Research Why I Appreciate My #StartWithERG. Regie

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Why I Appreciate My #StartWithERG

By Regie Santos-Cortez, M.D., Ph.D.

I grew up in metro Manila and received my medical degree from the University of the Philippines Manila College of Medicine–Philippine General Hospital, where I also did a residency in otorhinolaryngology. Because of my interest in the genetics of hearing loss, I received scholarships to study genetic epidemiology at the Erasmus Medical Centre in Rotterdam, the Netherlands, and at Baylor College of Medicine in Houston. After obtaining my Ph.D., I practiced otolaryngology in the Philippines while initiating a project on otitis media (middle ear infection) genetics. Eventually I made the decision to move to the United States and give up my surgical career. I decided to go into research full-time instead of going back into residency or fellowship training.

It was a huge leap of faith for me. The Emerging Research Grant (ERG) awarded to me by Hearing Health Foundation was the first grant I received as an early-career researcher in the U.S. and set me on the right path. ERG funding was instrumental in transforming an incubator research project on otitis media genetics into a research program that is the basis for my current lab where I am an independent principal investigator. However, even though I am no longer involved in clinical practice, my experience as an otolaryngologist has continued to inform my research and helps me to understand the perspectives of both clinicians and patients.

Genetic Discovery

The ERG grant was awarded for 2011–2013, and continued until 2014 thanks to a no-cost extension year. The project was titled “Identification of genes that predispose to chronic otitis media in an indigenous Filipino population.” ERG funds were used for genetic sequencing (specifically, exome sequencing and follow-up Sanger sequencing) using DNA samples from an indigenous population that had a very high prevalence of chronic otitis media.

Using the sequence data, we identified the first rare variant for otitis media in humans. This is in the A2ML1 gene which encodes a protease inhibitor. This was published in Nature Genetics in 2015, with HHF cited as a funding source.

Based on our A2ML1 finding, our group of collaborators obtained an R01 grant from the National Institute on Deafness and Other Communication Disorders (NIDCD) that was funded from 2016 to 2022. The aims of the R01 study were to identify novel variants that contribute to otitis media susceptibility and induce changes in the middle ear microbiome.

University of Colorado associate professor Regie Santos-Cortez, M.D., Ph.D. (second from left), and her team.

This R01 grant also had follow-up supplements, including for research training of a resident in the lab. As an offshoot of this project, we received a small campus grant that also looked at the microbiota of the middle ears and nasopharynges of children with otitis media and Down syndrome.

Institutional Cooperation

Thanks to the funding from these grants, over the past seven years we have published 15 papers that describe various aspects of otitis media, including six genes with variants co-segregating in families or associated with otitis media, differentially expressed genes in tissues from patients with otitis media, and shifts in the middle ear or nasopharyngeal microbiota that are associated with carrying specific genetic variants. Additionally, we have several manuscripts under review or for submission, and these studies describe novel genes and variants and associations between otitis media and microbiota.

From an initial collaborative group of seven institutions in the U.S. and in the Philippines for the ERG project, we have expanded our otitis media group to include 12 institutions internationally. This has helped me spearhead another project on genomic hearing loss with six institutions, both in the U.S. and abroad, that was recently funded as an R01 grant by the NIDCD until 2026.

More importantly the initial A2ML1 study funded by ERG has spawned so many other studies that we are not limited to gene identification alone but are now embarking on multi-omic studies that help place our findings within a clinical context. We are also working on an A2ML1-knockout mouse model that we hope will be useful for translational research. I am grateful that receiving the ERG 11 years ago helped me on this stimulating research path that has led to new discoveries, fresh perspectives, and international alliances.

Thanks to the funding from these grants, over the past seven years we have published 15 papers that describe various aspects of middle ear infection.

Regie Santos-Cortez, M.D, Ph.D., is an associate professor in the department of otolaryngology–head and neck surgery at the University of Colorado Anschutz Medical Campus. A 2011–2012 Emerging Research Grants alumna, she presented her research on chronic pediatric ear infections and related hearing loss in a webinar in January 2022, viewable at hhf.org/webinar.

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