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229Robert W. Mason, Ph.D. <p>Adjunct Associate Professor</p> <p>Head, Clinical Biochemistry Laboratory and Director, Cell Science Core, A.I. duPont Hospital for Children</p> <p>Affiliated Faculty, Delaware Biotechnology Institute </p>(302) 651-6885 (302) 651-6767 rmason@nemours.org A.I. duPont Hospital for Children A.I. duPont Hospital for Children Department of Research Suite 3B, Room 338 P.O. Box 269 Wilmington, DE 19899 <ul class="list-no-indent"> <li><strong>B.Sc. (Hons)</strong> - Bath University (United Kingdom) <li><strong>Ph.D.</strong> - Leeds University (United Kingdom) <li><strong>Postdoctoral</strong> - Food Research Institute (United Kingdom) <li><strong>Postdoctoral</strong> - SRL (United Kingdom) </li></ul><p>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.</p> <p>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.</p> <p>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.</p> <p>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.</p><ul class="list-no-indent"> <li>NIH, Proteomic Analysis of Apoptotic Mechanisms in Cancer. <li>Nemours Research, Biological Roles of Placental Proteases. <li>Nemours Research, Role of Proteases in Neuroblastoma. </li></ul><ul class="list-no-indent"> <li><strong>Bruce Korant, Ph.D.</strong> - Research Fellow <li><strong>Anjan Matlapudi, Ph.D.</strong> - Research Associate <li><strong>Mohamed Hassanein, M.S.</strong> - Graduate Student <li><strong>Lisa Glazewski, M.S.</strong> - Research Assistant <li><strong>Guizhen Lu, B.S.</strong> - Research Assistant <li><strong>Summi Rai, B.S.</strong> - Graduate Student </li></ul><ul class="list-no-indent"> <li>Mason RW. <a href="http://dx.doi.org/10.1016/j.placenta.2008.02.006">Emerging functions of placental cathepsins.</a> Placenta. 2008;29(5):385–390. <li>Sireesha GV, Mason RW, Hassanein M, et al. <a href="http://dx.doi.org/10.1093/molehr/gan026">Role of cathepsins in blastocyst hatching in the golden hamster.</a> Mol Hum Reprod. 2008;14(6):337–346. <li>Hassanein M, Korant BD, Lu G, Mason RW. <a href="http://dx.doi.org/10.1016/j.placenta.2006.11.007">Expression of cathepsin P mRNA, protein and activity in the rat choriocarcinoma cell line, Rcho-1, during giant cell transformation.</a> Placenta. 2007;28(8-9):912–919. <li>Hassanein M, Xue F, Seto CT, Mason RW. <a href="http://dx.doi.org/10.1016/j.abb.2007.04.019">Development of a specific inhibitor for the placental protease, cathepsin P.</a> Arch Biochem Biophys. 2007;464(2):288–294. <li>Bulynko YA, Hsing LC, Mason RW, Tremethick DJ, Grigoryev SA. <a href="http://dx.doi.org/10.1128/MCB.00135-06">Cathepsin L stabilizes the histone modification landscape on the Y chromosome and pericentromeric heterochromatin.</a> Mol Cell Biol. 2006;26(11):4172–4184. <li>Puzer L, Barros NMT, Oliveira V, et al. <a href="http://dx.doi.org/10.1016/j.abb.2004.12.007">Defining the substrate specificity of mouse cathepsin P.</a> Arch Biochem Biophys. 2005;435(1):190–196. <li>Mason RW, Bergman CA, Lu G, Frenck Holbrook J, Sol-Church K. <a href="http://dx.doi.org/10.1042/BJ20031548">Expression and characterization of cathepsin P.</a> Biochem J. 2004;378(Pt 2):657–663. <li>Mason RW, Hopp L, Lloyd JB. <a href="http://dx.doi.org/10.1111/j.1440-1681.2004.03989.x">Nitric oxide does not mediate promotion of cellular potassium release by phenolphthalein in COS-7 cells.</a> Clin Exp Pharmacol Physiol. 2004;31(4):271–273. <li>Mason RW, Simpson-Small T, Hopp L. <a href="http://www.ncbi.nlm.nih.gov/pubmed/12940878">Regulation of 86Rb+ ion transport across polarized human colonocytes by bis-phenolic compounds.</a> Clin Exp Pharmacol Physiol. 2003;30(9):623–626. <li>Sol-Church K, Picerno GN, Stabley DL, et al. <a href="http://dx.doi.org/10.1016/S0006-291X%2802%2900167-5">Evolution of placentally expressed cathepsins.</a> Biochem Biophys Res Commun. 2002;293(1):23–29. <li>Sol-Church K, Frenck J, Bertenshaw G, Mason RW. <a href="http://www.ncbi.nlm.nih.gov/pubmed/11004518">Characterization of mouse cathepsin R, a new member of a family of placentally expressed cysteine proteases.</a> Biochim Biophys Acta. 2000;1492(2-3):488–492. <li>Sol-Church K, Frenck J, Mason RW. <a href="http://dx.doi.org/10.1006/bbrc.1999.2051">Cathepsin Q, a novel lysosomal cysteine protease highly expressed in placenta.</a> Biochem Biophys Res Commun. 2000;267(3):791–795. <li>Sol-Church K, Frenck J, Mason RW. <a href="http://www.ncbi.nlm.nih.gov/pubmed/10760593">Mouse cathepsin M, a placenta-specific lysosomal cysteine protease related to cathepsins L and P.</a> Biochim Biophys Acta. 2000;1491(1-3):289–294. <li>Sol-Church K, Frenck J, Troeber D, Mason RW. <a href="http://www.ncbi.nlm.nih.gov/pubmed/10510293">Cathepsin P, a novel protease in mouse placenta.</a> Biochem J. 1999;343 Pt 2:307–309. <li>Sol-Church K, Shipley J, Beckman DA, Mason RW. <a href="http://dx.doi.org/10.1006/abbi.1999.1520">Expression of cysteine proteases in extraembryonic tissues during mouse embryogenesis.</a> Arch Biochem Biophys. 1999;372(2):375–381. <li>Hall A, Ekiel I, Mason RW, Kasprzykowski F, Grubb A, Abrahamson M. <a href="http://dx.doi.org/10.1021/bi971197j">Structural basis for different inhibitory specificities of human cystatins C and D.</a> Biochemistry. 1998;37(12):4071–4079. <li>Mason RW, Sol-Church K, Abrahamson M. <a href="http://www.ncbi.nlm.nih.gov/pubmed/9480898">Amino acid substitutions in the N-terminal segment of cystatin C create selective protein inhibitors of lysosomal cysteine proteinases.</a> Biochem J. 1998;330 ( Pt 2):833–838. <li>Xing R, Mason RW. <a href="http://www.ncbi.nlm.nih.gov/pubmed/9841879">Design of a transferrin-proteinase inhibitor conjugate to probe for active cysteine proteinases in endosomes.</a> Biochem J. 1998;336 ( Pt 3):667–673. <li>Xing R, Addington AK, Mason RW. <a href="http://www.ncbi.nlm.nih.gov/pubmed/9601080">Quantification of cathepsins B and L in cells.</a> Biochem J. 1998;332 ( Pt 2):499–505. <li>Xing R, Wu F, Mason RW. <a href="http://www.ncbi.nlm.nih.gov/pubmed/9500448">Control of breast tumor cell growth using a targeted cysteine protease inhibitor.</a> Cancer Res. 1998;58(5):904–909. </li></ul>

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  • Department of Biological Sciences
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