Robert W. Mason, Ph.D.

Adjunct Associate Professor
Head, Clinical Biochemistry Laboratory and Director, Cell Science Core, A.I. duPont Hospital for Children
Affiliated Faculty, Delaware Biotechnology Institute

Contact

Mason

A.I. duPont Hospital for Children
Department of Research
Suite 3B, Room 338
P.O. Box 269
Wilmington, DE 19899

Phone: (302) 651-6885
Fax: (302) 651-6767
E-mail: rmason@nemours.org

Education

B.Sc. (Hons): Bath University, United Kingdom
Ph.D.: Leeds University, United Kingdom
Postdoctoral: Food Research Institute, United Kingdom
Postdoctoral: SRL, United Kingdom

Research Interests

The focus of the Clinical Biochemistry Laboratory headed by Robert W. Mason, Ph.D. is on defining biological roles of proteases in growth and development of both normal and cancerous tissues. Two major projects are being pursued, one to examine roles that proteases play in cancer and the other to determine the roles of proteases in placental function.

The cancer project currently focuses on neuroblastoma, a cancer of childhood. We have discovered that inhibition of two proteases, cathepsins B and L, induces apoptosis of neuroblastoma cells such that cells die within 3 days of treatment. This is unique to neuroblastoma; other cells grow less aggressively in the presence of the inhibitors but do not die. Inhibition of only one of these enzymes fails to kill neuroblastoma cells, indicating that the enzymes have overlapping functions in tumor cell proliferation and survival. We are developing animal models of neuroblastoma to determine the efficacy protease inhibition to controlling cancer progression. This preclinical study is complemented by a proteomic study to identify the mechanism by which protease inhibition leads to apoptosis. Our working hypothesis is that protease inhibition increases levels of receptor/ligand complexes that induce terminal differentiation and subsequent apoptosis of neuroblastoma cells. The long-term goal of this research is to identify new therapies to treat pediatric cancers.

We are continuing work on a family of proteolytic enzymes that we found to be exclusively expressed in rodent placenta. Dysregulation of the activity human orthologs these proteases can lead to preeclampsia or birth defects. The human enzymes appear to have multiple functions in many tissues, but gene duplications in rodents have led to the evolution of more specific proteases. We have developed proteomic protocols to identify placental substrate proteins for these enzymes with the goal of identifying proteolytic pathways in placenta that are critical to human embryonic development. In this project we use combinatorial libraries of substrates and inhibitors to determine the specificity of recombinant enzymes, examine the regulation of expression of the enzymes in cells and tissues, and develop cellular techniques that regulate expression of the proteases to define their function. The long-term goal of this project is to understand how placental proteases contribute to normal embryonic growth and development.

The overall philosophy of the lab is to take rigorous biochemical approaches into cellular systems to identify important functions of individual proteases. The laboratory houses the Cell Biology Core facility that provides resources and expertise to assist Nemours scientists to perform rigorous cell biological and proteomic analyses. Facility staff work closely with Nemours scientists to design and perform state-of-the-art 2D differential gel electrophoresis (DIGE) to analyze alterations in protein expression followed by identification of individual proteins by mass spec analysis of tryptic fragments.

Current Projects

• NIH, Proteomic Analysis of Apoptotic Mechanisms in Cancer.
• Nemours Research, Biological Roles of Placental Proteases.
• Nemours Research, Role of Proteases in Neuroblastoma.

Research Group

• Bruce Korant, Ph.D. - Research Fellow
• Anjan Matlapudi, Ph.D. - Research Associate
• Mohamed Hassanein, M.S. - Graduate Student
• Lisa Glazewski, M.S. - Research Assistant
• Guizhen Lu, B.S. - Research Assistant
• Summi Rai, B.S. - Graduate Student

Clinical Biochemistry Laboratory Group

Selected Publications

Bulynko, Y.A., Hsing, L.C., Mason, R.W., Tremethick, D. and Grigoryev, S.A. (2006) Cathepsin L stabilizes histone modification landscape on Y chromosome and pericentromeric heterochromatin. Mol. Cell. Biol. 26, 4172-4184.

Puzer, L., Barros, N.T., Oliveira, V., Juliano, M.A., Lu, G., Hassanein, M., Juliano, L., Mason, R.W., and Carmona, A.K. (2005) Defining the substrate specificity of mouse cathepsin P. Arch. Biochem. Biophys. 435:190-6.

Mason, R.W., Hopp, L, and Lloyd, J.B. (2004) Nitric oxide does not mediate promotion of cellular potassium release by phenolphthalein in COS-7 cells. Clin Exp Pharmacol Physiol. 31, 271-3.

Mason, R.W., Bergman, C.A., Lu, G., Frenck Holbrook, J., and Sol-Church, K. (2004) Expression and characterization of Cathepsin P. Biochem. J. 378, 657-63.

Mason, R.W. Simpson-Small, T. and Hopp, L. (2003) Regulation of 86Rb+ ion transport across polarized human colonocytes by bis-phenolic compounds Clin. Exp. Pharm. Pharmacol. 30, 623-626.

Sol-Church, K., Picerno, G.N., Stabley, D.L., Frenck, J., Xing, S., Bertenshaw, G. and Mason R. W. (2002) Evolution of Placentally Expressed Cathepsins. Biochem. Biophys. Res. Commun. 293, 23-29.

Sol-Church, K, Frenck, J., and Mason, R.W. (2000) Cathepsin Q, a Novel Lysosomal Cysteine Protease Highly Expressed in Placenta. Biochem. Biophys. Res Commun. 267, 791-795.

Sol-Church, K. Frenck, J. and Mason, R.W. (2000) Mouse Cathepsin M, a Placental-Specific Lysosomal Cysteine Protease Related to Cathepsins L and P. Biochim. Biophys. Acta. 1491, 289-294.

Sol-Church, K., Frenck, J., Bertenshaw, G., and Mason, R.W. (2000) Characterization of mouse cathepsin R, a new member of a family of placentally expressed cysteine proteases (PECs). Biochim. Biophys. Acta. 1492, 488-492.

Sol-Church, K, Shipley, J., Beckman, D.A. and Mason, R.W. (1999) Expression of cysteine proteases in extraembryonic tissues during mouse embryogenesis, Arch. Biochem. Biophys. 372, 375-381.

Sol-Church, K, Frenck, J., Troeber, D. and Mason, R.W. (1999) Cathepsin P, a novel protease in mouse placenta. Biochem. J., 343, 307-309.

Xing, R., and Mason, R.W. (1998) Design of a transferrin-proteinase inhibitor conjugate to probe for active cysteine proteinases in endosomes. Biochem. J. 336, 667-673.

Xing, R., Addington, A.K., and Mason, R.W. (1998) Quantitation of cathepsins B and L in cells. Biochem. J., 332, 499-505.

Hall, A., Ekiel, I., Mason, R.W., Kasprzykowski, F., Grubb, A., and Abrahamson, M. (1998) Structural basis for different inhibitory specificities of human cystatins C and D. Biochemistry, 37, 4071-4079.

Mason, R.W., Sol-Church, K. and Abrahamson, M. (1998) Amino acid substitutions in the N-terminal segment of cystatin C create selective protein inhibitors of lysosomal cysteine proteinases, Biochem. J. 330, 833-838.

Xing, R., Wu, F., and Mason, R.W. (1998) Control of breast tumor cell growth using a targeted cysteine protease inhibitor, Cancer Res., 58, 904-909.