Professor, Biochemistry and Molecular Biology
Phone: 402-559-5776 (Office)
Ph.D., Case Western Reserve University, 1975
Student research opportunities in my lab:
Primary Research/Clinical Interests/Expertise:
Regulation of mucin glycan biosynthesis in lung diseases and cancer
Mucin-type carbohydrates are carbohydrates covalently linked to serine/threonine on the peptide backbone through N-acetylgalactosamine. They are present in secreted and membrane-tethered mucins, and the primary determinants of their functions. Mucin-type carbohydrate constitutes 80-90% of the secreted mucins, which help retain water, and are very heterogeneous in structure, which help trap airborne and ingested pathogens. These two properties allow the secreted mucins to exercise their protective functions by maintaining dehydration of the mucus and facilitating clearance of the pathogens. Decrease in carbohydrate content and heterogeneity in secreted mucins would result in chronic inflammation and development of diseases, such as colitis and colon cancer. Mucin-type carbohydrate also makes up a significant portion of the membrane-bound mucins. They serve as the selectin ligands to direct leukocyte migration. Loss or uncontrolled expression of these ligands all leads to compromised immune functions. Over-expression of these ligands in cancer cells would facilitate metastasis. Thus, we are interested in understanding how the synthesis of mucin-type carbohydrate is regulated.
- Determination of Golgi targeting,retention, and recycling mechanisms of glycosyltransferases
- Determination of the mechanism of Golgi:fragmentation mediated interaction of non-musle myosin IIA with glycosyltransferases
- Identification of the glycosyltransferases that work on secreted and membrane-bound mucins
- Regulation of mucin glycans involved in cancer progression and metastasis
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 glycolsytransferases: 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. (http://dx.doi.org/10.1016/j.bbr.2011.03.031).
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.
Kumar S, Rajendran M, Alam SM, Lin F-F, Cheng P-W, and Lin M-F. Steroids up-regulate p66Shc longevity protein in growth regulation by inhibiting its ubiquitination. PLoS ONE 6(1): e15942, 2011.doi:10.1371/ journal.pone.0015942.
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 dimethylsulfoxide 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.
Hashimoto M, Tan S, Mori N, Cheng H, and Cheng PW. Mucin biosynthesis: Molecular cloning and expression of mouse mucus-type core 2 β1,6 N-acetylglucosaminyltransferase. Glycobiology 17(9):994-1006, 2007. DOI: 10.1093/glycol/cwm068.
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-acetylglusaminyl-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.
Sharma NM, Radhakrishnan P, Tan S, and Cheng PW. B3GNT6 (UDP-GlcNAc:βGal β-1,3-N-acetylglucosaminyltransferase 6 (core 3 synthase)). Atlas GenetCytogenet Oncol Haematol. May 2009.
Radhakrishnan P and Cheng PW. GCNT3 (glucosaminyl (N-acetyl) transferase 3, mucin type). Atlas Genet Cytogenet Oncol Haematol. November 2007.
Petrosyan A and Cheng P-W. 2013 Golgi fragmentation induced by heat shock or inhibition of heat shock protiens is mediated by non-musle myosin IIA via its interaction with glycosyltransferases. Cell Stress & Chaperones (In press) DOI 10.1007/s12192-013-0450-y
Current Grants and Contracts:
Veteran Administration Merit Award
Title: Golgi localization mechanism of mucin glycosyltransferases
10/1/2011 - 9/30/2015
National Institutes of Health
Title: Macrophages, NR2B-containing NMDA receptors and HIV dementia
4/1/2009 - 3/31/2014
Nebraska LB506 Tobacco Smoking Research
Title: ER retention of glycosyl transferases in cancer cells
7/1/2013 - 6/30/2014
National Cancer Institute, National Institutes of Health
Cancer Biology Training Grant
Principal Investigator: Angie Rizzino, Ph.D.(Eppley Cancer Institute)
7/1/2008 - 6/30/2013
DOD PCRP of CDMRP
Collaborative Undergraduate HBCU Student Summer Training Program Award
Nebraska Prostate Cancer Research Program
Principal Investigator: Ming-Fong Lin, Ph.D.
4/20/2010 - 4/19/2015
Graduate Training in Structural Biology and Biophysics
U.S. Department of Education
Principal Investigator: Gloria Borgstahl/Luis Marky/Paul Sorgen
8/15/2009 - 8/14/2013
Nebraska Cancer and Smoking Disease Research (LB506)
Principal Investigator: Pi-Wan Cheng, Ph.D.
Title: ER retention of glycosyltranferases in cancer cells
7/1/2013 - 6/30/14
Surinder K. Batra
William G. Chaney
G. Stanley Cox
Richard G. MacDonald
Parmender P. Mehta
Robert F. Ramaley