Hela Azaiez, PhD
Assistant Professor of Medical & Molecular Genetics
- Address
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975. W Walnut Street IB454A
MMGE
IN
Indianapolis, IN
Bio
Throughout Dr Azaiez's academic and professional journey—beginning with foundational training in molecular genetics at the University of Sfax, Tunisia, and advancing through specialized research in human molecular genetics at the University of Iowa—She has focused on the genetics and genomics of hearing loss. At the University of Iowa’s Department of Otolaryngology–Head and Neck Surgery, Carver College of Medicine, Dr. Azaiez led the Hearing Loss Team at the Molecular Otolaryngology and Renal Research Laboratories (MORL).
She currently directs a research group that integrates state-of-the-art genomic technologies and bioinformatics tools to study genotype–phenotype correlations, investigate the molecular mechanisms of hearing and deafness, and improve the identification, interpretation, and clinical correlation of genomic variants. This work is inherently translational, connecting discoveries in molecular genetics to clinical applications.
Dr. Azaiez's projects are highly multidisciplinary, involving large international collaborations and providing training opportunities in genomic research. She spearheaded the creation of the Deafness Variation Database, the first comprehensive catalog of genes and variants linked to hearing loss, which is now accessed by more than 3,000 professionals worldwide each year.
During her tenure as Chair of the Hearing Loss Gene Curation Expert Panel (HL-GCEP) and Variant Curation Expert Panel (VCEP), she has contributed to the development of hearing loss–specific variant classification guidelines adopted internationally, improving the accuracy of genetic testing and diagnosis.
Looking ahead, Dr. Azaiez plans to integrate artificial intelligence and functional genomic technologies to better understand the impact of genetic variants and refine their interpretation to advance precision medicine in hearing health.
Key Publications
Smith RJH, Azaiez H. Branchiootorenal Spectrum Disorder. 1999 Mar 19 [updated 2025 Jun 26]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. PMID: 20301554.
Azaiez H, Thorpe RK, Odell AM, Smith RJH. OTOF-Related Hearing Loss. 2008 Feb 29 [updated 2025 Mar 13]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. PMID: 20301429.
Smith RJH, Azaiez H, Odell AM. SLC26A4-Related Sensorineural Hearing Loss. 1998 Sep 28 [updated 2025 Apr 3]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. PMID: 20301640.
Tshering KC, DiStefano MT, Oza AM, Ajuyah P, Webb R, Edoh E, Broeren E, Ratliff J, Gitau V, Paris K, Aburyyan A, Alexander J, Albano V, Bai D, Booth KTA, Buonfiglio PI, Charfeddine C, Dalamón V, Castillo ID, Moreno-Pelayo MA, Duzkale H, Dorshorst B, Faridi R, Kenna M, Lewis MA, Luo M, Lu Y, Mkaouar R, Matsunaga T, Nara K, Pandya A, Redfield S, Roux I, Schimmenti LA, Schrauwen I, Shaaban S, Shen J, Vona B, Smith RJ, Rehm HL, Azaiez H, Abou Tayoun AN, Amr SS; ClinGen Hearing Loss Clinical Domain Working Group. ClinGen recuration of hearing loss-associated genes demonstrates significant changes in gene-disease validity over time. Genet Med. 2025 Feb 19;27(5):101392. doi: 10.1016/j.gim.2025.101392. Epub ahead of print. PMID: 39987489.
Colbert BM, Lanting C, Smeal M, Blanton S, Dykxhoorn DM, Tang PC, Getchell RL, Velde H, Fehrmann M, Thorpe R, Chapagain P, Elkhaligy H, Kremer H, Yntema H, Haer-Wigman L, Redfield S, Sun T, Bruijn S, Plomp A, Goderie T, van de Kamp J, Free RH, Wassink-Ruiter JK, Widdershoven J, Vanhoutte E, Rotteveel L, Kriek M, van Dooren M, Hoefsloot L, de Gier HHW; DOOFNL Consortium; Schaefer A, Kolbe D, Azaiez H, Rabie G, Aburayyan A, Kawas M, Kanaan M, Holder J, Usami SI, Chen Z, Dai P, Holt J, Nelson R, Choi BY, Shearer E, Smith RJH, Pennings R, Liu XZ. The natural history and genotype-phenotype correlations of TMPRSS3 hearing loss: an international, multi-center, cohort analysis. Hum Genet. 2024 Apr 30. doi: 10.1007/s00439-024-02648-3. PMID: 38691166.
Smith RJH, Azaiez H, Booth K. GJB2-Related Autosomal Recessive Nonsyndromic Hearing Loss. 1998 Sep 28 [updated 2023 Jul 20]. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2023. PMID: 20301449.
Tollefson MR, Gogal RA, Weaver AM, Schaefer AM, Marini RJ, Azaiez H, Kolbe DL, Wang D, Weaver AE, Casavant TL, Braun TA, Smith RJH, Schnieders MJ. Assessing variants of uncertain significance implicated in hearing loss using a comprehensive deafness proteome. Hum Genet. 2023 Jun;142(6):819-834. doi: 10.1007/s00439-023-02559-9. PMID: 37086329.
Faridi R, Yousaf R, Gu S, Inagaki S, Turriff AE, Pelstring K, Guan B, Naik A, Griffith AJ, Adadey SM, Aboagye ET, Awandare GA, Morell RJ, Tsilou E, Noyes AG, Sulmonte LAG, Wonkam A, Schrauwen I, Leal SM, Azaiez H, Brewer CC, Riazuddin S, Hufnagel RB, Hoa M, Zein WM, de Dios JK, Friedman TB. Variants of LRP2, encoding a multifunctional cell-surface endocytic receptor, associated with hearing loss and retinal dystrophy. Clin Genet. 2023 Jun;103(6):699-703. doi: 10.1111/cge.14312. PMID: 36807241.
Klimara MJ, Nishimura C, Wang D, Kolbe DL, Schaefer AM, Walls WD, Frees KL, Smith RJH, Azaiez H. De novo variants are a common cause of genetic hearing loss. Genet Med. 2022 Dec;24(12):2555-2567. doi: 10.1016/j.gim.2022.08.028. PMID: 36194208.
Bu F, Zhong M, Chen Q, Wang Y, Zhao X, Zhang Q, Li X, Booth KT, Azaiez H, Lu Y, Cheng J, Smith RJH, Yuan H. DVPred: a disease-specific prediction tool for variant pathogenicity classification for hearing loss. Hum Genet. 2022 Apr;141(3-4):401-411. doi: 10.1007/s00439-022-02440-1. PMID: 35182233.
Orvis J, Gottfried B, Kancherla J, Adkins RS, Song Y, Dror AA, Olley D, Rose K, Chrysostomou E, Kelly MC, Milon B, Matern MS, Azaiez H, Herb B, Colantuoni C, Carter RL, Ament SA, Kelley MW, White O, Bravo HC, Mahurkar A, Hertzano R. gEAR: Gene Expression Analysis Resource portal for community-driven, multi-omic data exploration. Nat Methods. 2021 Aug;18(8):843-844. doi: 10.1038/s41592-021-01200-9. PMID: 34172972.
Thorpe RK*, Azaiez H*, Wu P, Wang Q, Xu L, Dai P, Yang T, Schaefer GB, Peters BR, Chan KH, Schatz KS, Bodurtha J, Robin NH, Hirsch Y, Rahbeeni ZA, Yuan H, Smith RJH. The natural history of OTOF-related auditory neuropathy spectrum disorders: a multicenter study. Hum Genet. 2021 Aug 23. doi: 10.1007/s00439-021-02340-w. Epub ahead of print. PMID: 34424407. *Co-first authors.
Azaiez H, Thorpe RK, Smith RJH. OTOF-Related Deafness. 2008 Feb 29 [updated 2021 Jan 21]. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2022. PMID: 20301429.
Patel MJ, DiStefano MT, Oza AM, Hughes MY, Wilcox EH, Hemphill SE, Cushman BJ, Grant AR, Siegert RK, Shen J, Chapin A, Boczek NJ, Schimmenti LA, Nara K, Kenna M, Azaiez H, Booth KT, Avraham KB, Kremer H, Griffith AJ, Rehm HL, Amr SS, Tayoun ANA; ClinGen Hearing Loss Clinical Domain Working Group. Disease-specific ACMG/AMP guidelines improve sequence variant interpretation for hearing loss. Genet Med. 2021 Jul 6. doi: 10.1038/s41436-021-01254-2. Epub ahead of print. PMID: 34230634.
Vona B, Mazaheri N, Lin SJ, Dunbar LA, Maroofian R, Azaiez H, Booth KT, Vitry S, Rad A, Rüschendorf F, Varshney P, Fowler B, Beetz C, Alagramam KN, Murphy D, Shariati G, Sedaghat A, Houlden H, Petree C, VijayKumar S, Smith RJH, Haaf T, El-Amraoui A, Bowl MR, Varshney GK, Galehdari H. A biallelic variant in CLRN2 causes non-syndromic hearing loss in humans. Hum Genet. 2021 Jun;140(6):915-931. doi: 10.1007/s00439-020-02254-z. Epub 2021 Jan 26. PMID: 33496845; PMCID: PMC8099798.
Mohseni M, Babanejad M, Booth KT, Jamali P, Jalalvand K, Davarnia B, Ardalani F, Khoshaeen A, Arzhangi S, Ghodratpour F, Beheshtian M, Jahanshad F, Otukesh H, Bahrami F, Seifati SM, Bazazzadegan N, Habibi F, Behravan H, Mirzaei S, Keshavarzi F, Nikzat N, Mehrjoo Z, Thiele H, Nothnagel M, Azaiez H, Smith RJ, Kahrizi K, Najmabadi H. Exome sequencing utility in defining the genetic landscape of hearing loss and novel-gene discovery in Iran. Clin Genet. 2021 Jul;100(1):59-78. doi: 10.1111/cge.13956. Epub 2021 Mar 24. PMID: 33713422; PMCID: PMC8195868.
Hirsch Y, Tangshewinsirikul C, Booth KT, Azaiez H, Yefet D, Quint A, Weiden T, Brownstein Z, Macarov M, Davidov B, Pappas J, Rabin R, Kenna MA, Oza AM, Lafferty K, Amr SS, Rehm HL, Kolbe DL, Frees K, Nishimura C, Luo M, Farra C, Morton CC, Scher SY, Ekstein J, Avraham KB, Smith RJH, Shen J. A synonymous variant in MYO15A enriched in the Ashkenazi Jewish population causes autosomal recessive hearing loss due to abnormal splicing. Eur J Hum Genet. 2021 Jun;29(6):988-997. doi: 10.1038/s41431-020-00790-w. Epub 2021 Jan 4. PMID: 33398081; PMCID: PMC8187401.
Booth KT, Ghaffar A, Rashid M, Hovey LT, Hussain M, Frees K, Renkes EM, Nishimura CJ, Shahzad M, Smith RJ, Ahmed Z, Azaiez H*, Riazuddin S*. Novel loss-of-function mutations in COCH cause autosomal recessive nonsyndromic hearing loss. Hum Genet. 2020 Dec;139(12):1565-1574. PMID: 32562050; PMCID: PMC7572817. *Co-corresponding authors.
Booth KT, Azaiez H, Smith RJH. DFNA5 (GSDME) c.991-15_991-13delTTC: Founder Mutation or Mutational Hotspot? Int J Mol Sci. 2020 May 31;21(11):3951. PMID: 32486382; PMCID: PMC7312536.
Walls WD, Moteki H, Thomas TR, Nishio SY, Yoshimura H, Iwasa Y, Frees KL, Nishimura CJ, Azaiez H, Booth KT, Marini RJ, Kolbe DL, Weaver AM, Schaefer AM, Wang K, Braun TA, Usami SI, Barr-Gillespie PG, Richardson GP, Smith RJ, Casavant TL. A comparative analysis of genetic hearing loss phenotypes in European/American and Japanese populations. Hum Genet. 2020 Oct;139(10):1315-1323. PMID: 32382995; PMCID: PMC7487054.
Stiff HA, Sloan-Heggen CM, Ko A, Pfeifer WL, Kolbe DL, Nishimura CJ, Frees KL, Booth KT, Wang D, Weaver AE, Azaiez H, Kamholz J, Smith RJH, Drack AV. Is it Usher syndrome? Collaborative diagnosis and molecular genetics of patients with visual impairment and hearing loss. Ophthalmic Genet. 2020 Apr;41(2):151-158. PMID: 32281467; PMCID: PMC7489297.
Morín M, Borreguero L, Booth KT, Lachgar M, Huygen P, Villamar M, Mayo F, Barrio LC, Santos Serrão de Castro L, Morales C, Del Castillo I, Arellano B, Tellería D, Smith RJH, Azaiez H, Moreno Pelayo MA. Insights into the pathophysiology of DFNA10 hearing loss associated with novel EYA4 variants. Sci Rep. 2020 Apr 10;10(1):6213. PMID: 32277154; PMCID: PMC7148344.
| Year | Degree | Institution |
|---|---|---|
| 2010 | Postdoctoral Training | University of Iowa |
| 2008 | PhD | University of Sfax |
| 2000 | MS | University of Sfax |
| 1998 | BS | University of Sfax |
Dr. Azaiez's research investigates the genetics and genomics of hearing loss, with an emphasis on translating discoveries into improved diagnostics and patient care. Using high-throughput sequencing, bioinformatics, and functional genomics, her research team studies genotype–phenotype relationships, the molecular mechanisms of hearing and deafness, and the interpretation of genomic variants.
Dr. Azaiez and her team lead collaborative, multidisciplinary projects that develop resources for the clinical genetics community, including the Deafness Variation Database and expert-curated gene and variant classification guidelines for hearing loss. Their current research focus explores the integration of artificial intelligence and functional genomic technologies to refine variant interpretation and assess the biological effects of genetic changes, with the goal of advancing precision medicine in hearing health.