OHNS News

 

December 17, 2021

The Otology and Neurotology Division welcomes a new member, Dr. Stankovic

Her translational research aims to improve diagnosis and treatment of hearing loss; recent press releases: Antihypertension drug may help patients with noncancerous brain tumors affecting hearing, COVID-19 can infect the inner ear, and HRRP-funded investigators develop miniature imaging probe to visualize cellular pathology in the inner ear.

December 17, 2021

Novel treatments in the management of Zenker’s diverticulum

Our division continues to experience outstanding results and high patient satisfaction using a technique we developed to remove Zenker’s diverticuli entirely transorally. Patient dissatisfaction with the 20% recurrence rates associated with transoral stapling led us to develop a method for endscopic resection of the criccopharyngeus muscle and diverticulum, with endoscopic manual suture closure. This technique has allowed us to combine the advantages and safety of endoscopic surgery with long term outcomes associated with traditional open approaches. We continue to offer this as the mainstay of treatment for patients interested in a long-term endoscopic approach to their swallowing difficulties. More information about our results can be found in our publications:

Junlapan A, Boonipat T, Sung CK, Damrose EJ. Endoscopic treatment of Zenker’s Diverticulum- the modified transoral approach. J Vis Surg 2020;6: 42 https://jovs.amegroups.com/article/view/42321/html

 and Junlapan A, Abu-Ghanem S, Sung CK, Damrose EJ. Outcomes in modified transoral resection of diverticula for Zenker's diverticulum. Eur Arch Otorhinolaryngol. 2019 May;276(5):1423-1429.

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December 17, 2021

Understanding the cause of idiopathic subglottic stenosis

Our division is currently involved in understanding the mechanism underpinning idiopathic subglottic stenosis, a progressive and refractory scarring disorder of the larynx which principally affects middle-aged women. We recently identified the presence of an estrogen receptor subtype which has been implicated in abnormal wound healing and may help to explain the female preponderance of the disease. Work is ongoing to determine how this receptor is normally distributed, its normal function, and its possible role in this disease. You may read more about these findings in our publication:

Damrose EJ, Campbell RD, Darwish S, Erickson-DiRenzo E. Increased Expression of Estrogen Receptor Beta in Idiopathic Progressive Subglottic Stenosis. Laryngoscope. 2020 Sep;130(9):2186-2191.

Figure 1: Representative images of ER-α (A-D) and ER-β (E-H) in subglottic tissue of controls and specimens with idiopathic progressive subglottic stenosis (IPSS). Immunofluorescence demonstrated positive staining (green) for estrogen receptors. DAPI (blue) was used as a nuclear stain. A, no staining of ER-α in epithelium (Ep) and lamina propria (LP) of control specimen; B, strong staining of ER-α in Ep and LP in IPSS specimen; C, mild staining of ER-α in glands and ducts (G&D) of control; D, mild staining of ER-α in G&D of IPSS specimen; E, mild staining of ER-β in epithelium (Ep) and lamina propria (LP) of control; F, strong staining of ER-β in Ep and mild staining in LP of IPSS specimen; G, mild staining of ER-β in G&D of control; H, strong staining of ER-β in G&D of IPSS specimen.

Figure 2: Subglottic tissue from patient with idiopathic subglottic stenosis, stained with hematoxylin and eosin. Arrowhead = epithelium; arrow = lamina propria.

December 17, 2021

OHNS 2021 Education Updates

Our immensely talented trainee population includes 27 OHNS residents and 12 fellows/instructors, of which 3 are ACGME accredited fellows (one in pediatrics, two in neurotology), and the other 9 are instructors (two each in head and neck surgery, rhinology and sleep surgery, one in facial plastics and reconstructive surgery, one in laryngology, and one in pediatrics).  We also have several graduate students, post-doctoral research fellows/instructors, and visiting scholars. Dozens of Stanford and visiting medical students are on rotation throughout the year.

The department has two residency tracks: a five-year “clinical track” (CT) and a seven-year “clinician scientist training program” (CSTP), which integrates two years of dedicated research following the third year of clinical training.  The CSTP is a National Institute of Child Health and Human Development (NICHD) funded training program. The NIDCD supports and conducts research in the areas of hearing, balance, taste, smell, voice, speech, and language. their grant covers studies addressing the prevention, screening, diagnosing, and treatment of disorders of human communication.

More than 75% of our graduates have completed fellowship training.  Recent residency graduates have taken positions attending Cornell University, Stanford, University of Chicago, University of Michigan, UCLA, and UCSF as well as in private practice settings such as Kaiser Permanente and Stanford’s University Health Alliance. 

At the heart of the department’s education programs, the residency program provides a rigorous foundation of clinical training with a broad range of experiences in head and neck surgery, otology, rhinology, laryngology, facial plastic surgery, sleep surgery, audiology, allergy and pediatric otolaryngology.  Furthermore, residents are exposed to diverse patient populations in various clinical settings. Besides Stanford Health Care (SHC Palo Alto), the primary site that residents spend approximately 35 months in, residents rotate between the Veterans Affairs Palo Alto Health Care System (VA), Santa Clara Valley Medical Center (SCVMC), and Lucile Packard Children’s Hospital Stanford (LPCH). They also spend time in SHC sites in East Palo Alto (Stanford Ear Institute) and Redwood City (sleep surgery).

Residents are required to meet all ACGME and American Board of Otolaryngology standards and expected to master the cognitive, clinical, procedural and professional skills required to function as attending otolaryngologists.  They are assessed according to the ACGME Milestones and core competencies rubrics. 

The program’s educational curriculum is designed to help each resident achieve their program goals while ensuring professional and personal growth in all possible directions whether basic or translational science, patient-oriented research, bio-technological innovation, or clinical practice and medical education. 

December 17, 2021

OHNS 2021 Basic Science Research Updates

2021 is a year of new beginnings. Our research teams have transitioned into a new research space, the Biomedical Innovations building, and we have a new Chair, Konstantina Stankovic, onboarding and joining the ranks of outstanding clinician scientists within our group. As a team, we remain cognizant and grateful of our good fortune in being able to continue our research and teaching endeavors throughout the continued challenges created by the pandemic, social and political unrest, and wildfires and droughts. These challenges have strengthened us as a community, helped us focus on our priorities and furthered our resolve to be the best department and research group in the world. We continue to adapt, grow and support each other and our broad community to ensure that we all succeed together.

Research in OHNS crosses many boundaries from basic science to clinical studies, from cancer research to cell biology to big data RNAseq to single molecule tracking, and from hearing to smell to larynx to new surgical technologies. This breadth continues to grow with multiple ongoing searches in progress. To summarize everything happening would take a book, not a newsletter.

The following are highlights from this year. Stefan Heller’s team had published seven papers culminated from multi-year projects centered around identifying the biochemical pathways controlling hair cell regeneration in birds with a goal of mapping this pathway then stimulating it in mammalian systems. To this end, their parallel work in growing inner ear organoids had also made important breakthroughs. Dr. Cheng had published 13 papers with major contributions using single cell transcriptomics to define the heterogeneity of cell types in the mouse utricle. Drs. Grillet and Ó Maoiléidigh have started a robust collaboration to characterize hair cell and hair bundle morphology as a first step toward developing computational models on hair bundle mechanics. This work also resulted in a major publication. Dr. Nicolson had identified a novel genetic mutation that alters central processing of auditory information and shifted to this new direction to develop the tools needed for investigating central auditory defects. Dr. Ricci had four major publications with one focused on age-related hearing loss and another on aminoglycoside ototoxicity. And finally, we are proud to say that one of our lab mates who has worked in our core facility for the past 2.5 years, Murray Bartho, has been accepted into medical school and so will be leaving us to pursue these higher goals. As providing opportunities for training experiences is a priority of our group, we are excited for his progress and look forward to his future contributions.

There have been numerous other contributions from the scientists within our department and we will be highlighting them throughout the next year via our website and social media platforms, do check them out!

December 17, 2021

Pediatric Otolaryngology

The Pediatric Otolaryngology division continues its mission to train future pediatric otolaryngologists and has expanded to 2 fellows this July. They welcome Brooke Su-Velez, MD, MPH, who completed her residency training at UCLA, and Taseer Din, MBChB, who completed his residency training at University of Cape Town, South Africa.

We would also like to congratulate Mai Thy Truong for her appointment as the Clinic Chief, and Kara Meister as the Associate Clinic Chief, in the division of Pediatric Otolaryngology at Stanford Children's Health. They will be part of the executive team that helps lead our growing clinical operations.

December 17, 2021

Treating advanced skin cancers with immunotherapy

Dr. Vasu Divi is transforming the way advanced skin cancers are treated — beginning not with surgery, but with immunotherapy.

In 2018 and 2020, the US FDA approved the use of immune checkpoint inhibitors (often called immunotherapy or an immuno-oncology; or IO) for the treatment of advanced skin cancer (cutaneous squamous cell carcinoma CutSCC). The central mechanism of IO is that immunotherapy “turns on” a patient’s immune system to identify then eliminate cancer cells. Many cancers (such as CutSCC) evade detection by tricking the human body to ignore cancerous growth, expressing a receptor or “tag” that turns off the body’s own natural defenses.  These new IO treatments are shown a dramatic response for patients with CutSCC, eliminating all visible cancer in 10-20% of patients, with at least some meaningful response in almost half of all patients. The question is what to do after IO.

At Stanford, we believe that every patient benefits from a multi-disciplinary approach involving surgery, medical oncology, and radiation oncology. Dr. Divi’s study opens up new options for patients with advanced CutSCC, optimizing how the multidisciplinary team treats each individual patient precisely and with less toxicity and disfigurement.

December 17, 2021

Olfactory dysfunction

Dr. Zara M. Patel, Associate Professor, is an endoscopic sinus and skull base surgeon who has also been researching olfactory dysfunction for the last decade. The current therapies being utilized to treat COVID19 related smell loss are largely based on research that she and others have performed on patients with olfactory loss prior to the pandemic (https://pubmed.ncbi.nlm.nih.gov/29901865/ ; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5527365/https://pubmed.ncbi.nlm.nih.gov/31950156/).

Although these options can be helpful, there are still many patients who remain without their sense of smell despite treatment. Dr. Patel has thus continued her research in this area, recently culminating in Stanford University who filed a full US and International patent on her behalf.  Although this patent initially centered around the invention of an endoscopic electrical stimulation device to speed regeneration of the olfactory nerve, due to her experience with endoscopic sinus and skull base surgery, it was broadened to include endoscopic electrical stimulation of all cranial nerves and ganglia as well as other tissues responsive to electrical stimulation that can be accessed endoscopically through the nasal cavity. The potential for improving patients’ lives spans disorders such as chronic sinusitis, facial pain, facial paralysis, visual problems, endocrine problems, and more.

Dr. Patel also creates biweekly reports on global, national, state and regional data regarding the COVID19 pandemic to inform the leadership of Stanford School of Medicine and the Stanford community at large. She has assumed the role from Dr. Robert Jackler, who founded the report service early in the COVID19 pandemic in order to bring essential information to the community at a critical time. Dr. Patel releases these reports to the public as well to help as many people as possible make informed decisions to keep themselves and their families safe and healthy. See: https://youtu.be/sj3dteQnbQo

Dr. Nayak, along with his laboratory group in the Department of Otolaryngology, have secured 5 years of competitive research funding from the National Institutes of Health (NIH) on March 1, 2021.  This $2.4M federal grant, termed an R01 award, was bestowed by the National Heart, Lung and Blood Institute (NHLBI) in Bethesda, MD until at least January 2026 to support Dr. Nayak’s groundbreaking work in optimizing the transplantation and long-term engraftment of human airway stem cells in live animal models.

This R01 grant was supported by contributions from several co-Investigators on this award, all within Stanford University. They include Drs. Matthew Porteus (Department of Pediatrics and Biochemistry), Tushar Desai (Department of Pulmonary Critical Care Medicine), Y. Peter Yang (Department of Orthopedics), and Jeffrey Wine (Department of Psychology, CF Biology).

Dr. Hwang, Professor and Chief of the Division of Rhinology & Endoscopic Skull Base Surgery, was recently awarded a Presidential Citation from the American Rhinologic Society in recognition of his distinguished service to the society.  Dr. Hwang has served in a variety of leadership roles over the years, including Board of Directors, Secretary, and President.  He continues to serve as founder and co-director of the society's Mentorship Program.

December 17, 2021

Stanford founding a world center for comprehensive sleep medicine and surgery.

The pioneering work done here by William Dement, Christian Guilleminault, Richard Goode, Robert Riley and Nelson Powell established the original Stanford Sleep Surgery protocol.  Inheriting this remarkable legacy are Robson Capasso, MD, FAASM, Chief of the Sleep Surgery Division and dual trained and board-certified in both Sleep Medicine and Head and Neck Surgery, and Stanley Liu, MD, DDS, dual trained and board certified in Maxillofacial Surgery and Sleep Surgery. 

Drs. Capasso and Liu collaborate closely to meet the needs of any OSA patient and continue to refine and expand the original Stanford Sleep Surgery protocol to offer precise, individualized care. 

However, this poses several challenges. Defining the best OSA surgical treatment path hinges on the accurate definition of “successful result”; Some of the commonly used sleep study metrics have little to no correlation with clinically meaningful outcomes and offer limited perspectives on the ideal surgical procedure for each individual. In addition, decisions around procedure selection and perioperative routines are based on less-than-ideal evidence to support or refute its usefulness.

To target this issue, Dr. Capasso gathered multidisciplinary talent and assembled a team with computer science and statistics expertise aiming to collect, refine and analyze large volumes of data to generate Real World Evidence that can assist in defining clinically relevant deliverables and peri-operative efficient routines.  In the future, AI in the form of algorithmic agents may permeate such an environment and work in tandem with the human members of our care team.

Craniofacial procedures can offer complexity on its planning and execution. Dr Liu is developing scholar work on novel surgical techniques aiming to improve the upper airway following facial skeletal procedures while preserving facial balance and adequate occlusion. A novel aspect, however, is the improvement of nasal breathing following targeted distraction osteogenesis maxillary expansion (DOME)a procedure with limited morbidity and usually fast recovery.

July 14 , 2021

Antihypertension drug may help patients with noncancerous brain tumors affecting hearing

Losartan prevented tumor-induced hearing loss and augmented radiation efficacy in mice.

BOSTON – New research led by investigators at Massachusetts General Hospital (MGH) and Massachusetts Eye and Ear indicates that the blood pressure drug losartan may benefit patients with neurofibromatosis type 2 (NF2), a hereditary condition associated with vestibular schwannomas, or noncancerous tumors along the nerves in the brain that are involved with hearing and balance. The findings, which are published in Science Translational Medicine, are especially important because vestibular schwannomas are currently treated with surgery and radiation therapy (which carry risks of nerve damage), and no drug is approved by the U.S. Food and Drug Administration to treat these tumors or their associated hearing loss.

“Developing effective therapeutics to preserve hearing function in patients with NF2 is an urgent unmet medical need. The greatest barrier to managing NF2-related auditory impairment is our incomplete understanding of how schwannomas cause hearing loss,” says co–senior author Lei Xu, MD, PhD, an investigator in the Steele Laboratories for Tumor Biology within the MGH Department of Radiation Oncology. A previous report showing that scarring, or fibrosis, exists in schwannomas and correlates with hearing loss prompted the team to test whether a drug that blocks fibrosis might be effective.

Losartan blocks a component of the renin-angiotensin system, which is involved not only in regulating blood pressure but also in stimulating fibrosis and inflammation. The entire class of angiotensin-targeting drugs, which includes losartan, has been shown to reduce collagen accumulation in cardiac and kidney fibrotic disease. Using a mouse model of NF2, Xu  and her colleagues found that losartan treatment had several effects on vestibular schwannomas and the brain: It reduced inflammatory signaling and swelling and thus prevented hearing loss, and it increased oxygen delivery to enhance the effectiveness of radiation therapy (which may help lower the radiation dose needed to control tumor growth and limit radiation-associated toxicities). 

In preparation to translate these findings into the clinic, co–senior author Konstantina Stankovic, MD, PhD, former chief of the Division of Otology and Neurotology at Massachusetts Eye and Ear, now Bertarelli Professor and Chair of the Department of Otolaryngology – Head and Neck Surgery at Stanford University School of Medicine, examined patient samples and data. Her team found that vestibular schwannomas associated with poor hearing had more pronounced inflammatory signaling than tumors associated with good hearing. This inflammatory signaling in tumors was capable of directly damaging cochlear cells that are essential for hearing. Also, patients with vestibular schwannoma who took losartan or other drugs in its class experienced no progression in hearing loss, unlike patients on other or no antihypertensive drugs. This study illustrates the advantages offered by an integrated approach and teamwork that spans basic research, translational investigation and clinical care.

The findings support the need for a prospective clinical trial of losartan in patients with NF2 and vestibular schwannomas. “As one of the most commonly prescribed drugs for hypertension, the safety and low cost of losartan warrants rapid translation of our research to patients with vestibular schwannomas to try to prevent tumor-induced sensorineural hearing loss,” Stankovic says.

Xu is an assistant professor at Harvard Medical School. Co-authors included Limeng Wu, Sasa Vasilijic, Yao Sun, Jie Chen, Lukas D. Landegger, Yanling Zhang, Wenjianlong Zhou, Jun Ren, Samuel Early, Zhenzhen Yin, William W. Ho, Na Zhang, Xing Gao, Grace Y. Lee, Meenal Datta, Jessica E. Sagers, Alyssa Brown,Alona Muzikansky, Anat Stemmer-Rachamimov, Luo Zhang, Scott R. Plotkin and Rakesh K. Jain.

This study was supported by the Department of Defense, the Children’s Tumor Foundation Drug
Discovery Initiative, the National Cancer Institute, the Advanced Medical Research Foundation, Jane’s Trust Foundation, the Lustgarten Foundation, the Ludwig Center at Harvard, the National Foundation for Cancer
Research, the Gates Foundation, the Cancer Research Institute, the American Association of Cancer Research, the National Institute on Deafness and Other Communication Disorders, Nancy Sayles Day Foundation, Lauer Tinnitus Research Center, the Barnes Foundation, the Zwanziger Foundation, and Sheldon and Dorothea Buckler.

April 14, 2021

Grillet lab’s new high impact paper makes the cover of Journal of Neuroscience!

Vol. 41, Issue 15, 14 Apr 2021

Trouillet, Alix, Katharine K. Miller, Shefin Sam George, Pei Wang, Noor-E.-Seher Ali, Anthony Ricci, and Nicolas Grillet. “Loxhd1 Mutations Cause Mechanotransduction Defects in Cochlear Hair Cells.” The Journal of Neuroscience: The Official Journal of the Society for Neuroscience 41, no. 15 (April 14, 2021): 3331–43. https://doi.org/10.1523/JNEUROSCI.0975-20.2021.

Hearing loss occurs frequently due to the dysfunction of the auditory sensory cells in the inner ear, which transform mechanical stimulations into electric signals. Trouillet et al. demonstrate that the molecule LOXHD1 is required for this mechanotransduction process, but surprisingly, only in mature auditory cells. When LOXHD1 is mutated, some of the known molecules required for mechanotransduction are still correctly positioned in the sensory cells, suggesting that the mechanotransduction machinery is still present, but not activatable. Their research identified a new step in the auditory cell development. It will be critical to further understand them as they are responsible for congenital and age-related forms of hearing loss in humans.


About the Cover:

This scanning electron micrograph shows the hair bundle of a inner hair cell from a wild-type mouse cochlea. Sound-induced forces displace these mechanosensitive organelles, which comprise stereocilia organized into rows of increasing height. Hair bundle deflection tenses external filaments (called tip links) that connect stereocilia rows, and this gates mechanotransduction channels, initiating the auditory signal. A critical maturation step for hair bundle mechanotransduction that occurs between postnatal days 7 and 11 requires the integrity of the deafness gene LOXHD1. For more information, see the article by Trouillet et al. (pages 3331–3343). Cover image: Nicolas Grillet.

April 14, 2021

Dr. Santa Maria’s team publishes “Treatment with a Neutrophil Elastase Inhibitor and Ofloxacin Reduces P. Aeruginosa Burden in a Mouse Model of Chronic Suppurative Otitis Media,” in Open Access on April 6, 2021.

Dr. Santa Maria’s team publishes “Treatment with a Neutrophil Elastase Inhibitor and Ofloxacin Reduces P. Aeruginosa Burden in a Mouse Model of Chronic Suppurative Otitis Media,” in Open Access on April 6, 2021.

Abstract:
Chronic suppurative otitis media (CSOM) is a widespread, debilitating problem with poorly understood immunology. Here, we assess the host response to middle ear infection over the course of a month post-infection in a mouse model of CSOM and in human subjects with the disease. Using multiparameter flow cytometry and a binomial generalized linear machine learning model, we identified Ly6G, a surface marker of mature neutrophils, as the most informative factor of host response driving disease in the CSOM mouse model. Consistent with this, neutrophils were the most abundant cell type in infected mice and Ly6G expression tracked with the course of infection. Moreover, neutrophil-specific immunomodulatory treatment using the neutrophil elastase inhibitor GW 311616A significantly reduces bacterial burden relative to ofloxacin-only treated animals in this model. The levels of dsDNA in middle ear effusion samples are elevated in both humans and mice with CSOM and decreased during treatment, suggesting that dsDNA may serve as a molecular biomarker of treatment response. Together these data strongly implicate neutrophils in the ineffective immune response to P. aeruginosa infection in CSOM and suggest that immunomodulatory strategies may benefit drug-tolerant infections for chronic biofilm-mediated disease.

Khomtchouk, K. M., L. I. Joseph, B. B. Khomtchouk, A. Kouhi, S. Massa, A. Xia, I. Koliesnik, D. Pletzer, P. L. Bollyky, and P. L. Santa Maria. “Treatment with a Neutrophil Elastase Inhibitor and Ofloxacin Reduces P. Aeruginosa Burden in a Mouse Model of Chronic Suppurative Otitis Media.” Npj Biofilms and Microbiomes 7, no. 1 (December 2021): 31. https://bit.ly/3mKIaks

March 23, 2021

Chickens are an important animal model for hearing restoration research because they are naturally capable of regenerating cochlear hair cells. This fact is known for many years, but the mechanisms that initiate and control this regenerative ability are unknown. Likewise, the cochlea of neonatal mice bears the capacity to form new cells, including new hair cells. However, this feature disappears between the second and third week, around the onset of hearing in mice.

In a series of three high-profile publications in the journal Cell Reports, Dr. Stefan Heller’s laboratory led by postdoctoral fellows Marie Kubota, Amanda Janesick, and Nesrine Benkafadar reported several novel findings that lay the foundation for in-depth characterization of the cellular signaling that initiates cochlear hair cell regeneration in birds. The researchers identified a transiently existing cell group in the mammalian cochlea that is the source of the regenerative capacity that is observed in neonates. The later research is related to a project conducted by Dr. Alan Cheng’s laboratory, which will report more details on this cell population later this year.

The work uses single-cell RNA-sequencing. This technology provides insight into changes in the activity of all genes as cochlear cells respond to hair cell damage and death.

The research created a comprehensive “inventory” of more than 15,000 individual genes expressed in the different cell types of the chicken and the mouse inner ear. Moreover, it led to identifying new cell types and many new marker genes for virtually every cell group of the cochlea.

The next steps of this research are already progressing. Dr. Heller’s team is now focusing on changes in gene expression that happen when the inner ear is damaged by drugs that cause sensory hair cell death. Their goal is to identify the mechanisms that birds utilize to repair their inner ears and figure out why mice and humans cannot do the same thing. 

The majority of funding of this work came through SICHL and the Hearing Health Foundation.

Benkafadar, Nesrine, Amanda Janesick, Mirko Scheibinger, Angela H. Ling, Taha A. Jan, and Stefan Heller. “Transcriptomic Characterization of Dying Hair Cells in the Avian Cochlea.” Cell Reports 34, no. 12 (March 23, 2021). https://doi.org/10.1016/j.celrep.2021.108902.

Janesick, Amanda, Mirko Scheibinger, Nesrine Benkafadar, Sakin Kirti, Daniel C. Ellwanger, and Stefan Heller. “Cell-Type Identity of the Avian Cochlea.” Cell Reports 34, no. 12 (March 23, 2021). https://doi.org/10.1016/j.celrep.2021.108900.

Kubota, Marie, Mirko Scheibinger, Taha A. Jan, and Stefan Heller. “Greater Epithelial Ridge Cells Are the Principal Organoid-Forming Progenitors of the Mouse Cochlea.” Cell Reports 34, no. 3 (January 19, 2021). https://doi.org/10.1016/j.celrep.2020.108646.

March 1, 2021

NIH awards $2.4M to Dr. Nayak's research, March 1, 2021

Dr. Nayak's R-01 independent investigator grant application to the NIH was funded this morning (3/1/2021) by the National Heart, Lung and Blood Institute (NHLBI). This is a 5-year award (3/1/2021 - 1/31/2026) totaling $2.4M, to support his laboratory group's pre-clinical in vitro and in vivo animal model work to optimize the transplantation of CRISPR gene-corrected human stem cells into the airway epithelium, as a candidate treatment for cystic fibrosis sinusitis. Co-Investigators on this award, all within Stanford University, include Drs. Matthew Porteus (Pediatrics and Biochemistry), Tushar Desai (Pulmonary Critical Care Medicine), Y. Peter Yang (Orthopedics), and Jeffrey Wine (Psychology, CF Biology).