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Stephen M. Maricich, MD, PhD

Stephen M. Maricich, MD, PhD

Dr. Maricich, a native of greater Buffalo, has been interested in science since childhood. His father and mother were teachers. At five he carefully studied all that he could find about dinosaurs and decided to become a paleontologist. By eight he realized he was unlikely ever to encounter a dinosaur so he decided instead to become an astronomer, reading in even greater depth about the universe. At twelve his focus shifted to medicine and pathophysiology. He wished to help others but recognized the importance of improving understanding of mechanisms of disease. He attended SUNY Buffalo as an Honors Scholar, earning a BA in biology Summa Cum Laude in 1993. He obtained laboratory experience studying the functions of HIV gag and pol proteins in the laboratory of Dr. David Rekosh, with additional experience in the laboratory of Dr. Ken Takeuchi synthesizing and characterizing oxygen carrying ruthenium adducts. Dr. Takeuchi proved a particular influence and mentor, confirming the direction of Maricich’s career development and along the way teaching him how to waltz.

Undergraduate summer experiences included the NASA Space Life Sciences Training Program where he learned space biology and physiology – reviving interest in space within the context of human health. A summer in the laboratory of Dr. Donald Anderson at the Woods Hole Oceanographic Institute involved development of automated seawater sampling to detect neurotoxin generating dinoflagellate “red tide” blooms. Dr. Maricich’s biology honors thesis, based on work in the laboratory of Dr. Bruce Nicholson, concerned gap junction channel proteins, mediators of cell-cell transfer of ions and metabolites. These various research experiences imparted flexibility and persistence in encountering the uncertainties and obstacles associated with experimental science and the capacity to alter experimental approaches to overcome such things. Dr. Maricich’s undergraduate honors included the Freshman Chemistry Award, the Organic Chemistry Award and he was the recipient of both the Barry Goldwater Scholarship and the Grace Capen Memorial Scholarship. He was inducted into the Freshman Honor Society, the AED Pre-Medical Honor Society, the Golden Key Honor Society, the UB Launch Leadership Honor Society, and Phi Beta Kappa. In the year of his graduation he was designated Student of the Year by the Biology Department.

Dr. Maricich attended Case Western Reserve University in the Medical Science Training Program (1993-2000), receiving his PhD in 1998. His original intent was to become a geneticist or immunologist. The particular mentor he had intended to select left Case. Instead, the laboratory of Dr. Karl Herrup was selected. This “serendipitous event” led Dr. Maricich to developmental neuroscience and a mentor whose enthusiasm, emphasis on hypothesis-driven research, and capacity to balance guidance with encouragement of independence “left an indelible mark.” This included rendering his trainees capable of conveying their results clearly with interest and literary quality. Developmental neuroscience led Dr. Maricich to child neurology. His graduate thesis topic was “Compartmentation of the Developing Cerebellum.” For this he received the Irwin Lepow Student Research Day Dean’s First Prize. He was elected to AOA and received the Harry Resnick Memorial Fund Award and the Noether Memorial Fund Award in 2000, the year his MD degree was conferred. Dr. Maricich remained at Case Western Reserve for his pediatrics training (2000-2002), where he received an AAP Resident Research Grant in 2001 and the Resident Science Day Award of Rainbow Babies and Children’s Hospital in 2002.

Dr. Maricich moved to Baylor for training in child neurology (2002-2005). An important reason to select Baylor was the opportunity to work in the laboratory of Dr. Huda Zoghbi, where he might continue to study the role of particular genes in cerebellar developmental. He found his clinical training to be excellent and stimulating, Dr. Marvin Fishman having a particular influence on the development of Maricich’s approach to diagnosis and treatment. Dr. Maricich joined the Department of Pediatrics at Baylor briefly as Instructor and then as Assistant Professor (2005-2008). He undertook his research in the Zoghbi laboratory focusing on the topic of neuronal dependency upon genetic influence. The early phases of this work resulted in unexpectedly important observations concerning two different sensory systems. In addition to advanced genetic techniques, he learned from Dr. Zoghbi not only how approach scientific questions but also to dare to think big and to ask big questions. She taught him how to run a lab and write grants. His ABPN Certification in Neurology/Child Neurology was conferred in 2007. In 2008 Dr. Maricich returned from Baylor to Case Western Reserve, where he is currently an Assistant Professor in the Departments of Pediatrics, Neurosciences, and Otolaryngology.

Dr. Maricich has published sixteen original papers in peer- reviewed journals. The first of these (1995, cited 25 times) characterized undergraduate work in the Takeuchi laboratory concerning structural and chemical characteristics of several novel high oxidation state Ruthenium complexes. He was first author of his second paper (1997) reported the results of his graduate thesis topic, the study of cerebellar development in Lane’s naturally occurring mutant ataxic weaver mouse – a difficult model that for three decades cell death or lack of production accounted for abnormal cerebellar Purkinje cells development. Dr. Maricich’s meticulous quantitative study implicated migrational failure-related abnormal distribution and inadequate induction of connectivity leading to cell death, effects that rather than being limited to Purkinje cells involved all major cerebellar neurons. A particularly high cited paper (75) followed in 1999 that implicated the combination of transcription factor Pax-2 in association abnormalities of migration and connectivity as the cause of abnormal cerebellar development.

A thoughtful first-authored review of the role of tangential migration in the development of cerebral cortex and of cerebellum followed in Neuron in 2001. In 2003 Dr. Maricich was co-author of an additional report concerning the role of the homeodomain protein, Engrailed-1, in murine cerebellar development. Several intervening first-authored clinical reports in 2004, including a detailed account of neurological complications of a particular strain of influenza A (35 citations). Additional clinical reports included a negative study of CSF 5-methyltetrahydrofolate levels in individuals with Rett syndrome and a first-authored paper concerning the assessment with MRI of the pattern of myelination of young children with idiopathic developmental delay.

In 2009 three important papers representative of Dr. Maricich’s work in the Zoghbi laboratory appeared. This first-authored study published in Science convincingly demonstrated, after a century long interval of controversy, the indispensability of Merkel cell expression to the proper functional development of light-touch sensibility as well as the role of the transcription factor Atoh1 in Merkel cell expression. The was second demonstrated the importance Atol1 for the expression or survival of neurons in the spiral ganglion and rhombic lip derived neurons of the cochlear nucleus and accessory auditory nuclei of the brain stem that are essential for the development of hearing. This paper demonstrated in the mouse model that the first dew days of life were a critical period for the establishment of these neurons and helped define the developmental inter- relationship between the cochlear nucleus and the Atoh1- transcription factor-dependent neurons of both the peripheral and central auditory systems. The third paper solved a controversial question as to whether the lineage of Merkel cells is from skin or neural crest, incontrovertibly showing that these Atoh1-dependent cells are skin derivatives.

Dr. Maricich co-authored a 1999 study of aminergic neurotransmitter concentrations in individuals with Rett syndrome and in MeCP2-null mice demonstrating similarity of concentration and phenotypic pattern of neurotransmitters and the likelihood that disturbed MeCP2-dependent regulation of aminergic neurotransmitter synthesis accounts for specific patterns of behavioral abnormalities associated with Rett syndrome. This year Dr. Maricich co-authored a paper defining in a mouse mutation model the role that kinetic alterations in transduction in the human autosomal dominant hearing loss mutation alpha tectorin C1509G may play in deafness due to the loss of outer cochlear hair cells. This study demonstrated the role and that the protein prestin may play in outer hair cell loss and the mechanism of this effect. Currently in press is an additional first-author paper reviewing the classification and genetics of pontocerebellar hypoplasias, including the exclusion of mutations in several genes known to be important in cerebellar development as the cause for these hypoplasias.

Dr. Maricich’s wife Sharyl is a neuroscientist studying the contributions of developmental abnormalities of oligodendrocytes to the pathogenesis of multiple sclerosis. The couple were blessed with twin sons on August 27 of this year. Dr. Maricich has been an avid participant in many sports, a long distance cyclist, a kung fu black belt, and a musician (trumpet).