Dr. Roessler focuses on identifying human genetic mutations that contribute to birth defects and demonstrating how these mutations cause their pathophysiology. His work is performed within the Human Development Section, which is led by Dr. Maximilian Muenke, and involves detailed functional analyses of suspect genes and collaborations with scientists using model organisms to study equivalent genetic mutations. One of his main areas of interest is on the genetics of early embryonic development of the vertebrate axial midline and forebrain, and establishment of the left-right axis (laterality).
These crucial developmental steps occur during the first month in the life of a human fetus, and are critical for proper human development and cognitive function. Studies of the complex interplay between genetic and environmental influences on early development of the forebrain are an important foundation for future advances in molecular medicine and our detailed understanding of complex genetic mechanisms and signaling networks. Dr. Roessler has worked for many years with Dr. Muenke studying holoprosencephaly (HPE), a defect that occurs when the embryonic forebrain does not divide properly into the two lobes of the cerebral hemispheres.
HPE is the most common human structural birth defect affecting the brain. It occurs in one in every 250 conceptions and is associated with frequent fetal loss; only one case in 10,000 continues to birth. At birth, HPE can manifest in small head size, developmental delays, and facial deformities that range from cleft lip or closely set eyes to the much more severe condition, cyclopia (a single eye at the root of the nose), which results when forebrain cleavage never occurs. Working with Dr. Muenke and others, Dr. Roessler identified the first gene behind HPE in humans, known as Sonic Hedgehog, and demonstrated that the condition in well over a hundred affected families can be attributed to mutations in this gene. Since this discovery, over a dozen human genes have been shown to play a significant role in HPE. Dr. Roessler runs the clinical diagnostic laboratory performing mutation testing for a large number of these HPE genes, providing his expertise to clinicians worldwide.
Dr. Roessler also focuses on identifying new human genetic mutations within coding and regulatory elements that contribute to common birth defects, and demonstrating how these mutations lead to developmental disturbances. To specifically understand more about human birth defects, Dr. Roessler investigates and extrapolates from the basic mechanisms involved in vertebrate body plan development, since these conserved processes are directly implicated in the causation of human birth defects. Furthermore, these essential human-based studies demonstrate the similarities and differences between humans and model organisms with respect to the genetic and environmental influences on birth defect causation.
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Last Reviewed: August 19, 2013