Axel Schumacher

Dr. Axel Schumacher (b. 1969) is a scientist in the field of genetics and epigenetics. He received several international awards, such as the NARSAD Young Investigator award or the Michael Smith Award for schizophrenia research, which is awarded annually in memory of Dr. Michael Smith, the 1993 Nobel Prize winner in Chemistry.

Career History
Dr. Schumacher began his research career as a student in the laboratory of Dr. Wolf Reik at the Babraham Institute in Cambridge/UK. He then moved on to the lab of Prof. Walter Doerfler at the University of Cologne/Germany to work on his diploma thesis in the field of genomic imprinting and DNA methylation of transgenic organisms. He earned his PhD. in Genetics for the epigenetic characterization of neurobehavioral imprinting disorders such as Prader-Willi syndrome and Angelman syndrome and for the invention of a new in vitro method to differentiate murine ES cells to neurons, which uses the alkaloid staurosporine. After the completion of a collaborative work with the lab of Prof. Bernhard Horsthemke in Essen/Germany regarding imprinting control elements on human chromosome15 and the completion of his Ph.D. program he spent an additional year at the Centre for Molecular Medicine (ZMMK) in Cologne as a postdoc. In 2003 Dr. Schumacher went to work for the Centre for Addiction and Mental Health in Toronto/Can where he co-invented a high-throughput microarray technique to screen DNA methylation patterns in large chromosomal regions and complete genomes. Next to his position in Toronto he spent some time at the Rudbeck Laboratories in Uppsala/Sweden and at the University of St. Petersburg/Russia as visiting researcher.

Epigenetics
Currently, he leads the Epigenetics group at the Department of Medicine II, Klinikum Rechts der Isar (Technical University Munich) in Munich, Germany. His primary research interest is in the characterization of epigenetic patterns that are associated with human disease and the potential influence of environmental factors on the human genome (e.g. space travel, radiation, nanoparticles, diet etc..). His work is particularly focused on potential epigenetic changes in gastrointestinal tumors and in the brain of schizophrenia, bipolar disorder and Alzheimer's patients. Epigenetic factors, which can be inherited, regulate gene activity by chemically changing DNA (e.g. DNA methylation) or by having DNA interact with particular proteins. Some evidence shows epigenetic factors may be significant for brain development, and that certain epigenetic dysregulation of genes may explain unclear features of psychiatric diseases. Dr. Schumacher is the co-inventor of so called high-throughput "epigenetic microarrays," used for the analysis of epigenetic regulation of human genes. The approach may help explain why identical gene sequences in some individuals predispose to complex disease, while in other cases they do not. Results from the work may lead to new diagnostics and effective therapies. Some research shows that drugs which target the epigenetic machinery can restore normal gene activity. The epigenetic theory of complex diseases does not reject the role of DNA sequence variation but rather suggests that in Alzheimer’s or schizophrenia the contribution of epigenetic factors may be substantial, and DNA sequence variation within genes should be investigated in parallel with the epigenetic regulation of genes. The epigenetic model of complex disease (A. Schumacher & A. Petronis, 2006; see below) could be imagined as a result of a chain of aberrant epigenetic events that begins with a pre-epimutation during the maturation of the germline. The epigenetic misregulation can be tolerated to some extent, and the age of disease onset may depend on the multidirectional effects of tissue differentiation, stochastic factors, hormones, and external environmental factors (nutrition, infections, medications, addictions, etc). It may take decades until the epigenetic misregulation reaches a critical threshold beyond which the cell is no longer able to function normally. Only some predisposed individuals will reach the threshold of epigenetic misregulation that causes the phenotypic changes that meet the diagnostic criteria for a clinical disorder. Severity of epigenetic misregulation may fluctuate over time, which in clinical terms is called remission and relapse. In some cases, aging epimutations may start slowly regressing back to the norm. For example, in major psychosis, this is seen as fading psychopathology or even partial recovery which is consistent with age dependent epigenetic changes in the genome. The advantages of the epigenetic scenario in comparison to classical DNA sequence-based models is that the former is consistent with long years of ostensible health, critical susceptibility periods, fluctuating course, and even clinical improvement after decades of being affected with a debilitating disease.

Comic artist
Dr. Schumacher is not only known as a scientist; he also worked as a comic artist and author for the German Egmont/Ehapa Publishing house and for the Heavy Metal comic magazine, where he published alongside famous artists such as Enki Bilal, Jean Giraud (also known as Moebius), Phillippe Druillet, Oleg Yudin, Richard Corben and H.R. Giger. Dr. Schumacher is also an expert in computer chess, hosting the biggest online Blitz chess rating list for chess engines in the world.

Selected publications
Axel Schumacher, Karin Buiting, Michael Zeschnigk, Walter Doerfler & Bernhard Horsthemke (1998) Methylation analysis of the PWS/AS region does not support an enhancer-competition model. Nature Genet. 19: 324-325

Axel Schumacher, Paul Koetsier, Jennifer Hertz & Walter Doerfler (2000) Epigenetic and genotype-specific effects on the stability of the novo imposed methylation patterns in transgenic mice. J.Biol.Chem., 275: 37915-37921

Axel Schumacher (2001) Mechanisms and brain specific consequences of genomic imprinting in Prader-Willi and Angelman syndrome. ''Gene Funct. Dis.,'' 2: No.1, 1-19

A. Schumacher, S. Arnhold, K. Addicks & W. Doerfler (2003) Staurosporine is a potent activator of neuronal, glial and "CNS stem cell"-like neurosphere differentiation in murine embryonic stem cells. Mol Cell Neurosci., Aug;23(4):669-80

A. Schumacher (2003) Calculation of cell densities and layer-numbers in staurosporine induced ovoid-like neurospheres. Res Telegraph. (Rus), 1: 2-9

A. Schumacher & W. Doerfler (2004) Influence of in vitro manipulation on the stability of methylation patterns in the Snurf/Snrpn-imprinting region in mouse embryonic stem cells. ''Nucl. Acid Res.,'' Volume 32, issue 5, 1566-1576

T. Schwarzbraun, J.B. Vincent, A. Schumacher, D.H. Geschwind, J. Oliveira, Ch. Windpassinger, L. Ofner, M. Ledinegg, P.M. Kroisel, K. Wagner & E. Petek (2004) Cloning, genomic structure, and expression profiles of TULIP1 (GARNL1), a brain-expressed candidate gene for 14q13-linked neurological phenotypes, and its murine homologue. Genomics, Sep; 84(3):577-586

A. Schumacher & A. Petronis (2006) Epigenetics in complex diseases: from theory to laboratory praxis. Current Topics in Microbiology and Immunolgy: "DNA Methylation - an Important Genetic Signal"

A. Schumacher, P. Kapranov, J. Flanagan, Z. Kaminsky, A. Assadzadeh, P. Yau, C. Virtanen, J. Cheng, N. Winegarden, T. Gingeras, & A. Petronis (2006) Microarray-based DNA methylation profiling: technology and applications. ''Nucl. Acid Res''., Volume 34, No.2, 528-542

J. Flanagan, V. Popendikyte, N. Pozdniakovaite, M. Sobolev, A. Assadzadeh, A. Schumacher, M. Zangeneh, L. Lau, C. Virtanen, S-C. Wang & A. Petronis (2006) Intra- and Inter- Individual Epigenetic Variation in Human Germ Cells. American Journal of Human Genetics; in press