People

Dr Ralf Zwacka

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School of Life Sciences
Dr Ralf Zwacka

Profile

Biography

2005 - 2013 Lecturer, National University of Ireland Galway, National Centre for Biomedical Engineering Science, Ireland 2001 - 2005 Group Leader, Division of Gene Therapy, University of Ulm, Germany 1997 - 2001 Lecturer, University of Edinburgh, Dept. of Oncology 1995 - 1997 Post-doctoral fellow, University of Pennsylvania, Institute for Human Gene Therapy, USA 1990 - 1995 Ph.D., Open University and Forschungszentrum Karlsruhe, Germany 1988 - 1990 B.Sc. in Biochemistry, University of Manchester (UMIST) 1985 - 1988 Undergraduate courses in Biochemistry and Economics, Free University Berlin, Germany Prostate Cancer UK funded project: trail.essex.ac.uk/ Research Students Yasamin Mehrabadi https://www.essex.ac.uk/bs/staff/profile.aspx?ID=4048 Sylwia Jencz https://www.essex.ac.uk/bs/staff/profile.aspx?ID=4757 Tianyuan Chu https://www.essex.ac.uk/people/chuti18802/tianyuan-chu Natalia Krajewska https://www.essex.ac.uk/people/kraje47600/natalia-krajewska

Qualifications

  • BSc

  • PhD

  • MBA

Research and professional activities

Research interests

Mesenchymal stem cells and cancer therapy

Apoptosis pathways and treatment resistance mechansims in cancer

Cell death regulation in stem cells

Redox-regulated pathways in cancer and stem cells

Current research

We study the use of mesenchymal stem cells (MSC) as gene delivery vehicles and their role in tumour progression and metastasis development

We try to better understand apoptosis in stem cells and cancer cells and how it is regulated by epigenetic mechanisms including miRNAs and other non-coding RNAs in order to protect stem cells in inflammatory settings and during the aging process

We aim to elucidate the molecular mechanisms of TRAIL- and chemotherapy-induced cell death and to identify molecular resistance points in tumour cells with the goal to find better diagnostic tools and new therapeutic approaches

Teaching and supervision

Current teaching responsibilities

  • Issues in Biomolecular Science (BS304)

  • Issues in Biomedical Science (BS306)

  • Molecular Mechanisms of Disease (BS938)

Previous supervision

Yasamin Mehrabadi
Yasamin Mehrabadi
Thesis title: Regulation of Cytotoxic Drug-Induced Apoptosis By Death Receptor 5 in Human Colon Cancer Cells
Degree subject: Cell and Molecular Biology
Degree type: Doctor of Philosophy
Awarded date: 5/2/2019

Publications

Journal articles (55)

Mohr, A., Chu, T., Brooke, GN. and Zwacka, RM., (2019). MSC.sTRAIL Has Better Efficacy than MSC.FL-TRAIL and in Combination with AKTi Blocks Pro-Metastatic Cytokine Production in Prostate Cancer Cells. Cancers. 11 (4), 568-568

Mohr, A., Deedigan, L., Jencz, S., Mehrabadi, Y., Houlden, L., Albarenque, S-M. and Zwacka, RM., (2018). Caspase-10: a molecular switch from cell-autonomous apoptosis to communal cell death in response to chemotherapeutic drug treatment.. Cell Death and Differentiation. 25 (2), 340-352

Mohr, A. and Zwacka, RM., (2018). The future of mesenchymal stem cell-based therapeutic approaches for cancer – From cells to ghosts. Cancer Letters. 414, 239-249

Weiher, H., Pircher, H., Jansen-Dürr, P., Hegenbarth, S., Knolle, P., Grunau, S., Vapola, M., Hiltunen, JK., Zwacka, RM., Schmelzer, E., Reumann, K. and Will, H., (2016). A monoclonal antibody raised against bacterially expressed MPV17 sequences shows peroxisomal, endosomal and lysosomal localisation in U2OS cells. BMC Research Notes. 9 (1), 128-

Mohr, A., Yu, R. and Zwacka, RM., (2015). TRAIL-receptor preferences in pancreatic cancer cells revisited: Both TRAIL-R1 and TRAIL-R2 have a licence to kill. BMC Cancer. 15 (1), 494-

Yu, R., Albarenque, SM., Cool, RH., Quax, WJ., Mohr, A. and Zwacka, RM., (2014). DR4 specific TRAIL variants are more efficacious than wild-type TRAIL in pancreatic cancer. Cancer Biology & Therapy. 15 (12), 1658-1666

Yu, R., Deedigan, L., Albarenque, SM., Mohr, A. and Zwacka, RM., (2013). Delivery of sTRAIL variants by MSCs in combination with cytotoxic drug treatment leads to p53-independent enhanced antitumor effects. Cell Death & Disease. 4 (2), e503-e503

Büneker, CK., Yu, R., Deedigan, L., Mohr, A. and Zwacka, RM., (2012). IFN-γ combined with targeting of XIAP leads to increased apoptosis-sensitisation of TRAIL resistant pancreatic carcinoma cells. Cancer Letters. 316 (2), 168-177

Albarenque, SM., Zwacka, RM. and Mohr, A., (2011). Both human and mouse mesenchymal stem cells promote breast cancer metastasis. Stem Cell Research. 7 (2), 163-171

Mohr, A., Albarenque, SM., Deedigan, L., Yu, R., Reidy, M., Fulda, S. and Zwacka, RM., (2010). Targeting of XIAP Combined with Systemic Mesenchymal Stem Cell-Mediated Delivery of sTRAIL Ligand Inhibits Metastatic Growth of Pancreatic Carcinoma Cells. STEM CELLS. 28 (11), 2109-2120

Stadel, D., Mohr, A., Ref, C., MacFarlane, M., Zhou, S., Humphreys, R., Bachem, M., Cohen, G., Moller, P., Zwacka, RM., Debatin, K-M. and Fulda, S., (2010). TRAIL-Induced Apoptosis Is Preferentially Mediated via TRAIL Receptor 1 in Pancreatic Carcinoma Cells and Profoundly Enhanced by XIAP Inhibitors. Clinical Cancer Research. 16 (23), 5734-5749

Jäger, R. and Zwacka, RM., (2010). The Enigmatic Roles of Caspases in Tumor Development. Cancers. 2 (4), 1952-1979

Zwacka, (2009). The TRAIL-receptor-1: TRAIL-receptor-3 and -4 ratio is a predictor for TRAIL sensitivity of cancer cells. Oncology Reports. 21 (5), 1289-1295

Mohr, A., Büneker, C., Gough, RP. and Zwacka, RM., (2008). MnSOD protects colorectal cancer cells from TRAIL-induced apoptosis by inhibition of Smac/DIABLO release. Oncogene. 27 (6), 763-774

Murray, TVA., McMahon, JM., Howley, BA., Stanley, A., Ritter, T., Mohr, A., Zwacka, R. and Fearnhead, HO., (2008). A non-apoptotic role for caspase-9 in muscle differentiation. Journal of Cell Science. 121 (22), 3786-3793

Mohr, A., Lyons, M., Deedigan, L., Harte, T., Shaw, G., Howard, L., Barry, F., O'Brien, T. and Zwacka, R., (2008). Mesenchymal stem cells expressing TRAIL lead to tumour growth inhibition in an experimental lung cancer model. Journal of Cellular and Molecular Medicine. 12 (6b), 2628-2643

Weiher, H. and Zwacka, RM., (2007). Vitamin D3-24-Hydroxylase (CYP24) as a potential target for intervention with diabetic and nondiabetic nephropathy. Clinical Laboratory. 53 (1-2), 85-88

Mohr, A., Lyons, M., Mohr, W. and Zwacka, R., (2007). Gentherapeutische Strategien gegen das kolorektale Karzinom. DMW - Deutsche Medizinische Wochenschrift. 132 (11), 567-570

La Ferla-Brühl, K., Westhoff, MA., Karl, S., Kasperczyk, H., Zwacka, RM., Debatin, KM. and Fulda, S., (2007). NF-κB-independent sensitization of glioblastoma cells for TRAIL-induced apoptosis by proteasome inhibition. Oncogene. 26 (4), 571-582

MOHR, A. and ZWACKA, R., (2007). In situ trapping of initiator caspases reveals intermediate surprises. Cell Biology International. 31 (5), 526-530

Mohr, A., Lyons, M., Mohr, W. and Zwacka, R., (2007). Gentherapeutische Strategien gegen das kolorektale Karzinom. TumorDiagnostik & Therapie. 28 (3), 129-132

Braeuer, SJ., Buneker, C., Mohr, A. and Zwacka, RM., (2006). Constitutively Activated Nuclear Factor- B, but not Induced NF- B, Leads to TRAIL Resistance by Up-Regulation of X-Linked Inhibitor of Apoptosis Protein in Human Cancer Cells. Molecular Cancer Research. 4 (10), 715-728

Behrend, L., Mohr, A., Dick, T. and Zwacka, RM., (2005). Manganese Superoxide Dismutase Induces p53-Dependent Senescence in Colorectal Cancer Cells. Molecular and Cellular Biology. 25 (17), 7758-7769

Mohr, A., Zwacka, RM., Jarmy, G., Büneker, C., Schrezenmeier, H., Döhner, K., Beltinger, C., Wiesneth, M., Debatin, K-M. and Stahnke, K., (2005). Caspase-8L expression protects CD34+ hematopoietic progenitor cells and leukemic cells from CD95-mediated apoptosis. Oncogene. 24 (14), 2421-2429

Kasperczyk, H., La Ferla-Brühl, K., Westhoff, MA., Behrend, L., Zwacka, RM., Debatin, K-M. and Fulda, S., (2005). Betulinic acid as new activator of NF-κB: molecular mechanisms and implications for cancer therapy. Oncogene. 24 (46), 6945-6956

Mohr, A., Zwacka, RM., Debatin, K-M. and Stahnke, K., (2004). A novel method for the combined flow cytometric analysis of cell cycle and cytochrome c release. Cell Death & Differentiation. 11 (10), 1153-1154

Mohr, A., Henderson, G., Dudus, L., Herr, I., Kuerschner, T., Debatin, K-M., Weiher, H., Fisher, KJ. and Zwacka, RM., (2004). AAV-encoded expression of TRAIL in experimental human colorectal cancer leads to tumor regression. Gene Therapy. 11 (6), 534-543

Behrend, L., Henderson, G. and Zwacka, RM., (2003). Reactive oxygen species in oncogenic transformation. Biochemical Society Transactions. 31 (6), 1441-1444

Zhou, W., (2001). Subcellular site of superoxide dismutase expression differentially controls AP-1 activity and injury in mouse liver following ischemia/reperfusion. Hepatology. 33 (4), 902-914

STARK, LA., DIN, FVN., ZWACKA, RM. and DUNLOP, MG., (2001). Aspirin-induced activation of the NF-κB signaling pathway: a novel mechanism for aspirin-mediated apoptosis in colon cancer cells. The FASEB Journal. 15 (7), 1273-1275

Zanetti, M., Zwacka, RM., Engelhardt, JF., Katusic, ZS. and O’Brien, T., (2001). Superoxide Anions and Endothelial Cell Proliferation in Normoglycemia and Hyperglycemia. Arteriosclerosis, Thrombosis, and Vascular Biology. 21 (2), 195-200

Fritz, E., Friedl, AA., Zwacka, RM., Eckardt-Schupp, F. and Meyn, MS., (2000). The Yeast TEL1 Gene Partially Substitutes for Human ATM in Suppressing Hyperrecombination, Radiation-Induced Apoptosis and Telomere Shortening in A-T Cells. Molecular Biology of the Cell. 11 (8), 2605-2616

Zwacka, RM., Stark, L. and Dunlop, MG., (2000). NF-?B kinetics predetermine TNF-? sensitivity of colorectal cancer cells. The Journal of Gene Medicine. 2 (5), 334-343

Zwacka, RM., Stark, L. and Dunlop, MG., (2000). NF-κB kinetics predetermine TNF-α sensitivity of colorectal cancer cells. Journal of Gene Medicine. 2 (5), 334-343

Lam, EWN., Hammad, HM., Zwacka, R., Darby, CJ., Baumgardner, KR., Davidson, BL., Oberley, TD., Engelhardt, JF. and Oberley, LW., (2000). Immunolocalization and Adenoviral Vector-mediated Manganese Superoxide Dismutase Gene Transfer to Experimental Oral Tumors. Journal of Dental Research. 79 (6), 1410-1417

Fan, C., Zwacka, RM. and Engelhardt, JF., (1999). Therapeutic approaches for ischemia/reperfusion injury in the liver. Journal of Molecular Medicine. 77 (8), 577-592

Clozel, M., Hess, P., Fischli, W., Löffler, B., Zwacka, RM., Reuter, A. and Weiher, H., (1999). Age-dependent hypertension in Mpv17-deficient mice, a transgenic model of glomerulosclerosis and inner ear disease. Experimental Gerontology. 34 (8), 1007-1015

Brown, MR., Miller, FJ., Li, W-G., Ellingson, AN., Mozena, JD., Chatterjee, P., Engelhardt, JF., Zwacka, RM., Oberley, LW., Fang, X., Spector, AA. and Weintraub, NL., (1999). Overexpression of Human Catalase Inhibits Proliferation and Promotes Apoptosis in Vascular Smooth Muscle Cells. Circulation Research. 85 (6), 524-533

Epperly, MW., Bray, JA., Krager, S., Berry, LM., Gooding, W., Engelhardt, JF., Zwacka, R., Travis, EL. and Greenberger, JS., (1999). Intratracheal injection of adenovirus containing the human MNSOD transgene protects athymic nude mice from irradiation-induced organizing alveolitis. International Journal of Radiation Oncology*Biology*Physics. 43 (1), 169-181

Lam, EWN., Zwacka, R., Seftor, EA., Nieva, DRC., Davidson, BL., Engelhardt, JF., Hendrix, MJC. and Oberley, LW., (1999). Effects of antioxidant enzyme overexpression on the invasive phenotype of hamster cheek pouch carcinoma cells. Free Radical Biology and Medicine. 27 (5-6), 572-579

Zwacka, RM., Zhang, Y., Zhou, W., Halldorson, J. and Engelhardt, JF., (1998). Ischemia/reperfusion injury in the liver of BALB/c mice activates AP-1 and nuclear factor ?B independently of I?B degradation. Hepatology. 28 (4), 1022-1030

Woo, YJ., Zhang, JCL., Vijayasarathy, C., Zwacka, RM., Englehardt, JF., Gardner, TJ. and Sweeney, HL., (1998). Recombinant adenovirus-mediated cardiac gene transfer of superoxide dismutase and catalase attenuates postischemic contractile dysfunction. Circulation. 98 (19 SUPPL.), II255-II260

Zwacka, RM., Dudus, L., Epperly, MW., Greenberger, JS. and Engelhardt, JF., (1998). Redox Gene Therapy Protects Human IB-3 Lung Epithelial Cells Against Ionizing Radiation-Induced Apoptosis. Human Gene Therapy. 9 (9), 1381-1386

Reuter, A., Nestl, A., Zwacka, RM., Tuckermann, J., Waldherr, R., Wagner, E-M., Höyhtyä, M., zum Gottesberge, AMM., Angel, P. and Weiher, H., (1998). Expression of the Recessive Glomerulosclerosis Gene Mpv17 Regulates MMP-2 Expression in Fibroblasts, the Kidney, and the Inner Ear of Mice. Molecular Biology of the Cell. 9 (7), 1675-1682

Zwacka, RM. and Dunlop, MG., (1998). GENE THERAPY FOR COLON CANCER. Hematology/Oncology Clinics of North America. 12 (3), 595-615

Zwacka, RM., Zhou, W., Zhang, Y., Darby, CJ., Dudus, L., Halldorson, J., Oberley, L. and Engelhardt, JF., (1998). Redox gene therapy for ischemia/reperfusion injury of the liver reduces AP1 and NF-κB activation. Nature Medicine. 4 (6), 698-704

Fang, X., Weintraub, NL., Rios, CD., Chappell, DA., Zwacka, RM., Engelhardt, JF., Oberley, LW., Yan, T., Heistad, DD. and Spector, AA., (1998). Overexpression of Human Superoxide Dismutase Inhibits Oxidation of Low-Density Lipoprotein by Endothelial Cells. Circulation Research. 82 (12), 1289-1297

Gonzalez-Zulueta, M., Ensz, LM., Mukhina, G., Lebovitz, RM., Zwacka, RM., Engelhardt, JF., Oberley, LW., Dawson, VL. and Dawson, TM., (1998). Manganese Superoxide Dismutase Protects nNOS Neurons from NMDA and Nitric Oxide-Mediated Neurotoxicity. The Journal of Neuroscience. 18 (6), 2040-2055

Epperly, M., Bray, J., Kraeger, S., Zwacka, R., Engelhardt, J., Travis, E. and Greenberger, J., (1998). Prevention of late effects of irradiation lung damage by manganese superoxide dismutase gene therapy. Gene Therapy. 5 (2), 196-208

Zwacka, RM., Zhang, Y., Halldorson, J., Schlossberg, H., Dudus, L. and Engelhardt, JF., (1997). CD4(+) T-lymphocytes mediate ischemia/reperfusion-induced inflammatory responses in mouse liver.. Journal of Clinical Investigation. 100 (2), 279-289

Müller, M., Smolders, JWT., Meyer zum Gottesberge, AM., Reuter, A., Zwacka, RM., Weiher, H. and Klinke, R., (1997). Loss of auditory function in transgenic Mpv17-deficient mice. Hearing Research. 114 (1-2), 259-263

Lam, EWN., Zwacka, R., Engelhardt, JF., Davidson, BL., Domann, FE., Yan, T. and Oberley, LW., (1997). Adenovirus-mediated manganese superoxide dismutase gene transfer to hamster cheek pouch carcinoma cells. Cancer Research. 57 (24), 5550-5556

Schenkel, J., Zwacka, RM., Rutenberg, C., Reuter, A., Waldherr, R. and Weiher, H., (1995). Functional rescue of the glomerulosclerosis phenotype in Mpv17 mice by transgenesis with the human Mpv17 homologue. Kidney International. 48 (1), 80-84

Zwacka, RM., Reuter, A., Pfaff, E., Moll, J., Gorgas, K., Karasawa, M. and Weiher, H., (1994). The glomerulosclerosis gene Mpv17 encodes a peroxisomal protein producing reactive oxygen species.. The EMBO Journal. 13 (21), 5129-5134

Karasawa, M., Zwacka, RM., Reuter, A., Fink, T., Hsieh, CL., Lichter, P., Francke, U. and Welher, H., (1993). The human homolog of the glomerulosclerosis gene Mpv17: structure and genomic organization. Human Molecular Genetics. 2 (11), 1829-1834

Conferences (8)

Albarenque, SM., Mohr, A., Rui, Y., Reidy, M., Zwacka, RM. and Laura, LD., (2010). RNAi-Mediated Inhibition of XIAP Combined with Systemic Mesenchymal Stem Cell-mediated Delivery of STRAIL Inhibits Metastatic Growth of Pancreatic Carcinoma Cells

Mohr, A., Behrend, L. and Zwacka, RM., (2006). Overexpression of MnSOD induces mitochondrial depolarization and p53-dependent senescence

Mohr, A., Debatin, KM. and Zwacka, RM., (2003). 5-fluorouracil induced apoptotis inhuman colon cancer cells is mediated by caspase-8 and-2 and inhibition of thymidilate synthase in p53 deficient cells.

Mohr, A., Zwacka, RM., Schrezenmeier, H., Dohner, K., Wiesneth, M., Stahnke, K. and Debatin, KM., (2003). Caspase-8L expression contributes to the protection of CD34+hematopoietic progenitor cells from C95-mediated apoptosis.

Mohr, A., Henderson, G., Dudus, L., Herr, I., Debatin, KM., Weiher, H., Fisher, K. and Zwacka, RM., (2003). AAV encoded expression of TRAIL in experimental human colorectal tumor cells leads to tumor regression.

Stark, LA., Zwacka, RM. and Dunlop, MG., (1998). Development of novel genetic approaches for the treatment of hepatic metastasis of colorectal cancer

Woo, YJ., Zhang, JC., Vijayasarathy, C., Zwacka, RM., Englehardt, JF., Gardner, TJ. and Sweeney, HL., (1997). Recombinant adenoviral mediated cardiac gene transfer of superoxide dismutase and catalase attenuates post-ischemic contractile dysfunction

ZWACKA, RM., KARASAWA, M., REUTER, Z. and WEIHER, H., (1994). THE MOUSE STRAIN MPV-17, A DISEASE-MODEL LINKING GLOMERULOSCLEROSIS TO LOSS OF A PEROXISOMAL FUNCTION

Grants and funding

2016

MSC - Mediated delivery of TRAIL for the treatment of prostate cancer.

Prostate Cancer UK

2015

The role of RIP1 in anti-cancer cytotoxic drug-induced JNK activation and apoptosis

Wellcome Trust

Contact

rzwacka@essex.ac.uk
+44 (0) 1206 872036

Location:

3SW.5.15, Colchester Campus