Jeffrey Neul attended the University of Illinois at Urbana-Champaign for four years, graduating magna cum laude (College of Liberal Arts and Sciences), summa cum laude (School of Chemical Sciences), and Phi Beta Kappa in 1991 with a Bachelor of Science degree in chemistry. His senior thesis concerned the ubiquinol pathway. He spent the following nine years in the Medical Scientist Training Program of the Pritzker School of Medicine, University of Chicago. Five of these training years were spent in the laboratory of the distinguished developmental geneticist/biologist, Edwin Ferguson. This laboratory has been interested in the most fundamental evolutionary and developmental aspects of embryonic cellular identity, particularly with regard to the determination of dorsal or ventral identification of cell position, as well as the manner in which that positioning influences ensuing development and modulation of synaptic activity within a specific location. One rich area of exploration in the laboratory has been characterization of the morphogenetic Decapentaplegic protein (DPP) signaling pathway function as determinants of asymmetric development of cellular orientation during embryonic development.
Just three years into his work in the Ferguson laboratory, Dr. Neul was a major contributor (second of eight authors) to the characterization of the manner in which a particular dorsalizing factor found in Drosophila, named “noggin,” promotes the development of dorsal anlage that in turn give rise to the development of the central nervous system. This fundamental contribution to neuroscience (cited 157 times to date) was published in Cell in 1996. In 1998 Dr. Neul was first author of a second important contribution to the understanding of the DPP pathway and spatially-restricted activation of receptors that perform critical roles in embryonic functional development. He demonstrated the manner in which such spatially-restricted activation by two ligand receptors DPP and SAX (in the somewhat eccentric manner of molecular genetic naming and abbreviation for saxophone) contributes to the determination of axial sub specialization in the direction of dorsality of localization of cellular development (cited 66 times to date).
The technically highly sophisticated undertakings of both of Dr. Neul’s papers contribute importantly to the emerging understanding of the elegant world of activity gradients that determine cellular developmental fate. They contribute information that is fundamental in understanding the astonishing world of evolutionary capacity and developmental specificity of germ cells, and the working out of the degree of accuracy with which an organism expresses the development sequence intended by an initiating genetic code. Dr. Neul was to receive the Committee Thesis Award for Outstanding Performance in the Field of Developmental Biology upon his graduation in 1999. In 1998 Dr. Neul expanded his scientific education further at the Genetic-Epidemiological Studies of Complex Diseases symposium of UCSF’s remarkable statistical geneticist/genetic epidemiologist, Neil Risch, held at Wood’s Hole. Not satisfied with the identification of genes underlying specific diseases, Risch has play a major role in revising understanding of the genetic forces underlying the appearance and expression of disease-related genes. THE “PhD portion” of Dr. Neul’s education thus equipped him with methods and points of view that prepared him to apply himself with particular elegance to definition of both genetic and physiologic aspects of neurologic function.
Thus armed, Dr. Neul returned to complete the clinical rotations required for his medical degree. The result was the achievement of recognition for his clinical aptitude and devotion. He was awarded Clinical Honors in Medicine, Pediatrics, Surgery, Obstetrics/Gynecology, and Psychiatry. Between 2000 and 2005, Dr. Neul trained in pediatrics, neurology, and child neurology at Baylor. During the second year of his neurology training, Dr. Neul co-authored with Dr. Huda Zoghbi a thoughtful review (cited 38 times) of the role MeCP2 plays in regulation of gene expression and chromatin formation in individuals with Rett syndrome, devoting particular attention to the mechanisms that may underlie the widening spectrum of phenotypic expression of MeCP2-related disease. He also reviewed the state of current capacity to study Rett diseases and its variants in both in vivo and in vitro models. In that same year he was co-author of a paper concerning the neurological complications of the 2003-2004 outbreak of Influenza A in Houston. The following year he co-authored a case report concerning a case of folinic acid-responsive encephalopathy. His third year of neurology training was devoted to a post-doctoral fellowship in Dr. Zoghbi’s laboratory.
Dr. Neul joined the Baylor faculty as Assistant Professor in 2005. In the ensuing four years he has co-authored four and first-authored one paper from the Zoghbi laboratory. Each of these papers is of considerable importance. The co-authored papers include
1) demonstration that mutated MeCP2 gene copy number determines variation in neurodevelopmental phenotypes of “male” Rett syndrome in humans;
2) demonstration that the degree of fractional expression of mutant MeCP2 as compared to normal MeCP2 governs phenotypic expression of deficits in motor skills and intellectual capacity, as well as expression of anxiety, social behavior, pain recognition, and regulation of breathing patterns in mice; 3) demonstration of the developmental role that hypothalamic MeCP2 expression plays in the development of feeding behavior, manifestation of aggression, and response to stress, also in mice; and 4) a hypothesis-driven investigation of the effects that folate and betaine may play in the amelioration of clinical features of Rett syndrome in young ladies with the disorder.
Dr. Neul’s first-authored paper is a cross-sectional study of 245 girls and women with typical Rett syndrome comparing detailed analysis of their clinical features (particularly ambulation capacity, hand use, and language ability) with the specific mutations that they manifest. He and his associates found that the R168X pattern (large DNA deletions) was associated with greater likelihood and degree of abnormality in all three domains. They found that the R306C pattern conferred a much milder phenotype, chiefly affecting language. The paper reflects as well on an approach to the design and testing of therapies aimed at specific clinico-genetic patterns of disability. Dr. Neul is co-author of a paper recently submitted to the New England Journal of Medicine summarizing the relationship of patterns of disturbance of biogenic amine function to clinical and neurochemical deficits. Dr. Neul has been awarded two NIH/NINDS grants as Primary Investigator to support his basic science investigations of the function of the dopamine system in Rett syndrome and to characterize the role of chromatin-remodeling protein networks in mental retardation. He is Co-Investigator with Dr. Zoghbi of an NIH/NINDS grant aimed at further molecular pathogenic studies of Rett syndrome; is P.I of a grant from the International Rett Syndrome Association underwriting basic studies of biogenic amines in murine Rett syndrome; and is Co-Investigator with Monica Justice of investigation of modifiers of MeCP2 expression in mice.
In 2008 Dr. Neul was named the Anthony and Cynthia Petrello Scholar of the Jan and Dan Neurological Research Institute of the Texas Children’s Hospital. He also assumed the position of Assistant Medical Director of the Blue Bird Circle Rett Center.
His professional activities have also included serving as Ad Hoc reviewer for seven prestigious journals, membership on the CNS Scientific Selection and Annual Meeting Planning Committee, and serves on both the Scientific Review and the Medical Advisory Boards of the International Rett Syndrome Foundation. He has delivered twenty invited presentations. Dr. Huda Zoghbi is struck by Dr. Neul’s boundless enthusiasm, and the fact that he is very bright, highly creative, and full of ideas. He is hard-working and strongly motivated. He has excellent hands at the bench, displays uncommon rigor in experimental design and execution, and manifests a not wholly unexpected tendency to perfectionism and self criticism. Dr. Zoghbi has enjoyed every minute of her contribution to his training and is now enjoying the great satisfaction of having him as a colleague.