Lab Members

Maria Barbolina


Position:

Postdoctoral Fellow

Email:

[email protected]

Research Interests:

Microenvironmental and epigenetic regulation of ovarian cancer metastases.

Education and Postdoctoral Training:

  • 2003-present: PostDoctoral Fellow in Dr. Sharon Stack lab. Project: Microenvironmental and epigenetic regulation of ovarian cancer metastases.
  • 2002-2003: Instructor in the laboratory of Prof. Paul Gollnick, State University Of New York at Buffalo, Buffalo, NY. Project: Kinetic mechanism of RNA binding to the trp RNA-binding attenuation protein (TRAP).
  • 2001-2003: PostDoctoral Fellow in the laboratory of Prof. Paul Gollnick, State University Of New York at Buffalo, Buffalo, NY. Project: Kinetic mechanism of RNA binding to the trp RNA-binding attenuation protein (TRAP).
  • 2001: PhD in the laboratory of Dr. Tatyana V. Demidkina, Engelhardt institute of Molecular Biology of Russian Academy of Sciences, Moscow, Russia. Project: Mechanism of action of a vitamin-B6 dependent enzyme tyrosine phenol-lyase.
  • 1996: Engineer, Lomonosov Moscow State Academy of Fine Chemical Technology, Moscow, Russia

Awards:

Penny Severns Breast, Cervical and Ovarian Cancer Research Fund. 09/01/2005 – 06/30/2006. Project: Epigenetic Regulation of Ovarian Cancer Metastasis.

Publications:

  • 1. Barbolina M.V., Li X., Gollnick P. Bacillus subtilis TRAP binds to its RNA target by a 5′ to 3′ directional mechanism. J.Mol.Biol. 2005, 345(4):667-79.
  • 2. Demidkina T.V., Barbolina M.V., Faleev N.G., Sundararaju B., Gollnick P.D., Phillips R.S. Threonine-124 and phenylalanine-448 in Citrobacter freundii tyrosine phenol-lyase are necessary for activity with L-tyrosine. Biochem J. 2002, 363:745-52.
  • 3. Faleev N.G., Zhukov Y.N., Khurs E.N., Gogoleva O.I., Barbolina M.V., Bazhulina N.P., Belikov V.M., Demidkina T.V., Khomutov R.M. Interaction of tyrosine phenol-lyase with phosphoroorganic analogues of substrate amino acids. Eur J Biochem. 2000, 267(23):6897-902.
  • 4. Barbolina M.V., Phillips R.S., Gollnick P.D., Faleev N.G., Demidkina T.V. Citrobacter freundii tyrosine phenol-lyase: the role of asparagine 185 in modulating enzyme function through stabilization of a quinonoid intermediate. Protein Eng. 2000, 13(3):207-15.
  • 5. Sundararaju B., Antson A.A., Phillips R.S., Demidkina T.V., Barbolina M.V., Gollnick P., Dodson G.G., Wilson K.S. The crystal structure of Citrobacter freundii tyrosine phenol-lyase complexed with 3-(4′-hydroxyphenyl)propionic acid, together with site-directed mutagenesis and kinetic analysis, demonstrates that arginine 381 is required for substrate specificity. Biochemistry. 1997 May 27;36(21):6502-10.

Jaime Symowicz

Position:

Pre-Doctoral Student

Email:

[email protected]

Project:

Microenvironment regulation of proteinase expression and E-cadherin ectodomain generation in ovarian carcinoma

Education:

  • PhD in Cancer Biology, Integrated Graduate Program (IGP) in the Life Sciences, Northwestern University, 2001-
  • BS in Genetics, University of Wisconsin-Madison, 1995-1999.

Publications:

  • Woo, M.M.M., Salamanca, C.M., Symowicz, J., Stack, M.S., Leung, P.C.K., Huntsman, D., Gilks, C.B., Auersperg, N. SV40 T/t antigen promotes neoplastic progression of serous borderline ovarian tumors. Manuscript in Preparation.
  • Symowicz, J., Adley, B.P., Woo, M.M.M., Auersperg, N., Hudson, L.G., Stack, M.S. (2005) Cyclooxygenase-2 functions as a mediator of lysophosphatidic acid to promote aggressive behavior in ovarian carcinoma cells. Cancer Research 65:2234-2242.
  • Schroeder, M.D., Symowicz, J., Schuler, L.A. (2002) Prolactin modulates cell cycle regulators in mammary tumor epithelial cells. Molecular Endocrinology 16:45-57.

Supurna Ghosh

Position:

Research Assistant Professor

Email:

[email protected]

Education:

  • PhD in Biomedical Sciences, Creighton University, Omaha, NE (1992-1998).
  • MS in Human Physiology, University of Calcutta,India (1990)
  • BS in Human Biology (Physiology), University of Calcutta, India (1988)

Project:

  • Microenvironment regulation of proteinase
  • Integrin regulation of proteases in human oral keratinocytes with special focus on urokinase receptor-integrin interaction and consequent intracellular signaling events .
  • Effects of downregulating urokinase receptor on tumorigenesity of human oral cancer cells in orthotopic mouse model .
  • Immune reaction modulation by MT1MMP in oral tumor.
  • Contribution of cadherins (using Fc-ECad engineered proteins) in protease regulation in human malignant and premalignant oral keatinocytes.
  • Effects of laminin and laminin derived peptides in tumorigenicity of human oral cancer cells.

Selected Scientific Publications

  • Ghosh S., Johnson, J., Sen R., Mukhopadhyay S., Liu YY., Zhang F., Wei Wei ., Chapman HA and Stack MS. Functional Relevance of Urinary-type Plasminogen Activator Receptor (uPAR)-α3β1 Integrin Association in Proteinase Regulatory Pathways. J.Biol.Chem. 2006 Mar 1; [Epub ahead of print]
  • Ghosh S., Munshi HG, Sen R, Linz-McGillem LA, Goldman RD, Lorch J, Green KJ, Jones JCR and Stack MS (2002) Loss of Adhesion-Regulated Proteinase Production in Correlated with Invasive Activity in Oral Squamous Cell Carcinoma. Cancer 95 (12):2524-33.
  • Ghosh S *, Munshi HG *, Mukhopadhyay S., Wu YI, Sen R, Green KJ, and Stack MS. (2002) Proteinase Suppression by E-Cadherin Mediated Cell-Cell Attachment In Premalignant Oral Keratinocytes. J.Biol.Chem 277(41):38159-67.
  • *each author contributed equally to this work
  • Ghosh S, Wu Y, and Stack MS (2001) Ovarian Cancer-Associated Proteinases in Cancer Treatment and Research: Ovarian Cancer, Stack, M.S. and Fishman, D.A., Editors Kluwer Academic Publishers, pp.331-351.(Book Chapter)
  • Ghosh, S., Brown, R, Jones, JCR, Ellerbroek, S and Stack, MS (2000) Urinary-type plasminogen activator (uPA) expression and uPA receptor localization are regulated by α3β1 integrins in oral keratinocytes. J.Biol.Chem. 275(31):23869-76.
  • Ghosh S and Stack MS.(2000) Proteolytic modifications of laminin: functional consequences. Biology of the laminins Microsc. Res. Tech. 51(3) 238-46.
  • Ghosh S, Ellerbroek SE, Wu Y. and Stack MS (2000) Tumor cell-mediated proteolysis: Regulatory mechanisms and functional consequences. Fibrinolysis and Proteolysis 14(2/3): 87-97.
  • Bagchi M, Ghosh S, Bagchi D, Hassoun E, Stohs SJ (1995) Protective effects of lazaroid U74389F (16-desmethyl tirilazad) on endrin-induced lipid peroxidation and DNA damage in brain and liver and regional distribution of catalase activity in rat brain. Free Radic Biol Med 19(6):867-72.

Manuscripts under preparation:

  • Effects of downregulating urokinase receptor on tumorigenesity of oral cancer cells in orthotopic mouse model. Ghosh S, Koblinski JE., Johnson J, Liu YY, Kleinman HK and Stack MS.
  • The expression level of PTB is important for the transformation phenotypes. (Ghosh S in collaboration with Huang S and Wang C of Northwestern University).

Selected Conference Presentations:

  • uPAR-α3β1 Integrin Association Modulates Proteinase Regulatory Pathways. S. Ghosh, J. Johnson, R. Sen, S. Mukhopadhyay, Y. Liu, F. Zhang , Y. Wei, H. A. Chapman & M.S. Stack. 4th General Meeting of the International Proteolysis Society, Quebec City, Canada, 2005.
  • uPAR/α3β1 Association and Proteinase Regulation. S. Ghosh, J. Johnson, R. Sen, S. Mukhopadhyay, F. Zhang, H.A. Chapman and M.S. Stack. Xth International Workshop on Molecular and Cellular Biology of Plasminogen Activation,Potomac, MD, 2004.Selected for oral presentation
  • Loss of Adhesion-Regulated Proteinase Expression Accompanies Malignant Progression of the Oral Epithelium. S.Ghosh, S. Mukhopadhyay, R. Sen, HG Munshi, JCR Jones and MS Stack AACR Special Conference: Proteases, Extracellular Matrix and Cancer, Hilton Head Island, SC, 2002.(received special award).
  • Proteinase Suppression by E-Cadherin Mediated Cell-Cell Attachment in Premalignant Oral Keratinocyte. M.S. Stack, S. Ghosh, H.G. Munshi, Y.I.Wu, K.J. Green. VIIIth International Workshop on Molecular and Cellular Biology of Plasminogen Activation, USA 2001. (Selected for oral presentation).
  • A Multifunctional Interaction of the uPAR System with Oral Squamous Cell Carcinoma Integrins. S. Ghosh, H.G.Munshi, R.Sen and M.S. Stack. VIIIth International Workshop on Molecular and Cellular Biology of Plasminogen Activation, USA 2001.
  • Loss of adhesion-regulated proteinase production is correlated with invasive activity of oral squamous cell carcinoma. S. Ghosh, R. Sen, H.G. Munshi, J. Lorch, K.J. Green, M.S. Stack. Proc Amer Ass Cancer Res 2001; 42: A5087.
  • Loss of cell-cell adhesion upregulates proteinaexpression in premalignant oral keratinocytes. H.G.Munshi, S.Ghosh, Y.I.Wu, R.Sen, K.J. Green, M.S. Stack. Proc Amer Ass Cancer Res 2001; 42: A5081.
  • uPA regulation in ovarian cancer (OVCA). S.E. Ellerbroek, S.Ghosh, D.A. Fishman and M.S.Stack. 15th International Congress on fibrinolysis and proteolysis. Japan, 2000. (Selected for oral presentation).
  • A functional link between β1 integrin aggregation, uPA expression and uPAR Localization in premalignant oral epithelial cells. S.Ghosh, R.Brown, S. Rohde, J.C.R. Jones and M.S. Stack. Thrombolysis Gordon Conference, CA, 2000. (Selected for oral presentation).
  • Matrigel stimulates invasion and increases urokinase type plasminogen activator activity in human osteosarcoma cells. Midwest Student Research Forum, Omaha, NE 1996 (Third place, oral presentation Midwest Student Research Forum).
  • Urokinase levels and matrix degradation in invasive and non-invasive variants of an osteosarcoma cell line. S.Ghosh, L.Yan, M.H.McGuire, E.B. Patterson and J.A.Yee. The American Society for Cell Biology, International Meeting, 1996.
  • Matrigel increases urokinase-type plasminogen activator activity in human osteosarcoma cells. S. Ghosh, L.Yan, M.H.McGuire, E.B. Patterson and J.A.Yee. The American Society for Cell Biology, Annual Meeting, 1995.
  • Effects of TGF-β1 on uPA mRNA levels in OSPR and MG63 cells. S.Ghosh, L.Yan, M.H.McGuire, E.B. Patterson and J.A.Yee. Midwest Student Research Forum, 1994 (Third place, poster presentation Midwest Student Research Forum).
  • Expression of uPA, PAI- 1, and uPAR genes by human osteosarcoma cells. S. Ghosh, L.Yan, M.H.McGuire, E.B. Patterson and J.A.Yee. The American Society for CellBiology, Annual Meeting, 1994.
  • Protective Effects of Lazaroids on the Endrin-Induced Changes in Lipid Peroxidation DNA Damage and Regional Distribution of Catalase Activity in Rat Brain. M.Bagchi, S.Ghosh, D.Bagchi, E.Hassoun, and S.J.Stohs. Society of Toxicology, Annual Meeting, 1994.
  • uPAR, a potential biomarker for invasive osteosarcoma. Indian Science Congress, Calcutta, India, 1994 and All India Institute of Medical Sciences, New Delhi, India, 1994 (Invited Lecture).

Yueying Liu


Current Position:

Laboratory Manager


Project:

Everything!


Education:

Capital Institute of Medicine, Beijing. China. Major: Medicine


Publications:

  • Rao CN., Liu YY. Peavey CL., Woodley DT.(1995) Novel extracellular matrix-associated serine proteinase inhibitors from human skin fibroblasts. Archives of Biochemistry & Biophysics. 317(1):311-4.
  • Rao CN., Peavey CL., Liu YY., Lapiere JC., Woodley DT.(1995) Partial characterization of matrix-associated seine protease inhibitors from human skin cells. Journal of Investiggative Dermatology. 104(3):379-83.
  • Iwasaki T., Olivry T., Lapiere JC., Chan LS., Peavey C., Liu YY., Jones JC. Ihrke PJ. Woodley DT. (1995) Canine bullous pemphigoid (BP): identification of the 180-kd canine BP antigen by circulating antoantibodies. Veterinary Pathology. 32(4):387-93.
  • Rao CN. Ladin DA. Liu YY. Chilukuri K. Hou ZZ. Woodley DT. (1995) Alpha 1-antitrypsin is degraded and non-functional in chronic wounds but intact and functional in acute wounds: the inhibitor protects fibronectin from degradation by chronic wound fluid enzynes. Journal of Investigative Dermatology. 105(4):572-8.
  • Rao CN. Reddy P., Liu Y. O’Toole E., Reeder D. Foster DC., Kisiel W. Woodley DT. (1996) Extracellular matrix-associated serine protease inhibitors ( Mr 33,000, 31,000, and 27,000) are sigle-gene products with differential glycosylation: cDNA cloning of the 33-kDa inhibitor reveals its identity to tissue factor pathway inhibitor-2. Archives of Biochemistry & Biophysics. 335(1): 82-92.
  • Rao, C.N., Cook, B., Liu, Y., Chilukuri, K., Stack, M.S., Foster, D.C., Kisiel, W., and Woodley, D.T. (1998) HT-1080 Fibrosarcoma Cell Matrix Degradation and Invasion Are Inhibited by the Matrix-Associated Serine Protease Inhibitor TFPI-2/33 kDa MSPI. Int. J. Cancer 76:749-756.
  • Liu, Y, Stack, MS, Lakka, SS, Khan, AJ, Woodley, DT, Rao, JS, and Rao, CN (1999) Matrix Localization of TFPI-2/MSPI Involves Arginine-Mediated Ionic Interactions with Heparin and Dermatan Sulfate: Heparin Accelerates the Activity of TFPI-2/MSPI Towards Plasmin. Archives Biochem. Biophys. 370:112-118.
  • Rao, C.N., Reddy, P., Reeder, D.J., Liu, Y., Stack, S., Kisiel, W., and Woodley, D.T. (2000) Prokaryotic Expression, Purification, and Reconstitution of Biological Activities (Antiprotease, Antitumor, and Heparin-Binding) for Tissue Factor Pathway Inhibitor-2. Biochem. Biophys. Res. Commun. 276: 1286-1294.
  • Fishman, D., Liu, Y. Ellerbroek, S.M., Stack, S., (2001) Lysophosphatidic Acid Promotes Matrix Metalloproteinase (MMP) Activation and MMP-dependent Invasion in Ovarian Cancer Cells. Cancer Resarch. 61: 3194-99.
  • Ning, Y., Zeineldin, R., Liu, Y., Stack, M.S., and Hudson, L.G. (2005) Downregulation of Integrin a2 Surface Expression by Mutant Epidermal Growth Factor Receptor (EGFRvIII) Induces Aberrant Cell Spreading and Focal Adhesion Formation. Cancer Research 65:9280-6.
  • Ghosh, S., Johnson J.J., Sen, R., Mukhopadhyay S., Liu, Y., Zhang, F., Wei, Y., Chapman, H.A., and Stack, M.S. (2006) Functional Relevance of Urinary-type Plasminogen Activator Receptor (uPAR)-alpha3beta1 Integrin Association in Proteinase Regulatory Pathways. J. Biol. Chem., in press.

Kara Gleason

Position:

Pre-Doctoral Student

Email:

[email protected]

Education:

B.S. University of Minnesota


Current Project:

Role of microenvironmental regulators on ovarian cancer metastasis to the peritoneum

Mike Rabin

Position:

Pre-Doctoral Student

Email:

[email protected]

Project:

The urokinase activator plasminogen receptor (uPAR) exists in lipid rafts on the mammalian epithelial cell surface and its expression is elevated in oral squamous cell carcionma. Since the receptor lacks both intracellular and transmembrane domains, it acts as a lateral ligand to overcome the structural limitations. My project is aimed at charatcerizing proteins capable of interacting with uPAR and modulating integrin function to promote oral cancer metastasis.

Education:

B.S. Cell & Molecular Biology & Genetics, 2002

Publications:

Rajan S, Plant LD, Rabin ML, Butler MH, Goldstein SA: Sumoylation silences the plasma membrane leak K+ channel K2P1. Cell 121; 37-47, 2005.

Natalie M. Moss

Position:

Pre-Doctoral Student

Current Position:

Pre-Doctoral Student

Project:

Regulation of Membrane Type 1 Matrix Metalloproteinase in Ovarian Cancer

Education:

Mercer University, Macon, GA, BSc. in Biology/Chemistry, B.A. in English Literature (2002)

Publications:

  • Moss, N., Foster, S.A., and Chipley, J. (2001) Analysis of chlorophyll levels in transgenic and mutant proliferous lines of Arabidposis thaliana in response to varying amounts of the synthetic cytokinin kinetin. 44th Annual Meeting of Beta Beta Beta, Southeastern Region, New Orleans, LA
  • Moss, N. and Hensel, L.L. (2000) Analysis of Arabidopsis thaliana cytokinin levels in transgenic and mutant proliferous lines. Georgia Journal of Science 58:45.
  • Moorman, D., Longerhan, L., Moss, N. and Hensel, L.L. (1999) Analysis of Arabidopsis thaliana transgenic lines crossed with proliferous lines. Georgia Journal of Science 57:34.

Jeff Johnson

Position:

Research Technologist II

Email:

[email protected]

Current Projects:

Characterization of murine tumors initiated from cells with normal, depressed, and elevated expression of uPAR. Effect of uPAR as a lateral integrin ligand. Characterization of murine tumors initiated from cells with normal and elevated expression of MT1-MMP.

Education:

B.S., University of Chicago, Chicago, IL (Dec., 1982).

Publications:

  • Supurna Ghosh, Jeff J. Johnson, Ratna Sen, Shubhendu Mukhopadhyay, Feng Zheng, Ying Wei, Harold A. Chapman and M. Sharon Stack. (2006 March 1) Functional Relevance of Urinary-type Plasminogen Activator (uPAR)-a3B1 Integrin Association in Proteinase Regulatory Pathways.
  • JBC – In Press. Kenneth G. Geles, Jeffrey J. Johnson, Sena Jong, and Stephen A. Adam. (2002 Sept). A Role for Caenorhabditis elegans Importin IMA-2 in Germ Line and Embryonic Mitosis. Molecular Biology of the Cell 13: 3138-3147.
  • Graham PL, Johnson JJ, Wang S, Sibley MH, Gupta MC, Kramer JM. (1997 June 2). Type IV Collagen is detectable in most, but not all, basement membranes of Caenorhabditis elegans and assembles on tissues that do not express it. J Cell Biol 137(5): 1171-83.
  • Kramer JM, Johnson JJ. (1993 Dec). Analysis of mutations in the sqt-1 and rol-6 collagen genes of Caenorhabditis elegans. Genetics 135(4): 1035-1045.
  • Sibley MH, Johnson JJ, Mello CC, Kramer JM. (1993 Oct). Genetic identification, sequence, and alternative splicing of the Caenorhabditis elegans alpha 2(IV) collagen gene. J Cell Biol 123(1): 255-64.
  • Guo XD, Johnson JJ, Kramer JM. (1991 Feb). Embryonic lethality caused by mutations in basement membrane collagen of C. elegans. 349(6311): 707-9.
  • Kramer JM, French RP, Park EC, Johnson JJ. (1990 May). The Caenorhabditis elegans rol-6 gene, which interacts with the sqt-1 gene to determine organismal morphology, encodes a collagen. 10(5): 2081-9.
  • Kramer JM, Johnson JJ, Edgar RS, Basch C, Roberts S. (1988 Nov 18). The sqt-1 gene of C elegans encodes a collagen critical for organismal morphogenesis. 55(4):.555-65.