User:Walter Doerfler

Wikipedia Walter Doerfler (English language version) Walter Doerfler (* 11 August 1933 in Weißenburg/Bayern) is a molecular geneticist and virologist who works in Cologne and Erlangen, Germany.

Family: Walter Doerfler was born into a family of physicians. His paternal grandfather, Hans Doerfler (1863–1942) was a pioneer of abdominal surgery and author of the successful book Für die Praxis (2 volumes 1935 and 1938). Heinrich Doerfler (1864-1937), Hans’s brother, developed a new technique for Cesarean sections (1929). His father Hermann Doerfler (1897-1992) was an experienced practitioner of medicine. On the maternal side (Hermine, neé Kreuter 1905-1978), his ancestors were engineers (water, railroads). Franz Jakob Kreuter (1813–1889) was an internationally active architect and civil engineer in Vienna, Austria. Walter Doerfler has been married to Helli, neé Schleich since 1960. Their son Markus (* 1965) practices law.

Training in Medicine and Molecular Biology: After the Abitur (final high school Examen), he attended Medical Schools in Erlangen, Munich (LMU) and Hamburg. In 1959, he earned an MD degree from LMU for a thesis in Functional Anatomy and his Medical License (Approbation) in 1961, after internships at University Hospital Munich and a one year rotating internship at Mercer Hospital in Trenton, NJ, USA 1959/1960 (fellow of the Ventnor Foundation). He completed postdoctoral training in biochemistry and molecular biology at the Max-Planck-Institute for Biochemistry in Munich (Wolfram Zillig, 1961-1963) and in the Department of Biochemistry, Stanford University, Stanford, CA, USA (David S. Hogness, 1963-1966).

Faculty appointments: The Rockefeller University, New York, NY, USA, 1966-1969 (Assistant Professor), 1969-1971 (Associate Professor), 1971-1978 (Adjunct Professor); Uppsala University, Uppsala, Sweden 1971-1972 (Guest Professor); Universität zu Köln, Germany 1972-2002 (Professor of Molecular Genetics), and 2002- (Emeritus Professor); Friedrich-Alexander University (FAU) Erlangen-Nürnberg 2002- (Guest Professor). Visiting Scientist/Professor at Stanford U. 1978 and 1993; Princeton U. 1986 and 1999; Vanderbilt U. 2006; also at Академия наук, Moсква 1990; Kawasaki Medical School in Kurashiki, Japan 1988, 1995, 1998; and at Uppsala Universitet 2002, 2006, 2007, 2009.

Major contributions to Molecular Genetics: His research has been focused on the fate of foreign DNA and on the regulation of gene expression in mammalian systems, studying adenoviruses and medically important human genes. He is one of the pioneers in studies on DNA methylation and epigenetics as well as on foreign DNA integration. (i)	Starting in 1968, results on the chromosomal integration of adenovirus type 12 (Ad12) DNA into the hamster cell genome earned interest among the tumor virus groups [1]. These projects led to the identification of (non-specific) Ad12 DNA integrations sites in the mammalian genome [2-4]. (ii)	In 1975, his research group started to investigate CpG DNA methylation in viral and cellular systems and discovered that integrated Ad12 DNA was de novo methylated, whereas viral DNA inside the virus particle was unmethylated [2, 5, 6]. His laboratory’s documentation of an inverse correlation between the levels of CpG methylation in integrated Ad12 DNA and their transcriptional activity initiated world-wide projects on the long-term silencing of CpG methylation in eukaryotic promoters [6, 7]. This field later-on developed into the area of Epigenetics. (iii)	The integration of foreign DNA into mammalian genomes caused genome-wide alterations in transcriptional and CpG methylation profiles [8-11]. This finding led to the notion that CpG methylation patterns could be subject to change upon the entry and/or genomic insertion of foreign DNA. Methylation patterns have been interpreted as guardians of genome stability [11]. (iv)	Food-ingested foreign DNA can be transiently traced in the murine gastrointestinal tract, in small amounts and in fragmented form. This DNA can be followed in spurious quantities into the blood stream and several organs, but not in the germ line [12, 13]. There is evidence that this DNA might be linked to cellular DNA in the spleen. (v)	In genomes of the human epi-genetically caused fragile X syndrome (FXS) with severe cognitive impairment plus psychological and physical disorders, the promoter of the fragile X mental retardation gene 1 is heavily methylated. His group identified a distinct DNA methylation boundary in the upstream region of this gene’s promoter. This boundary is maintained in all human cell types irrespective of age, gender, tissue of origin, developmental stage, or malignant transformation, but is lost in FXS genomes [14]. The boundary is also present in the mouse genome. The boundary sequence binds to nuclear proteins from human cells and may play a major role in stabilizing the human genome in this region.

Selected references [1] Doerfler W. 1968. Proc Nat Acad Sci USA 60:636-643. [2] Sutter D, Westphal M, Doerfler W. 1978. Cell 14:569-585. [3] Doerfler W, Gahlmann R, Stabel S, Deuring R, Lichtenberg U, Schulz M, Eick D, Leisten R. 1983. Current Topics Microbiol Immunol 109:193-228. [4] Deuring R, Winterhoff U, Tamanoi F, Stabel S, Doerfler W. 1981. Nature 293:81-84. [5] Günther U, Schweiger M, Stupp M, Doerfler W. 1976. Proc Nat Acad Sci USA 73:3923-3927. [6] Sutter D, Doerfler W. 1980. Proc Nat Acad Sci USA 77:253-256. [7] Doerfler W. 1983. Annu Rev Biochem 52:93-124. [8] Heller H, Kämmer C, Wilgenbus P, Doerfler W. 1995. Proc Nat Acad Sci USA 92:5515-5519. [9] Naumann A, Kraus C, Hoogeveen A, Ramirez CM, Doerfler W. 2014. J Mol Biol 426:2554-2566. [10] Weber S, Hofmann A, Herms S, Hoffmann P, Doerfler W. 2015. Epigenomics 7:745-755. [11] Doerfler W, Weber S, Naumann A. 2018. Epigenetics 14, DOI: 10.1080/15592294.2018.1549463. Published online: 12 Dec 2018. [12] Schubbert R, Renz D, Schmitz B, Doerfler W. 1997. Proc Nat Acad Sci USA 94:961-966. [13] Hohlweg U, Doerfler W. 2001. Mol Genet Genomics 265:225-233. [14] Naumann A, Hochstein N, Weber S, Fanning E, Doerfler W. 2009. Am J Human Genet 85:606-616.

Prizes and Honors Fellow of the Ventnor Foundation, Ventnor City, N.J., USA, 1959 to 1960. Career Scientist of the Public Health Research Council of the City of New York, 1969-1971. Stipend of the Swedish Cancer Society, 1971 to 1972. Member European Molecular Biology Organization (EMBO), 1976. Aronson Prize Berlin, 1981. Robert-Koch-Prize Bonn, 1984. Stipend of the Japanese Society for the Advancement of Science, Tokyo, 1985. Plaque of Appreciation, Biochemical Society, the Republic of Korea, Seoul, 1988. Member Nationale Akademie der Wissenschaften Leopoldina. Halle Germany, 1997. Certificate of Appreciation, President Kawasaki Medical School, Kurashiki, Japan, 1998. Kurzzeit Dozentur DAAD (German Academic Exchange Service) (Vanderbilt), 2006. Fellow American Association for the Advancement of Science (AAAS), 2007. Löffler-Frosch Medal of the Gesellschaft für Virologie, 2013. Dr. med. h. c. Uppsala universitet, Uppsala, Sweden, 2018.