Ulrich Siler is lecturer for Gene and Cell Therapeutic Systems at the University of Applied Arts and Sciences Northwestern Switzerland (FHNW) since 2022. With more than 18 years of hands-on experience in the development of retroviral vectors, in pre-clinal GLP-conform animal studies and in clinical gene therapy, his research now focuses now on in vivo gene delivery.

Prior to joining the Institute for Pharmaceutical Technology at FHNW, Ulrich Siler was heading a research lab first at University Children`s Hospital Zürich from 2004 to 2020 and subsequently at University of Zürich, focusing on gene therapy. There he was involved in the first temporarily successful clinical gene therapy trial to cure patients suffering from X-linked Chronic Granulomatous Disease (X-CGD). In parallel, he developed a lentiviral gene therapy vector for the treatment of patients suffering from p47phox-deficient form of CGD, which is nearing clinical application. In 2017, he completed the habilitation process at Medical Faculty of the University of Zürich with his inaugural lecture, which was awarded by the Venia Legendi for Pediatric Immunology, Experimental Immunology and Gene Therapy.

Ulrich Siler graduated in Biochemistry from the University of Tübingen (Germany) in 1997, where he also received his PhD in 2001 for his research on the extracellular matrix of human bone marrow in the working group of Prof. Gerd Klein. After his PhD, Dr. Siler spent three years as postdoctoral researcher at Roche Vitamins Ltd which became DSM Nutritional Products during this time. Thereafter, he left industry and returned to academia in 2004.

• ResearchGate
  

• Joly J, Hudik E, Lecart S, Roos D, Verkuijlen P, Wrona D, Siler U, Reichenbach J, Nüsse O, Dupré-Crochet S. Membrane Dynamics and Organization of the Phagocyte NADPH Oxidase in PLB-985 Cells. Front Cell Dev Biol. (2020) 8:608600. doi: 10.3389/fcell.2020.608600.

• Wrona D, Pastukhov O, Pritchard R, Raimondi F, Tchinda J, Jinek M, Siler U*, and Reichenbach J*. CRISPR-directed therapeutic correction at the NCF1 locus is challenged by frequent incidence of chromosomal deletions. Molecular Therapy - Methods & Clinical Development (2020) 17:936-943. doi: 10.1016/j.omtm.2020.04.015. * Equal contribution

• Wrona D, Siler U*, Reichenbach J*. Novel Diagnostic Tool for p47 phox -Deficient Chronic Granulomatous Disease Patient and Carrier Detection. Mol Ther Methods Clin Dev. (2019) 13:274-278. doi: 10.1016/j.omtm.2019.02.001. * Equal contribution

• Meda Spaccamela V, Valencia RG, Pastukhov O, Duppenthaler A, Dettmer MS, Erb J, Steiner UC, Hillinger S, Speckmann C, Ehl S, Reichenbach J, Siler U. High Levels of IL-18 and IFN-γ in Chronically Inflamed Tissue in Chronic Granulomatous Disease. Front Immunol. (2019) 10: 2236. doi: 10.3389/fimmu.2019.02236. eCollection 2019.

• Wrona D, Siler U* & Reichenbach J*. Novel Diagnostic Tool for p47phox -Deficient Chronic Granulomatous Disease Patient and Carrier Detection. Mol Ther Methods Clin Dev. (2019) 13: 274-278. doi: 10.1016/j.omtm.2019.02.001. eCollection 2019 Jun 14. * These authors contributed equally

• Moens L, Gouwy M, Bosch B, Pastukhov O, Nieto-Patlàn A, Siler U, Bucciol G, Mekahli D, Vermeulen F, Desmet L, Maebe S, Flipts H, Corveleyn A, Moshous D, Philippet P, Tangye SG, Boisson B, Casanova JL, Florkin B, Struyf S, Reichenbach J, Bustamante J, Notarangelo LD, Meyts I. Human DOCK2 Deficiency: Report of a Novel Mutation and Evidence for Neutrophil Dysfunction. J Clin Immunol. (2019) 39: 298-308. doi: 10.1007/s10875-019-00603-w.

• Haenseler W*, Kuzmenko E, Smalls-Mantey A, Browne C, Seger R, James WS, Cowley SA†, Reichenbach J†, Siler U*†. Lentiviral gene therapy vector with UCOE stably restores function in iPSC-derived neutrophils of a CDG patient. Matters 2018; DOI: 10.19185/matters.201805000005. † Equal contribution.

• Wrona D, Siler U* & Reichenbach J*. CRISPR/Cas9-generated p47phox-deficient cell line for Chronic Granulomatous Disease gene therapy vector development. Scientific Reports, Sci Rep., 2017; 7:44187. * These authors contributed equally

• Vaas M, MSc, Enzmann G, Perinat T, Siler U, Reichenbach J, Licha K, Kipar A, Rudin M, Engelhardt B, Klohs J. Non-invasive near-infrared fluorescence imaging of the neutrophil response in a mouse model of transient cerebral ischemia. Journal of Cerebral Blood Flow & Metabolism, 2017, 271678-16676825.

• Siler U, Romao S, Tejera E, Pastukhov O, Kuzmenko E, Valencia R,  Meda Spaccamela V, Belohradsky BH, Speer O, Schmugge M, Kohne E, Hoenig M, Freihorst J, Schulz AS, Reichenbach R. Severe G6PD-deficiency leads to susceptibility to infection and absent NETosis. J. Allergy Clin. Immunol., 2017, 139: 212-219.

• Weisser M, Demel UM, Stein S, Chen-Wichmann L, Touzot F, Santilli G, Sujer S, Brendel C, Siler U, Cavazzana M, Thrasher AJ, Reichenbach J, Essers MA, Schwäble J, Grez M. Hyperinflammation in patients with chronic granulomatous disease leads to impairment of hematopoietic stem cell functions. J Allergy Clin Immunol., 2016, 138: 219-228.e9.

• Romao S., Tejera Puente E., Nytko K.J., Siler U., Münz C., Reichenbach J. Defective nuclear entry of hydrolases prevents neutrophil extracellular trap formation in patients with chronic granulomatous disease. J. Allergy Clin. Immunol., 2015;136: 1703-1706.e5.

• Dreyer A.K., Hoffmann D., Lachmann N., Ackermann M., Steinemann D., Timm B., Siler U., Reichenbach J., Grez M., Moritz T., Schambach A., CathomenT. TALEN mediated functional correction of X-linked chronic granulomatous disease in patient derived induced pluripotent stem cells.  Biomaterials, 2015; 69: 191-200.

• Siler U †, Paruzynski A †, Holtgreve-Grez H, Kuzmenko E, Koehl U, Renner ED, Alhan C, van de Loosdrecht AA, Schwäble J, Pfluger T, Tchinda J, Schmugge M, Jauch A, Naundorf S, Kühlcke K, Notheis G, Güngör T, v. Kalle C, Schmidt M +, Grez M +, Seger R +, Reichenbach J. Successful Combination of Sequential Gene Therapy and Rescue allo-HSCT in two Children with X-CGD – importance of timing. Current Gene Therapy, 2015;15: 416-27; †, + These authors contributed equally to the work

• Fiaschetti G, Abela L, Nonoguchi N, Dubuc AM, Remke M, Boro A, Grunder E, Siler U, Ohgaki H, Taylor MD, Baumgartner M, Shalaby T, Grotzer MA. Epigenetic silencing of miRNA-9 is associated with HES1 oncogenic activity and poor prognosis of medulloblastoma. Br J Cancer. 2014; 110: 636-47

• Brendel C*., Hänseler W*., Wohlgensinger V*., Bianchi M*., Tokmak S., Chen-Wichmann L., Kouzmenco E., Cesarovic N., Nicholls F., Reichenbach J., Seger R., Grez M*., Siler U*. Human miR223 Promoter as Novel Myelospecific Promoter for CGD Gene Therapy. Hum Gene Ther Methods. 2013; 24:151-9. * These authors contributed equally

• Jiang Y*, Cowley S.A.*, Siler U*, Melguzo D, Tilgner K, Browne C, deWilton A, Pryzborski S, Saretzki G, James W.S., Seger R.A. , Reichenbach J,  Lako M and Armstrong L. Derivation and functional analysis of patient specific induced pluripotent stem cells as an in vitro model of Chronic Granulomatous Disease. Stem Cells. 2012; 30:599-611. * These authors contributed equally to the work

• Bianchi M, Niemiec MJ, Siler U, Urban CF and Reichenbach J. Restoration of anti-Aspergillus defense by NETs in human CGD after Gene Therapy is Calprotectin-dependent J Allergy Clin Immunol. 2011; 127:1243-52.e7

• Wohlgensinger V, Seger RA, Ryan MD, Reichenbach J., Siler U. Signed outside: A surface marker system for transgenic cytoplasmic proteins. Gene Ther. 2010;17:1193-9

• Reichenbach J., Lopatin U., Mahlaoui N., Beovic B., Siler U., Zbinden R., Seger RA., Galmiche L., Brousse N., Kayal S., Güngör T., Blanche S., and Holland SM. Actinomyces in Chronic Granulomatous Disease: An Emerging and Unanticipated Pathogen Clin Infect Dis. 2009, 49: 1703-10

• Bianchi M, Rahamathullah AH, Brinkmann V, Siler U, Seger RA, Zychlinsky A, Reichenbach J. Restoration of NET formation by gene therapy in CGD controls aspergillosis. Blood 2009; 114: 2619-22

• Reichenbach J, Van de Velde H, De Rycke M, Staessen C, Platteau P, Baetens P, Güngör T, Ozsahin H, Scherer F, Siler U, Seger RA, Liebaers I. First Successful Bone Marrow Transplantation for X-linked Chronic Granulomatous Disease by Using Preimplantation Female Gender Typing and HLA Matching. Pediatrics. 2008; 122: e778-82.

• Junge S, Kloeckener-Gruissem B, Zufferey R, Keisker A, Salgo B, Fauchere JC, Shalaby T, Grotzer M, Siler U, Seger R, Güngör T. Correlation between recent thymic emigrants and CD3(+) (PECAM-1) CD4(+) T cells in normal individuals during aging and in lymphopenic children. Eur J Immunol. 2007, 37: 3270-80.

• Ott MG*, Schmidt M*, Schwarzwaelder K*, Stein S*, Siler U*, Koehl U, Glimm H, Kuhlcke K, Schilz A, Kunkel H, Naundorf S, Brinkmann A, Deichmann A, Fischer M, Ball C, Pilz I, Dunbar C, Du Y, Jenkins NA, Copeland NG, Luthi U, Hassan M, Thrasher AJ, Hoelzer D, von Kalle C, Seger R, Grez M. Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1. Nat Med. 2006; 12: 401-9. * These authors contributed equally to the work. 

• Herzog A*, Siler U*, Spitzer V, Seifert N, Denelavas A, Buchwald Hunziker P, Hunziker W, Goralczyk R & Wertz K. Lycopene reduces gene expression of steroid targets and inflammatory markers in normal rat prostate. FASEB J. 2005; 19: 272-274; * These authors contributed equally to this work.

• Siler U, Barella L, Spitzer V, Schnorr J, Lein M, Goralczyk R & Wert K. Lycopene and Vitamin E interfere with autocrine/paracrine loops in the Dunning prostate cancer model. FASEB J. 2004; 18: 1019-1021

• Siler U, Rousselle P, Müller C, Klein G. Laminin 2 chain as a stromal marker of the human bone marrow microenvironment. Br J Haematology 2002; 119: 212-220

• Kutlesa S,* Siler U,* Speriser A, Wessel JT, Virtanen I, Rousselle P, Sorokin LM, Mueller CA, Klein G. Developmentally regulated interactions of human thymocytes with different laminin isoforms. Immunology 2002; 106: 1-17; * These authors contributed equally to the work

• Siler U, Seiffert M, Puch S, Richards A, Torok-Storb B, Muller CA, Sorokin, Klein G. Characterization and functional analysis of laminin isoforms in human bone marrow. Blood 2000; 96: 4194-4203

Reviews

• Lanini L, Prader S, Siler U, Reichenbach J. Modern management of phagocyte defects. J. Allergy Clin. Immunol., 2017 28: 124-134.
• Kaufmann KB, Chiriaco M, Siler U, Finocchi A, Reichenbach J, Stein S and Grez M. Gene Therapy for Chronic Granulomatous Disease: Current Status and Future Perspectives. Curr Gene Ther. 2014, 14: 447-60
• Ott MG, Seger R, Stein S, Siler U, Hoelzer D, Grez M. Advances in the treatment of chronic granulomatous disease by gene therapy. Curr Gene Ther. 2007, 7: 155-61.
• Stein S, Siler U, Ott MG, Seger R, Grez M. Gene therapy for chronic granulomatous disease. Curr Opin Mol Ther. 2006; 8: 415-22.
• Siler U, Herzog A, Spitzer V, Seifert N, Denelavas A, Hunziker PB, Barella L, Hunziker W, Lein M, Goralczyk R, Wertz K. Lycopene effects on rat normal prostate and prostate tumor tissue. J Nutr. 2005; 135: 2050S-2S.
• Wertz K, Siler U, Goralczyk R. Lycopene: mode of action to promote prostate health. Arch. Biochem. Biophys. 2004; 430: 127-134

Book Chapters

• Siler U, Reichenbach J and Thrasher AJ. (2017) Gene Therapy for CGD, Chapter 12 in Seger RA, Roos D. Segal BH, Kuijpers TW. Chronic Granulomatous Disease: genetics, Biology and Clinical Management. Nova scientific publishers, ISBN # 978-1-53612-498-9
• Wertz K, Siler U, Barella L & Goralczyk R. (2004) Nutrigenomics in Research on Cancer Prevention, Nutrigenomics uncovers new Modes of Action for Lycopene in Prostate Cancer Prevention. In The Increased Role of Nutrition and Genomics in the Prevention and Management of Desease; ed. Ysbrand Poortman; VSOP, Soestdijk, The Netherlands; Chapter 7, pp. 71-86
• Goralczyk R. & Siler U. (2003) The role of Lycopene in Human Health. In Phytochemicals in Health and Disease; Bao Y. & Fenwick R. ed. Marcel Decker, Inc.: New York; Chapter 14, pp. 285-309

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ORCID 0000-0002-2458-2629