Prof. Schulz/MHH
Prof. Dr. med. T. F. Schulz

Gruppenleiter

  • Prof. Dr. med. Thomas F. Schulz

Medizinische Hochschule Hannover
Institut für Virologie, OE5230
Carl-Neuberg-Str. 1
30625 Hannover

Tel: +49 511 532 4308
Sekretariat: +49 511 532 6736
Labor: +49 511 532 4324
Fax: + 49 511 532 8736

Email Schulz.Thomas@MH-Hannover.de

Prof. Dr. med. T. Schulz erwarb sein medizinisches Staatsexamen in Mainz (1979), arbeitete zunächst in der Inneren Medizin (1979 - 1981) und danach im Institut für Med. Mikrobiologie, Mainz (1981 - 1983) und im Institut für Hygiene, Innsbruck (1983 - 1988). Nach Habilitation 1986 ging er 1988 als EMBO Fellow an das Institute of Cancer Research in London, wo er 1988 - 1995 vor allem mit den humanen Retroviren HIV-1, -2 und HTLV-I, seit 1994 mit KSHV/HHV8, arbeitete. 1995 erhielt er eine Professur im Dept. Medical Microbiology der Universität Liverpool, wo er vor allem mit KSHV/HHV8 arbeitete. Vom 01.04.2000 bis zum 31.03.2024 war er Leiter des Instituts für Virologie der Medizinischen Hochschule Hannover. Dr. Schulz ist Sprecher des Sonderforschungsbereichs 900 („Chronische Infektionen: Mikrobielle Persistenz und ihre Kontrolle“) und des Exzellenzclusters 2155 RESIST („Resolving Infection Susceptibility“). Er ist Koordinator des Themenbereichs „Infektionen des immunkompromittierten Wirts“ (TTU IICH) des Deutschen Zentrums für Infektionsforschung (DZIF).

 

Mitglieder der Arbeitsgruppe

Stein, Saskia, Dr., Postdoktorandin
    +49 511 532 6493 | Stein.Saskia@MH-Hannover.de

Wachs, Amelie Sophie, Dr., Postdoktorandin
    +49 511 532 6493 | Schloesser.Amelie@MH-Hannover.de

Zischke, Jasmin, Dr. , Postdoktorandin
    +49 511 532 6493 | Zischke.Jasmin@MH-Hannover.de

Tikla, Tanvi, Msc, Doktorandin
    +49 511 532 8323 | Tikla.Tanvi@MH-Hannover.de

Schulze, Marie-Sophie, Doktorandin
    +49 511 532 4225 | Schulze.Marie-Sophie@MH-Hannover.de

Schneider, Talia Samara, Msc, Doktorandin
    +49 511 532 6493 | Schneider.Talia@MH-Hannover.de

Steinbrück, Lars, MTA
    +49 511 532 4313 | Steinbrueck.Lars@MH-Hannover.de

Rückert, Jessica, MTA
    +49 511 532 4324 | Rueckert.Jessica@MH-Hannover.de

 

Alumni of the Group

Azadegan, Azadeh, Dr. rer. nat
Jandhyala, Sunayana Shyam, Dr. rer. nat
Götting, Jasper, Dr. rer. nat.
Waldmann, Ja-Yun, Mag. rer.nat.
Freise, Anika, Dr. rer. nat.
Cramer, Johannes, Dr.
Kroglowski, Alessandra, MA
Naimo, Eleonora, PhD

Alamirew, Bizunesh, PhD
Alkharsah, Khaled, PhD
Bala, Kiran, PhD
Beauclair, Guillaume, PhD
Bosco, Rafaella, PhD
Brinkmann, Melanie, Dr. rer. nat.
Damas, Modester, PhD
Dedicoat, Martin, PhD
Dhingra, Akshay, PhD
Gellermann, Eva, Dr. rer. nat.
Gramolelli, Silvia, PhD
Gupta, Saumya, PhD
Haas, Darya, PhD
Hävemeier, Anika, Dr. rer. nat.
Hage, Elias, PhD
Hartmann, Silke, Dr. rer. nat.
Jäger, Wiebke, Dr. rer. nat.
Kati, Emrah, Dr. med.
Kati, Semrah, Dr. rer. nat.
Koch, Sandra, Dr. rer. nat.
Lotke, Rishikesh, PhD
Mariggiò, Giuseppe, PhD

Nivia, David, PhD
Ottinger, Matthias, Dr. rer. nat.
Pietrek, Marcel, Dr. rer. nat.
Richter, Ulrike, Dr. rer. nat.
Samarina, Naira, Dr. rer. nat.
Santag, Susan, Dr. rer. nat.
Singh, Vivek, PhD
Soltani, Samira, Dr. med.
Schmidt, Merle, Dr. med.
Wang, Linding, PhD
Weidner-Glunde, Magdalena, PhD
Yakushko, Yuri, PhD

Zhang, Guigen, PhD


AG Schulz Labor

Forschungsschwerpunkt

KSHV Arbeitsgruppe

Das Kaposi Sarkom-assoziierte Herpesvirus (KSHV), oder Humane Herpesvirus 8 (HHV8), ist die infektiöse Ursache des Kaposi Sarkoms (KS), eines aus Endothelzellen abgeleiteten vaskulären Tumors. KS findet sich häufig in AIDS Patienten und ist heute der häufigste Krebs bei Männern in den Ländern Afrikas südlich der Sahara. Daneben spielt dieser Tumor bei Transplantatpatienten aus Ländern eine Rolle, in denen dieses Virus häufig ist. Zusätzlich ist dieses Virus die Ursache der Plasmazellvariante der Castleman’schen Erkrankung (,Multicentric Castleman’s Disease’) sowie des primären Effusionslymphoms (’Primary effusion lymphoma’). KSHV/HHV8 wurde von Drs. Yuan Chang und Patrick Moore im Jahr 1994 entdeckt und ist eines 7 bekannten und von der International Agency for Research against Cancer (IARC) anerkannten humanen Tumorviren.

Wie alle Herpesviren persistiert KSHV/HHV8 nach der Erstinfektion lebenslang in infizierten Individuen. Während dieser Persistenz nimmt das Virus eine latente, nicht-replikative Form an, in der kein neues Virus produziert wird, aber dafür gesorgt ist, dass sich das virale Genom weiter vermehren kann. Wie diese Latenz auf der molekularen Ebene funktioniert ist der Gegenstand unserer Forschung. Dabei interessieren uns vor allem die folgenden Themen:

Publikationen

Wichtige Originalveröffentlichungen zu KSHV/HHV8:

Koch S, Damas M, Freise A, Hage E, Dhingra A, Rückert J, Gallo A, Tegge W, Brönstrup M, Brune W, Schulz TF Kaposi’s sarcoma-associated herpesvirus vIRF2 protein utilizes an IFN-dependent pathway to regulate viral early gene expression. PLoS Pathogens 2019; 15(5):e1007743

Abere B, Samarina N, Gramolelli S, Rückert J, Gerold G, Pich A, Schulz TF Kaposi’s sarcoma-associated Herpesvirus nonstructural membrane protein pK15 recruits the class II phosphatidylinositol 3-kinase PI3K-C2a to activate productive viral replication. J. Virol. 2018; 92:e00544-18. doi.org/10.1128/JVI.00544-18

Abere B, Mamo TM, Hartmann S, Samarina N, Hage E, Rückert J, Hotop SK, Büsche G, Schulz TF The Kaposi’s Sarcoma-associated Herpesvirus (KSHV) non-structural membrane protein K15 is required for viral lytic replication and may represent a therapeutic target. PLoS Pathog. 2017; 3(9): e1006639. doi: 10.1371/journal.ppat.1006639

Mariggiò G, Koch S, Zhang G, Weidner-Glunde M, Rückert J, Kati S, Santag S, Schulz TF Kaposi Sarcoma Herpesvirus Latent Nuclear Antigen (LANA) recruits components of the MRN (Mre11-Rad50-Nbs1) complex to modulate an innate immune signaling pathway and viral latency. PLoS Pathog. 2017; 13:e1006335. doi: 10.1371/journal.ppat.1006335.

Zhang G, Chan B, Samarina N, Abere B, Weidner-Glunde M, Buch A, Pich A, Brinkmann MB, Schulz TF. Cytoplasmic isoforms of Kaposi Sarcoma Herpesvirus LANA recruit and antagonize the innate immune sensor cGAS. Proc Natl Acad Sci U S A. 2016; 113(8):E1034-43. doi: 10.1073/pnas.1516812113.

Gramolelli S, Weidner-Glunde M, Abere B, Viejo-Borbolla A, Bala K, Rückert J, Kremmer E, Schulz TF. Inhibiting the recruitment of PLCg1 to Kaposi’s Sarcoma Herpesvirus K15 protein reduces the invasiveness and angiogenesis of infected endothelial cells. PLoS Pathog. 2015; 11(8):e1005105. doi: 10.1371/journal.ppat.1005105

Hellert J, Weidner-Glunde M, Krausze J, Lünsdorf H, Ritter C, Schulz TF*, Lührs T*. The 3D-structure of Kaposi’s sarcoma herpesvirus LANA c-terminal domain bound to DNA. Proc Natl Acad Sci U S A. 2015; 112: 6694-9. *joint senior author

Hävemeier A, Gramolelli S, Pietrek M, Jochmann R, Stürzl M, Schulz TF. Activation of NFkB by the Kaposi Sarcoma Hepresvirus K15 protein involves recruitment of the NFkB-inducing kinase, IkB kinases, and phosphorylation of p65. J Virol. 2014; 88:13161-72. doi: 10.1128/JVI.01766-14.

Hellert J, Weidner-Glunde M, Krausze J, Richter U, Adler H, Fedorov R, Pietrek M, Rückert J, Ritter C, Schulz TF*, Lührs T*. A structural basis for BRD2/4-mediated host chromatin interaction and oligomer assembly of Kaposi Sarcoma Herpesvirus and murine gammaherpesvirus LANA proteins. PLoS Pathogens 2013; 9(10):e1003640. doi: 10.1371 *joint senior authors

Haas DA, Bala K, Büsche G, Weidner-Glunde M, Santag S, Kati S, Gramolelli S, Damas M, Dittrich-Breiholz O, Kracht M, Rückert J, Varga Z, Keri G, Schulz TF The inflammatory kinase MAP4K4 promotes reactivation promotes reactivation of Kaposi’s Sarcoma Herpesvirus and enhances the invasiveness of infected endothelial cells. PLoS Pathogens 2013; 9(11):e1003737. doi: 10.1371/ journal.ppat.1003737.

Gupta SS, Maetzig T, Maertens GN, Sharif A, Rothe M, Weidner-Glunde M, Galla M, Schambach A, Cherepanov P, Schulz TF Bromo- and ET domain (BET) chromatin regulators serve as co-factors for murine leukemia virus integration. J. Virol. 2013; 87:12721-36. doi: 10.1128/JVI.01942-13

Santag S, Jäger W, Karsten C, Kati S, Pietrek M, Steinemann D, Sarek G, Ojala P, Schulz TF Recruitment of the tumour suppressor protein p73 by Kaposi Sarcoma Herpesvirus latent nuclear antigen contributes to the survival of primary effusion lymphoma cells. Oncogene, 2012; doi: 10.1038/onc.2012.385.

Bala K, Bosco R, Gramolelli S, Haas DA, Kati S, Pietrek M, Hävemeier A, Yakushko Y, Singh VV, Dittrich-Breiholz O, Kracht M, Schulz TF Kaposi´s Sarcoma Herpesvirus K15 protein contributes to virus-induced angiogenesis by recruiting PLCg1 and activating NFAT1-dependent RCAN1 expression. PLoS Pathogens 2012; 8:e1002927. doi: 10.1371

Jäger W, Santag S, Weidner-Glunde M, Gellermann E, Pietrek M, Viejo-Borbolla A, Schulz TF  The ubiquitin-specific protease USP7 modulates the replication of KSHV latent episomal DNA. J. Virol., 2012; 86: 6745-57

Alkharsah KR, Schulz TF. A role for the internal repeat of the Kaposi's sarcoma-associated herpesvirus latent nuclear antigen in the persistence of an episomal viral genome. J. Virol. 2012; 86:1883-7.

Alkharsah KR, Singh VV, Bosco R, Santag S, Grundhoff A, Konrad A, Sturzl M, Wirth D, Dittrich-Breiholz O, Kracht M, Schulz TF. Deletion of Kaposi's sarcoma-associated herpesvirus FLICE inhibitory protein, vFLIP, from the viral genome compromises the activation of STAT1-responsive cellular genes and spindle cell formation in endothelial cells. J. Virol. 2011; 85:10375-88.

Pietrek M, Brinkmann MM, Glowacka I, Enlund A, Havemeier A, Dittrich-Breiholz O, Kracht M, Lewitzky M, Saksela K, Feller SM, Schulz TF. Role of the Kaposi's sarcoma-associated herpesvirus K15 SH3 binding site in inflammatory signaling and B-cell activation. J. Virol. 2011; 84:8231-40.

Ottinger M, Pliquet D, Christalla T, Frank R, Stewart JP, Schulz TF. The interaction of the gammaherpesvirus 68 orf73 protein with cellular BET proteins affects the activation of cell cycle promoters. J. Virol. 2009; 83:4423-4434

Brinkmann M, Pietrek M, Dittrich-Breiholz O, Kracht M, Schulz TF Modulation of host gene expression by the K15 protein of Kaposi’s sarcoma-associated herpesvirus J. Virol. 2007; 81: 42-58.

Ottinger M, Christalla T, Nathan K, Brinkmann M, Viejo-Borbolla A, Schulz TF The Kaposi’s Sarcoma-Associated Herpesvirus LANA-1 interacts with the short variant of BRD4 and releases cells from a BRD4- and BRD2/RING3- induced G1 cell cycle arrest J. Virol. 2006; 80: 10772-86

Viejo-Borbolla A, Ottinger M, Bruning E, Burger A, Konig R, Kati E, Sheldon JA, Schulz TF. Brd2/RING3 interacts with a chromatin-binding domain in the Kaposi's Sarcoma-associated herpesvirus latency-associated nuclear antigen 1 (LANA-1) that is required for multiple functions of LANA-1. J Virol. 2005; 79:13618-29.

Dedicoat M, Newton R, Alkharsah K.R, Sheldon J, Szabados I, Ndlovu B, Page T, Casabonne D, Gilks CF, Cassol SA, Whitby D, Schulz TF Mother to child transmission of human herpesvirus 8 in South Africa. J. Inf. Dis. 2004; 190:1068-75

Brinkmann MM, Glenn M, Rainbow L, Kieser A, Henke-Gendo C, Schulz TF  Activation of mitogen-activated protein kinase and NF-kappaB pathways by a Kaposi's sarcoma-associated herpesvirus K15 membrane protein. J Virol. 2003; 77: 9346-58

Viejo-Borbolla A, Kati E, Sheldon J, Nathan K, Mattsson K, Szekely L, Schulz TF A domain in the C-terminal region of latency - associated nuclear antigen (LANA-1) of KSHV affects transcriptional activation and binding to nuclear heterochromatin. J Virol. 2003; 77: 7093-100.

Barozzi P, Luppi M, Facchetti F, Mecucci C, Alu M, Sarid R, Rasini V, Ravazzini L, Rossi E, Festa S, Crescenzi B, Wolf DG, Schulz TF, Torelli G. Post-transplant Kaposi sarcoma originates from the seeding of donor-derived progenitors. Nature Medicine 2003; 9: 554-61.

Luppi M, Barozzi P, Schulz TF, Setti G, Staskus K, Trovato R, Narni F, Donelli A, Maiorana A, Marasca R, Sandrini S, Torelli G, Sheldon J. (2000) Bone Marrow failure associated with Human Herpesvirus 8 infection after transplantation N Engl J Med 2000; 343: 1378-1385

Greensill J, Sheldon J, Renwick NM, Beer B, Norley S, Goudsmit J, Schulz TF Two distinct 2 herpesviruses in African Green monkeys: a second 2 herpesvirus lineage among Old World primates? J. Virol. 2000; 74: 1572 - 1577.

Greensill J, Sheldon JA, Murthy KK, Bessonette JS, Beer BE, Schulz TF A chimpanzee rhadinovirus closely related to Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8: increased detection after HIV-1 infection in the absence of disease. AIDS 2000; 14: F129 - 135

Glenn, M., Rainbow, L., Aurade, F., Davsion, A., Schulz, T.F. Identification of a multiply spliced gene of KSHV/HHV8 with similarities to the latent membrane proteins of EBV. J.Virol. 1999; 73: 6953 – 6963

Platt GM, Simpson GR, Mittnacht S, Schulz TF Latent nuclear antigen of Kaposi's sarcoma-associated herpesvirus interacts with RING3, a homolog of the Drosophila female sterile homeotic (fsh) gene."J. Virol. 1999; 73: 9789 - 9795.

Farge D, Lebbé C, Marjanovic Z, Tuppin P, Mouquet C, Peraldi MN, Lang P, Hiesse C, Antoine C, Legendre C, Bedrossian J, Gagnadoux MF, Loirat C, Pellet C, Sheldon J, Golmard JL, Agbalika F, Schulz TF. Human herpesvirus 8 (HHV 8) and other risk factors for Kaposi’s sarcoma in kidney transplant recipients. Transplantation 1999; 67: 1236 – 1242

Cook PM, Whitby D, Calabro ML, Luppi M, Kakoola DN, Hjalgrim H, Ariyoshi K, Ensoli B, Davison AJ, Schulz TF, and the International Collaborative Group. Variability and evolution of Kaposi's sarcoma-associated herpesvirus in Europe and Africa. AIDS 1999; 13: 1165 - 1176

Melbye M, Cook PM, Hjalgrim H, Begtrup K, Simpson GR, Biggar RJ, Ebbesen P, Schulz TF. "Risk factors for Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8) seropositivity in a cohort of homosexual men, 1981 - 1996." Int. J. Cancer, 1998; 77: 543-548

Mayama S, Cuevas L, Sheldon J, Smith D, Okong P, Silvel B, Schulz TF. "Prevalence of Kaposi’s sarcoma associated herpesvirus (Human herpesvirus 8) in a young Ugandan population." Int. J. Cancer, 1998; 77: 817-820

Renwick N, Halaby T, Weverling GJ, Simpson GR, Coutinho RA, Lange JMA, Schulz TF, Goudsmit J Seroconversion for Kaposi’s sarcoma-associated herpesvirus is highly predictive of KS development in HIV-1 infected individuals. AIDS 1998; 12: 2481 - 2488

Rainbow, L., Platt, G.M., Simpson, G.R., Sarid, R., Gao, S.-J., Stoiber, H., Herringston, C.S., Moore, P.S., Schulz, T.F.  The 222-234 kd nuclear protein (LNA) of Kaposi's sarcoma - associated herpesvirus (KSHV/HHV 8) is encoded by orf73 and a component of the latency-associated nuclear antigen (LANA). J.Virol. 1997; 71: 5915-5921

Simpson, G.R., Schulz,T.F.*, Whitby,D., Cook,P.M., Boshoff, C., Rainbow, L., Howard, M., Gao, S.-J., Bohenzky, R.A., Simmonds, P., Lee, C., de Ruiter, A., Hatzakis, A., Tedder, R.S., Weller, I.V.D., Weiss, R.A., Moore, P.S. Prevalence of Kaposi's sarcoma associated herpesvirus infection measured by antibodies to recombinant capsid protein and latent immunofluorescence antigen. Lancet 1996; 348:1133 – 1138 *corresponding author

Whitby D, Howard MR, Tenant-Flowers M, Brink NS, Copas A, Boshoff C, Hatzioannou T, Suggett FEA, Aldam DM, Denton AS, Miller RF, Weller IVD, Weiss RA, Tedder RS, Schulz TF. Detection of Kaposi's sarcoma associated herpesvirus in peripheral blood of HIV-infected individuals and progression to Kaposi's sarcoma. Lancet 1995; 346:799-802.

Boshoff C, Schulz TF, Kennedy MM, Graham AK, Fisher C, Thomas A, McGee J, Weiss RA, O'Leary JJ Kaposi's sarcoma-associated herpesvirus infects endothelial and spindle cells. Nature Medicine 1995; 1: 1274-1278