• DEPARTMENT:

        Biochemistry and Molecular Biology

• NAME/TRAINING:

Pi-Wan Cheng, Ph.D.

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ACADEMIC DEGREES:

Graduate School:	Ph.D. in Biochemistry (1975) Case Western Reserve University School of Medicine Cleveland, OH
Post-doctoral Positions:	Department of Pediatrics (Pulmonary Division) Case Western Reserve University

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Contact Name: Pi-Wan Cheng, Ph.D., Professor
                     Biochemistry and Molecular Biology
Office:            12706A LTC
Phone Number: 402-559-5776
e-mail address: pcheng@unmc.edu

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• GRANT SUPPORT (last 3 years):

Agency: NIH RO1 HL48282-6
Title: Biosynthesis of Tracheal Mucous Glycoproteins
Role on Project: PI (50% effort)
Dates & direct cost of entire project: 1/1/01 - 12/3/05; $1,075,000

Agency: NIHRO1 HL56190-3
Title: Gene Transfer to Airway Epithelial Cells
Role on Project: PI (30% effort)
Dates & direct cost of entire project: 1/1/1998-12/31/2001; $427,793

Agency: Nebraska Department of Health LB506
Title: Modification of Mucin Glycans with Sialytransferase
Role on Project: PI (5% effort)
Dates & total direct cost: 7/1/01-6/30/02; $40,000

Agency: Nebraska Department of Health LB506
Title: Characterization of Mucin Core 2-M Transcripts
Role on Project: PI (5% effort)
Dates & total direct cost: 07/01/02-06/30/03; $40,000

Agency: Nebraska Research Initiative
Title: Gene Therapy Program
Role on Project: PI (5 % effort)
Dates & total direct cost: 7/1/98-6/30/04; $1,800,000.

Agency: Nebraska Research Initiative (PI: Michael Hollingsworth)
Title: Center of Excellence in Glycobiotechnology
Role on Project: Co-I (3% effort)
Dates & total direct cost: 7/1/00-6/30/04; $1,400,000

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• PUBLICATIONS (last 3-5 years):

Beum P, Singh J, Burdick M, Hollingsworth M, and Cheng P-W: Generation of sialyl Lewis x by transfection of human pancreatic adenocarcinoma cells with core 2 glycosyltransferase cDNA. J. Biol. Chem. 274: 24641-8, 1999. Yanagihara K and Cheng P-W: Lectin enhancement of lipofection efficiency in human lung carcinoma cells. Biochim. Biophys. Acta. 1472:25-33, 1999.

Li CM, Adler KB, and Cheng P-W: Development of monoclonal antibodies against bovine mucin core 2 β6 N-acetylglucosaminyltransferase. Glycoconjugate J. 16:555-562,1999.

Yanagihara K Cheng H, and Cheng P-W: Effects of epidermal growth factor, transferrin, and insulin on the lipofection efficiency in lung carcinoma cells. Cancer Gene Ther 7:59-65, 2000.

Beum P and Cheng P-W: Biosynthesis and Function of β1-6 Branching Mucin-Type Glycans in Molecular Immunology of Complex Carbohydrates-2 (Wu, Albert, ed) Advances in Experimental Medicine and Biology, Kluwer Plenum Press, NY, NY. PP.279-323, 2001.

Yanagihara K, Seki, F, and Cheng P-W: Lipolopysaccharide induction of mucus cell metaplasia in mouse lung. Am J Respir Cell & Mol Biol. 24:66-73, 2001.

Bastola, DR, Pahwa, GS, Lin, M-F, and Cheng, P-W: Downregulation of PTEN/NMAC/TEP1 expression in human prostate cancer cell line DU145 by growth stimuli. Mol. Cell. Biochem. (in press)

Seki, M, Iwakawa, J, Cheng, H, and Cheng, P-W: p53 and PTEN/NMAC1/TEP1 gene therapy of human prostate PC-3 carcinoma xenograft employing transferrin-facilitated lipofection gene delivery strategy. Hum. Gene Ther. (in press).

Joshee, N., Bastola, DR, and Cheng, P-W: Transferrin-facilitated gene delivery strategy: characterization of the transfection complexes and intracellular trafficking. Hum. Gene Ther. (in press).

Beum P, Bastola DR, and Cheng P-W: Mucin biosynthesis: EGF downregulates core 2 enzymes in a human airway adenocarcinoma cell line. Am. J. Respir. Cell and Mol. Biol. 29-48-56, 2003.

Choi, K., Osorio, F., and Cheng, P.-W.: Mucin biosynthesis: C2GnT-M gene, tissue-specific expression, and bovine herpes virus-4 homologue. Am. J. Respir. Cell and Mol. Biol. 30:1-10, 2004. 

Amrite, A.C., Cherruvu, N.P.S., Sundaram, S., Aravalli, R., Cheng, P.-W., and Kompella, L.B.: Lung Gene Therapy: Clinical and Regulatory Issues.  Clinical Res. and Regulatory Affairs (Accepted for publication). 

Basma, H., El-Refaey, H., Sgagias, M.K., Cowan, K. H., and Cheng, P.-W.: Bcl-2 antisense enhances cisplatin-induced apoptosis in isogenic MCF-7 breast cancer lines with and without functional p53. Breast Cancer Res. (under revision). 

Beum, P.V., Basma, H., Bastola, D.R., and Cheng, P.-W.: Mucin biosynthesis: upregulation of core 2b1,6 N-acetylglucosaminyltransferase by retinoic acid and Th2 cytokines in a human airway epithelial cell line. J. Cell Phyciol.-Lung Cell. and Mol. Physiol. (under revision). 

Beum, P.V., Bastola, D.R., and Cheng, P.-W.: Mucin biosynthesis: butyrate increases core 2 b1,6 N-acetylglucosaminyltransferase expression and core 2-based carbohydrate structures in a pancreatic adenocarcinoma cell line. Eur. J. Biochem. (under revision). 

Singh, J., Khan, G., Kinarsky, L., Choi, K., Cheng, H., Wilken, J., Bedows, E., Sherman, S., and Cheng, P.-W.: Identification of disulfide bonds among the nine core 2 N-acetylglucosaminyltransferase-M cysteines conserved in mucin b6 N-acetylglucosaminyltransferase family. J. Biol. Chem. (under revision).

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Stuart Levin, Medical Student at University of North Carolina at Chapel Hill, won the first prize in medical student research presentation competition with the work done in my laboratory.
James Sherman, M.D., Professor and Chief of Pediatric Pulmonology, Univ. of Florida at Gainsville
Margaret Leigh, M.D., Professor and Chief of Pediatric Pulmonology, UNC-Chapel Hill.
Michael Konstan, M.D., Professor of Pediatric Pulmonology, Case Western Reserve University.
William Wingert, Ph.D., Clinical Chemist, Trenton, New Jersey.
Philip Ropp, Ph.D., Biochemist, Durham, North Carolina.
Cheng-Ming Li, Ph.D., Postdoctoral Research Associate, North Carolina State University.
Paul Beum, Ph.D., Postdoctoral Fellow, Eppley Institute, UNMC.
Katsunori Yanagihara, MD-PhD, Assistant Professor, Nagasaki University, Japan.
Masafumi Seki, MD-PhD, Assistant Professor, Nagasaki University, Japan.

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The two research areas in my laboratory are gene therapy and glycobiology. In gene therapy area, we are trying to understand the mechanism of gene delivery strategy we have developed and to perform animal studies to lay the foundation for human gene therapy trials. The nonviral gene delivery formulation includes a cationic liposome, a ligand, and a plasmid DNA. Formulation of the gene targeting vector can be optimized by varying these three components. Employing a vector composed of DIMRIE-cholesterol and mouse transferrin to deliver intratracheally a CMV-driven lacZ report gene to the airway cells of a mouse model, we showed high transfection efficiency and essentially no immune response to the vector. We are in the process of testing this gene delivery strategy to perform cystic fibrosis gene therapy in a cystic fibrosis ablation mouse model. Same vector has also been used to deliver wild-type p53 gene intratumorally in a mouse xenograft model of human prostate cancer PC-3 cells. Expression of p53 results in suppression of tumor growth and increase in survival through bystander effects, which we showed to be natural killer cell-dependent. We are currently trying to elucidate the mechanism of the bystander effects. These results have given us optimism that further development of this gene delivery strategy should help us produce formulation that is useful for treating patients with cystic fibrosis and cancers. In glycobiology area, we are studying the structure and function of glycoconjugates in health and disease. We try to manipulate the carbohydrate structures by modulating the expression of some key glycosyltransferases through over-expression and/or redirecting Golgi localization of these enzymes and then monitoring the effects on selectin binding and metastasis of cancer cells. Other projects include biochemical and X-ray crystal structural characterization of glycosyltransferases, regulation of the expression of glycosytransferase genes, and employment of lectin or carbohydrate for gene targeting.

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• SPECIALIZED LABORATORY/CLINICAL RESEARCH RESOURCES:

None