Recap: Annual Department Research Day

November 9, 2020

 

 

On November 9, 2020, the OHNS department hosted 11th annual Research Day — first time virtually. For a half of the day, the members of the department gathered to present, learn and discuss their research with OHNS colleagues.

Vision:
preeminent national and global leader in clinical care, research, education, and diversity

 

 

Why Do We Have an Annual OHNS Research Retreat?

Stanford is a Research Intensive School of Medicine
We are a Research Intensive Department

Reinforce our commitment to pursuing innovation and discovery

  • Learn about research plans for the coming year across the department
  • To improve our upcoming research through constructive criticism
  • Establish research collaborations
  • Help trainees identify mentors
  • Bring together research and clinical communities
  • Give us a forum to reflect ways by which each of us can strive to discover new ways to understand and to overcome human disease

 

 

 

Why is Research Day Important to the OHNS Mission?

The three cornerstones of academic medicine are clinical expertise, scientific discovery, and clinical teaching.  These goals are interdependent. For example, clinical expertise relies on both scientific discovery and clinical teaching. Scientific discovery, in turn, can be informed by clinical experience. Our Research Day promotes and celebrates these types of exchanges.

Takeaway for Participants

Our department is committed to improving our clinical specialty through rigorous scientific work. There is a strong spirit of collaboration that welcomes input and new ideas.

 

 

 

Nayak Lab Members in the Lab

 

Introductions

Jon-Paul Pepper, MD
Assistant Professor of Otolaryngology — Head & Neck Surgery (OHNS)

Robert K. Jackler, MD
Edward C. and Amy H. Sewall Professor of Otolaryngology — Head & Neck Surgery (OHNS) and, by courtesy, of Neurosurgery and Surgery
Department Chair

Lloyd B. Minor, MD
The Carl and Elizabeth Naumann Professorship for the Dean of the School of Medicine, Professor of Otolaryngology — Head & Neck Surgery (OHNS), by courtesy, of Neurobiology and Bioengineering
School of Medicine Dean

Konstantina Stankovic, MD, PhD
Associate Professor of Otolaryngology — Head & Neck Surgery (OHNS)
Chief of the Division of Otology and Neurotology at Massachusetts Eye and Ear
Stanford OHNS Department Chair, June 2021


New Research Facilities for Stanford OHNS

The plans and construction are currently underway for the new OHNS wet and dry research spaces.

Permanent Lab Space

3172 Porter Drive 
Permanent wet lab space (estimate 2024) 
Permanent dry research space (estimate 2023)

Temporary Lab Space

1701 Page Mill Rd., Palo Alto
Temporary wet lab + dry research space

Wet Lab Research Space

desks

benches

faculty offices


Dry Lab Research Space

desks

faculty offices

Presentations

New Insights into Aminoglycoside uptake into hair cells using in vivo cochlear imaging

Anthony Ricci, PhD
Edward C. and Amy H. Sewall Professor of Otolaryngology — Head & Neck Surgery (OHNS) and, by courtesy, of Molecular and Cellular Physiology
Chief of Research


The Sunwoo Lab is focused on understanding the interface between cancer and the immune system and ways to modulate these interactions for therapy. The types of questions that our group is interested in answering include: (1) What are tumor cell-intrinsic features that influence immune cell infiltration into the microenvironment? (2) What does the tumor microenvironment do to the “states” of the infiltrating cells and how can these states be modulated for improved tumor cell targeting? (3) How can we induce neoantigens on tumor cells for recognition by the immune system? One project that will be discussed is the investigation of a histone methyltransferase called NSD1, which is mutated in ~10% of head and neck squamous cell carcinomas. Our data indicate that inactivation of NSD1 confers an “immune cold” phenotype with few infiltrating lymphocytes in the microenvironment. Results from our lab will be presented to support a strategy for reversing this phenotype to improve immunotherapy response.

John B. Sunwoo, MD 
Edward C. and Amy H. Sewall Professor of Otolaryngology — Head & Neck Surgery (OHNS), and, by courtesy, of Dermatology
Director of Head & Neck Cancer Research


In normal physiology, epithelial and mucus cells protect the laryngeal mucosa from the ~25 million pollutant, viral, and bacterial insults inhaled each day. Using a combination of ex vivo, in vivo, and in vitro experimental approaches, we examine the role of laryngeal epithelial and mucus cells as modulators of mucosal remodeling in injury and disease and defensive barriers between the external environment and the underlying tissue. Currently, we utilize exposure to tobacco products as a clinically relevant model of laryngeal injury. We will provide an update regarding the development of an in vivo mouse model of cigarette smoke exposure that we have used to characterize acute and chronic derangements in laryngeal epithelial and mucus cell structure.

Elizabeth DiRenzo, PhD, CCC-SLP
Assistant Professor of Otolaryngology — Head & Neck Surgery (OHNS) and, by courtesy, of Music


Molecular Genetics of the Inner Ear

We focus on the understanding of the deafness gene LOXHD1. We found this gene as required for the mechanotransduction function of cochlear hair cells. We will present how we use mouse genetics to dissect its role.

Nicolas Grillet, PhD
Assistant Professor of Otolaryngology — Head & Neck Surgery (OHNS)


Development of Transtympanic Nanoparticle for Theranostics

We present our most recent work on nanoparticle carriers for fluorescent dyes and antibiotics. We will explore two fluorescent probes for bacterial infection monitoring based on sugar metabolism and a second one based on inflammatory markers for Cathepsin. Our nanoparticle carriers can also transport antibiotics to the middle ear without an incision in the tympanic membrane.

Tulio A. Valdez, MD, MSc
Associate Professor of Otolaryngology — Head & Neck Surgery (OHNS) and, by courtesy, of Pediatrics


Pre-clinical translation of CRISPR gene edited stem cells into animal models
COVID-19 Research: ACE2 Receptor Protein Expression in the Upper Airways

I.) In this first collaboration between 3 Stanford laboratory groups (Porteus, Desai, Nayak), we have previously published (Cell Stem Cell) the use of CRISPR technology to restore 30-40% function to the defective cystic fibrosis (CF) chloride transport gene termed CFTR in primary upper airway basal (stem) cells (UABCs) from CF patients. Over the past year, we have extended these gene correction efforts, to develop a method to replace the entire CFTR gene on chromosome 11 in UABCs from CF patients, which restores ~75% of Cl- transport to these stem cells. We are now testing CFTR gene-corrected UABC stem cells in rodent models to develop and optimize method(s) for efficient airway stem cell transplant and engraftment into the upper airways in vivo. II.) In a separate collaboration with the labs of Peter Jackson and Garry Nolan, we assessed the expression of nasal receptors and cofactors exploited by SARS-CoV-2. We have now shown that the angiotensin converting enzyme 2 (ACE2) primary receptor for the SARS-CoV-2 Spike (S) protein is highly expressed within the cilia of nasal epithelial cells, and that this protein expression is  unaffected by use of ACE/ARB inhibitors. Nasal tissue specimens taken at autopsy following infection from COVID-19, show the presence of the SARS-CoV-2 viral RNA exclusively within ciliated epithelial cells co-expressing ACE2 protein.

Jayakar V. Nayak, MD, PhD
Associate Professor of Otolaryngology — Head & Neck Surgery (OHNS) and, by courtesy, of Neurosurgery


Measuring Cochlear Duct Length: Methods for the Objective Assessment of Preoperative Imaging

The accurate assessment of cochlear morphology could potentially improve cochlear implantation customized for a particular individual.  We have assessed methods to determine the cochlear duct length from preoperative clinical CT datasets, and have developed an automated method based on machine learning and 3D model analysis.  The implication for this approach, and its potential applicability to inform other surgical decisions based on patient-specific anatomic characteristics will be presented.

Nikolas H. Blevins, MD
Larry and Sharon Malcolmson Professor of Otolaryngology — Head & Neck Surgery (OHNS) and, by courtesy, of Neurosurgery and Psychiatry
Chief of Otology & Neurotology


Persister Cells Cause Antibiotic Therapy Failure in Chronic Biofilm Disease

Peter Luke Santa Maria, MBBS, PhD
Assistant Professor of Otolaryngology — Head & Neck Surgery (OHNS)


Tracing Facial Nerve Regeneration in a Mouse Model

After nerve transection injury, there is a microscopic gap that separates the two cut ends of the nerve.  Peripheral nerves are capable of regeneration across this microscopic gap.  The molecular signals that drive this native regenerative process in mouse models are important to understand so that we can improve nerve regeneration in humans by modulating the key pathways that drive early nerve tissue repair in the mouse

Jon-Paul Pepper, MD
Assistant Professor of Otolaryngology — Head & Neck Surgery (OHNS)


Keynote Presentation

Alexander Hillel, MD, PhD

Immunoregulation in Laryngotracheal Stenosis, Translating Discovery into Patient Care

Laryngotracheal stenosis (LTS) is a debilitating rare disease where progressive scar tissue narrows the airway, severely limiting an individual’s ability to breathe and communicate.  Despite significant advances in our understanding of LTS pathophysiology and outcomes, there is a clear and urgent need to improve treatment. This lecture will present data on immune mechanisms of LTS and discuss current efforts to translate scientific discoveries into patient care through both the development of a drug eluting stent and the design of a randomized, placebo-controlled clinical trial.  These translational steps may be generalized to Otolaryngologic diseases and discovery to improve the care for our patients.