A Boost for Research: The Triological Society’s grants help physician-scientists launch investigative careers

It can be difficult to launch a career as a physician–scientist, especially when budget cuts are making research funding harder to find—and this is doubly true for a small specialty like otolaryngology. That challenge is the reasoning behind the Triological Society’s grant programs. The society, which has awarded more than $2.5 million in grants since 1994, promotes research into the causes and treatments of ear, nose and throat diseases.

One of the grant programs, the Career Development Award, provides up to $40,000 for research career development support over a one- or two-year period. The grants are meant for young physicians specializing in otolaryngology–head and neck surgery who can use the funds to springboard their research careers. (Visit triological.org to learn how to apply for a grant.)

ENT Today talked to the two physicians awarded the 2011 grants to learn about their research and what the grant money means to their scientific investigations and careers.

Research: Dr. Tan’s research seeks to test the hypothesis that some patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have an autoimmune component that exacerbates the severity of their disease. Dr. Tan is also working to evaluate whether recently discovered innate immune defects of the nasal epithelium may contribute to the B-cell dysregulation and autoimmunity observed in CRSwNP.

Question: How did you first become interested in this topic?

Answer: When I came to the lab at Northwestern, the principal investigator I worked with had made an interesting discovery that the epithelial cells in the nasal mucosa make a very potent cytokine that activates B cells. This cytokine was found specifically in the form of chronic sinusitis that is associated with nasal polyps. Our research indicates that there are a lot of B cells found within nasal polyps, and they frequently organize into little clusters. When you find these clusters elsewhere in the body, they signify that the B cells are proliferating and also changing the receptivity of the antibodies. These clusters are frequently found in inflammatory diseases such as rheumatoid arthritis and Sjögren’s syndrome. We were intrigued that similar processes were going on locally within a nasal polyp and did some experiments that found that self-reactive antibodies were found at higher levels in nasal polyps. We are interested in whether or not these self-reactive antibodies may result in more severe inflammation and cause disease to recur.

Q: What is it about B cells that has kept you interested since medical school?

A: They are a very dynamic cell in that they can form antibodies…and these antibodies are sort of at the heart of the immune system and in many ways influence the ability of your body to remember material or infectious agents it has encountered in the past. Also, they have the ability to mount an increasing reaction in the presence of an infectious agent. I’ve always thought that these cells were very dynamic and are able to serve as sentinels as well as be able to really ramp up the immune process when an infectious agent or virus is encountered.

Q: What do you hope will be the broader application of your research goals?

A: If chronic sinusitis with nasal polyps is possibly an autoimmune process, the broader application is that there are whole different families of anti-inflammatory medications that could be used to treat chronic sinusitis with nasal polyps.

Q: Is this research the opening leg of what you’d like to do over time?

A: I think that it is opening research into an area that has not been explored much in chronic sinusitis. If the research pans out, it would be a very interesting area because you would have the ability to test patients to see if they have this autoimmune form of chronic sinusitis, perhaps be able to counsel patients who are unlikely to respond to existing therapies and perhaps treat those patients with a different therapeutic agent. That would be the ideal situation. It certainly can be an opening salvo into a radically different way of treating some patients with chronic sinusitis.

Q: This grant program is meant to provide infrastructure, money and resources to spur more research within the otolaryngology community. How important is that support?

A: Programs like this are incredibly important. One of the challenges in otolaryngology is balancing the clinical demands of the specialty and finding mechanisms to fund studies in our relatively small specialty. Unfortunately, compared to some other specialties, we don’t have many resources in place to support young investigators in the field. Resources like the CORE [Centralized Otolaryngology Research Efforts] grant are very important for launching the careers of new investigators in the field. [Visit entnet.org/EducationAndResearch/coreGrants.cfm to learn more about the CORE program.]

 

Research: Dr. Hertzano plans to develop a protocol for efficient and reliable cell type–specific chromatin immunoprecipitation (ChIP) from a limited number of sorted cells of mouse inner ears and characterize the downstream effector targets of Zeb1.

Question: How did you first become interested in this research?

Answer: I think I’ve always been interested in hearing. My mother was the chief audiologist for Israel and her office was in the school for the deaf, across the street from my high school. I had a lot of exposure to hearing-impaired individuals.

Q: You graduated from medical school and earned a PhD at Tel Aviv University. What brought you to the U.S.?

A: Early in medical school, it was clear I wanted a combined research and medicine career.…I came to the U.S. for residency training at the University of Maryland School of Medicine. Our department chair, Professor Scott Strome, MD, is very supportive of surgeon-scientists and gave me the support to build a research group and continue to do research in parallel to my residency training. What we did was take my skill set in inner ear development and genetics and his skills as a cancer immunologist to develop a different way to study the ear. We developed a protocol that allows us to study the inner ears of wild-type mice using a cell type–specific approach. We use flow cytometry, combine that with genomics and identify transcription factors that determine cell fate in the ear.

Q: What does this award mean to your career?

A: Truthfully, this award and all the process associated with getting it are really terrific.…Just applying for these grants, it’s a great learning experience. Getting the grant is very helpful because $40,000 is a lot of money for a beginning researcher. It allows me to secure research time and cover some of the expenses associated with whole-genome sequencing. It’s a stepping-stone to applying for larger grants, such as [National Institutes of Health] grants, as it will allow me to produce necessary preliminary data.

Q: What will you use the grant for?

A: We plan on using our protocol of cell type–specific studies in the ear to adapt ChIP to the inner ear, using an approach called ChIP-sequencing. We hope to identify many of the immediate targets of transcription factors that are absolutely essential to the development and survival of hair cells, as well as other cell types in the ear. We hope to identify genes that underlie hearing loss and identify specific targets that can be important for hair cell survival or for driving stem cells towards specific cell types in the ear. While these methods have been used in cell culture where millions of cells are available, adapting these approaches to the ear where, for example, a mouse cochlea has less than 5,000 hair cells, is a real challenge.

Q: Hypothetically, what would be the title of your first peer-reviewed article?

A: There are a few options. One would be ‘Unraveling the Transcriptional Cascade Necessary for Hair Cell Development and Survival.’ Or, ‘Regulatory Networks in the Ear Necessary for Inner Ear Development and Function.’

Q: What would you say about your research to a group of your peers at the next Triological Society meeting?

A: We’ve developed a protocol that reliably identifies in the ear immediate targets of transcription factors. We applied it to study three or four transcription factors and identified 30 candidate genes for hearing loss, [genes] that we are now validating in collaboration with other research groups that have collected DNA from families that suffer from hereditary forms of hearing loss. We hope to be able to apply these genes not only toward genetic screening, but also to better understand hearing and possibly develop therapeutic interventions in the future. ENT TODAY