Shelley D. Smith, Ph.D., is Professor of Pediatrics in the College of Medicine and B.A. Buehler Professor and Director of Developmental Neuroscience at the Munroe Meyer Institute for Genetics and Rehabilitation. She is also the Director of the MD/PhD Scholars program for the UNMC College of Medicine. She obtained her Ph.D. in Medical Genetics from Indiana University and is board certified as a Ph.D. Medical Geneticist by the American College of Medical Genetics. She completed a fellowship in pediatric genetics with Dr. Herbert Lubs at the University of Colorado Health Sciences Center and the University of Miami Mailman Center and subsequently held faculty positions at the University of Miami and at Boys Town National Research Hospital (BTNRH) before coming to UNMC in 1999. Her research has been in the localization and identification of genes affecting hereditary deafness and developmental language and learning disorders, particularly reading disability, language impairment, speech sound disorder, and ADHD. She is Principal Investigator for the Nebraska Center for the Molecular Biology of Neurosensory Systems, an NIH Center of Biomedical Research Excellence (COBRE). Until 2010, she was active in regional genetics clinics across Nebraska and in the multidisciplinary Neurosensory Genetics clinic staffed by clinicians from UNMC and BTNRH.
Ph.D., Medical Genetics, Indiana University, Indianapolis
B.A., Biology, Grinnell College, Grinnell, Iowa
PEDS 911, Human Genetics and Cytogenetics Principles
GCBA 900, Advanced Concepts in Molecular Genetics
Research Interests and Projects:
- Neurosensory Disorders: Hearing Loss and Vision
Nebraska Center for the Molecular Biology of Neurosensory Systems (S.D. Smith, PI)
NIH:NCRR 2P20 RR18788
This Center of Biomedical Research Excellence (COBRE) is in its third 5-year period of funding and supports the development of research into the molecular mechanisms of hearing, vision, and balance disorders. The goals of this Center are to define the genetic and molecular pathways that are involved in the development and maintenance of the auditory and visual systems so that effective means of prevention or reversal of disabilities can be discovered. This is a multi-institutional program including researchers from UNMC, Creighton University, and Boys Town National Research Hospital. This research is facilitated by building an interactive group of senior researchers, supporting the research of new faculty, and by enhancing the research infrastructure. The Center contributes to three scientific core facilities at UNMC, Mouse Genome Engineering, Histology and Molecular Phenotyping, and Gene Expression and Sequencing and provides funding for research projects and mentoring to support the career development of junior faculty members.
- Reading Disability and ADHD
Differential Diagnosis in Learning Disabilities (R.K Olson, PI): Project IV: Genomic Analysis (S.D. Smith, PI)
NIH-NICHD 3P50 HD027802-19S1
The Colorado Learning Disabilities Research Center is one of 4 Learning Disabilities Centers funded by the Eunice Kennedy Shriver National Institute for Child Health and Development of the National Institutes of Health. The Center is based at the Institute for Behavior Genetics at the University of Colorado, and includes researchers at the University of Colorado, University of Denver, and UNMC. The Center studies the genetic and environmental influences on reading disability (dyslexia) and ADHD. Identification of the genes and their cognitive phentoypes can lead us to the genetic pathways that affect the developmental processes used by the central nervous system to learn to read and to direct attention. By understanding the underlying causes of these disorders, diagnostic characteristics and therapies can be refined. Dr. Smith’s project within the Center is focused on the DNA studies to identify the genes that contribute to these disorders, and provides molecular genetic information to the rest of the Center. We currently have over 1500 DNA samples from fraternal twins and their families, and these studies have identified the major loci contributing to reading disability on chromosome 6p. We are continuing to study these and additional genes to determine the genetic effects on their regulation and the phenotypic effects of their interactions.
- Specific Language Impairment
Morphosyntactic Abilities of SLI Probands and Families. (M.L. Rice, PI, S.D. Smith, Co-investigator)
NIH:NIDCD R01 NIH0064386
NIH:NIDCD R01 DC001803-14S1
Specific Language Impairment (SLI) is a common childhood developmental disorder that affects a child’s ability to understand and use language. Molecular genetic studies have localized several candidate genes influencing language impairment, but until recently the genetic influences on language were thought to be separate from those influencing reading. In collaboration with Dr. Mabel Rice at the University of Kansas, we have been studying the effects of genes that influence one or both disorders to determine the cognitive processes that distinguish them. Since this is a longitudinal study, we will be able to determine the influence of these genes on the development of language as the children get older.
- Twins and Singletons with Specific Language Impairment. (M.L. Rice, PI. S.D. Smith, co-investigator)
NIH-NIDCD R01 DC005226
In this second collaboration with Dr. Rice, we are working with Curtin University in Perth, Australia in a longitudinal study of twins ascertained before birth. This will give us the opportunity to follow very early characteristics of language development and see the language and reading outcomes. The molecular genetic component of this study will study these developing phenotypes to determine how genetic interactions contribute to language abilities at different points in time. Thorough characterization of a gene’s effects over time can help define the “endophenotype”, that is, the underlying cognitive process affected by the gene, and thus bring us closer to the neurodevelopmental factors that are critical for language development.
- Smith, S.D., Kimberling, W.J., Pennington, B.F., Lubs, H.A. (1983). Specific reading disability: Identification of an inherited form through linkage analysis. Science, 219, 1345-1347.
- Cardon, L.R., Smith, S.D., Fulker, D.W., Pennington, B.F., Kimberling, W.J., and DeFries, J.C. (1994) Quantitative trait locus on chromosome 6 predisposing to reading disability. Science, 266:276-279. correction. Science, 268:1553.
- Van Camp, G.V., Coucke, P.J., Kinst, H., Schatteman, I., Van Velzen, D., Marres, H., Van Ewijk, M., Declau, F., Van Hauwe, P., Meyers, J., Kenyon, J., Smith, S.D., Smith, R.J.H., Djelantik, B., Cremers, C.W.R.J., Van de Heyning, P.H., Willems, P.J. (1997) Linkage analysis of progresive hearing loss in five extended families maps the DFNA2 gene to a 1.25 Mb region on chromosome 1p. Genomics, 41:70-74.
- Smith, S.D., Kimberling, W.J., Schaefer, G.B., Horton, M.B., Tinley, S.T. (1998) Medical genetic evaluation for the etiology of hearing loss in children. Journal of Communication Disorders. 31(5):371-88.
- Smith, S.D., Kelley, P.M., Brower, A.M. (1998) Molecular approaches to the genetic analysis of specific reading disability. Human Biology, 70:239-256.
- Gayan, J., Smith, S.D., Cherny, S.S., Cardon, L., Fulker, D.W., Brower, A.M., Olson, R.K., Pennington, B.F., DeFries, J.C. (1999) Quantitative trait locus for specific language and reading disability on chromosome 6p. American Journal of Human Genetics, 64:157-164.
- Van Hauwe, P., Coucke, P.J., Declau, F., Kunst, H,, Ensink, R.J., Marres, H.A., Cremers, C.W., Djelantik, B., Smith, S.D., Kelley, P., Van de Heyning, P.H., Van Camp, G. (1999) Deafness linked to DFNA2: one locus but how many genes? Nature Genetics, 21(3):263.
- Coucke, P.J., Van Hauwe, P., Kelley, P.M., Kunst, H., Schatteman, I., Van Velzen, D., Meyers, J., Ensink, R.J., Verstreken, M., Delau, F., Marres, H., Kastury, K., Bhasin, S., McGuirt, W.T., Smith, R.J.H., Cremers, C.W.R.J., Van de Heyning, P., Willems, P.J., Smith, S.D., Van Camp, G. (1999) Mutations in the KCNQ4 gene are responsible for autosomal dominant deafness in four DFNA2 families. Human Molecular Genetics, 8(7):1321-1328.
- Talebizadeh, Z., Kelley, P.M., Askew, J.W., Beisel, K.W., Smith S.D. (1999) A novel mutation in the KCNQ4 gene in a large kindred with dominant progressive hearing loss. Human Mutation, 14(6):493-501.
- Smith, S.D., Kelley, P.M., Kenyon, J.B., Hoover, D.(2000) Tietz syndrome (hypopigmentation/deafness) caused by mutation of MITF. Journal of Medical Genetics, 37:446-448.
- Smith, S.D. (2001) Relationships between neurologic disorders and hereditary hearing loss. In Clinical Neurogenetics, G.B. Schaefer (Ed). Seminars in Pediatric Neurology 8:147-159.
- Smith, S.D., Kelley, P.M., Askew, J.W., Hoover, D.M., Deffenbacher, K.E., Gayán, J., Brower, A.M., Olson, R.K., DeFries, J.C. (2001) Reading disability and chromosome 6p21.3: Evaluation of MOG as a candidate gene. In J.W. Gilger, Genetics, Neuropsychology, and Learning Disorders, (Ed); Special issue, Journal of Learning Disabilities, 34:512-519.
- Willcutt, E.G., Pennington, B.F., Smith, S.D., Cardon, L.R., Gayán, J., Knopik, V.S., Olson, R.K., DeFries, J.C. (2002) Quantitative trait locus for reading disability on chromosome 6p is pleiotropic for ADHD. American Journal of Medical Genetics, 114:260-268.
- Fisher, S.E., Francks, C., Marlow, A.J., MacPhie, I.L., Newbury, D.F., Cardon, L.R., Ishikawa-Brush, Y., Richardson, A.J., Talcott, J.B., Gayán, J., Olson, R.K., Pennington, B.F., Smith, S.D., DeFries, J.C., Stein, J.F., Monaco, A.P. (2002) Independent genome-wide scans identify a chromosome 18 quantitative-trait locus influencing dyslexia. Nature Genetics, 30(1):86-91.
- Kaplan, D.E., Gayán, J., Ahn, J., Won, T.-W., Pauls, D., Olson, R., DeFries, J.C., Wood, F., Pennington, B., Page, G.P., Smith, S.D., Gruen, J.R. (2002) Evidence for linkage and association with reading disability on 6p21.3-22. American Journal of Human Genetics, 70(5):1287-98.
- Bodensteiner JB, Smith SD, Schaefer GB. (2003) Hypotonia, congenital hearing loss, and hypoactive labyrinths. Journal of Child Neurology, 18(3):171-3.
- Deffenbacher KE, Kenyon JB, Hoover DM, Olson RK, Pennington BF, DeFries JC, Smith SD. (2004) Refinement of the 6p21.3 quantitative trait locus influencing dyslexia: linkage and association analyses. Human Genetics, 115: 128-138.
- Francks C, Paracchini S, Smith, SD, Richardson AJ, Scerri, TS, Cardon LR, Marlow AJ, MacPhie IL, Walter J, Pennington BF, Fisher SE, Olson RK, DeFries JC, Stein JF, Monaco AP. (2004) A 77-Kilobase Region of Chromosome 6p22.2 Is Associated with Dyslexia in Families From the United Kingdom and From the United States. American Journal of Human Genetics, 75:1046-1058.
- Smith, S.D., Pennington, B.F., Boada, R., Shriberg, L. (2005) Linkage of Speech Sound Disorder to Reading Disability Loci. Journal of Child Psychology and Psychiatry, 46(10), 1057-66.
- Meng H, Hager K, Held M, Page GP, Olson RK, Pennington BF, Defries JC, Smith SD, Gruen JR. (2005) TDT-Association Analysis with EKN1 and Dyslexia in a Colorado Twin Cohort. Human Genetics, 16:1-4.
- Meng, H., Smith, S.D. , Hager, K., Held, M., Liu, J., Olson, R.K., Pennington, B.F., DeFries, J.C., Gelernter, J. O’Reilly-Pol, T., Somlo, S., Skudlarski, P., Shaywitz, S.F., Shaywitz, B.A., Marchione, K., Wang, Y., Paramasivam, M., LoTurco, J.J., Page, G.P., Gruen, J.R. (2005) DCDC2 is Associated with Reading Disability and Modulates Neuronal Migration in the Brain. Proc Natl Acad Sci USA, 102(47):17053-8.
- Deupree, JD, Smith, SD, Kratochvil, CJ, Bohac, D., Ellis CR, Polaha, J. Bylund, DB. (2006) Possible Involvement of Alpha-2A Adrenergic Receptors in Attention Deficit Hyperactivity Disorder: Radioligand Binding and Polymorphism Studies, American Journal of Medical Genetics B, 141(8), 877-884.
- Smith, SD. (2007) Genes, language development, and language disorders. Ment Retard Dev Disabil Res Rev. 2007;13(1):96-105.
- Peterson RL, McGrath LM, Smith SD, Pennington BF. (2007) Neuropsychology and genetics of speech, language, and literacy disorders. Pediatr Clin North Am. 54(3):543-61.
- McGrath LM, Pennington BF, Willcutt EG, Boada R, Shriberg LD, Smith SD. (2007) Gene x Environment interactions in speech sound disorder predict language and preliteracy outcomes. Dev Psychopathol. Fall;19(4):1047-72.
- Rice, M., Smith, S.D., Gayán, J. (2009) Convergent genetic linkage and associations to language, speech and reading measures in families of probands with Specific Language Impairment. Journal of Neurodevelopmental Disorders, 1(4) 264-282, epub September 26, 2009. PMCID:PMC2788915.
- Smith, S.D., Grigorenko, E.L., Willcutt, E., Pennington, B.F., Olson, R.K., DeFries, J.C. (2010) Etiologies and molecular mechanisms of communication disorders. J Devel Behav Pediatr, 31(7):555-63 PMCID: PMC2943674.
- Willcutt, E.G., Pennington, B.F., Duncan, L., Smith, S.D., Keenan, J.M., Wadsworth, S., Defries, J.C., Olson, R.K. (2010) Understanding the complex etiologies of developmental disorders: behavioral and molecular genetic approaches. J Dev Behav Pediatr 31(7):533-44 PMCID: PMC2953861.
- Bidwell, L.C., Willcutt, E.G., McQueen, M.B., DeFries, J.C., Olson, R.K., Smith, S.D., Pennington, B.F. (2011) A family based association study of DRD4, DAT1, and 5HTT and continuous traits of Attention-Deficit Hyperactivity Disorder. Behav Genet. 41(1):165-74. PMCID: PMC3674022.
- Smith, S.D. (2011) Approach to epigenetic analysis in language disorders. Journal of Neurodevelopmental Disabilities, 3(4):356-64. PMCID: PMC3261263.
- Eicher JD, Powers NR, Miller LL, Mueller KL, Mascheretti S, Marino C, Willcutt EG, Defries JC, Olson RK, Smith SD, Pennington BF, Tomblin JB, Ring SM, Gruen JR. (2014) Characterization of the DYX2 locus on chromosome 6p22 with reading disability, language impairment, and IQ. Hum Genet. 869-81. PMCID:PMC4053598.
- Gialluisi A, Newbury DF, Wilcutt EG, Olson RK, DeFries JC, Brandler WM, Pennington BF, Smith SD, Scerri TS, Simpson NH, The SLI Consortium, Luciano M, Evans DM, Bates TC, Stein JF, Talcott JB, Monaco AP, Paracchini S, Francks C, Fisher,SE (2014). Genome-wide screening for DNA variants associated with reading and language traits. Genes Brain Behav 686-701. PMCID:PMC4165772.
- Eicher JD, Stein CM, Deng F, Ciesla AA, Powers NR, Boada R, Smith SD, Pennington BF, Iyengar SK, Lewis BA, Gruen JR (2015) The DYX2 locus and neurochemical signaling genes contribute to speech sound disorder and related neurocognitive domains. Genes Brain Behav 14(4):377-85. PMCID:PM4492462.
- Powers NR, Eicher JD, Miller LL, Kong Y, Smith SD, Pennington BF, Willcutt EG, Olson RK, Ring SM, Gruen JR. (2016) The regulatory element READ1 epistatically influences reading and language, with both deleterious and protective alleles. J Med Genet. 2016 Mar;53(3):163-71. PMCID: PMC4789805.
- Gialluisi A, Visconti A, Willcutt EG, Smith SD, Pennington BF, Falchi M, DeFries JC, Olson RK, Francks C, Fisher SE. (2016) Investigating the effects of Copy Number Variants on reading and language performance. Journal of Neurodevelopmental Disorders 8:17 PMCID-PMC4868026.
- Truong, D.T., DeMille, M.M.C., Adams, A.K., Nato, A.Q., Smith, S.D., Shriberg, L.D., Gruen, J.R. (2016) Multipoint genome-wide linkage scan for nonword repetition in a multigenerational family further supports chromosome 13q as a locus for verbal trait disorder. Human Genetics 135(12):1329-1341.
- Devanna P, Chen XS, Ho J., Gajewski D, Smith SD, Gialluisi A, Francks C, Fisher SE, Newbury DF, Vernes SC (2017). Next-gen sequencing identifies non-coding variation disrupting miRNA-binding sites in neurological disorders. (September 2016) Molecular Psychiatry, , 1–10. http://doi.org/10.1038/mp.2017.30 advance online publication.
Selected Books and Monographs:
- Smith, S.D. (Ed.), Genetics of Learning Disabilities, (pp. 47-65). San Diego: College-Hill Press.
- Smith, S.D. (1995) Overview of genetic auditory syndromes. In Jacobson, J., (Ed.), Hereditary and other childhood auditory deficits. Journal of the American Academy of Audiology, 6(1), 1-14.
- Fisher, S.E., Smith, S.D. (2001) Progress towards the identification of genes influencing developmental dyslexia. In Dyslexia, Theory and Good Practice, A.J. Fawcett (Ed), London: Whurr Publishing. pp 39-64.
- Smith, S.D., Gilger, J.W., Pennington, B.F. (2002) Dyslexia and other language/learning disorders. Rimoin, D.L., Conner, J.M., and R. Pyeritz (Eds), Emery and Rimoin's Principles and Practice of Medical Genetics,4th Edition. New York: Churchill Livingstone, 2827-2865.
- Smith, S.D. (2004) Localization and identification of genes influencing language and learning disorders. In Rice, M.L. and Warren, S.F. (Eds), Developmental Language Disorder: From Phenotype to Etiologies, Lawrence Erlbaum Associates, pp. 329-354.
- Smith, S.D., Gilger, J.W. (2007) Dyslexia and Other Specific Learning Disorders. In Rimoin, David L., Connor, J. Michael, Pyeritz, Reed E., Korf, Bruce R., and Emery, Alan E. H., (Eds), Emery and Rimoin’s Principles and Practice of Medical Genetics, 4th Ed.. New York, Elsevier. pp 2548-2568.
- Smith, S.D. (2011) Human Genetic Contributions to the Neurobiology of Dyslexia. In McCardle, M., Ren, J., Tzeng, O. (Eds) Dyslexia Across Languages: Orthography and the Brain-Gene-Behavior Link. Baltimore, MD, Brookes Publishing Co. pp 239-253.
- Smith, S.D. (2012) Learning Disabilities. In Nurnberger, J.I. and Berrettini, W.H. (Eds), Principles of Psychiatric Genetics, Cambridge University Press, pp 160-167.
- Toriello, H.V., and Smith, S.D. (Eds) (2013) Hereditary Hearing Loss and Its Syndromes. Oxford University Press.
- Smith, S.D. (2013) Nonsyndromic Hearing Loss. In Toriello, H.V., and Smith, S.D. (Eds) Hereditary Hearing Loss and Its Syndromes. Oxford University Press, pp.98-209.
- American College of Medical Genetics
- American Society of Human Genetics
- Association for Research in Otolaryngology
- Behavior Genetics Association
UNMC Distinguished Scientist Award, 2006
UNMC Scientist Laureate, 2010