Experimental Pathology

Gary A. Clawson, M.D., Ph.D. Professor of Pathology, and Biochemistry and Molecular Biology Director of the Gittlen Cancer Research Foundation
	Office:  Room C7768J Telephone: (717) 531-5632 Email: gac4@psu.edu     Areas of interest: carcinogenesis, liver

There are a number of research projects currently being conducted in Dr. Gary Clawson’s laboratories, with the major area of interest focused upon early changes in carcinogenesis. Carcinogens induce early permanent changes in compartmentation of RNA, along with a marked nuclear enlargement with associated changes in the nuclear scaffold (NS), a proteinaceous structure that provides support for nuclear form and function. Investigations currently focus upon two areas. One is the nature of the RNA transcripts showing altered compartmentation. Another focuses upon the nuclear proteinase which appears to be important in transformation. Experimental techniques include reverse transcription/polymerase chain reaction amplification and analysis of expressed mRNAs, in situ immunohistochemistry and hybridizations, laser capture microdissection, real-time PCR, gene array expression analyses, cloning and sequencing, subcellular fractionation procedures, isolation of identified polypeptides (including the NS proteinase) for amino acid microsequencing, and effects of proteinase inhibitors, antisense oligonucleotides and triple ribozyme constructs on cell growth and transformation. 

A major emphasis is currently focused on development of novel therapeutic ribozyme reagents for treatment of human papillomavirus and hepatitis B-virus related diseases, with the expectation that clinical trials will commence in the near future.

Other collaborative projects examine mechanisms by which estrogens may act as an initiator via redox cycling, and development of in vivo models for study and treatment of prostate and breast cancers.

Education and Certification:

M.D., University of Miami, 1983

Ph.D., Michigan State University, 1976

Postdoctoral Training, University of California, 1977-1981

Publications (selected):

• Norris J, Hoel B, Voeks D, Maggonta F, Dahm M, Pan W, Clawson G.  Design and testing of ribozymes for cancer gene therapy.  Adv Exp Med Biol 465:293-301, 2000.

• Pan W, Devlin HF, Kelley C, Isom HC, Clawson GA.  A selection system for identifying accessible sites in Target RNAs.  RNA 7:610-621, 2001.

• Thiboutot D, Sivarajah A, Gilliland K, Cong Z, Clawson G.  The Melanocortin 5 Receptor is expressed in human sebaceous glands and rat preputial cells.  J Invest Derm 115:614-619, 2002.

• Zhang M-Y, Huang N-N, Clawson GA, Osmani SA, Pan W, Xin P, Razzaque MS, Miller BA.  Involvement of the fungal nuclear migration gene nudC human homolog in cell proliferation and mitotic spindle formation.  Exp Cell Res  273:73-84, 2002.

• Clawson G, Pan W.  A novel strategy for the identification of ribozyme accessible sites in target RNAs, In Methods in Molecular Biology (Mouldy S, Ed), Catalytic Nucleic Acid Protocols.  Ribozyme Protocols, 2^nd edition, Catalytic Nucleic Acid Enzymes, Humana Press, NJ, In press, 2003.

• Pan W, Xin P, Bui V, Clawson G.  Rapid identification of efficient target cleavage sites using a hammerhead ribozyme library in an iterative manner.  Molecular Therapy 7(1):129-139, 2003.

• Thiboutot D, Jabara S, McAllister JM, Sivarajah A, Gilliland K, Cong Z, Clawson G.  Human skin is a steroidogenic tissue:  Steroidogenic enzymes and cofactors are expressed in epidermis, normal sebocytes, and an immortalized sebocyte cell line (SEB-1).  J Invest Derm 120:905-914, 2003.

• Gestl S, Clawson G.  Effects of cytoplasmic expression of a non-coding, repetitive B2 RNA transcript.  Cancer Res (under revision).

• Clawson GA, Miranda GQ, Sivarajah A, Xin P, Pan W, Thiboutot D, Christensen ND.  Inhibition of papilloma progression using antisense oligonucleotides targeted to HPV 11 E6/E7 RNA.  Gene Therapy, In press, 2004.

• Pan W-H, Xin P, Morrey JD, Clawson GA.  A self-processing ribozyme cassette:  Utility against human papillomavirus 11 E6/E7 mRNA and hepatitis B virus.  Molecular Therapy 9(4):596-606, 2004.

• Pan W, Clawson GA.  Identification of efficient cleavage sites in long-target RNAs.  In Methods in Molecular Biology, Vol. 252: Ribozymes and siRNA Protocols, 2nd edition, Humana Press: 125-144, 2004.

• Erin N, Clawson GA.  Parameters affecting substance P measurement in heart, lung, and skin tissue.  BioTechniques, In press, 2004.

• Drubin DA, Clawson GA.  Spontaneous transformation of an immortalized hepatocyte cell line:  Potential role of a nuclear protease.  Cancer Letters, In press, 2004.

• Erin N, Boyer PJ, Bonneau RH, Clawson GA.  Capsaicin-mediated denervation of sensory neurons promotes mammary tumor metastasis to lung and heart.  AntiCancer Res, In press, 2004.

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