KSEF); Crech Science Foundation (GACR)

2016-pre          ULM Excellent Award committee member

2017-pre          Ad-Hoc Reviewer, the Basic Mechanisms of Cancer Therapeutics (BMCT) and NCI Program Project III (P01) for NIH/NCI.

2020-pre          Scientific Advisory Board for Sanofi-Genzyme

Awards and Honors:

2015               Foundation Award for Excellent in Research, University of Louisiana at Monroe

2012               Honorary Chair, the Annual Race for the Cure, Komen-NELA

2012               Distinguished Research, LBRN/NIH

2000-03         Joseph B. Gould Fellow in Breast Cancer

1995               Fellowship in University of Rome-Tor Vergata, Italy

1993-94         Fellowship of National Biomedical Institute, Italy

Patents: Ceramide-Rubusoside nanomicelles and their use in cancer therapy (PCT/US2015/029379)

Representative Publications  

1. Roy KR, Uddin MB, Roy CS, Hill RA, Marshall J, Li YT, Chamcheu JC, Lu H and Liu YY. 2020. Gb3-cSrc complex in glycosphingolipid-enriched microdomains contributes to the expression of p53 mutant protein and cancer drug resistance via β-catenin activated RNA methylation. FASEB BioAdvances (accepted online)

2. Khiste SK, Liu Z, Roy KR, Uddin MB, Hosain SB, Gu X, Nazzal S, and Liu YY. 2020. Ceramide-Rubusoside nanomicelles, a potential therapeutic approach to target cancers carrying p53 missense mutations. Mol Cancer Ther 19:564-74 PMID: 31645443

3. Uddin MB, Roy KR, Hosain SB, Khiste SK, Hill RA, Jois SD, Zhao Y, Tackett AJ and Liu YY. 2019. An N6-methyladenosine at the transited codon 273 of p53 pre-mRNA promotes the expression of R273H mutant protein and drug resistance of cancer cells. Biochem Pharmacol 160:134-145. PMID: 30578766

4. Khiste SK, Hosain SB, Dong X, Uddin MB, Roy K, Hill R, Liu Z and Liu YY. 2017. Incorporation of Fluorescence Ceramide-Based HPLC Assay for Rapidly and Efficiently Assessing Glucosylceramide Synthase In Vivo. Sci Rep 7(1):2976. PMID: 28592871

5. Hosain SB, Khiste SK, Uddin MB, Vorubindi V, Igram C, Zhang S, Hill RA, Gu X and Liu YY. 2016. Inhibition of glucosylceramide synthase eliminates the oncogenic function of p53 R273H mutant in the epithelial-mesenchymal transition and induced pluripotency of colon cancer cells. Oncotarget 7(37):60575-92 PMID: 27517620 (recommended in F1000Primer, citation>20)

6. Patwardhan GA, Hosain SB, Liu DX, Khiste SK, Zhao Y, Bielawski J, Jazwinski SM, Liu Y.Y. 2014. Ceramide modulates pre-mRNA splicing to restore the expression of wild-type tumor suppressor p53 in deletion-mutant cancer cells. Biochim Biophys Acta 1841(11):1571-1580 PMID: 25195822 (recommended in F1000Prime, citation>20)

7. Liu, Y.Y., Hill, R.A. and Li, Y.T. Ceramide glycosylation catalyzed by glucosylceramide synthase and cancer drug resistance. 2013. Adv Cancer Res 117:59-89 (citation>90)

8. Gupta, V., Liu, Y.Y. 2013. New insights on glucosylceramide synthase in cancer drug resistance and myelosuppression. Biochem & Pharmacol 2:120

9. Hosain, S.B., Hill, R.A., and Liu, Y.Y. 2013. The role of sphingolipids in modulating pluripotency of stem cells. Trends in Stem Cell Proliferation and Cancer Research by Rodrigo Resende, Henning Ulrich, Springer, ISBN 978-94-007-6210-7, p167-191

10. Gupta, V., Bhinge, K.N., Hosain, S.B., Xiong, K., Gu, X., Shi, R., Ambudkar, S., Jazwinski, S.M. and Liu, Y. Y. 2012. Ceramide glycosylation catalyzed by glucosylceramide synthase is a critical process maintaining the stemness of breast cancer stem cells. J Biol Chem 278(44):37195-205 (highlighted in ASBMB News, citation>50)

11. Bhinge, K., Gupta, V., Hosain, S.B., Meyer, S.A., Blaylock, B., Zhang, Q., Liu, Y.Y. 2012. The opposite effects of doxorubicin on bone marrow stem cells versus breast cancer stem cells depend on glucosylceramide synthase. Int. J. Biochem. Cell Biol. 44(11):1770-1778

12. Liu, Y.Y. 2011. Resuscitation of wild-type p53 tumor suppressor by disrupting ceramide glycosylation: a novel approach to target mutant p53 tumors. Cancer Res. 71(20):6295-99

13. Liu, Y.Y., Patwardhan, G.A., Xie, P., Gu, X., Giuliano, A.E., and Cabot, M.C. 2011. Glucosylceramide synthase, a factor in modulating multidrug resistance, is overexpressed in metastatic breast carcinoma. Int. J Oncol 39:425-431 (citation>60)

14. Liu, Y.Y., Patwardhan, G.A., Bhinge, K., Gupta, V., Gu, X., and Jazwinski, S.M., 2011. Suppression of glucosylceramide synthase restores p53-dependent apoptosis in mutant p53 cancer cells. Cancer Res. 71(6):2276-85 (citations>70)

15. Gupta, V., Zhang, Q. and Liu, Y.Y. 2011. Evaluation of anticancer agents using flow cytometry analysis of cancer stem cells. Methods Mol Biol. 716:179-91.

16. Patwardhan, G.A., Liu, Y.Y. 2011. Sphingolipids and expression regulation of genes in cancer. Prog. Lipid Res. 50:104-114 (Most Read Article in 2011, citations>90)

17. Liu, Y.Y., Gupta, V., Patwardhan, G.A., Yin, D., Bhinge, K., Zhao, Y., Bao, J., Mehendale, H., Cabot, M. C., Li, Y., and Jazwinski, S.M. 2010. Glucosylceramide Synthase upregulates MDR1 expression in the regulation of cancer drug resistance through cSrc and beta-catenin signaling. Mol Cancer 9(1):145 (highly accessed, citations>120)

18. Patwardhan, G.A., Gupta, V., Huang, J., Gu, X., Liu, Y.Y. 2010. Direct assessment of P-glycoprotein to determine tumor response to chemotherapy. Biochem. Pharmcol. 80:72-79 (citation>30)

19. Gupta, V., Patwardhan, G.A., Zhang, Q., Senkal, C.E., Ogretmen, B., Cabot, M.C., Jazwinski, S.M., and Liu, Y.Y. 2010. Direct quantitative determination of ceramide glycosylation in vivo: a new approach to evaluate the enzyme activity of glucosylceramide synthase. J. Lipid Res 51:866-874 (highlighted in ASBMB Today; citation>30).

20. Patwardhan, G.A., Zhang, Q., Yin, D., Gupta, V., Bao, J., Senkal, C.E., Ogretmen, B., Cabot, M.C., Jazwinski, S.M., Liu, Y.Y. 2009. A new mixed-backbone oligonucleotide against glucosylceramide synthase sensitizes multidrug-resistant tumors to apoptosis. PLoS One 4(9):e6938 (citations>50)

21. Liu, Y.Y., Yu, J.Y., Yin, D., Patwardhan, G., Gupta, V., Hirabayashi, Y., Holleran, W.M., Jazwinski, S.M., Giuliano, A.E., Gouaze-Andersson, V., Consoli, D.P., Cabot, M.C. 2008. A role for ceramide in driving cancer cell resistance to doxorubicin. FASEB J. 22, 2541-2551 (citations >100)

22. Liu, Y.Y., Han, T.Y, Yu, J.Y., Bitterman, A., Le, A., Giuliano, A.E., and Cabot, M.C. 2004. Oligonucleotides blocking glucosylceramide synthase expression selectively reverse drug resistance in cancer cells. J Lipid Res 45:933-940 (citations >90)

23. Liu, Y.Y., and Cabot, M.C. 2004. Development of a mammalian Tet-on expression cell line: glucosylceramide synthase regulates TNF--induced apoptosis. Methods Mol. Biol. 249:177-192

24. Liu, Y.Y., Han, T.Y., Giuliano, A.E. and Cabot, M.C.  2001.  Ceramide glycosylation potentiates cellular multidrug resistance. FASEB J. 15:719-730 (citations >340) 

25. Liu, Y.Y., Han, T.Y., Giuliano, A.E., Hansen, N., and Cabot, M.C.  2000.  Uncoupling ceramide glycosylation by transfection of glucosylceramide synthase antisense reverses adriamycin resistance. J. Biol. Chem. 275:7138-7143 (citation>160). 

26. Liu Y.Y., Han, T.Y, Giuliano A.E., and Cabot, M.C.  1999.  Glucosylceramide synthase potentiates cellular resistance to TNF- induced apoptosis. Exp. Cell Res. 252:464-470 (citations >100).

27. Liu Y.Y., Rajkumar K. and Murphy L.J.  1999.  Hepatic regeneration in insulin-like growth factor binding protein-1 transgenic mice. J. Hepatol. 30:674-80. PMID:10207810

28. Liu Y.Y., Han T.Y., Giuliano A.E. and Cabot M.C.  1999.  Expression of glucosylceramide synthase converting ceramide to glucosylceramide impacts adriamycin resistance in human breast cancer cells. J. Biol. Chem. 274:1140-1146 (citation>320). 

Research Interests

Tumor cell response to chemotherapy and gene regulation.

We are investigating how genetic alterations affect cancer cell resistance to chemotherapy, aimed at discovering therapeutic approaches. Drug resistance or poor response to chemotherapy is a crucial reason for treatment failure, which occurs among 60% of patients with metastatic tumors during chemotherapy. Cell response to anticancer agents relies on the functions of certain group of genes involved in cells apoptosis and drug transportation, such as p53 mutation, multidrug resistance-1 (MDR1) and glucosylceramide synthase (GCS). Using state-of-the-art technologies and precision strategy in gene manipulation, we are identifying targets are causes of drug resistance in cancer cells, particularly in cancer stem cells.

Our program is distinguished by characterizing the roles of glycosphingolipids and sphingolipids playing in cancer drug resistance and in regulation of gene expression. We continuously study in:

Project 1: Glycosphingolipids and cancer stem cells. Among glycosphingolipids (GSLs), globotriosylceramide (Gb3/CD77), GD2 and others are highly associated with pluripotency of breast cancer cells. Gb2 can activate cSrc and β-catenin signaling pathways and upregulate stem cell factors.     

Project 2: pre-mRNA splicing and expression restoration of p53 mutation. Intriguingly, ceramide can restore p53 tumor suppressor and the anticancer activity in cancer cells carrying p53 mutants (deletion-, missense-mutation). Most likely, ceramide modulates pre-mRNA splicing process and the later determines cells expressing wild-type or mutant proteins by epigenetic mechanism.

Project 3: Epigenetic therapy approaches for cancer drug resistance. With collaborations, we characterize and develop nanoparticles based on natural materials to effectively deliver poor water-soluble agents targeting p53 mutant cells and cancer stem cells.        

The goal of our research interests is to discover and develop gene-based therapy that would overcome drug resistance and improve the treatments of cancers, particularly solid tumors in breast and colon.

Recent Publications

Uddin, M. B., Roy, K. R., Roy, S. C., Gu, X., Hill, R. A., Zhang, Q., Liu, Y. Missense p53 mutant G242A defies natural killer cells in sheltering mouse cancer cells against immune suppression. PLoS One.
Hill, R. A., Liu, Z., Liu, Y. (2020). Small Ceramide Tames Big p53 Mutant Beast (pp. 3418-19). Oncotarget.
Roy, K. R., Uddin, M. B., Roy, S. C., Hill, R. A., Marshall, J., Li, Y., Chamcheu, J. C., Lu, H., Liu, Y. (2020). Gb3-cSrc complex in glycosphingolipid-enriched microdomains contributes to the expression of p53 mutant protein and cancer drug resistance via beta-catenin activated RNA-methylation (pp. 653-667). FASEB BioAdvances.
Chen, J., Khiste, S. K., Fu, X., Roy, K. R., Dong, Y., Zhang, J., Liu, M., Liu, Y., Liu, Z. (2020). Rubusoside-assisted solubilization of poorly soluble C6-Ceramide for a pilot pharmacokinetic study (pp. 1-8). Prostaglandins & Other Lipid Mediators.
Khiste, S. K., Liu, Z., Roy, K. K., Uddin, M. B., Hosain, S. B., Gu, X., Nazzal, S., Hill, R. A., Liu, Y. (2020). Ceramide-Rubusoside Nanomicelles, a Potential Therapeutic Approach to Target Cancers Carrying p53 Missense Mutations (pp. 564-74). Molecular Cancer Therapeutics.
Roy, K. R., Khiste, S., Liu, Y. (2019). Fluorescence HPLC Analysis of the in-vivo Activity of Glucosylceramide Synthase (pp. e3269). Bio-protocol.
Uddin, M. B., Roy, K. R., Hosain, S., Khiste, S. K., Hill, R. A., Jois, S. D., Zhao, Y., Liu, Y. (2019). An N6-methyladenosine at the transited codon 273 of p53 pre-mRNA promotes the expression of R273H mutant protein and drug resistance of cancer cells (pp. 134-145). Biochemical Pharmacology/ELSEVIER.
Khiste, S. S., Liu, Y. (2017). Incorporation of Fluorescence Ceramide-Based HPLC Assay for Rapidly and Efficiently Assessing Glucosylceramide Synthase In Vivo (pp. 2976). Nature: Scientific Report.
Hosain, S., Liu, Y. (2016). Inhibition of glucosylceramide synthase eliminates the oncogenic function of p53 R273H mutant in the epithelial-mesenchymal transition and induced pluripotency of colon cancer cells (pp. 60575-92). Oncotarget.
Patwardhan, G. A., Hosain, S. B., Liu, D. X., Khiste, S. K., Zhao, Y., Bielawski, J., Jazwinski, S. M., Liu, Y. (2014). Ceramide modulates pre-mRNA splicing to restore the expression of wild-type tumor suppressor p53 in deletion-mutant cancer cells. (pp. 1571-1580). Biochimica et Biophyca Acta.
Gupta, V., Bhinge, K. N., Hosain, S., Xiong, K., Gu, X., Shi, R., Ho, M., Khoo, K., Li, S., Li, Y., Ambudkar, S. V., Jazwinski, S. M., Liu, Y. (2012). Ceramide glycosylation catalyzed by glucosylceramide synthase is a critical process maintaining the stemness of breast cancer stem cells. (pp. 37195-205). Rockville, MD: Journal Biological Chemistry.
Bhinge, K., Meyer, S., Liu, Y. (2012). Bhinge, K., V. Gupta, S. Hosain. S.D. Satyanarayanajois S.A.Meyer, B. Blaylock. Q.J. Zhang, and Y.Y. Liu. The opposite effects of doxorubicin on bone marrow stem cells versus breast cancer stem cells depend on glucosylceramide synthase. (pp. 1770-1778). Int. J. Biochem. Cell Biol..
Liu, Y. (2009). Effect of B7.1 costimulation on T-cell based immunity against TAP-negative cancer can be facilitated by TAP1 expression. (pp. e6385). PLoS One.
Liu, Y., Hill, R. A., Li, Y. (2013). Ceramide glycosylation catalyzed by glucosylceramide synthase and cancer drug resistance (pp. 59-89). Academic Press: Advances in Cancer Research.
Gupta, V., Zhang, Q., Liu, Y. (2011). Evaluation of anticancer agents using flow cytometry analysis of cancer stem cells (pp. 179-191). Methods in Molecular Biology.
Wang, F., Liu, J., Robbins, D., Morris, K., Sit, A., Liu, Y., Zhao, Y. (2011). Mutant p53 exhibits trivial effects on mitochondrial functions which can be reactivated by ellipticine in lymphoma cells (pp. 301-310). Apoptosis.
Patwardha, G., Liu, Y. (2011). Sphingolipids and expression regulation of genes in cancer (pp. 104-114). Progress in Lipid Research.
Liu, Y., Patwardhan, G., Bhinge, K., Gupta, V., Gu, X., Jazwinski, M. (2011). Suppression of glucosylceramide synthase restores p53-dependent apoptosis in mutant p53 cancer cells (pp. 2276-2285). Cancer Research.
Liu, Y. (2010). Direct quantitative determineation of ceramide glycosylation in vivo: a new appraoch to evaluate cellular enzyme activity of glucosylceramide synthase (pp. 866-874). Journal of Lipid Research.
Chapman, J., Gouaze-Andersson, V., Messner, M., Flowers, M., Karimi, R., Barth, B., Liu, X., Liu, Y., Giuliano, A., Cabot, M. (2010). Metabolism of short-chair ceramide by human cancer cells-implications for therapeutic approaches (pp. 308-315). Biochemical Pharmacology.
Siddiqui, A., Patwardhan, G., Liu, Y., Nazzal, S. (2010). Mixed backbone antisense glucosylceramide synthase oligonucleotide (MBO-asGCS) loaded solid lipid nanoparticles: in vivo characterization and reversal of multidrug resistance in NCI/ADR-RES cells (pp. 251-259). International Journal of Pharmaceutics.
Liu, Y., Gupta, V., Patwardhan, G., Bhinge, K., Zhao, Y., Bao, J., Mehendale, H. M., Cabot, M., Li, Y., Jazwinski, M. (2010). Glucosylceramide synthase upregulated MDR1 expression in the regulation of cancer drug resistance through cSrc and beta-catenin signaling (pp. 145: 1-15). Molecular Cancer.
Liu, Y. (2010). Direct assessment of P-glycoprotein efflux to determine tumor response to chemotherapy (pp. 72-79). Biochemical Pharmacology.
Liu, Y. (2009). A new mixed-backbone oligonucleotide targeting GCS sensitizes multidrug-resistant tumors to apoptosis (pp. e6938). PLoS One.
Liu, Y. (2008). In vivo survivors of transformed mouse ovarian surface epithelial cells display diverse phenotypes for gene expression and tumorigenicity (pp. 359-370). Tumor Biol.
Wang, H., Maurer, B., Liu, Y. (2008). N-(4-hydroxyphenyl)retinamide increases dihydroceramide and synergizes with dimethlsphingosine to enhance cancer cell killing (pp. 1-10). Molecular Cancer Therapeutics.
Liu, Y. (2008). A role of ceramide in driving cancer cell resistance to doxorubicin (pp. 2541-2551). FASEB J.
Liu, Y. (2004). Oligodeoxyribonucleotides blocking glucosylceramide synthase expression selective reverse drug resistance in cancer cells (pp. 933-940). J Lipid Research.

Research Grants

Liu, Y. (Principal), "Ceramide glycosylation determines the stemness of cancer stem cells" (Funded), Sponsored By NIH/NCI, The University of Louisiana at Monroe, $419,700. (April 01 2013 - March 30 2016).
El Sayed, K. (Principal), Sylvester, P. W. (Co-Principal), Liu, Y. (Co-Principal), "Design of novel c-Met inhibitors inspired by olive phenolics-1R15CA167475-01" (Funded), Sponsored By NIH/NCI, External to The University of Louisiana at Monroe, $420540. (February 01 2013 - January 31 2016).
Liu, Y. (Principal), "Globo-series glycosphingolipids and the stemness of cancer stem cells" (Funded), Sponsored By Mizutani Foundation for Glycoscience, The University of Louisiana at Monroe, $48,000. (March 01 2012 - February 30 2013).

Awards & Honors

April 2020 Excellent in Team Teaching Award.

April 2020 Scientific Advisory Board Member.

March 2018 Ad Hoc Member.

September 2015 Foundation Award for Excellent in Reseaarch.

March 2013 NIH grant.

February 2012 Research grant.

January 2012 Distinguished Reseacher.

June 2008 Travel Grants for Emerging Faculty.

January 2008 Ajunct Assistant Professor.

January 2008 Ajunct Assistant Professor.

Courses Taught

PHAR 4036Pharmacology Lab, 1 course(s)

PHAR 5016STERILE PRODUCTS, 1 course(s)

PHAR 5022ADV PHARMACOLOGY LAB, 7 course(s)

PHRD 4012PATHOPHYSIOLOGY I, 11 course(s)

PHRD 4027PRINCIPLES OF DRUG ACTION II, 6 course(s)

PHRD 4035PATHOPHYSIOLOGY II, 11 course(s)

PHRD 4072THERAPEUTICS II, 3 course(s)

PHRD 4074ENDOCRINE MODULE, 7 course(s)

PHRD 4083GASTRO NUTRITION & HEPTIC MOD, 7 course(s)

PHRD 5022THERAPEUTICS VI, 2 course(s)

PHRD 5031RESPIRATORY MODULE, 7 course(s)