Stephen Maricich, Ph.D., M.D.

Steve Maricich, Ph.D.
Assistant Professor
Department of Neurosciences
Case Western Reserve University


School of Medicine
10900 Euclid Ave
Cleveland OH, 44106-4975

Phone : (216) 368-2194
Fax : (216) 368-4650
Email : smm18@case.edu
 
 

RESEARCH INTERESTS

Disorders of sensation are inherent to a variety of inherited and acquired human diseases. Our goal is to understand the molecular signals that control sensory system development and how derangements of development affect animal behavior. In this way, we hope to gain insight into the pathogenesis of human diseases and to discover novel therapeutic strategies to treat them.

Central deafness

Hearing loss affects approximately 15% of the US population and often leads to difficulties with communication and decreased quality of life. Great strides have been made toward understanding the pathogenesis of hearing loss associated with disorders of the ear. However, hearing loss arising from disruptions or developmental perturbations of the central nervous system is poorly understood.

This project examines the development of the brainstem components of the central auditory system. The ultimate goals are to understand where these structures arise, the developmental relationships of the neurons in these structures, and how perturbations of one part of the system effect the development and function of other components. To accomplish these goals, we use conditional knockout strategies in mice to disrupt gene expression in both space and time. This approach led us to the creation of the first mouse models of central deafness and has uncovered interesting relationships between the peripheral and central auditory pathways. We are now in the process of characterizing the effects of central neuronal loss on the ear and identifying genes that direct the specification and development of auditory neurons in different regions of the brainstem. We use a combination of behavioral, electrophysiological, histological and molecular biological techniques to determine how various disruptions affect both structure and function.

Figure 1 New

Touch sensation

The cutaneous somatosensory system detects mechanical stimuli interpreted by the brain as the sense of touch. Defects in the central and peripheral components of this system occur in a number of human diseases including injury, stroke, and neurobehavioral disorders.

Four main classes of sensory receptors in mammalian skin mediate different aspects of the sense of touch. One of these specialized structures, the Merkel cell-neurite complex, is thought to be important for two-point discrimination and the detection of texture, shape and curvature. These receptors consist of Merkel cells, a distinct cell population found at the epidermal/dermal border, and the afferent somatosensory fibers that innervate them. Merkel cell-neurite complexes are found in touch-sensitive areas of the skin including whisker follicles, glabrous (hair-less) skin surfaces such as the hands and feet, and specialized epithelial structures in the hairy skin called touch domes.

This project studies the development of Merkel cell-neurite complexes with the goals of understanding where they come from and what they do. We use a variety of behavioral tests to study the effects of Merkel cell loss on mouse behavior, and we are exploring the genetic pathways that control the development of these cells and the neurons that innervate them.

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SELECTED PUBLICATIONS

  1. A Xia, SS Gao, T Yaun, A Osborn, A Bress, M Pfister, SM Maricich, FA Pereira, JS Oghalai. (2010)
    Deficient forward transduction and enhanced reverse transduction in the alpha tectorin C1509G human hearing loss mutation. Dis Model Mech. 3(3-4):209-223.
  2. R Samaco, C Mandel-Brehm, H-T Chao, C Ward, S Fyffe-Maricich, J Ren, K Hyland, C Thaller, SM Maricich, P Humphreys, J Greer, A Percy, D Glaze, HY Zoghbi, JL Neul. (2009)
    Loss of MeCP2 in aminergic neurons causes cell-autonomous defects in neurotransmitter synthesis and specific behavioral abnormalities. PNAS. 106:21966-21971.
  3. KM Morrison, GR Miesegaes, EA Lumpkin, SM Maricich. (2009)
    Mammalian Merkel cells are descended from the epidermal lineage. Dev Biol. 336(1):76-83.
  4. SM Maricich, A Xia, VY Wang, JS Oghalai, B Fritzsch & HY Zoghbi. (2009)
    Atoh1-lineal neurons in the cochlear nucleus are required for hearing and for the survival of brainstem accessory auditory and spiral ganglion neurons. J Neurosci. :In Press.
  5. SM Maricich, SA Wellnitz, AM Nelson, DR Lesniak, GJ Gerling, EA Lumpkin & HY Zoghbi. (2009)
    Merkel cells are essential for light tough responses. Science. 324:1580-1582..
  6. SM Maricich, P Azizi, JY Jones, MC Morriss, JV Hunter, EO Smith & G Miller. (2007)
    Myelination as assessed by conventional MRI is normal in young children with idiopathic developmental delay. AJNR. 2007; 28(8):1602-5.
  7. SM Maricich & HY Zoghbi. (2006)
    Getting back to basics. Cell. 2006 Dec 17; 126(1):11-15.
  8. SM Maricich & HY Zoghbi. (2006)
    The cerebellum and the hereditary ataxias. :11-15.
  9. JL Neul, SM Maricich, M Islam, J Barrish, EO Smith, T Bottiglieri, K Hyland, P Humphreys, A Percy & D Glaze. (2005)
    Spinal fluid 5-methyltetrahydrofolate levels are normal in Rett Syndrome. Neurology. 2005; 64(12):2151-52.
  10. SM Maricich, JL Neul, TE Lotze, AC Cazacu, TM Uyeki, GJ Demmler & GD Clark. (2004)
    Neurologic complications associated with influenza A in children during the 2003-04 influenza season in Houston, Texas. Pediatrics. 2004; 114(5):e626-33.
  11. SM Maricich, RA Rouch & PJ Foreman. (2004)
    Cerebral air embolism during transbronchial biopsy. Neurology. 2004; 62:1438.
  12. NA Bilovocky, RR Romito-DiGiacomo, CL Murcia, SM Maricich & K Herrup. (2003)
    Factors in the genetic background suppress the engrailed-1 cerebellar phenotype. J Neurosci. 2003; 23(12):5105-5112.
  13. *SM Maricich, *EC Gilmore & K Herrup. (2001)
    The role of tangential migration in the establishment of mammalian cortex. Neuron. 2001; 31:175-8.
  14. SM Maricich & K Herrup. (1999)
    Pax-2 expression defines a subset of GABAergic interneurons and their precursors in the developing murine cerebellum. J Neurobiol. 1999; 41(2):281-294.
  15. *E Walther, *M Dichgans, *SM Maricich, RR Romito, F Yeng, S Dziennis, S Zackson, R Hawkes & K Herrup. (1998)
    enomic sequences of aldolase C (Zebrin II) direct lacZ expression exclusively in non-neuronal cells of transgenic mice. PNAS. 1998; 95(5):2615-20.
  16. SM Maricich, J Soha, E Trenkner & K Herrup. (1997)
    Failed cell migration and death of Purkinje cells and deep nuclear neurons in the weaver cerebellum. J Neurosci. 1997; 17:3675-3683.
  17. LF Szczepura, SM Maricich, RF See, MR Churchill, & KJ Takeuchi (1995)
    Synthesis, characterization, and reactivity of an oxoruthenium (IV) complex containing a bis(oxazoline) ligand- crystal-structure of [RU((S)-BPOP)(CL)(TRPY)](BF4). Inorganic Chemistry. 1995; 34(16):4198-4205.
 
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