Donald L Swiderski

Donald L Swiderski
University of Michigan | U-M · Department of Otolaryngology - Head and Neck Surgery

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115
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Publications

Publications (115)
Preprint
Some species have evolved the ability to use the sense of hearing to modify existing vocalizations, or even create new ones. This ability corresponds to various forms of vocal production learning that are all possessed by humans, and independently displayed by distantly related vertebrates. Among mammals, a few species, including the Egyptian fruit...
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Modularity and integration are fundamental properties of organisms and central to theories of complex adaptation. Modularity and integration of shape can provide valuable information about the geometry and spatial structure of modules, but a recent study contends that Procrustes superimposition yields alarmingly high frequencies of statistically si...
Article
Identifying the drivers of adaptation is key to understanding the origin and evolution of diversity. Here we study the morphological evolution of tooth morphology, a classic example of a conserved structure, to gain insights into the conditions that can overcome resistance to evolutionary change. We use geometric morphometrics of the occlusal surfa...
Article
The cochlear implant (CI) is widely considered to be one of the most innovative and successful neuroprosthetic treatments developed to date. Although outcomes vary, CIs are able to effectively improve hearing in nearly all recipients and can substantially improve speech understanding and quality of life for patients with significant hearing loss. A...
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Allometry has been a paradigm of constraints, including intrinsic constraints on the evolvability of allometry, as a source of developmental and genetic constraints on the evolution of form, and of functional constraints, maintaining functional equivalence as body size evolves. Yet, allometry may be the simplest case of varied constraints, and of m...
Article
Outcomes of cochlear implantation are likely influenced by the biological state of the cochlea. Fibrosis is a pathological change frequently seen in implanted ears. The goal of this work was to investigate the relationship between fibrosis and impedance. To that end, we employed an animal model of extensive fibrosis and tested whether aspects of im...
Article
Spatial patterns of species richness, phylogenetic and morphological diversity are key to answering many questions in ecology and evolution. Across spatial scales, geographical and environmental features, as well as evolutionary history and phenotypic traits, are thought to play roles in shaping both local species communities and regional assemblag...
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Trade‐offs are inherent features of many biomechanical systems and often are seen as evolutionary constraints. Structural decoupling may provide a way to escape those limits in some systems, but not for structures that transmit large forces, like mammalian mandibles. For such structures to evolve in multiple directions on a complex adaptive landsca...
Article
It is generally believed that the efficacy of cochlear implants is partly dependent on the condition of the stimulated neural population. Cochlear pathology is likely to affect the manner in which neurons respond to electrical stimulation, potentially resulting in differences in perception of electrical stimuli across cochlear implant recipients an...
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Pathogenic variants in GJB2, the gene encoding connexin 26, are the most common cause of autosomal recessive hereditary deafness. Despite this high prevalence, pathogenic mechanisms leading to GJB2-related deafness are not well understood, and cures are absent. Humans with GJB2-related deafness retain at least some auditory hair cells and neurons a...
Article
Mice with chronic cochlear implants can significantly contribute to our understanding of the relationship between cochlear health and implant function because of the availability of molecular tools for controlling conditions in the cochlea and transgenic lines modeling human disease. To date, research in implanted mice has mainly consisted of short...
Article
The auditory sensory epithelium of the mammalian inner ear is a highly organized structure that contains sensory hair cells (HCs) and non-sensory supporting cells (SCs). Following the partial loss of HCs after cochlear insults such as overstimulation or ototoxic drugs, SCs seal the luminal epithelial surface (reticular lamina) and reorganize its ce...
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Mature mammalian cochlear hair cells (HCs) do not spontaneously regenerate once lost, leading to life-long hearing deficits. Attempts to induce HC regeneration in adult mammals have used over-expression of the HC-specific transcription factor Atoh1, but to date this approach has yielded low and variable efficiency of HC production. Gfi1 is a transc...
Article
This study examined how multiple measures based on the electrically evoked compound action potential (ECAP) amplitude-growth functions (AGFs) were related to estimates of neural [spiral ganglion neuron (SGN) density and cell size] and electrode impedance measures in 34 specific pathogen free pigmented guinea pigs that were chronically implanted (4....
Article
Fibrous tissue and/or new bone are often found surrounding a cochlear implant in the cochlear scalae. This new intrascalar tissue could potentially limit cochlear implant function by increasing impedance and altering signaling pathways between the implant and the auditory nerve. In this study, we investigated the relationship between intrascalar ti...
Article
A classic hypothesis posits that lineages exhibiting long‐term stasis are broadly adapted generalists that remain well‐adapted despite environmental change. However, lacking constraints that steepen adaptive peaks and stabilize the optimum, generalists’ phenotypes might drift around a broad adaptive plateau. We propose that stasis would be likely f...
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The electrically-evoked compound action potential (ECAP) is correlated with spiral ganglion neuron (SGN) density in cochlear implanted animals. In a previous study, we showed that ECAP amplitude growth function (AGF) linear slopes for stimuli with a constant interphase gap (IPG) changed significantly over time following implantation. Related studie...
Article
Sclerostin antibody (Scl‐Ab) is an anabolic bone agent that has been shown to increase bone mass in clinical trials of adult diseases of low bone mass, such as osteoporosis and osteogenesis imperfecta (OI). Its use to decrease bone fragility in pediatric OI has shown efficacy in several growing mouse models, suggesting translational potential to pe...
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Background and Objectives The antioxidant ebselen will be able to limit or prevent the ototoxicity arising from 2-hydroxypropyl-β-cyclodextrin (HPβCD). Niemann-Pick Type C (NPC) disease is a disorder of lysosomal storage manifested in sphingolipidosis. Recently, it was noted that experimental use of HPβCD could partially resolve the symptoms in bot...
Book
The revised "A Practical Companion to Geometric Morphometrics for Biologists: Running analyses in freely-available software (Second Edition)" focuses on doing geometric morphometric analyses in R
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CHD7, an ATP-dependent chromatin remodeler, is disrupted in CHARGE syndrome, an autosomal dominant disorder characterized by variably penetrant abnormalities in craniofacial, cardiac, and nervous system tissues. The inner ear is uniquely sensitive to CHD7 levels and is the most commonly affected organ in individuals with CHARGE. Interestingly, upre...
Article
The damaged vestibular sensory epithelium of mammals has a limited capacity for spontaneous hair cell regeneration, which largely depends on the transdifferentiation of surviving supporting cells. Little is known about the response of vestibular supporting cells to a severe insult. In the present study, we evaluated the impact of a severe ototoxic...
Article
Because cochlear implants function by stimulating the auditory nerve, it is assumed that the condition of the nerve plays an important role in the efficacy of the prosthesis. Thus, considerable research has been devoted to methods of preserving the nerve following deafness. Neurotrophins have been identified as a potential contributor to neural hea...
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Hair cells in the mature cochlea cannot spontaneously regenerate. One potential approach for restoring hair cells is stem cell therapy. However, when cells are transplanted into scala media (SM) of the cochlea, they promptly die due to the high potassium concentration. We previously described a method for conditioning the SM to make it more hospita...
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Convergence is widely regarded as compelling evidence for adaptation, often being portrayed as evidence that phenotypic outcomes are predictable from ecology, overriding contingencies of history. However, repeated outcomes may be very rare unless adaptive landscapes are simple, structured by strong ecological and functional constraints. One such co...
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Synaptopathy in the cochlea occurs when the connection between inner hair cells and the auditory nerve is disrupted, leading to impaired hearing and nerve degeneration. Experiments using transgenic mice have shown that overexpression of NT3 by supporting cells repairs synaptopathy caused by overstimulation. To accomplish such therapy in the clinica...
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In experimental animal models of auditory hair cell (HC) loss, insults such as noise or ototoxic drugs often lead to secondary changes or degeneration in non-sensory cells and neural components, including reduced density of spiral ganglion neurons, demyelination of auditory nerve fibers and altered cell numbers and innervation patterns in the cochl...
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Integrating studies of ontogeny with analyses of disparity can reveal important and surprising insights into the origins of disparity and why it varies among groups. One such potentially surprising insight is that disparity could be constant over ontogeny even though species differ in both rates and timings of development and in their ontogenetic c...
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Scientific Reports 6: Article number: 2269010.1038/srep22690; published online: March112016; updated: April202016 This Article contains errors in the legend of Fig. 5. “Post-weaning dietary supplement slowed or reversed hearing loss in Diap3-Tg mutant mice.” should read: “Post-weaning dietary supplement accelerated hearing loss in Diap3-Tg muta...
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Dietary supplements consisting of beta-carotene (precursor to vitamin A), vitamins C and E and the mineral magnesium (ACEMg) can be beneficial for reducing hearing loss due to aminoglycosides and overstimulation. This regimen also slowed progression of deafness for a boy with GJB2 (CONNEXIN 26) mutations. To assess the potential for treating GJB2 a...
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Connexins are components of gap junctions which facilitate transfer of small molecules between cells. One member of the connexin family, Connexin 26 (Cx26), is prevalent in gap junctions in sensory epithelia of the inner ear. Mutations of GJB2, the gene encoding Cx26, cause significant hearing loss in humans. The vestibular system, however, does no...
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The most common reason for sensorineural deafness is death of hair cells (HCs). Heat shock proteins (HSPs) are molecular chaperones that participate in folding, targeting, and degrading proteins. HSP expression is increased in response to various environmental stresses to protect cells from damage. Here, we tested whether viral-mediated overexpress...
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Several theories predict that rapidly diversifying clades will also rapidly diverge phenotypically; yet, there are also reasons for suspecting that diversification and divergence might not be correlated. In the widely distributed squirrel clade (Sciuridae), we test for correlations between per-lineage speciation rates, species richness, disparity a...
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Cochlear hair cell loss results in secondary regression of peripheral auditory fibers (PAFs) and loss of spiral ganglion neurons (SGNs). The performance of cochlear implants (CI) in rehabilitating hearing depends on survival of SGNs. Here we compare the effects of adeno-associated virus vectors with neurotrophin gene inserts, AAV.BDNF and AAV.Ntf3,...
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CHARGE syndrome is a multiple anomaly disorder in which patients present with a variety of phenotypes, including ocular coloboma, heart defects, choanal atresia, retarded growth and development, genitourinary hypoplasia and ear abnormalities. Despite 70-90% of CHARGE syndrome cases resulting from mutations in the gene CHD7, which encodes an ATP-dep...
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The mammalian auditory epithelium (AE) cannot replace supporting cells and hair cells once they are lost. Therefore, sensorineural hearing loss associated with missing cells is permanent. This inability to regenerate critical cell types makes the AE a potential target for cell replacement therapies such as stem cell (SC) transplantation. Inserting...
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Mutations in the connexin 26 gene (GJB2) are the most common genetic cause of deafness, leading to congenital bilateral non-syndromic sensorineural hearing loss. Here we report the generation of a mouse model for a connexin 26 (Cx26) mutation, in which cre-Sox10 drives excision of the Cx26 gene from non-sensory cells flanking the auditory epitheliu...
Article
The mouse mandible is a popular model system that continues to be the focus of studies in evo-devo and other fields. Yet, little attention has been given to the role of postnatal growth in producing the adult form. Using cleared and stained specimens, we describe the timing of tooth and jaw development and changes in jaw size and shape from postnat...
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CHARGE syndrome is a multiple congenital anomaly disorder that leads to life-threatening birth defects such as choanal atresia and cardiac malformations as well as multiple sensory impairments that affect hearing, vision, olfaction, and balance. CHARGE is caused by heterozygous mutations in CHD7, which encodes an ATP-dependent chromatin remodeling...
Chapter
In this chapter, we discuss application of geometric morphometrics to the study of shape evolution. Because many of these studies examine multiple species, we pay particular attention to the role of phylogenetic information in analyses of phenotypic differences. We also present methods of quantifying and comparing morphological diversity (also know...
Chapter
Studies of evolving ontogenies are grounded in two important insights. The first is that all evolutionary change arises from changes in ontogeny and therefore we need to understand how ontogenies evolve in order to understand the origins of morphological diversity. The second is that organisms have time-extended phenotypes. An organism’s phenotype...
Chapter
Landmarks are discrete anatomical loci that can be recognized as the same point in all specimens in the study. They are often termed “homologous points” because these points can be matched up, one by one, as “the same point” in all individuals in the study. We could restrict the analysis to these points but we might miss a great deal of the morphol...
Chapter
In the forensic sciences, as in biology, anthropology and paleontology, there is much interest in comparing the shapes of objects. There are several specific areas of forensics in which morphometric methods, both traditional and geometric, have been applied. In this chapter, we will first look at a morphometric approach that retains size informatio...
Chapter
This chapter covers the basic theory of shape, beginning with the definition of shape and proceeding through the characterization of several theoretical spaces. Some of the mathematics may look a bit difficult, but it is important to grasp the basic ideas, which is presented verbally as well as mathematically. Interestingly, many of the techniques...
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This chapter discusses methods for analyzing variational properties, phenotypic plasticity, canalization, developmental stability, morphological integration and the related property of modularity. This chapter is organized primarily by subject matter rather than by methods. We first discuss methods for analyzing plasticity, then canalization and th...
Chapter
This chapter focuses on complex statistical models, such as models that include multiple categorical plus continuous factors, and those that include both fixed and random factors and those that include nested as well as crossed factors. All these models are special cases of the General Linear Model (GLM). We begin by introducing the GLM for simple...
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Current therapy for patients with hereditary absence of cochlear hair cells, who have severe or profound deafness, is restricted to cochlear implantation, a procedure that requires survival of the auditory nerve. Mouse mutations that serve as models for genetic deafness can be utilized for developing and enhancing therapies for hereditary deafness....
Book
The first edition of Geometric Morphometrics for Biologists has been the primary resource for teaching modern geometric methods of shape analysis to biologists who have a stronger background in biology than in multivariate statistics and matrix algebra. These geometric methods are appealing to biologists who approach the study of shape from a varie...
Chapter
The thin-plate spline provides a visually interpretable description of a deformation, with the same number of variables as there are statistical degrees of freedom, and it employs the Procrustes distance as a metric. Even if we were not concerned with the advantages of the spline for graphical analysis, we might still want to use it for purposes of...
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Cochlear gene therapy can be a new avenue for the treatment of severe hearing loss by inducing regeneration or phenotypic rescue. One necessary step to establish this therapy is the development of a safe and feasible inoculation surgery, ideally without drilling the bony cochlear wall. The round window membrane (RWM) is accessible in the middle-ear...
Article
Heterozygous mutations in the gene encoding chromodomain-DNA-binding-protein 7 (CHD7) cause CHARGE syndrome, a multiple anomaly condition which includes vestibular dysfunction and hearing loss. Mice with heterozygous Chd7 mutations exhibit semicircular canal dysgenesis and abnormal inner ear neurogenesis, and are an excellent model of CHARGE syndro...
Article
Routine surveillance of guinea pigs maintained within a barrier facility detected guinea pig adenovirus (GPAdV) in sentinel animals. These guinea pigs served as models of induced hearing loss followed by regeneration of cochlear sensory (hair) cells through transdifferentiation of nonsensory cells by using human adenoviral (hAV) gene therapy. To de...
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In the absence of a substantial functional shift, morphological evolution is usually expected to follow an allometric trajectory, however, studies of tree squirrel jaws have found isometry across most of their size range. This isometry appears to reflect the integration of a small number of lever arm lengths that are critical for generating bite fo...
Article
Previous studies have shown that residual acoustic hearing supplements cochlear implant function to improve speech recognition in noise as well as perception of music. The current study had two primary objectives. First, we sought to determine how cochlear implantation and electrical stimulation over a time period of 14 to 21 months influence cochl...
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The mammalian mandible is a developmentally modular but functionally integrated system. Whether morphological integration can evolve to match the optimal pattern of functional integration may depend on the developmental origin of integration, specifically, on the role that direct epigenetic interactions play in shaping integration. These interactio...
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Summary Several models explain how a complex integrated system like the rodent mandible can arise from multiple developmental modules. The models propose various integrating mechanisms, including epigenetic effects of muscles on bones. We test five for their ability to predict correlations found in the individual (symmetric) and fluctuating asymmet...
Article
The survival of the auditory nerve in cases of sensorineural hearing loss is believed to be a major factor in effective cochlear implant function. The current study assesses two measures of cochlear implant thresholds following a post-deafening treatment intended to halt auditory nerve degeneration. We used an adenoviral construct containing a gene...
Article
Following hair cell elimination in severely traumatized cochleae, differentiated supporting cells are often replaced by a simple epithelium with cuboidal or flat appearance. Atoh1 (previously Math1) is a basic helix-loop-helix transcription factor critical to hair cell differentiation during mammalian embryogenesis. Forced expression of Atoh1 in th...
Article
CHD7 is a chromodomain gene mutated in CHARGE syndrome, a multiple anomaly condition characterized by ocular coloboma, heart defects, atresia of the choanae, retarded growth and development, genital hypoplasia, and ear defects including deafness and semicircular canal dysgenesis. Mice with heterozygous Chd7 deficiency have circling behavior and sem...
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Full-text available
MYOSIN XV is a motor protein that interacts with the PDZ domain-containing protein WHIRLIN and transports WHIRLIN to the tips of the stereocilia. Shaker 2 (sh2) mice have a mutation in the motor domain of MYOSIN XV and exhibit congenital deafness and circling behavior, probably because of abnormally short stereocilia. Whirler (wi) mice have a simil...
Article
Spiral ganglion neurons often degenerate in the deaf ear, compromising the function of cochlear implants. Cochlear implant function can be improved by good preservation of the spiral ganglion neurons, which are the target of electrical stimulation by the implant. Brain derived neurotrophic factor (BDNF) has previously been shown to enhance spiral g...
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: A report on the Sixth Molecular Biology of Hearing and Deafness Conference, Hinxton, UK, 11-14 July 2007.
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In epithelial sheets, clearance of dead cells may occur by one of several routes, including extrusion into the lumen, phagocytic clearance by invading lymphocytes, or phagocytosis by neighboring cells. The fate of dead cochlear outer hair cells is unclear. We investigated the fate of the "corpses" of dead outer hair cells in guinea pigs and mice fo...
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p27(Kip1) (p27) has been shown to inhibit several cyclin-dependent kinase molecules and to play a central role in regulating entry into the cell cycle. Once hair cells in the cochlea are formed, p27 is expressed in non-sensory cells of the organ of Corti and prevents their re-entry into the cell cycle. In one line of p27 deficient mice (p27(-/-)),...
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The mammalian organ of Corti, the sensory epithelium of the inner ear, is a mosaic composed of sensory cells (hair cells) and non- sensory supporting cells. All cells are highly differentiated in structure and function. Because no undifferentiated cells are held in reserve to replace damaged cells, hearing impairment due to loss of hair cells is pe...
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Full-text available
In the mammalian auditory system, sensory cell loss resulting from aging, ototoxic drugs, infections, overstimulation and other causes is irreversible and leads to permanent sensorineural hearing loss. To restore hearing, it is necessary to generate new functional hair cells. One potential way to regenerate hair cells is to induce a phenotypic tran...
Chapter
This chapter discusses two methods for describing the diversity of shapes in a sample: principal components analysis (PCA) and canonical variates analysis (CVA). The discussion of these methods draws heavily on expositions presented by Morrison (1967), Chatfield and Collins (1980), and Campbell and Atchley (1981). Both methods are used to simplify...
Chapter
This chapter presents a method for obtaining shape variables that is both simple and visually informative. Called “the two-point registration,” this method produces a set of shape coordinates, sometimes called “Bookstein shape coordinates,” that can be used both for graphical displays and formal statistical tests. Bookstein shape coordinates (BC) p...
Chapter
Systematists use morphometrics to answer three types of questions. The first, “taxonomic,” asks whether populations are drawn from multiple species, and, if so, by what variable(s) they are most effectively discriminated. The second, “phylogenetic,” asks about phylogenetic relationships among taxa. Although they cannot be used to construct cladogra...