Otorhinolaryngology-Head & Neck Surgery
Frenkil building, 16 S Eutaw St., Suite 500 Laboratory location: 800 West Baltimore St. Room 405, and 400M
Education and Training
1995-1998 B.Sc. Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
1995–2006 M.D. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
2000–2005 Ph.D. Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
2006-2011 Resdiency, Otorhinolaryngology Head and Neck Surgery - University of Maryland School of Medicine, Baltimore
I am an otolaryngologist surgeon-scientist. My clinical practice focuses on the diagnosis and treatment of diseases of the ear, with a specific emphasis on hearing restoration. As such, I see and treat patients of all ages that suffer from hereditary and non-hereditary auditory and vestibular dysfunction. Sixty percent of my time is dedicated to research, where my goal is to make significant contributions towards the treatment of congenital and acquired auditory and vestibular dysfunction. Towards hearing restoration, I work to unravel the regulatory signaling cascades that lead to the proper development of the ear and specifically the hair cells. My team develops and applies a variety of approaches for cell type-specific genomic analyses of the ear. We couple the results of these studies with informatics analyses to identify key regulators of gene expression in hair cell development, and cell type-specific signaling cascades in acquired hearing loss. Several years ago, I realized that the lack of intuitive tools for the non-informatics trained biologists for visualization and analysis of omics data presents a major barrier to effective dissemination, sharing and analysis of expression data by cellular and molecular biologists. This led to the inception and development of the gEAR – a portal of gene Expression for Aanalysis Resource (gear.igs.umaryland.edu), a portal for intuitive visualization, analysis and sharing of gene expression data, which is an exciting addition to our research portfolio. Finally, I have a special interest in mentoring of undergraduates, medical students, residents, graduate students and post-docs.
Hearing Loss, Hearing Restoration, Cochlear Implants, Otosclerosis, Cholesteatoma, Genetic Hearing Loss Genomics, Regulation of Gene Expression, Gene Therapy, Transcription Factors in Inner Ear Development, Noise Induced Hearing loss
Cell type-specific signaling cascades in inner ear development: the inner ear sensory epithelium is complex and consists of multiple cell types. Cell type-specific analyses are helpful in defining the regulatory pathways that determine cell fate. In order to define cell type-specific regulatory pathways in inner ear development, we characterized the expression of transmembrane cell surface proteins (CD proteins) in the inner ear. We subsequently identified combinations of markers that could allow for inner ear cell type-specific isolation using flow cytometry. Taking this approach, we were able to not only identify the genetic fingerprint of different cell types in the ear, but also RFX, Zeb1 and miR200b as regulators of cell fate/maturation/survival. We continue to develop new approaches for cell type transcriptome and translatome analysis in the ear, and are actively involved in their dissemination in the field.
Hertzano R, Puligilla C, Chan SL, Timothy C, Depireux DA, Ahmed Z, Wolf J, Eisenman DJ, Friedman TB, Riazuddin S, Kelley MW and Strome SE. (2010) CD44 is a marker for the outer pillar cell in the early post-natal mouse inner ear. J Assoc Res Otolaryngol 11:407-18. –Article featured on journal cove
Hertzano R and Elkon R. (2012) High throughput gene expression analysis of the inner ear. Hear Res. 288:77-88 **this article was listed in Faculty 1000
Hertzano R, Elkon R, Kurima K, Morrisson A, Chan SL, Sallin M, Biedlingmaier A, Darling DS, Griffith AJ, Eisenman DJ and Strome SE. (2011) Cell type-specific transcriptome analysis reveals a major role for Zeb1 and miR-200b in mouse inner ear morphogenesis. PLoS Genet. 7:e1002309.
Elkon R, Milon B, Morrison L, Shah M, Vijayakumar S, Racherla M, Leitch CC, Silipino L, Hadi S, Weiss-Gayet M, Barras E, Schmid CD, Ait-Lounis A, Barnes A, Song Y, Eisenman DJ, Eliyahu E, Frolenkov GI, Strome SE, Durand B, Zaghloul NA, Jones SM, Reith W and Hertzano R. (2015) RFX transcription factors are essential for hearing in mice. Nat Commun. Oct 15;6:8549. doi: 10.1038/ncomms9549
The POU4F3 transcriptional cascade in hair cell development: POU4F3 is an inner ear hair cell-specific transcription factor that is expressed in the hair cells from shortly after they are formed. Mutations in POU4F3 underlie human hereditary hearing loss. In the mouse, loss of Pou4f3 results in early degeneration of all inner ear hair cells. My graduate thesis work focused on identification and characterization of the targets of POU4F3 in hair cells. Several of these targets have been subsequently identified to be important for hearing in human (LHX3) or critical for increasing the efficiency of transforming stem cells to hair cells (GFI1). My laboratory now continues to study the function of this signaling cascade, with a specific focus on GFI1 and its role in hair cell development.
Hertzano R, Montcouquiol M, Rashi-Elkeles S, Elkon R, Yücel R, Frankel WN, Rechavi G, Möröy T, Friedman TB, Kelley MW and Avraham KB.(2004) Transcription profiling of inner ears from Pou4f3ddl/ddl identifies Gfi1 as a target of the Pou4f3 deafness gene. Hum Mol Genet. 13:2143-53. –Article featured on journal cover
Hertzano R, Dror AA, Montcouquiol M, Ahmed Z, Ellsworth B, Camper S, Friedman TB, Kelley MW and Avraham KB. (2007) Lhx3, a LIM domain transcription factor, is regulated by Pou4f3 in the auditory, but not in the vestibular system. Eur J Neurosci. 25:999-1005. –Article featured on journal cover
Clough RL, Sud R, Davis-Silberman N, Hertzano R, Avraham KB, Holley M, Dawson SJ. (2004) Brn-3c (POU4F3) regulates BDNF and NT-3 promoter activity. Biochem Biophys Res Commun. 5;324:372-81.
Fiolka K, Hertzano R, Zeng H, Hermesh O, Avraham KB, Dührsen U and Möröy T. (2006) Gfi1 and Gfi1b act equivalently in haematopoiesis, but have distinct, non-overlapping functions in inner ear development. EMBO Reports. 7:326-33.
Identification and characterization of genes that underlie hearing and balance disorders in human and in mice: hereditary hearing loss is highly heterogeneous with over 150 genes estimated to underlie congenital non-syndromic hearing loss. Less is known about the genetic basis of, the more common, age related hearing loss. The significance in identification of genes that underlie hereditary hearing loss is purely translational. As more genes are identified, patients can get better genetic counseling, and in the future, possibly personally-tailored hearing restoration. My work on the identification of genes that underlie hearing loss ranges from projects that I spearheaded, using ENU-induced mouse mutants, to contributions to collaborative projects in human or mouse. Our recently identified hair cell-enriched transcripts in mouse, have been translated into a diagnostic discovery panel in collaboration with Richard Smith, PhD. Patients who test negative for mutations in the known deafness genes using the Otoscope platform are screened using the discovery panel.
Rhodes CR*, Hertzano R*, Fuchs H, Bell RE, Hrabé de Angelis M, Steel KP, Avraham KB. (2004) A Myo7a mutation co-segregates with stereocilia defects and low frequency hearing impairment. Mamm Genome. 15:686-97.
Hertzano R*, Shalit E*,Rzadzinska AK*, Dror AA, Song L, Ron U, Tan JT, Starovolsky Shitrit A, Fuchs A, Hasson T, Ben-Tal N, Sweeney HL, Hrabe de Angelis M, Steel KP and Avraham KB. (2008) A Myo6 mutation destroys coordination between the myosin heads, revealing new functions of myosin VI in the stereocilia of mammalian inner ear hair cells. PLoS Genetics. 4:e1000207.
Kurima K, Hertzano R, Gavrilova O, Monahan K, Shpargel KB, Nadaraja G, Kawashima Y, Lee KY, Ito T, Higashi Y, Eisenman DJ, Strome SE and Griffith AJ. (2011) A noncoding point mutation of Zeb1 causes multiple developmental malformations and obesity in Twirler mice. PLoS Genet. 7:e1002307.
Matern M, Margulies Z, Milon B, Song Y, Vijayakumar S, Elkon R, Zhang X, Jones SM and Hertzano R. (2017) Gfi1Cre mice have early onset mid- to high-frequency hearing loss and induce recombination in numerous inner ear non-hair cells. Scientific Reports - Accepted.
- Signaling pathways in inner ear development
- Singlaing pathways in acquired hearing loss
- Genomics and Genetics of inner ear development and hearing loss
- Herediatary auditory and vestibular dysfunction
- Mouse and Zebrafish models for hearing loss
- Gene Therapy
- Tools for multi-omic data sharing and analysis
- Hearing loss and hearing restoration for patients of all ages
- Genetic and Acquired Hearing Loss
- Cochlear Implants
- Ossicular Chain Reconstruction
- Middle ear tumors
- Meniere's Disease
- Superior Semicircular Canal Dehiscence
2002 Distinguished MD Thesis Award, Sackler School of Medicine, Tel Aviv University.
2003 Association for Research in Otolaryngology, Graduate Student Travel Award.
2003 Switzerland Institute for Developmental Biology Award.
2003 Foulkes Foundation Fellowship Award, three-year physician-scientist fellowship (2004-2006).
2007 Association for Research in Otolaryngology, Resident Travel Award.
2008 Association for Research in Otolaryngology, Resident Travel Award
2008 Maryland Society of Otorhinolaryngology, Resident Research Award
2008 Department of OHNS, University of Maryland, Resident Research Award
2008 CORE AAO-HNSF Resident Research Award (see grants)
2009 Maryland Society of Otorhinolaryngology, Resident Research Award
2009 Department of OHNS, University of Maryland, Resident Research Award
2009 CORE AAO-HNSF Resident Research Award (returned as received a DRF grant, see grants)
2010 Association for Research in Otolaryngology, Resident Travel Award
2010 Maryland Society of Otorhinolaryngology, Resident Research Award
2010 AAO-HNSF Resident Travel Award
2011 Triological Society Career Development Award (see grants)
2013 The Daily Record Very Important Professionals (VIP) List of Successful by 40 Award
2014 Burt Evans Young Investigator Award, by the National Organization of Hearing Research
2016 Brian E. Emery, M.D., Outstanding Teaching Award, UMSOM, department of
“Autosomal Dominant Non-Syndromic Hearing Loss”
NIH R01, DC003544 - Co-I
“Towards a Molecular Understanding of Noise Induced Hearing Loss”
DOD, MR130240 - PI
“Cell Type Specific Transcriptional Cascades in Inner Ear Development”
NIH R01, DC013817 - PI
“Implementing the gEAR for data sharing within the HRP”
Hearing Health Foundation - PI
12/28/2012 CNN Health. An article featuring one of my patients, discussing cochlear implantation in the aging population, accessed at: http://www.cnn.com/2012/12/28/health/cochlear-implants
8/7/2013 Science Daily. Heart pump with behind-the-ear power connector, accessed at http://www.sciencedaily.com/releases/2013/08/130807204445.htm
10/3/2013 ENT Today. An article discussing cochlear implants in older adults interviewing several experts in the field, accessed at: http://www.enttoday.org/details/article/5295901/Cochlear_Implants_Effective_in_Older_Patients_with_Age-Related_Hearing_Loss.html
10/15/2015 Science Daily. An article describing our finding of RFX having a critical role in hair cell survival (published that week in Nature Communications). www.sciencedaily.com/releases/2015/10/151015083403.htm
10/15/2015 NIDCD website. Featured news regarding the publication of a role for RFX in hair cell survival.http://www.nidcd.nih.gov/news/releases/15/Pages/10152015.aspx
3/4/2016 Fox News. An article featuring one of my patients, an 8-year old girl that was abandoned by her parents in Uganda as she was born deaf. She was subsequently adopted by an American couple and shortly after arriving to the United States received a cochlear implant. http://video.foxnews.com/v/4787109617001/leticias-story-a-young-girls-quest-to-hear/?#sp=show-clips
Basic and advanced molecular and cellular biology
Gene transfer and gene therapy - mouse and zebrafish models
Multi-omic approaches for analysis of gene expression and regulation
Auditory and vestibular assesment - neurophysiologic testing