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Ronna Hertzano, MD, PhD

Academic Title:

Associate Professor

Primary Appointment:

Otorhinolaryngology-Head & Neck Surgery

Secondary Appointment(s):

Anatomy Neurobiology

Location:

Frenkil building, 16 S Eutaw St., Suite 500 Laboratory location: 800 West Baltimore St. Room 405, and 400M

Phone (Primary):

410-328-1892

Phone (Secondary):

410-706-4761

Fax:

410-328-5827

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

Biosketch

I am an otolaryngologist surgeon-scientist. My clinical practice focuses on the diagnosis and treatment of diseases of the ear, with an 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. Over 60% 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. I lead a collaborative team that develops and applies a variety of approaches for cell type-specific multi-omic analyses of the ear. We couple the results of these studies with state-of-the-art informatics analyses to identify key regulators of gene expression in hair cell development, and cell type-specific signaling cascades in acquired hearing loss (e.g., noise induced or age related 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 dat. Finally, I have a special interest in mentoring of undergraduates, medical students, residents, graduate students and post-docs. 

 

Research/Clinical Keywords

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

Highlighted Publications

 

Identification and characterization of transcription factors with key roles in inner ear development:
Disabling hearing loss afflicts over 50% of the population over the age of 70 and the final common pathway of most forms of hearing loss involves the loss of hair cells, the sensory cells of the ear. Our team takes a cell type-specific multi-omic approach to identify key regulators of cell type-specific differentiation in the ear, which could later be applied towards hair cell regeneration. Four of our key findings have been the identification of ZEB1 and miR-200b as the major determining factors of epithelial fate in the ear; RFX1 and RFX3 as transcription factors that are necessary for the terminal differentiation and survival of early postnatal auditory hair cells in mice; IKZF2 as a regulator of outer hair cell functional maturation; and most recently, the molecular mechanism by which GFI1 promotes hair cell differentiation during early development (‘GFI1 functions to repress neuronal gene expression in developing hair cells’ manuscript in preparation). RFX and IKZF2 are amongst very few regulators that have been shown to play a role in hair cell terminal differentiation – a necessary step for successful hair cell regeneration.

 

  1. 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. PMCID: PMC3183091
  2. Chessum L*, Matern M*, Kelly MC, Johnson SL, Ogawa Y, Milon B, McMurray M, Driver EC, Parker A, Song Y, Codner G, Esapa CT, Prescott J, Trent G, Wells S, Dragich AK, Frolenkov GI, Kelley MW, Marcotti W, Brown SDM, Elkon R, Bowl MR, and Hertzano R (2018) Ikzf2/helios is a key transcriptional regulator of outer hair cell maturation. Nature Nov;563(7733):696-700. PMCID: PMC6542691
  3. Hertzano R, Gwilliam K, Rose KP, Milon B and Matern M (2020) Cell Type-Specific Expression Analysis of the Inner Ear – A Technical Report. The Laryngoscope (Triologic Thesis) Jun 24. 
  4. 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. PMCID: PMC4634137

 

 

Development and application of approaches for cell type-specific analysis in the ear and data sharing: 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. We continue to develop and apply new approaches for cell type transcriptome and translatome analysis in the ear in both mouse and zebrafish and are actively involved in their dissemination in the field. Finally, we developed and maintain the gEAR portal (gene Expression Analysis Resource umgear.org), a website for cell type-specific visualization, sharing and analysis. The gEAR portal has now turned into a primary site for multi-omic data sharing for researchers in the ear field and has been cloned to serve additional research communities (e.g., nemoanalytics.org for neuroscience).

 

  1. 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
  2. Song Y, Milon B, Ott S, Zhao X, Sadzewicz, Shetty A, Boger ET, Tallon LJ, Morell RJ, Mahurkar A and Hertzano R (2018) A comparative analysis of library prep approaches for sequencing low input translatome samples. BMC Genomics 2018 Sep 21;19(1):696. PMCID: PMC6151020
  3. Kolla L, Kelly MC, Mann ZF, Anaya-Rocha A, Ellis K, Lemons A, Palermo AT, So KS, Mays JC, Orvis J, Burns JC, Hertzano R, Driver EC and Kelley MW. (2020) Characterization of the development of the cochlear epithelium at the single cell level. Nature Communications May 13;11(1):2389.
  4. Matern MS, Beirl A, Ogawa Y, Song Y, Paladugu N, Kindt KS, Hertzano R. (2018) Transcriptomic Profiling of Zebrafish Hair Cells Using RiboTag. Front Cell Dev Biol. 2018 May 1;6:47. doi: 10.3389/fcell.2018.00047. eCollection 2018. PMCID: PMC5939014

 

 

The POU4F3 and GFI1 transcriptional cascades in hair cell development: POU4F3 is an inner ear hair cell-specific transcription factor that is expressed in the hair cells 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 the GFI1 signaling cascade in hair cell development.

 

  1. 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.
  2. 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. PMCID: PMC1456886
  3. 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. Sci Rep. 7:42079 PMCID: PMC5299610
  4. Matern M, Milon B, Ogawa Y, Tkaczuk A, McMurray M, Song Y, Elkon R, and Hertzano R. (2019) Reconstructing the Transcriptional Network Downstream of GFI1 in Hair Cell Development. Association for Research in Otolaryngology, 42TH Annual MidWinter Meeting, Baltimore (MD), USA

 

Understanding the molecular basis of noise induced hearing loss (NIHL) and sex differences in hearing – a step towards therapeutics: NIHL afflicts 5% of the population worldwide. To date there are no effective interventions to prevent or treat NIHL. Through a project funded by the Department of Defense we worked towards developing the blueprint of the cell type-specific molecular changes that occur as a result of NIHL, we have shared many of the results pre-publication, as podium or poster presentations (manuscripts in preparation). However, in the process of performing the NIHL studies we identified striking sex-related differences in the response of male and female mice to noise trauma and its possible treatments. We are actively studying the molecular basis of sex differences in hearing, have published and shared some of our results, and plan to harness our findings to develop novel therapeutic interventions.    

 

  1. Milon B, Mitra S, Song Y, Margulies Z, Casserly R, Drake V, Mong JA, Depireux DA, Hertzano R. (2018) The impact of biological sex on the response to noise and otoprotective therapies against acoustic injury in mice. Biol Sex Differ. Mar 12;9(1):12. PMCID: PMC5848513
  2. Hertzano R, Milon B, Mitra S, Ogawa Y, Shetty A, Zhang X, Depireux D and Elkon R. (2018) A Cell Type-Specific Blueprint of the Molecular Changes Following Noise Exposure; Association for Research in Otolaryngology, San Diego, CA, USA
  3. Shuster BZ, Depireux DA, Mong JA and Hertzano R. (2019) Sex differences in hearing: Probing the role of estrogen signaling. 145, 3656. PMCID: PMC6588519
  4. Shuster B, Casserly R, Viechweg S, Lipford E, Davidson K, Olszewski R, Enoch J, McMurray M, Milon B, Rutherford M, Ohlemiller K, Hoa M, Depireux D, Mong J and Hertzano R (2020) Evaluating estrogen’s multi-modal modulatory potential: a framework for understanding protection from noise-induced hearing loss; Association for Research in Otolaryngology, San Jose, CA, USA.

 

Identification and characterization of genes that function in inner ear development and 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. 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, 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 (as part of NIH R01, DC003544).

 

  1. 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. Oct3;4(10):e1000207. PMCID: PMC2543112
  2. 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. PMCID: PMC3183090
  3. Jung JS, Zhang KD, Wang Z, McMurray M, Tkaczuk A, Ogawa Y, Hertzano R and Coate TM. (2019) Semaphorin-5B Controls Spiral Ganglion Neuron Branch Refinement During Development. J Neurosci. 17 Jun 2019 [Epub ahead of print]. PMCID: PMC6697390
  4. Brooks PM, Rose KP, MacRae ML, Rangoussis KM, Gurjar M, Hertzano R, Coate TM. (2020) Pou3f4-expressing otic mesenchyme cells promote spiral ganglion neuron survival in the postnatal mouse cochlea. J Comp Neurol. Jan 29 [Epub ahead of print]. PMCID – In Process

 

 

Research Interests

- 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

Clinical Specialty Details

- Hearing loss and hearing restoration for patients of all ages

- Genetic and Acquired Hearing Loss

- Cochlear Implants

- Baha

- Ossicular Chain Reconstruction

- Otosclerosis

- Cholesteatoma

- Middle ear tumors

- Meniere's Disease

- Superior Semicircular Canal Dehiscence

Awards and Affiliations

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
            Otorhinolaryngology.

2020    Distinction Award in Alternative/Basic Science for the Triological Society Thesis.

Grants and Contracts

3/1/2015-3/31/2021
Cell Type Specific Transcriptional Cascades in Inner Ear Development
NIH R01, DC013817 - PI

10/1/2018-9/30/2021
Illuminating Neurodevelopment through Integrated Analysis and Visualization of Multi-Omic Data
NIH R24 MH114815-01A1, Hertzano-PI, White-MPI

7/1/2018-6/30/2023
Cellular and Molecular Mechanisms of Cochlear Innervation
NIH, R01, R01DC016595, Coate-PI, Hertzano-Co-I

5/1/2019-9/30/2020
Implementing the gEAR for data sharing within the Hearing Restoration Project (HRP)
Hearing Restoration Project of the Hearing Health Foundation, Hertzano-PI

10/1/2019-8/31/2022
Genomic delineation of transcriptional networks that determine auditory hair cell fate
BSF2017218 (Binational Scientific Founation, BSF), Elkon-PI, Hertzano-MPI

In the News

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

Science Daily. Heart pump with behind-the-ear power connector, accessed at http://www.sciencedaily.com/releases/2013/08/130807204445.htm

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

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

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

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 

Press releases and radio interviews following the presentation of the historical CPC at the alumni event of the University of Maryland School of Medicine, deciphering the disease that resulted in Goya’s deafness. Below are a few examples. The New Scientist: https://www.newscientist.com/article/2129187-did-goya-get-an-autoimmune-disease-before-his-art-went-scary/ Fox News: http://www.foxnews.com/tech/2017/05/01/after-real-detective-work-theory-on-goyas-mysterious-illness.html El Pais: http://elpais.com/elpais/2017/04/28/ciencia/1493369467_634675.html 

An article featuring Dr. Hertzano: Hearing Health Magazine: https://view.publitas.com/p222-4764/hearing-health-spring-2018/page/36-37. 5/2018

An article featuring news regarding the identification of Ikzf2 as a critical regulator of outer hair cell differentiation (published in Nature): The Hearing Review: http://www.hearingreview.com/2018/11/researchers-identify-gene-associated-age-related-hearing-loss/

An article highlighting the utility of the gEAR and the workshops that Dr. Hertzano organizes to support data visualization and analysis in our field. Hearing Health Foundation Journal: https://view.publitas.com/p222-4764/hearing-health-spring-2020-issue/page/42-43 

 

Lab Techniques and Equipment

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