Professor, Biochemistry and Molecular BiologyPhone: 402-559-5776 (Office)
Location: DRC1 7042
Location: DRC1 7034
Ph.D., Case Western Reserve University, 1975
Student research opportunities in my lab:
High school students
Primary Research/Clinical Interests/Expertise:
Altered glycans as biomarkers and therapeutic targets of aggressive cancers
The research focus of our laboratory is to elucidate the fundamental mechanism of glycosylation to help understand how glycosylation is altered in various diseases, including cancer progression. Recently, we have identified the Golgi targeting sites of glycosyltransferases, the Golgi retention proteins for some of them, and the roles of non-muscle myosin IIA in recycling of glycosyltransferases and Golgi fragmentation. We have found that giantin is the exclusive targeting site for core 2 enzymes and the primary targeting site for all glycosyltransferases and mannosidases except core 1 synthase. Core 1 synthase uses GM130-GRASAP65 as the primary targeting site and GM130-giantin as the targeting site when GRASP65 is not available. When giantin is defective as is seen in aggressive cancer cells and cells under stress, core 2 enzymes cannot get to Golgi and are degraded, and all other glycosyltransferases and mannosidases still can reach the Golgi using GM130-GRASP65. The dysregulated glycosylation environment at the GM130-GRASP65 site results in altered glycosylation, such as formation of high mannose N-glycans and tumor-associated carbohydrate antigens of mucin O-glycans (Figure 1). These altered glycans are being developed as biomarkers and therapeutic targets of aggressive cancers.
- Determination of Golgi targeting,retention, and recycling mechanisms of glycosyltransferases
- Determination of the alcohol effect on mucus defense in the lungs.
- Identification of the glycosyltransferases that work on secreted and membrane-bound mucins
- Regulation of mucin glycans involved in cancer progression and metastasis
Bhat G, Hothpet V-R, Lin MF, and Cheng P-W. Shifted Golgi targeting of glycosyltransferases and α-mannosidase IA from giantin to GM130-GRASP65 results in formation of high mannose N-glycans in aggressive prostate cancer cells. BBA - General Subjects (2017), http://dx.doi.org/10.1016/j.bbagen.2017.08.006
Petrosyan A, Casey C A, and Cheng P-W. The role of Rab6a and phosphorylation of non-muscle myosin IIA tailpiece in alcohol-induced Golgi disorganization. Sci. Rep. 6: 31962, 2016. doi: 10.1038/srep31962.
Petrosyan A, Cheng P-W, Clemens D L and Casey C A. Downregulation of the small GTPase SAR1A: a key event underlying alcohol-induced Golgi fragmentation in hepatocytes. Sci. Rep. 5:17127, 2015. Doi:10.1038/srep17127 (PMID:26607390)(PMCID:4660820) PWC
Chachadi VB, Bhat G, and Cheng P-W. Glycosyltransferases involved in the synthesis of MUC-associated metastasis-promoting selectin ligands. Glycobiology (In press) Published online May 14, 2015. doi: 10.1093/glycob/cwv030
Petrosyan A, Ali M, and Cheng P-W. Keratin 1 plays a critical role in Golgi localization of Core 2 N-acetylglucosaminyltransferase M via interaction with its cytoplasmic tail. J Biol Chem 290(10):6256-69, 2015. Published online Jan. 20, 2015 Doi: 10.1074/jbc.M114.618702. (PMID:25605727)
Petrosyan A, Holzapfel MS, Muirhead DE and Cheng P-W. Restoration of compact Golgi morphology in advanced prostate cancer enhances susceptibility to galectin 1-induced apoptosis by modifying mucin O-glycan synthesis. Mol Cancer Res 12(12): 1704-16, 2014. published online First August 1, 2014; doi:10.1158/1541-7786. MCR-14-0291-T. (PMID:25086069) (PMCID: 4272641)
Petrosyan A and Cheng P-W. Golgi fragmentation induced by heat shock or inhibition of heat shock proteins is mediated by non-muscle myosin IIA via its interaction with glycosyltransferases. Cell Stress & Chaperones 19(2):241-54, 2014. 10.1007/s12192-013-0450-y. ISSN:1355-8145.PMID:23990450 (PMCID: 3933620)
Chachadi V, Ali MF, and Cheng P-W. Prostatic cell-specific regulation of the synthesis of MUC1-associated sialyl Lewis a. PLoS One. 2013 8(2):e57416. doi:10.1371/journal pone.0057416.
Petrosyan A and Cheng P-W. A non-enzymatic function of Golgi glycosyltransferases: mediation of Golgi fragmentation by interaction with non-muscle myosin IIA. Glycobiology 23(6):690-908, 2013. doi:101093/glycob/ewt009.
Ali MF, Chachadi VB, Petrosyan A, and Cheng P-W. Golgi phosphoprotein 3 determines cell binding properties under dynamic flow by controlling golgi localization of Core 2 N-acetylglucosaminyltransferase 1. J. Biol. Chem. 2012 Nov 16;287(47):39564-77. doi: 10.1074/jbc.M112.346528. Epub 2012 Oct 1.
Petrosyan A, Ali M, and Cheng P-W. Glycosyltransferase-specific golgi targeting mechanisms. J. Biol. Chem. 2012 Nov 2; 287 (45):37621-7. doi: 10.1074/jbc.C112-403006. Epub 2012 Sep 17.
Gao Y, Chachadi VB, Cheng P-W, and Brockhausen I. Glycosyltransferase activities and mRNA expression in human prostate cancer cell lines. Glycoconjugate J. 29(7):525-37, 2012. doi: 10.1007/s10719-012-9428-8. Epub 2012 July 28.
Petrosyan A, Ali MF, Verma SK, Cheng H, and Cheng P-W. Non-muscle myosin IIA transports a Golgi enzyme to the ER by binding to its cytoplasmic tail. Int. J. Biochem. Cell Biol. 44:1153-65, 2012. doi: 10.1016/j.biocel.2012.04.004.
Arpke RW and Cheng P-W. Characterization of human serum albumin-facilitated lipofection gene delivery strategy. J. Cell Sci. Ther. 2(3):108, 2011 doi:10.4272/2157-7013. 1000108.
Radhakrishnan P, Chachadi V, Lin M-F, Singh R, Kannagi R and Cheng P-W. TNFα enhances the motility and invasiveness of prostatic cancer cells by stimulating the expression of selective glycosyl- and sulfotransferase genes involved in the synthesis of selectin ligands. Biochem. Biophys. Res. Commun. 409:436-441, 2011. doi: 10.1016/j.bbrc.2011.05.019.
Chachadi VB, Cheng H, Klinkebiel D, Christman JK, and Cheng P-W. 5-Aza-2’-deoxycytidine Increases Sialyl Lewis X on MUC1 by stimulating β-Galactoside α2,3-Sialyltransferase 6 Gene. Int. J. Biochem. Cell Biol. 43(4): 586–593, 2011. DOI:10.1016/j.biocell. 2010.12.015.
Radhakrishnan P, Lin MF, and Cheng PW. Elevated expression of L-selectin ligand in lymph node-derived human prostate cancer cells correlates with increased tumorigenicity. Glycoconjugate J. 26(1):75-81, 2009. DOI: 10.1007/s10719-008-9167-z.
Radhakrishnan P*, Basma H*, Klinkebiel D, Christman J, and Cheng PW. Cell type-specific activation of the cytomegalovirus promoter by dimethyl sulfoxide and 5-aza-2'-deoxycytidine. Int. J. Biochem. Cell. Biol. 40(9):1944-55, 2008. DOI: 10.1016/j.biocel.2008.02.014 (*equal contribution).
Tan S and Cheng PW. Mucin biosynthesis: identification of the cis-regulatory elements of human C2GnT-M gene. Am. J. Respir. Cell and Mol. Biol. 36:737-45, 2007. DOI:10.1165/rcmb.2006-03340C.
Radhakrishnan P, Beum P, and Cheng PW. Butyrate induces the synthesis of sialyl Lewis x carbohydrate epitope in a pancreatic adenocarcinoma cell line. Biochem. Biophys. Res. Commun. 359:457-62, 2007. DOI: 10.1016/j.bbrc.2007.05.165.
Beum PV, Basma H, Bastola DR, and Cheng PW. Mucin biosynthesis: upregulation of core 2β1,6 N-acetylglucosaminyltransferase by retinoic acid and Th2 cytokines in a human airway epithelial cell line. J. Cell Phyciol-Lung Cell and Mol. Physiol. 288:L1126-L124, 2005. DOI:10.1152/ajplung.00370.2003.
Choi KH, Basma H, Singh J, and Cheng PW. Enhancement of the expression of CMV promoter-controlled glycosyltransferase and β-galactosidase transgenes by butyrate, tricostatin A, and 5-aza-2'-deoxycytidine. Glycoconjugate J. 22:63-9, 2005.
Bandi N, Ayalasomayajula SP, Iwakawa J, Cheng PW, and Kompella UB. Intratracheal budesonide-poly(lactide-co-glycolide) microparticles ameliorate early biochemical changes in benzo(a)pyrene-fed mouse model. J. of Pharm. and Pharmacol. 57:851-60, 2005.
Basma H*, El-Refaey H*, Sgagias MK, Cowan KH, Luo X, and Cheng PW. Bcl-2 antisense enhances cisplatin-induced apoptosis in isogenic MCF-7 breast cancer lines with and without function p53. J. Biomed. Sci. 12:999-1011, 2005. (* Equal contribution) DOI: 10.1007/s11373-005-9025-y.
Choi K, Osorio F, and Cheng PW. Mucin biosynthesis: C2GnT-M gene, tissue-specific expression, and bovine herpes virus-4 homologue. Am. J. Respir. Cell and Mol. Biol. 279:38969-77, 2004. DOI: 10.1165/rcmb.2003-02020C.
Singh J, Khan G, Kinarsky L, Choi K, Cheng H, Wilken J, Bedows E, Sherman S, and Cheng PW. Identification of disulfide bonds among the nine core 2 N-acetyl-glucosaminyltransferase-M cysteines conserved in mucin β6 N-acetylglucosaminyl-transferase family. J. Biol. Chem. 279:38969-77, 2004.
Cheng P-W and Radhakrishnan P. (2010) Mucin glycan branching enzymes: structure, function and gene regulation. In Molecular Immunology of Complex Carbohydrates-3 (Wu, Albert, Ed.) Advances in Experimental Medicine and Biology, Plenum Press, N.Y., N.Y. pp. 511-42.
Current Grants and Contracts:
NIH NIAAA KO1 Award KO1AA022979-01
Title: Alcohol effect on Golgi morphology and function
PI: Armen Petrosyan
Dates: Sep. 1, 2014 – Aug. 30, 2019
State of Nebraska LB506 Tobacco smoking research #2017-15
Title: Mechanism of the formation of tumor-associated carbohydrate antigens
Dates: July 1, 2016 – June 30, 2017
Veteran Affairs Merit Award 1 I01 BX000985-05
Title: Glycosyltransferase Golgi Retention Mechanism
State of Nebraska LB506 Tobacco smoking research #2016-08
Title: Altered N-glycans in Golgi Enzymes of Aggressive Cancer
Dates: July 1, 2015 – June 30, 2016
Nebraska cancer and smoking disease research (LB506)(#2015-013)
Title: Mechanism of altered O-glycosylation in prostate cancer
Dates: 7/1/2014 – 6/30/2015