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George P. Tuszynski, PhDGeorge P. Tuszynski, PhD

 

Professor, Neuroscience

Location: Room 754 MERB

Telephone:  215-707-6451

Fax:  215-707-4888

Email: gpt@temple.edu

 

Department of Neuroscience

 

Educational Background:

 

Rutgers University, Camden, NJ

1964-1968, B.A., Chemistry

 

University of Pennsylvania, Philadelphia, PA

1968-1973, Ph.D., Biochemistry

 

University of Pennsylvania, Philadelphia, PA

1973-1975, Postdoctoral Fellow, Cancer Biology

 

Wistar Institute, Philadelphia, PA

1975-1978, Postdoctoral Fellow, Cancer Biology

 

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Research Interests:

 

The focus of our laboratory is the development of novel experimental therapeutics for the treatment and early detection of glioma. Our laboratory has focused its efforts on targeting angiocidin, a small tumor associated protein, for the treatment of brain cancer. Angiocidin is 41 kilodalton protein that can function as a cell signaling molecule inducing cancer cells to secrete a cocktail of cytokines and chemokines that inhibit tumor progression and promote cell differentiation. In glioma , angiocidin up-regulates a variety of cytokines such as IL-6 and GMCSF that act in an autocrine manner promoting cell differentiation, and inhibition of invasion. We have identified angiocidin peptide domains and cell receptors that mediate these anti-tumor activities. Studies are underway to investigate the mechanism of these and anti-tumor activities and preclinical patient studies are being conducted to develop angiocidin and its active site peptides for the treatment of brain cancer.

 

In a collaboration with Dr. Marcinkiewicz in the Biology Department we are also targeting cell surface integrins as targets for the treatment of brain cancer. We have identified the integrins alpha2beta1 and alpha9beta1 as playing important roles in glioma cell progression. We are developing antagonists of these integrins that include a number of disintegrins, potent specific peptides that bind these integrins and inhibit their adhesive activity. We are also investigating specific domains of matrix proteins such as thrombospondin-1 that could be used to target angiogenesis, an important component of glioma progression.

 

Additionally, we are also investigating new serum biomarkers in brain malignancies. These markers were discovered in patient sera using a novel electrophoretic separation technology developed by Dr. Frank Chang, Professor of Biology in the College of Science and Technology at Temple University. We have discovered more than 10 new markers. One of these markers, G-protein Coupled Receptor-Associated Sorting Protein 1 (GASP-1), is highly expressed in glioma. We are currently investigating the mechanism of GASP-1 mediated cancer progression, developing GASP-1 antagonists as novel glioma therapeutics, and evaluating the potential of GASP-1 as an early serum marker for brain cancer.

 

Finally, in a collaboration with Fox Chase and the Lankenau Medical Research Center, we are evaluating the clinical significance of angiocidin auto-antibodies in cancer sera. We have detected high titer antibody levels in the sera of brain cancer patients. Studies are underway to evaluate the role of these antibodies in tumor progression and develop human hybridoma antibody secreting clones using patient blood. The goal of these studies is to develop human angiocidin antibodies for the treatment of glioma.

 

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PUBMED PUBLICATIONS :


Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)

24036285. Tuszynski GP, Rothman VL, Angiocidin induces differentiation of acute myeloid leukemia cells. Exp Mol Pathol 95:3(249-54)2013 Dec

22483848. Zheng X, Chang F, Zhang X, Rothman VL, Tuszynski GP, G-protein coupled receptor-associated sorting protein 1 (GASP-1), a ubiquitous tumor marker. Exp Mol Pathol 93:1(111-5)2012 Aug

21791203. Tuszynski GP, Rothman VL, Zheng X, Gutu M, Zhang X, Chang F, G-protein coupled receptor-associated sorting protein 1 (GASP-1), a potential biomarker in breast cancer. Exp Mol Pathol 91:2(608-13)2011 Oct

21241690. Godek J, Sargiannidou I, Patel S, Hurd L, Rothman VL, Tuszynski GP, Angiocidin inhibits breast cancer proliferation through activation of epidermal growth factor receptor and nuclear factor kappa (NF-?B). Exp Mol Pathol 90:3(244-51)2011 Jun

21193465. Willis AI, Sadowitz B, Fuse S, Maier KG, Lee TS, Wang XJ, Tuszynski GP, Sumpio BE, Gahtan V, Thrombospondin 1, fibronectin, and vitronectin are differentially dependent upon RAS, ERK1/2, and p38 for induction of vascular smooth muscle cell chemotaxis. Vasc Endovascular Surg 45:1(55-62)2011 Jan

20631908. John AS, Rothman VL, Tuszynski GP, Thrombospondin-1 (TSP-1) Stimulates Expression of Integrin alpha6 in Human Breast Carcinoma Cells: A Downstream Modulator of TSP-1-Induced Cellular Adhesion. J Oncol 2010:(645376)2010

19931242. L'Heureux DZ, Rothman VL, Tuszynski GP, The interaction of angiocidin with tissue transglutaminase. Exp Mol Pathol 88:1(15-25)2010 Feb

19747478. John AS, Hu X, Rothman VL, Tuszynski GP, Thrombospondin-1 (TSP-1) up-regulates tissue inhibitor of metalloproteinase-1 (TIMP-1) production in human tumor cells: exploring the functional significance in tumor cell invasion. Exp Mol Pathol 87:3(184-8)2009 Dec

19519434. Gaurnier-Hausser A, Tuszynski GP, The immunomodulatory role of angiocidin, a novel angiogenesis inhibitor. Curr Pharm Des 15:17(1937-48)2009

19502781. Staniszewska I, Walsh EM, Rothman VL, Gaathon A, Tuszynski GP, Calvete JJ, Lazarovici P, Marcinkiewicz C, Effect of VP12 and viperistatin on inhibition of collagen-receptor-dependent melanoma metastasis. Cancer Biol Ther 8:15(1507-16)2009 Aug

19074980. Brown MC, Staniszewska I, Lazarovici P, Tuszynski GP, Del Valle L, Marcinkiewicz C, Regulatory effect of nerve growth factor in alpha9beta1 integrin-dependent progression of glioblastoma. Neuro Oncol 10:6(968-80)2008 Dec

18712720. Brown MC, Staniszewska I, Del Valle L, Tuszynski GP, Marcinkiewicz C, Angiostatic activity of obtustatin as alpha1beta1 integrin inhibitor in experimental melanoma growth. Int J Cancer 123:9(2195-203)2008 Nov 1

18632645. Gaurnier-Hausser A, Rothman VL, Dimitrov S, Tuszynski GP, The novel angiogenic inhibitor, angiocidin, induces differentiation of monocytes to macrophages. Cancer Res 68:14(5905-14)2008 Jul 15

18230652. Staniszewska I, Sariyer IK, Lecht S, Brown MC, Walsh EM, Tuszynski GP, Safak M, Lazarovici P, Marcinkiewicz C, Integrin alpha9 beta1 is a receptor for nerve growth factor and other neurotrophins. J Cell Sci 121:Pt 4(504-13)2008 Feb 15

17719063. Liebig C, Agarwal N, Ayala GE, Verstovsek G, Tuszynski GP, Albo D, Angiocidin inhibitory peptides decrease tumor burden in a murine colon cancer model. J Surg Res 142:2(320-6)2007 Oct

17413041. Staniszewska I, Zaveri S, Del Valle L, Oliva I, Rothman VL, Croul SE, Roberts DD, Mosher DF, Tuszynski GP, Marcinkiewicz C, Interaction of alpha9beta1 integrin with thrombospondin-1 promotes angiogenesis. Circ Res 100:9(1308-16)2007 May 11

17188426. Sabherwal Y, Rothman VL, Poon RT, Tuszynski GP, Clinical significance of serum angiocidin levels in hepatocellular carcinoma. Cancer Lett 251:1(28-35)2007 Jun 18

16762342. Sabherwal Y, Rothman VL, Dimitrov S, L'Heureux DZ, Marcinkiewicz C, Sharma M, Tuszynski GP, Integrin alpha2beta1 mediates the anti-angiogenic and anti-tumor activities of angiocidin, a novel tumor-associated protein. Exp Cell Res 312:13(2443-53)2006 Aug 1

16643892. Sharma MR, Koltowski L, Ownbey RT, Tuszynski GP, Sharma MC, Angiogenesis-associated protein annexin II in breast cancer: selective expression in invasive breast cancer and contribution to tumor invasion and progression. Exp Mol Pathol 81:2(146-56)2006 Oct

16643891. Sharma MR, Rothman V, Tuszynski GP, Sharma MC, Antibody-directed targeting of angiostatin's receptor annexin II inhibits Lewis Lung Carcinoma tumor growth via blocking of plasminogen activation: possible biochemical mechanism of angiostatin's action. Exp Mol Pathol 81:2(136-45)2006 Oct

16222312. Dimitrov S, Sabherwal Y, Raymond DD, L'Heureux DZ, Lu Q, Tuszynski GP, Endothelial apoptotic activity of angiocidin is dependent on its polyubiquitin binding activity. Br J Cancer 93:6(662-9)2005 Sep 19

15217952. Poon RT, Chung KK, Cheung ST, Lau CP, Tong SW, Leung KL, Yu WC, Tuszynski GP, Fan ST, Clinical significance of thrombospondin 1 expression in hepatocellular carcinoma. Clin Cancer Res 10:12 Pt 1(4150-7)2004 Jun 15

15172186. Albo D, Tuszynski GP, Thrombospondin-1 up-regulates tumor cell invasion through the urokinase plasminogen activator receptor in head and neck cancer cells. J Surg Res 120:1(21-6)2004 Jul

15095410. Zhou J, Rothman VL, Sargiannidou I, Dimitrov S, Qiu C, Smith E, Sheffield J, Sharma M, Tuszynski GP, Cloning and characterization of angiocidin, a tumor cell binding protein for thrombospondin-1. J Cell Biochem 92:1(125-46)2004 May 1

15034804. Sargiannidou I, Qiu C, Tuszynski GP, Mechanisms of thrombospondin-1-mediated metastasis and angiogenesis. Semin Thromb Hemost 30:1(127-36)2004 Feb

14754403. Albo D, Wang TN, Tuszynski GP, Antiangiogenic therapy. Curr Pharm Des 10:1(27-37)2004

14743398. Sharma MR, Tuszynski GP, Sharma MC, Angiostatin-induced inhibition of endothelial cell proliferation/apoptosis is associated with the down-regulation of cell cycle regulatory protein cdk5. J Cell Biochem 91:2(398-409)2004 Feb 1

12727812. Marcinkiewicz C, Weinreb PH, Calvete JJ, Kisiel DG, Mousa SA, Tuszynski GP, Lobb RR, Obtustatin: a potent selective inhibitor of alpha1beta1 integrin in vitro and angiogenesis in vivo. Cancer Res 63:9(2020-3)2003 May 1

12453439. Tuszynski GP, Sharma MR, Rothman VL, Sharma MC, Angiostatin binds to tyrosine kinase substrate annexin II through the lysine-binding domain in endothelial cells. Microvasc Res 64:3(448-62)2002 Nov

12443715. Albo D, Shinohara T, Tuszynski GP, Up-regulation of matrix metalloproteinase 9 by thrombospondin 1 in gastric cancer. J Surg Res 108:1(51-60)2002 Nov

12384074. Krishnaswami S, Ly QP, Rothman VL, Tuszynski GP, Thrombospondin-1 promotes proliferative healing through stabilization of PDGF. J Surg Res 107:1(124-30)2002 Sep

12219015. Wang TN, Albo D, Tuszynski GP, Fibroblasts promote breast cancer cell invasion by upregulating tumor matrix metalloproteinase-9 production. Surgery 132:2(220-5)2002 Aug

12087300. Centeno RF, Albo D, Rothman VL, Granick MS, Tuszynski GP, Thrombospondin-1 may modulate keloid formation through up-regulation of the matrix-associated plasminogen/plasmin system. Plast Reconstr Surg 110:1(363-5)2002 Jul

11882904. Qian X, Rothman VL, Nicosia RF, Tuszynski GP, Expression of thrombospondin-1 in human pancreatic adenocarcinomas: role in matrix metalloproteinase-9 production. Pathol Oncol Res 7:4(251-9)2001

11520937. Sargiannidou I, Zhou J, Tuszynski GP, The role of thrombospondin-1 in tumor progression. Exp Biol Med (Maywood) 226:8(726-33)2001 Sep

11332689. Wakiyama T, Shinohara T, Shirakusa T, John AS, Tuszynski GP, The localization of thrombospondin-1 (TSP-1), cysteine-serine-valine-threonine-cysteine-glycine (CSVTCG) TSP receptor, and matrix metalloproteinase-9 (MMP-9) in colorectal cancer. Histol Histopathol 16:2(345-51)2001 Apr

10917542. Albo D, Rothman VL, Roberts DD, Tuszynski GP, Tumour cell thrombospondin-1 regulates tumour cell adhesion and invasion through the urokinase plasminogen activator receptor. Br J Cancer 83:3(298-306)2000 Aug

10842153. Willis AI, Fuse S, Wang XJ, Chen E, Tuszynski GP, Sumpio BE, Gahtan V, Inhibition of phosphatidylinositol 3-kinase and protein kinase C attenuates extracellular matrix protein-induced vascular smooth muscle cell chemotaxis. J Vasc Surg 31:6(1160-7)2000 Jun

10757078. Zhou J, Sargiannidou I, Tuszynski GP, The role of adhesive proteins in the hematogenous spread of cancer. In Vivo 14:1(199-208)2000 Jan-Feb

10482694. Albo D, Berger DH, Vogel J, Tuszynski GP, Thrombospondin-1 and transforming growth factor beta-1 upregulate plasminogen activator inhibitor type 1 in pancreatic cancer. J Gastrointest Surg 3:4(411-7)1999 Jul-Aug

10455885. Gahtan V, Wang XJ, Willis AI, Tuszynski GP, Sumpio BE, Thrombospondin-1 regulation of smooth muscle cell chemotaxis is extracellular signal-regulated protein kinases 1/2 dependent. Surgery 126:2(203-7)1999 Aug

10359937. Gahtan V, Wang XJ, Ikeda M, Willis AI, Tuszynski GP, Sumpio BE, Thrombospondin-1 induces activation of focal adhesion kinase in vascular smooth muscle cells. J Vasc Surg 29:6(1031-6)1999 Jun

10340867. Roth JJ, Sung JJ, Granick MS, Solomon MP, Longaker MT, Rothman VL, Nicosia RF, Tuszynski GP, Thrombospondin 1 and its specific cysteine-serine-valine-threonine-cysteine-clycine receptor in fetal wounds. Ann Plast Surg 42:5(553-63)1999 May

10328956. Pijuan-Thompson V, Grammer JR, Stewart J, Silverstein RL, Pearce SF, Tuszynski GP, Murphy-Ullrich JE, Gladson CL, Retinoic acid alters the mechanism of attachment of malignant astrocytoma and neuroblastoma cells to thrombospondin-1. Exp Cell Res 249:1(86-101)1999 May 25

10090848. Albo D, Berger DH, Rothman VL, Tuszynski GP, Role of urokinase plasminogen activator receptor in thrombospondin 1-mediated tumor cell invasion. J Surg Res 82:2(331-8)1999 Apr

9848038. Roth JJ, Hughes WB, DeClement FA, Hensell DO, Granick MS, Tuszynski GP, The 1998 Moyer Award. Characteristics of thrombospondin-1 and its cysteine-serine-valine-threonine-cysteine-glycine receptor in burn wounds. J Burn Care Rehabil 19:6(487-93)1998 Nov-Dec

9810490. Roth JJ, Buckmire MA, Rolandelli RH, Granick MS, Tuszynski GP, Localization of thrombospondin-1 and its cysteine-serine-valine-threonine-cysteine-glycine receptor in colonic anastomotic healing tissue. Histol Histopathol 13:4(967-71)1998 Oct

9706163. O'Mahony CA, Albo D, Tuszynski GP, Berger DH, Transforming growth factor-beta 1 inhibits generation of angiostatin by human pancreatic cancer cells. Surgery 124:2(388-93)1998 Aug

9698533. O'Mahony CA, Seidel A, Albo D, Chang H, Tuszynski GP, Berger DH, Angiostatin generation by human pancreatic cancer. J Surg Res 77:1(55-8)1998 Jun

9695745. Albo D, Berger DH, Tuszynski GP, The effect of thrombospondin-1 and TGF-beta 1 on pancreatic cancer cell invasion. J Surg Res 76:1(86-90)1998 Apr

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