Patrick A. Baeuerle

Patrick Baeuerle (born 24 November 1957 in Friedrichshafen) is a German molecular biologist, Honorary Professor for Immunology at the University of Munich (LMU), and Chief Scientific Officer of the biopharmaceutical company Micromet, Inc. According to a survey of the Institute for Scientific Information, he was Germany’s most frequently cited biomedical researcher from 1991–2000, and ranked 38th worldwide.[1] He has an h-index of 87 points.[2]

Patrick Baeuerle did seminal work on tyrosine sulfation of proteins, transcription factor NF-kappaB, and on development of bi-specific T-cell engagers for therapy of cancer.

Education

Patrick Baeuerle studied biology at the University of Konstanz, Germany. He did his Ph.D. work with Wieland B. Huttner at the Max Planck Institute of Neurobiology in Martinsried, Germany, and at the European Molecular Biology Laboratory in Heidelberg, and received his Ph.D. degree (summa cum laude) from the Ludwig Maximilian University of Munich. His postdoctoral training was with Nobel laureate David Baltimore at the Whitehead Institute in Cambridge, Massachusetts.

Career

In 1989, Patrick Baeuerle started an independent research group at Klinikum Großhadern in Martinsried, Germany. In 1993, he became Chair of Biochemistry and Molecular Biology at the medical school of University of Freiburg. Three years later, he joined the start-up company Tularik in South San Francisco as its Director of Drug Discovery. In 1998, he moved back to Germany to head research and development of Micromet AG, a Munich-based biopharmaceutical company. By acquisition of CancerVax in 2006, Patrick Baeuerle became Chief Scientific Officer of NASDAQ -listed Micromet now headquartered in Bethesda, Maryland, with a research centre in Munich, Germany.

Research Activities

As a student, Patrick Baeuerle showed that tyrosine sulfation is a trans-Golgi-specific modification of secretory proteins.[3] As a postdoctoral fellow, he discovered the inhibitory subunit I-kappa B of transcription factor NF-kappa B,[4][5] and became inventor of the controversial NF-kappa B patent ‘516.[6] His own research group studied the function of purified I-kappaB proteins,[7] supported cloning of NF-kappa B subunits p50 and p65/RelA,[8][9] identified NF-kappa as a redox-controlled transcription factor[10] demonstrated the trans-activating potential of p65/RelA,[11] showed that NF-kappa B is binding to DNA as a heterodimer,[12] studied how I-kappa B proteins control nuclear translocation of NF-kappaB,[13][14] and unravelled the basic mechanism of NF-kappa B activation, involving phosphorylation of I-kappa B[15][16] and its subsequent degradation by the proteasome.[17] His group was also first to show that NF-kappa B plays a functional role in the nervous system.[18] Patrick Baeuerle authored more than 150 publications on NF-kappa B and related research.

Since 1998, Patrick Baeuerle investigates the therapeutic potential of T cell-engaging BiTE antibodies for therapy of cancer,[19][20][21][22] and has been responsible at Micromet for the development of blinatumomab and several other antibody therapies. He authored more than 210 publications (Search in PubMed with author name “baeuerle p”).

References

  1. ↑ Focus Magazin, vol. 20, 2001 and press release by NewsRx
  2. ↑ Citation report created for “Patrick Baeuerle” by Web of Science data base on (site requires registration for Hirsch index calculation)
  3. ↑ Baeuerle, P. A.; Huttner, WB (1987). "Tyrosine sulfation is a trans-Golgi-specific protein modification". The Journal of Cell Biology. 105 (6): 2655–64. doi:10.1083/jcb.105.6.2655. PMC 2114704Freely accessible. PMID 3121635.
  4. ↑ Baeuerle, Patrick A.; Baltimore, David (1988). "Activation of DNA-binding activity in an apparently cytoplasmic precursor of the NF-κB transcription factor". Cell. 53 (2): 211–7. doi:10.1016/0092-8674(88)90382-0. PMID 3129195.
  5. ↑ Baeuerle, P A; Baltimore, D (1989). "A 65-kappaD subunit of active NF-kappaB is required for inhibition of NF-kappaB by I kappaB". Genes & Development. 3 (11): 1689–98. doi:10.1101/gad.3.11.1689.
  6. ↑ US patent 6410516, Baltimore, David et al., "Nuclear factors associated with transcriptional regulation", issued 2002-06-25
  7. ↑ Zabel, Ulrike; Baeuerle, Patrick A. (1990). "Purified human IκB can rapidly dissociate the complex of the NF-κB transcription factor with its cognate DNA". Cell. 61 (2): 255–65. doi:10.1016/0092-8674(90)90806-P. PMID 2184941.
  8. ↑ Kieran, Mark; Blank, Volker; Logeat, FrédéRique; Vandekerckhove, Joël; Lottspeich, Frledrich; Le Bail, Odile; Urban, Manuela B.; Kourilsky, Philippe; et al. (1990). "The DNA binding subunit of NF-κB is identical to factor KBF1 and homologous to the rel oncogene product". Cell. 62 (5): 1007–18. doi:10.1016/0092-8674(90)90275-J. PMID 2203531.
  9. ↑ Ruben, S.; Dillon, P.; Schreck, R; Henkel, T; Chen, C.; Maher, M; Baeuerle, P.; Rosen, C. (1991). "Isolation of a rel-related human cDNA that potentially encodes the 65-kD subunit of NF-kappa B". Science. 254 (5028): 11. doi:10.1126/science.1925549.
  10. ↑ Schreck, R; Rieber, P; Baeuerle, PA (1991). "Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-kappa B transcription factor and HIV-1". The EMBO Journal. 10 (8): 2247–58. PMC 452914Freely accessible. PMID 2065663.
  11. ↑ Schmitz, ML; Baeuerle, PA (1991). "The p65 subunit is responsible for the strong transcription activating potential of NF-kappa B". The EMBO Journal. 10 (12): 3805–17. PMC 453117Freely accessible. PMID 1935902.
  12. ↑ Urban, MB; Schreck, R; Baeuerle, PA (1991). "NF-kappa B contacts DNA by a heterodimer of the p50 and p65 subunit". The EMBO Journal. 10 (7): 1817–25. PMC 452856Freely accessible. PMID 2050119.
  13. ↑ Henkel, Thomas; Zabel, Ulrike; Van Zee, Karen; Müller, Judith M.; Fanning, Ellen; Baeuerle, Patrick A. (1992). "Intramolecular masking of the nuclear location signal and dimerization domain in the precursor for the p50 NF-κB subunit". Cell. 68 (6): 1121–33. doi:10.1016/0092-8674(92)90083-O. PMID 1547506.
  14. ↑ Zabel, U; Henkel, T; Silva, MS; Baeuerle, PA (1993). "Nuclear uptake control of NF-kappa B by MAD-3, an I kappa B protein present in the nucleus". The EMBO Journal. 12 (1): 201–11. PMC 413192Freely accessible. PMID 7679069.
  15. ↑ Traenckner, EB; Wilk, S; Baeuerle, PA (1994). "A proteasome inhibitor prevents activation of NF-kappa B and stabilizes a newly phosphorylated form of I kappa B-alpha that is still bound to NF-kappa B". The EMBO Journal. 13 (22): 5433–41. PMC 395500Freely accessible. PMID 7957109.
  16. ↑ Traenckner, EB; Pahl, HL; Henkel, T; Schmidt, KN; Wilk, S; Baeuerle, PA (1995). "Phosphorylation of human I kappa B-alpha on serines 32 and 36 controls I kappa B-alpha proteolysis and NF-kappa B activation in response to diverse stimuli". The EMBO Journal. 14 (12): 2876–83. PMC 398406Freely accessible. PMID 7796813.
  17. ↑ Henkel, Thomas; MacHleidt, Thomas; Alkalay, Irit; Krönke, Martin; Ben-Neriah, Yinon; Baeuerle, Patrick A. (1993). "Rapid proteolysis of IκB-α is necessary for activation of transcription factor NF-κB". Nature. 365 (6442): 182–5. doi:10.1038/365182a0. PMID 8371761.
  18. ↑ Kaltschmidt, C.; Kaltschmidt, B.; Baeuerle, P. A. (1995). "Stimulation of Ionotropic Glutamate Receptors Activates Transcription Factor NF- B in Primary Neurons". Proceedings of the National Academy of Sciences. 92 (21): 9618–22. doi:10.1073/pnas.92.21.9618. PMC 40853Freely accessible. PMID 7568184.
  19. ↑ Bargou, R.; Leo, E.; Zugmaier, G.; Klinger, M.; Goebeler, M.; Knop, S.; Noppeney, R.; Viardot, A.; et al. (2008). "Tumor Regression in Cancer Patients by Very Low Doses of a T Cell-Engaging Antibody". Science. 321 (5891): 974–7. doi:10.1126/science.1158545. PMID 18703743.
  20. ↑ Baeuerle, PA; Kufer, P; Bargou, R (2009). "BiTE: Teaching antibodies to engage T-cells for cancer therapy". Current opinion in molecular therapeutics. 11 (1): 22–30. PMID 19169956.
  21. ↑ Lutterbuese, R.; Raum, T.; Kischel, R.; Hoffmann, P.; Mangold, S.; Rattel, B.; Friedrich, M.; Thomas, O.; et al. (2010). "T cell-engaging BiTE antibodies specific for EGFR potently eliminate KRAS- and BRAF-mutated colorectal cancer cells". Proceedings of the National Academy of Sciences. 107 (28): 12605–10. doi:10.1073/pnas.1000976107.
  22. ↑ Herrmann, Ines; Baeuerle, Patrick A.; Friedrich, Matthias; Murr, Alexander; Filusch, Susanne; Rüttinger, Dominik; Majdoub, Mariam W.; Sharma, Sherven; et al. (2010). Hartl, Dominik, ed. "Highly Efficient Elimination of Colorectal Tumor-Initiating Cells by an EpCAM/CD3-Bispecific Antibody Engaging Human T Cells". PLoS ONE. 5 (10): e13474. doi:10.1371/journal.pone.0013474. PMC 2956687Freely accessible. PMID 20976159.
  1. University of Munich
  2. Micromet, Inc.
  3. University of Konstanz
  4. Max-Planck Institute of Molecular Cell Biology and Genetics
  5. Max-Planck Institute for Neurobiology
  6. EMBL
  7. Whitehead Institute
  8. GeneCentre
  9. University of Freiburg
  10. NF-kappa B (516) patent
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