Burghardt Wittig

Burghardt Wittig (born 1947 in Celle, Germany) is the chairman of Foundation Institute MolBio2Math - Molecular Biology & Integral Biomathics, a non-profit foundation and a German professor of biochemistry and molecular biology at Freie Universitaet Berlin in Berlin (FUB), Germany.[1] He is known for his research in the fields of chromatin structure and gene regulation, DNA structures induced by torsional strain, signal transduction mediated by G-proteins, DNA- and cell-based vaccines and therapeutic immunomodulation.

Early life

Wittig was born in Celle, Germany, where he attended comprehensive secondary school, the classical “Gymnasium Ernestinum”. He started playing clarinet at the age of twelve and six years later won the clarinet competition of the renowned German classical music award “Jugend musiziert”. At the age of 14, he started rowing and later raced successfully in quads and double sculls. He graduated by the German Abitur in fall 1966, followed by two years of service in the German military. While already attending medical school, he also received training as an engineer specialized in hearing aids, and graduated by the German Gesellenpruefung.[1]

Career

Wittig studied Medicine at Freie Universität Berlin from 1968 to 1975. While he was still studying medicine, he joined laboratories at the Institute for Molecular Biology and Biochemistry (Institut für Molekularbiologie und Biochemie) of the Freie Universitaet Berlin and at the Max Planck Institute for Molecular Genetics, to perform the experimental work for his doctoral thesis. His principal thesis advisor was molecular biologist Hubert Gottschling with influential mentoring by V.A. Erdmann, O. Pongs, H.-J. Risse, H. Tiedemann and H.G. Wittmann. Wittig successfully defended his thesis “Purification and Characterization of the Four Lysine-Specific Transfer Ribonucleic Acids from Chicken Embryos” (Reinigung und Charakterisierung der vier lysinspezifischen Transfer-Ribonukleinsäuren aus Hühnerembryonen) in 1976. He continued at Freie Universitaet Berlin, first as a postdoc (1976-1978) and later as an assistant professor (1978-1987).

Between 1976 and 1986, in addition to his work as a researcher, Wittig attended a variety of physics courses as a visiting student at Freie Universität Berlin (FUB), Technische Universität Berlin (TUB), California Institute of Technology (CalTech) and Massachusetts Institute of Technology (MIT) to widen his scientific horizon. He received no official degree for these classes.

In 1980 Wittig habilitated for “Biochemistry and Molecular Biology” and became formally eligible for a full professorship in Germany.

Wittig was awarded a Heisenberg scholarship of the Deutsche Forschungsgemeinschaft (DFG) in 1982/83 and worked as a fellow of the program until 1989. During this time, he was invited by scholars Edward Trifonov, Weizmann Institute of Science, Rehovot, and the late Koki Horikoshi, Riken Institute (ERATO superbug project).

From 1984 to 1986, he was a visiting professor at Alexander Rich’s lab at MIT and also cooperated with Alexander Varshavsky; in Wittig's own words “entering the most career-shaping times of his life”.[2]

In 1987, Freie Universitaet Berlin awarded Wittig an extraordinary professorship (“außerplanmäßige Professur“). He continued to work as a visiting professor at MIT in Rich's lab until 1989, when he became a full professor (S-C4, tenure) at Freie Universitaet Berlin (FUB) and was awarded the Schering Professorship of FUB. One year later, Wittig was tenured (C4, German Full Professorship) as founding chair and department head of Molecular Biology and Bioinformatics at the Institute for Molecular Biology and Biochemistry (Institut für Molekularbiologie und Biochemie) at Freie Universitaet Berlin.

By political administration and change of Berlin law (Berliner Universitaetsmedizingesetz) his institute became an entity of the fused medical faculties of FUB and Humboldt-Universitaet zu Berlin, now named Charité – Universitaetsmedizin. Wittig served as Director of this new Institute of Molecular Biology and Bioinformatics until 2010.

Beginning in 1994, Wittig focused his research on the design, development, and clinical proof-of-concept of covalently closed DNA constructs for the treatment of cancer and for DNA-vaccines against infectious diseases. Two classes of DNA-molecules evolved through theoretical and experimental selection processes and became key technologies; MIDGE (minimalistic, immunogenically defined gene expression), and dSLIM for DNA-based immunomodulation.[3]

To enable the independent transition from basic research to clinical DNA medicines, he founded Mologen AG in 1998. The firm had their IPO at the German stock exchange in the same year.[4] Wittig served as CEO (Vorstandsvorsitzender) until the end of 2007, while maintaining his full professorship at FUB in a private-public-partnership.

In 2010, Wittig's institute returned to Freie Universitaet Berlin as a non-profit foundation with FUB as the trustee. He served as Chairman of the institute, now named "Foundation Institute Molecular Biology and Bioinformatics", until 2017.

In late 2019, Wittig founded MolBio2Math - Molecular Biology & Integral Biomathics (a non-profit foundation institute under the trusteeship of the Gentechnologiestiftung - Dr. Georg und Ingeburg Scheel Stiftung), of which he is currently the chairman.[5]

Wittig has published the results of his research in leading scientific journals, including Cell, Nature, PNAS, and Science.

Selected publications
  • Wittig, B; Reuter, S; Gottschling, H (1973). "Purification of the four lysine specific transfer ribonucleic acids from chick embryos". Biochim. Biophys. Acta. 331: 221–230. doi:10.1016/0005-2787(73)90435-8.
  • Allfrey VG, Arnott S, Bradbury EM, Bayev A, Chambon P, Crick FHC, Felsenfeld G, Mirzabekov AT, Noll M, Stern H, van Holde KE, Wittig B, Zachau HG, and Zweidler A (1976) „The Structure of Chromatin“ in: Organization and expression of chromosomes: Dahlem Konferenzen Life Sciences Research Report, 4; Allfrey AG, Bautz EKF, McCarthy BJ, Schimke RT, Tissieres A (Eds.) pp. 19–27; ISBN 3820012052 / ISBN 9783820012057, Abakon Verlagsgesellschaft, Berlin.
  • Wittig, B; Wittig, S (1979). "A phase relationship associates tRNA structural gene sequences with nucleosome cores". Cell. 18 (4): 1173–1183. doi:10.1016/0092-8674(79)90230-7.
  • Wittig, B; Wittig, S (1982). "Function of a tRNA gene promoter depends on nucleosome position". Nature. 297 (5861): 31–38. doi:10.1038/297031a0.
  • Wittig, B; Dorbic, T; Rich, A (1991). ""Transcription is associated with Z-DNA formation in metabolically active, permeabilized mammalian cell nuclei"(PDF)". Proc. Natl. Acad. Sci. USA. 88 (6): 2259–2263. doi:10.1073/pnas.88.6.2259. PMC 51210. PMID 2006166.
  • Kleuss, C; Hescheler, J; Ewel, C; Rosenthal, W; Schultz, G; Wittig, B (1991). "Assignment of G-protein subtypes to specific receptors inducing inhibition of calcium currents". Nature. 353 (6339): 43–48. doi:10.1038/353043a0. PMID 1679199.
  • Kleuss, C; Scherübl, H; Hescheler, J; Schultz, G; Wittig, B (1993). "Selectivity in signal transduction determined by gamma subunits of heterotrimeric G proteins". Science. 259 (832–834): 40. doi:10.1126/science.8094261.
  • Müller, V; Takeya, M; Brendel, S; Wittig, B; Rich, A (1996). "Z-DNA forming sites within the human b-globin gene cluster". Proc. Natl. Acad. Sci. USA. 93 (2): 780–784. doi:10.1073/pnas.93.2.780.
  • Möller, P; Sun, Y; Dorbic, T; Alijagic, S; Makki, A; Jurgovsky, K; Schroff, M; Henz, BM; Wittig, B; Schadendorf, D (1998). "Vaccination with IL-7 gene-modified autologous melanoma cells can enhance the anti-melanoma lytic activity in peripheral blood of patients with a good clinical performance status: a clinical phase I study". British Journal of Cancer. 77 (11): 1907–1916. doi:10.1038/bjc.1998.317.
  • Wittig, B; Märten, A; Dorbic, T; Weineck, S; Min, H; Niemitz, S; Trojaneck, B; Flieger, D; Kruopis, S; Albers, A; Löffel, J; Neubauer, A; Albers, P; Müller, S; Sauerbruch, T; Bieber, T; Huhn, D; Schmidt-Wolf, IGH (2001). "Therapeutic vaccination against metastatic carcinoma by expression-modulated and immunomodified autologous tumor cells: A first clinical Phase I/II trial". Human Gene Therapy. 12 (3): 267–278. doi:10.1089/10430340150218404. PMID 11177563.
  • López-Fuertes, L; Pérez-Jiménez, E; Vila-Coro, AJ; Sack, F; Moreno, S; Konig, SA; Junghans, C; Wittig, B; Timón, M; Esteban, M (2002). "DNA vaccination with linear minimalistic (MIDGE) vectors confers protection against Leishmania major infection in mice". Vaccine. 21 (3–4): 247–57. doi:10.1016/s0264-410x(02)00450-4.
  • Weihrauch, MR; Ansen, S; Jurkiewicz, E; Geisen, C; Xia, Z; Anderson, KS; Gracien, E; Schmidt, M; Wittig, B; Diehl, V; Wolf, J; Bohlen, H; Nadler, LM (2005). "Phase I/II combined chemoimmunotherapy with carcinoembryonic antigen-derived HLA-A2-restricted CAP-1 peptide and irinotecan, 5-fluorouracil, and leucovorin in patients with primary metastatic colorectal cancer". Clin Cancer Res. 11 (16): 5993–6001. doi:10.1158/1078-0432.ccr-05-0018. PMID 16115944.
  • Kneipp, J; Kneipp, H; Wittig, B; Kneipp, K (2007). "One- and two-photon excited optical ph probing for cells using surface-enhanced Raman and hyper-Raman nanosensors". Nano Lett. 7 (9): 2819–23. doi:10.1021/nl071418z. PMID 17696561.
  • Endmann, A; Baden, M; Weisermann, E; Kapp, K; Schroff, M; Kleuss, C; Wittig, B; Juhls, C (2010). "Immune response induced by a linear DNA vector: Influence of dose, formulation and route of injection". Vaccine. 28 (21): 3642–9. doi:10.1016/j.vaccine.2010.03.034. PMID 20362204.
  • Kapp, K; Kleuss, C; Schroff, M; Wittig, B (2014). "Genuine Immunomodulation With dSLIM". Mol Ther Nucleic Acids. 3: e170. doi:10.1038/mtna.2014.28.
  • Wittig, B; Schmidt, M; Scheithauer, W; Schmoll, HJ (2015). "MGN1703, an immunomodulator and toll-like receptor 9 (TLR-9) agonist: From bench to bedside". Crit Rev Oncol Haematol. 94 (1): 31–44. doi:10.1016/j.critrevonc.2014.12.002.
  • Volz, B; Schmidt, M; Heinrich, K; Kapp, K; Schroff, M; Wittig, B (2015). "Design and characterization of the tumor vaccine MGN1601, allogeneic fourfold gene-modified vaccine cells combined with a TLR-9 agonist". Mol Ther Oncolytics. 3: 15023. doi:10.1038/mto.2015.23.
  • Zhang, S.; Wittig, B. (2015). "Alexander Rich: 1924–2015". Nature Biotechnology. 33 (6): 593. doi:10.1038/nbt.3262. PMID 26057974.
  • Vibholm, L; Schleimann, MH; Højen, JF; Benfield, T; Offersen, R; Rasmussen, K; Olesen, R; Dige, A; Agnholt, J; Grau, J; Buzon, M; Wittig, B; Lichterfeld, M; Petersen, AM; Deng, X; Abdel-Mohsen, M; Pillai, SK; Rutsaert, S; Trypsteen, W; De Spiegelaere, W; Vandekerchove, L; Østergaard, L; Rasmussen, T; Denton, PW; Tolstrup, M; Søgaard, OS (2017). "Short-Course Toll-Like Receptor 9 Agonist Treatment Impacts Innate Immunity and Plasma Viremia in Individuals With Human Immunodeficiency Virus Infection". Clin Infect Dis. 64 (12): 1686–1695. doi:10.1093/cid/cix201.
  • Krarup, AR; Abdel-Mohsen, M; Schleimann, MH; Vibholm, L; Engen, PA; Dige, A; Wittig, B; Schmidt, M; Green, SJ; Naqib, A; Keshavarzian, A; Deng, X; Olesen, R; Petersen, AM; Benfield, T; Østergaard, L; Rasmussen, TA; Agnholt, J; Nyengaard, JR; Landay, A; Søgaard, OS; Pillai, SK; Tolstrup, M; Denton, PW (2018). "The TLR9 agonist MGN1703 triggers a potent type I interferon response in the sigmoid colon". Mucosal Immunol. 11 (2): 449–461. doi:10.1038/mi.2017.59.
  • Thomas, M; Ponce-Aix, S; Navarro, A; Riera-Knorrenschild, J; Schmidt, M; Wiegert, E; Kapp, K; Wittig, B; Mauri, C; Dómine Gómez, M; Kollmeier, J; Sadjadian, P; Fröhling, K-P; Huber, RM; Wolf, M (2018). "Immunotherapeutic maintenance treatment with toll-like receptor 9 agonist lefitolimod in patients with extensive-stage small cell lung cancer: results from the exploratory, controlled, randomized, international phase II IMPULSE study". Annals of Oncology. 29 (10): 2076–2084. doi:10.1093/annonc/mdy32.
  • Kapp, K; Volz, B; Oswald, D; Wittig, B; Baumann, M; Schmidt, M (2019). "Beneficial modulation of the tumor microenvironment and generation of anti-tumor responses by TLR9 agonist lefitolimod alone and in combination with checkpoint inhibitors". OncoImmunology. 8: e1659096. doi:10.1080/2162402X.2019.1659096.
  • Schleimann, MH; Kobberø, ML; Vibholm, LK; Kjær, K; Giron, LB; Busman-Sahay, K; Chan, CN; Nekorchuk, M; Schmidt, M; Wittig, B; Damsgaard, TE; Ahlburg, P; Hellfritzsch, MB; Zuwala, K; Rothemejer, FH; Olesen, R; Schommers, P; Klein, F; Dweep, H; Kossenkov, A; Nyengaard, JR; Estes, JD; Abdel-Mohsen, M; Østergaard, L; Tolstrup, M; Søgaard, OS; Denton, PW (2019). "TLR9 agonist MGN1703 enhances B cell differentiation and function in lymph nodes". EBioMedicine. 45: 328–340. doi:10.1016/j.ebiom.2019.07.005.
  • Schmidt M, Schroff M, Wittig B (2020) „Harnessing the Therapeutic Potential of Dendritic Cells” in:  Second Generation Cell and Gene-based Therapies, pp. 183–202; Alain A. Vertès, Devyn M. Smith, Nasib Qureshi, Nathan J. Dowden (Eds.) ISBN 978-0-12-812034-7, Academic Press, London
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References
  1. "Burghardt Wittig". www.fu-berlin.de. 2012-06-04. Retrieved 2018-07-09.
  2. Zhang, Shuguang; Wittig, Burghardt (2015-06-01). "Alexander Rich 1924–2015". Nature Biotechnology. 33 (6): 593–598. doi:10.1038/nbt.3262. ISSN 1087-0156. PMID 26057974.
  3. "dSLIMming the immune system". BioCentury. Retrieved 2018-07-09.
  4. "Biotech & Pharma". Cluster Gesundheitswirtschaft Berlin-Brandenburg (in German). Retrieved 2018-07-09.
  5. "– Researchers – Molecular Biology & Integral Biomathics". molbio2math.org. Retrieved 2020-03-25.
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