Bachelor of Arts, Harvard University (2009)
Doctor of Medicine, Stanford University, MED-MD (2015)
INTRODUCTION: Sound is integral to communication and connects us to the world through speech and music. Cochlear hair cells are essential for converting sounds into neural impulses. However, these cells are highly susceptible to damage from an array of factors, resulting in degeneration and ultimately irreversible hearing loss in humans. Since the discovery of hair cell regeneration in birds, there have been tremendous efforts to identify therapies that could promote hair cell regeneration in mammals. Areas covered: Here, we will review recent studies describing spontaneous hair cell regeneration and direct cellular reprograming as well as other factors that mediate mammalian hair cell regeneration. Expert opinion: Numerous combinatorial approaches have successfully reprogrammed non-sensory supporting cells to form hair cells, albeit with limited efficacy and maturation. Studies on epigenetic regulation and transcriptional network of hair cell progenitors may accelerate discovery of more promising reprogramming regimens.
View details for DOI 10.1080/14712598.2019.1564035
View details for PubMedID 30584811
PURPOSE OF REVIEW: The primary purpose of this review is to summarize current literature in the field of vestibular regeneration with a focus on recent developments in molecular and gene therapies.RECENT FINDINGS: Since the discovery of limited vestibular hair cell regeneration in mammals in the 1990s, many elegant studies have improved our knowledge of mechanisms of development and regeneration of the vestibular system. A better understanding of the developmental pathways of the vestibular organs has fueled various biological strategies to enhance regeneration, including novel techniques in deriving vestibular hair cells from embryonic and induced pluripotent stem cells. In addition, the identification of specific genetic mutations responsible for vestibular disorders has opened various opportunities for gene replacement therapy.SUMMARY: Vestibular dysfunction is a significant clinical problem with limited therapeutic options, warranting research on biological strategies to repair/regenerate the vestibular organs to restore function. The use of gene therapy appears promising in animal models of vestibular dysfunction.
View details for DOI 10.1097/MOO.0000000000000477
View details for PubMedID 30045104
In medically refractory chronic frontal sinusitis, ethmoidectomy without instrumentation of the frontal ostium may resolve frontal disease. Our aim was to determine the efficacy of ethmoidectomy alone for the treatment of chronic frontal sinusitis.Adults with chronic rhinosinusitis prospectively enrolled in a multicenter study who demonstrated frontal sinusitis on computed tomography were divided into 2 groups: (1) endoscopic sinus surgery (ESS) incorporating ethmoidectomy, but excluding frontal sinusotomy; and (2) ESS incorporating frontal sinusotomy. The primary outcome was improvement in 22-item Sino-Nasal Outcome Test (SNOT-22) scores. Secondary outcomes included endoscopic scores and use of corticosteroids and antibiotics.A total of 196 cases undergoing frontal sinusotomy and 30 cases treated with ethmoidectomy without frontal sinusotomy were analyzed and were comparable demographically. The prevalence of nasal polyps, previous ESS, asthma, and aspirin intolerance was more common in the frontal sinusotomy group (p < 0.050). Preoperative endoscopy and computed tomography scores were higher in the frontal sinusotomy group (p ≤ 0.001). Postoperatively, both groups showed comparable SNOT-22 scores with worse endoscopy scores in the frontal sinusotomy group (p = 0.038). Postoperative improvement in SNOT-22 total and subdomain scores was comparable between groups. Nasal endoscopy scores improved to a greater degree in the frontal sinusotomy group (p = 0.023). Duration of postoperative topical steroid use was higher in the frontal sinusotomy group (p = 0.007). Revision surgery was needed in 2.6% of frontal sinusotomy patients and 0% of patients without frontal sinusotomy.The treatment of chronic frontal sinusitis through ethmoidectomy is a potential alternative to frontal sinusotomy achieving similar quality of life (QOL) improvements in patients manifesting less severe sinus disease.
View details for DOI 10.1002/alr.21726
View details for Web of Science ID 000379700700007
View details for PubMedID 26879467
View details for PubMedCentralID PMC4921290
Wnt signaling is a highly conserved pathway crucial for development and homeostasis of multicellular organisms. Secreted Wnt ligands bind Frizzled receptors to regulate diverse processes such as axis patterning, cell division, and cell fate specification. They also serve to govern self-renewal of somatic stem cells in several adult tissues. The complexity of the pathway can be attributed to the myriad of Wnt and Frizzled combinations as well as its diverse context-dependent functions. In the developing mouse inner ear, Wnt signaling plays diverse roles, including specification of the otic placode and patterning of the otic vesicle. At later stages, its activity governs sensory hair cell specification, cell cycle regulation, and hair cell orientation. In regenerating sensory organs from non-mammalian species, Wnt signaling can also regulate the extent of proliferative hair cell regeneration. This review describes the current knowledge of the roles of Wnt signaling and Wnt-responsive cells in hair cell development and regeneration. We also discuss possible future directions and the potential application and limitation of Wnt signaling in augmenting hair cell regeneration.
View details for DOI 10.3389/fncel.2015.00066
View details for Web of Science ID 000352399400001
View details for PubMedID 25814927
View details for PubMedCentralID PMC4356074
Recruitment of endogenous progenitors is critical during tissue repair. The inner ear utricle requires mechanosensory hair cells (HCs) to detect linear acceleration. After damage, non-mammalian utricles regenerate HCs via both proliferation and direct transdifferentiation. In adult mammals, limited transdifferentiation from unidentified progenitors occurs to regenerate extrastriolar Type II HCs. Here we show that HC damage in neonatal mouse utricle activates the Wnt target gene Lgr5 in striolar supporting cells. Lineage tracing and time-lapse microscopy reveal that Lgr5+ cells transdifferentiate into HC-like cells in vitro. In contrast to adults, HC ablation in neonatal utricles in vivo recruits Lgr5+ cells to regenerate striolar HCs through mitotic and transdifferentiation pathways. Both Type I and II HCs are regenerated, and regenerated HCs display stereocilia and synapses. Lastly, stabilized ß-catenin in Lgr5+ cells enhances mitotic activity and HC regeneration. Thus Lgr5 marks Wnt-regulated, damage-activated HC progenitors and may help uncover factors driving mammalian HC regeneration.
View details for DOI 10.1038/ncomms7613
View details for PubMedID 25849379
View details for PubMedCentralID PMC4391285