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Stephen ArnoffAlexander Y. Tsygankov, PhD

 

Associate Professor, Microbiology and Immunology

Associate Professor, Sol Sherry Thrombosis Research

Center

Associate Professor, Fels Institute for Cancer Research and Molecular Biology

Telephone:  215-707-1745

Fax:  215-707-7788

Email: alexander.tsygankov@temple.edu

 

Department of Microbiology and Immunology

Sol Sherry Thrombosis Research Center

Fels Institute for Cancer Research and Molecular Biology

Temple Autoimmunity Center

 

Educational Background:

 

Bach Institute of Biochemistry, Moscow

 

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Research Interests:

 

Dr. Tsygankov's laboratory is studying the mechanisms of signal transduction mediated by protein kinases. Currently, his laboratory carries out two projects related to this topic. The first is focused on elucidating the biological role of c-Cbl and c-Cbl-associated proteins. Dr. Tsygankov's laboratory has mapped major tyrosine phosphorylation sites of c-Cbl and demonstrated that recruitment of signaling molecules to these sites is involved in regulation of cell adhesion, morphology and migration. This project is now focused on defining the molecular nature of the pathways linking c-Cbl to cell adhesion. Furthermore, TULA, a novel T-cellular protein interacting with c-Cbl, has been identified in the course of these studies. The latest studies from Dr. Tsygankov’s laboratory indicate that TULA exerts several regulatory effects, including activation of protein tyrosine kinases and apoptosis induction.

 

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selected publications:

 

Collingwood TS, Smirnova EV, Bogush M, Carpino N, Annan RS, Tsygankov AY, TULA affects cell death through a functional interaction with AIF, a key factor of caspase-independent apoptosis. J Biol Chem 2007 Aug 20.

 

Swaminathan G, Feshchenko EA, Tsygankov AY, c-Cbl-facilitated cytoskeletal effects in v-Abl-transformed fibroblasts are regulated by membrane association of c-Cbl. Oncogene 2007 Jun 14;26(28):4095-105)2007.

 

Swaminathan G, Tsygankov AY, The Cbl family proteins: ring leaders in regulation of cell signaling. J Cell Physiol 2006 Oct;209(1):21-43.

 

Teckchandani AM, Panetti TS, Tsygankov AY, c-Cbl regulates migration of v-Abl-transformed NIH 3T3 fibroblasts via Rac1. Exp Cell Res 2005 Jul 1;307(1):247-58.

 

Teckchandani AM, Birukova AA, Tar K, Verin AD, Tsygankov AY, The multidomain protooncogenic protein c-Cbl binds to tubulin and stabilizes microtubules. Exp Cell Res 2005 May 15;306(1):114-27.

 

Dangelmaier CA, Quinter PG, Jin J, Tsygankov AY, Kunapuli SP, Daniel JL, Rapid ubiquitination of Syk following GPVI activation in platelets. Blood 2005 May 15;105(10):3918-24.

 

Raymond AD, Hasham MG, Tsygankov AY, Henderson EE, Herpesvirus saimiri-encoded proteins Tip and StpC modulate human immunodeficiency virus type 1 replication in T-cell lines and lymphocytes independently of viral tropism. Virology 2004 Jun 20;324(1):60-6.

 

Feshchenko EA, Smirnova EV, Swaminathan G, Teckchandani AM, Agrawal R, Band H, Zhang X, Annan RS, Carr SA, Tsygankov AY, TULA: an SH3- and UBA-containing protein that binds to c-Cbl and ubiquitin. Oncogene 2004 Jun 10;23(27):4690-706.

 

Sorokina EM, Merlo JJ Jr, Tsygankov AY, Molecular mechanisms of the effect of herpesvirus saimiri protein StpC on the signaling pathway leading to NF-kappaB activation. J Biol Chem 2004 279(14):13469-77.

 

Tsygankov AY, Teckchandani AM, Feshchenko EA, Swaminathan G, Beyond the RING: CBL proteins as multivalent adapters. Oncogene 2001 20(44):6382-402.

 

Merlo JJ, Tsygankov AY. Herpesvirus saimiri oncoproteins Tip and StpC synergistically stimulate NF-kappaB activity and interleukin-2 gene expression.
Virology. 2001 Jan 5;279(1):325-38.

 

Levkowitz G, Waterman H, Ettenberg SA, Katz M, Tsygankov AY, Alroy I, Lavi S, Iwai K, Reiss Y, Ciechanover A, Lipkowitz S, Yarden Y. Ubiquitin ligase activity and tyrosine phosphorylation underlie suppression of growth factor signaling by c-Cbl/Sli-1. Mol Cell. 1999 Dec;4(6):1029-40.

 

Feshchenko EA, Shore SK, Tsygankov AY. Tyrosine phosphorylation of C-Cbl facilitates adhesion and spreading while suppressing anchorage-independent growth of V-Abl-transformed NIH3T3 fibroblasts. Oncogene. 1999 Jun 24;18(25):3703-15.

 

Feshchenko EA, Langdon WY, Tsygankov AY. Fyn, Yes, and Syk phosphorylation sites in c-Cbl map to the same tyrosine residues that become phosphorylated in activated T cells. J Biol Chem. 1998 Apr 3;273(14):8323-31.

 

Tsygankov AY, Mahajan S, Fincke JE, Bolen JB. Specific association of tyrosine-phosphorylated c-Cbl with Fyn tyrosine kinase in T cells. J Biol Chem. 1996 Oct 25;271(43):27130-7.

 

Wiese N, Tsygankov AY, Klauenberg U, Bolen JB, Fleischer B, Broker BM. Selective activation of T cell kinase p56lck by Herpesvirus saimiri protein tip. J Biol Chem. 1996 Jan 12;271(2):847-52.

 

Biesinger B, Tsygankov AY, Fickenscher H, Emmrich F, Fleckenstein B, Bolen JB, Broker BM. The product of the Herpesvirus saimiri open reading frame 1 (tip) interacts with T cell-specific kinase p56lck in transformed cells. J Biol Chem. 1995 Mar 3;270(9):4729-34.

 

Tsygankov AY, Spana C, Rowley RB, Penhallow RC, Burkhardt AL, Bolen JB. Activation-dependent tyrosine phosphorylation of Fyn-associated proteins in T lymphocytes. J Biol Chem. 1994 Mar 11;269(10):7792-800.

 

Tsygankov AY, Broker BM, Fargnoli J, Ledbetter JA, Bolen JB. Activation of tyrosine kinase p60fyn following T cell antigen receptor cross-linking. J Biol Chem. 1992 Sep 15;267(26):18259-62.

 

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PUBMED PUBLICATIONS :


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

24994594. Adapala NS, Holland D, Scanlon V, Barbe MF, Langdon WY, Tsygankov AY, Lorenzo JA, Sanjay A, Loss of Cbl-PI3K interaction in mice prevents significant bone loss following ovariectomy. Bone 67C:(1-9)2014 Jul 1

24845219. Liverani E, Kilpatrick LE, Tsygankov AY, Kunapuli SP, The Role of P2Y12 Receptor and Activated Platelets During Inflammation. Curr Drug Targets 15:7(720-8)2014

24470255. Adapala NS, Barbe MF, Tsygankov AY, Lorenzo JA, Sanjay A, Loss of Cbl-PI3K interaction enhances osteoclast survival due to p21-Ras mediated PI3K activation independent of Cbl-b. J Cell Biochem 115:7(1277-89)2014 Jul

24142066. Liverani E, Rico MC, Yaratha L, Tsygankov AY, Kilpatrick LE, Kunapuli SP, LPS-induced systemic inflammation is more severe in P2Y12 null mice. J Leukoc Biol 95:2(313-23)2014 Feb

23960082. Buitrago L, Bhavanasi D, Dangelmaier C, Manne BK, Badolia R, Borgognone A, Tsygankov AY, McKenzie SE, Kunapuli SP, Tyrosine phosphorylation on spleen tyrosine kinase (Syk) is differentially regulated in human and murine platelets by protein kinase C isoforms. J Biol Chem 288:40(29160-9)2013 Oct 4

23744514. Lee H, Tsygankov AY, Cbl-family proteins as regulators of cytoskeleton-dependent phenomena. J Cell Physiol 228:12(2285-93)2013 Dec

23149425. Back SH, Adapala NS, Barbe MF, Carpino NC, Tsygankov AY, Sanjay A, TULA-2, a novel histidine phosphatase, regulates bone remodeling by modulating osteoclast function. Cell Mol Life Sci 70:7(1269-84)2013 Apr

22689384. Tsygankov AY, TULA-family proteins: a new class of cellular regulators. J Cell Physiol 228:1(43-9)2013 Jan

20851882. Adapala NS, Barbe MF, Langdon WY, Nakamura MC, Tsygankov AY, Sanjay A, The loss of Cbl-phosphatidylinositol 3-kinase interaction perturbs RANKL-mediated signaling, inhibiting bone resorption and promoting osteoclast survival. J Biol Chem 285:47(36745-58)2010 Nov 19

20717917. Lee H, Tsygankov AY, c-Cbl regulates glioma invasion through matrix metalloproteinase 2. J Cell Biochem 111:5(1169-78)2010 Dec 1

20670933. Chen X, Ren L, Kim S, Carpino N, Daniel JL, Kunapuli SP, Tsygankov AY, Pei D, Determination of the substrate specificity of protein-tyrosine phosphatase TULA-2 and identification of Syk as a TULA-2 substrate. J Biol Chem 285:41(31268-76)2010 Oct 8

20585042. Thomas DH, Getz TM, Newman TN, Dangelmaier CA, Carpino N, Kunapuli SP, Tsygankov AY, Daniel JL, A novel histidine tyrosine phosphatase, TULA-2, associates with Syk and negatively regulates GPVI signaling in platelets. Blood 116:14(2570-8)2010 Oct 7

20400514. Daniel JL, Dangelmaier CA, Mada S, Buitrago L, Jin J, Langdon WY, Tsygankov AY, Kunapuli SP, Sanjay A, Cbl-b is a novel physiologic regulator of glycoprotein VI-dependent platelet activation. J Biol Chem 285:23(17282-91)2010 Jun 4

20392263. Adapala NS, Barbe MF, Langdon WY, Tsygankov AY, Sanjay A, Cbl-phosphatidylinositol 3 kinase interaction differentially regulates macrophage colony-stimulating factor-mediated osteoclast survival and cytoskeletal reorganization. Ann N Y Acad Sci 1192:(376-84)2010 Mar

20032419. Pappas J, Wolfson AD, Jung WJ, Oleszak EL, Helm CW, Freedman RS, Tsygankov AY, Platsoucas CD, Differential expression of CD3zeta message and protein in tumor infiltrating lymphocytes from solid tumor specimens and malignant ascites from patients with ovarian carcinoma. Anticancer Res 29:11(4673-82)2009 Nov

19585081. Tsygankov AY, TULA-family proteins: an odd couple. Cell Mol Life Sci 66:17(2949-52)2009 Sep

19197791. Tsygankov AY, Current developments in anti-HIV/AIDS gene therapy. Curr Opin Investig Drugs 10:2(137-49)2009 Feb

18403249. Lee H, Gaughan JP, Tsygankov AY, c-Cbl facilitates cytoskeletal effects in v-Abl transformed fibroblast through Rac1- and Rap1-mediated signaling. Int J Biochem Cell Biol 40:9(1930-43)2008

18344182. Tsygankov AY, Multidomain STS/TULA proteins are novel cellular regulators. IUBMB Life 60:4(224-31)2008 Apr

18006034. Smirnova EV, Collingwood TS, Bisbal C, Tsygankova OM, Bogush M, Meinkoth JL, Henderson EE, Annan RS, Tsygankov AY, TULA proteins bind to ABCE-1, a host factor of HIV-1 assembly, and inhibit HIV-1 biogenesis in a UBA-dependent fashion. Virology 372:1(10-23)2008 Mar 1

17949927. Salerno D, Hasham MG, Marshall R, Garriga J, Tsygankov AY, Graņa X, Direct inhibition of CDK9 blocks HIV-1 replication without preventing T-cell activation in primary human peripheral blood lymphocytes. Gene 405:1-2(65-78)2007 Dec 15

17709377. Collingwood TS, Smirnova EV, Bogush M, Carpino N, Annan RS, Tsygankov AY, T-cell ubiquitin ligand affects cell death through a functional interaction with apoptosis-inducing factor, a key factor of caspase-independent apoptosis. J Biol Chem 282:42(30920-8)2007 Oct 19

17337598. Avraamides C, Bromberg ME, Gaughan JP, Thomas SM, Tsygankov AY, Panetti TS, Hic-5 promotes endothelial cell migration to lysophosphatidic acid. Am J Physiol Heart Circ Physiol 293:1(H193-203)2007 Jul

17266559. Raymond AD, Hasham M, Tsygankov AY, Henderson EE, Herpesvirus saimiri terminal membrane proteins modulate HIV-1 replication by altering Nef and Tat functions. Curr HIV Res 5:1(79-86)2007 Jan

17237826. Swaminathan G, Feshchenko EA, Tsygankov AY, c-Cbl-facilitated cytoskeletal effects in v-Abl-transformed fibroblasts are regulated by membrane association of c-Cbl. Oncogene 26:28(4095-105)2007 Jun 14

16891001. Turner LS, Tsygankov AY, Henderson EE, StpC-based gene therapy targeting latent reservoirs of HIV-1. Antiviral Res 72:3(233-41)2006 Dec

16780912. Raymond AD, Hasham M, Tsygankov AY, Henderson EE, H. saimiri tyrosine-kinase interacting protein inhibits Tat function: a prototypic strategy for restricting HIV-1-induced cytopathic effects in immune cells. Virology 352:2(253-67)2006 Sep 1

16741904. Swaminathan G, Tsygankov AY, The Cbl family proteins: ring leaders in regulation of cell signaling. J Cell Physiol 209:1(21-43)2006 Oct

15922744. Teckchandani AM, Panetti TS, Tsygankov AY, c-Cbl regulates migration of v-Abl-transformed NIH 3T3 fibroblasts via Rac1. Exp Cell Res 307:1(247-58)2005 Jul 1

15878338. Teckchandani AM, Birukova AA, Tar K, Verin AD, Tsygankov AY, The multidomain protooncogenic protein c-Cbl binds to tubulin and stabilizes microtubules. Exp Cell Res 306:1(114-27)2005 May 15

15701717. Dangelmaier CA, Quinter PG, Jin J, Tsygankov AY, Kunapuli SP, Daniel JL, Rapid ubiquitination of Syk following GPVI activation in platelets. Blood 105:10(3918-24)2005 May 15

15389624. Tsygankov AY, Cell transformation by Herpesvirus saimiri. J Cell Physiol 203:2(305-18)2005 May

15183053. Raymond AD, Hasham MG, Tsygankov AY, Henderson EE, Herpesvirus saimiri-encoded proteins Tip and StpC modulate human immunodeficiency virus type 1 replication in T-cell lines and lymphocytes independently of viral tropism. Virology 324:1(60-6)2004 Jun 20

15180537. Tsygankov AY, Shore SK, Src: regulation, role in human carcinogenesis and pharmacological inhibitors. Curr Pharm Des 10:15(1745-56)2004

15107835. Feshchenko EA, Smirnova EV, Swaminathan G, Teckchandani AM, Agrawal R, Band H, Zhang X, Annan RS, Carr SA, Tsygankov AY, TULA: an SH3- and UBA-containing protein that binds to c-Cbl and ubiquitin. Oncogene 23:27(4690-706)2004 Jun 10

15016553. Hasham MG, Tsygankov AY, Tip, an Lck-interacting protein of Herpesvirus saimiri, causes Fas- and Lck-dependent apoptosis of T lymphocytes. Virology 320:2(313-29)2004 Mar 15

14724292. Sorokina EM, Merlo JJ Jr, Tsygankov AY, Molecular mechanisms of the effect of herpesvirus saimiri protein StpC on the signaling pathway leading to NF-kappaB activation. J Biol Chem 279:14(13469-77)2004 Apr 2

12742823. Wang S, Hasham MG, Isordia-Salas I, Tsygankov AY, Colman RW, Guo YL, Upregulation of Cdc2 and cyclin A during apoptosis of endothelial cells induced by cleaved high-molecular-weight kininogen. Am J Physiol Heart Circ Physiol 284:6(H1917-23)2003 Jun

12700079. Tsygankov AY, Non-receptor protein tyrosine kinases. Front Biosci 8:(s595-635)2003 May 1

11607840. Tsygankov AY, Teckchandani AM, Feshchenko EA, Swaminathan G, Beyond the RING: CBL proteins as multivalent adapters. Oncogene 20:44(6382-402)2001 Oct 1

11466305. Guse AH, Tsygankov AY, Weber K, Mayr GW, Transient tyrosine phosphorylation of human ryanodine receptor upon T cell stimulation. J Biol Chem 276:37(34722-7)2001 Sep 14

11313921. Teckchandani AM, Feshchenko EA, Tsygankov AY, c-Cbl facilitates fibronectin matrix production by v-Abl-transformed NIH3T3 cells via activation of small GTPases. Oncogene 20:14(1739-55)2001 Mar 29

11145913. Merlo JJ, Tsygankov AY, Herpesvirus saimiri oncoproteins Tip and StpC synergistically stimulate NF-kappaB activity and interleukin-2 gene expression. Virology 279:1(325-38)2001 Jan 5

10635327. Levkowitz G, Waterman H, Ettenberg SA, Katz M, Tsygankov AY, Alroy I, Lavi S, Iwai K, Reiss Y, Ciechanover A, Lipkowitz S, Yarden Y, Ubiquitin ligase activity and tyrosine phosphorylation underlie suppression of growth factor signaling by c-Cbl/Sli-1. Mol Cell 4:6(1029-40)1999 Dec

10544137. Henderson EE, Tsygankov AY, Merlo JJ, Romano G, Guan M, Altered replication of human immunodeficiency virus type 1 (HIV-1) in T cell lines retrovirally transduced to express Herpesvirus saimiri proteins StpC and/or Tip. Virology 264:1(125-33)1999 Nov 10

10391678. Feshchenko EA, Shore SK, Tsygankov AY, Tyrosine phosphorylation of C-Cbl facilitates adhesion and spreading while suppressing anchorage-independent growth of V-Abl-transformed NIH3T3 fibroblasts. Oncogene 18:25(3703-15)1999 Jun 24

10368641. Tsygankov AY, Romano G, Mechanisms of cell transformation by Herpesvirus saimiri. Anticancer Res 19:2A(973-83)1999 Mar-Apr

9703884. Merlo JJ, Romano G, Gordon SS, Feshchenko EA, Peng G, Henderson EE, Tsygankov AY, Human T cells transduced by a retroviral vector to express Herpesvirus saimiri proteins TIP and STPC. Anticancer Res 18:4A(2389-96)1998 Jul-Aug

9525940. Feshchenko EA, Langdon WY, Tsygankov AY, Fyn, Yes, and Syk phosphorylation sites in c-Cbl map to the same tyrosine residues that become phosphorylated in activated T cells. J Biol Chem 273:14(8323-31)1998 Apr 3

9266543. Rojavin MA, Tsygankov AY, Ziskin MC, Interaction of cyclophosphamide and ketamine in vivo. Neuroimmunomodulation 3:6(333-5)1996 Nov-Dec

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graduate students :

 

Tiffanny Newman

Certain Recent Graduates:


Anjali Teckchandani, PhD

Postdoctoral Fellow

University of Washington

 

Gayathri Swaminathan, PhD

Postdoctoral Fellow

University of Pennsylvania


Rachana Agrawal, PhD

Postdoctoral Fellow

University of Virginia

 

Hojin Lee

Postdoctoral Fellow

Yale University

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grant support :

 

Current or Recent Grant Support of Active Projects:

 

Alexander Tsygankov, PhD as Principal Investigator:

National Institutes of Health, 2 R01 CA78499
c-Cbl in Modulation of Cell Adhesion and Morphology

Alexander Tsygankov, PhD as Co-Investigator:

National Institutes of Health, T32 A107101, D. Ganea, PhD, Principal Investigator/Program Director; Microbiology and Immunology Training Program

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