Highlights

Konstantina Stankovic, MD, PhD was elected to the National Academy of Medicine in October 2024 for her contributions to understanding causes of and treatments for hearing loss. The National Academy of Medicine has more than 2,400 members who in turn elect new members through a process that recognizes individuals who have made major contributions to the advancement of the medical sciences, health care and public health. Announcements of the new members were released by the National Academy of Medicine and Stanford Medicine.

We congratulate Dr. Edward Damrose on his appointment to the National Navy Reserve Policy Board (NNRPB). The NNRPB was established to consider, recommend, and report to the Secretary of the Navy on reserve policy matters.  He was selected from over 100 active and reserve naval senior officers for this position.  Dr. Damrose will serve in this role through 2028 as assistant to RADM Robert Clark, Chief, NNRPB.

The proposal, “Combinatorial Screening to Overcome De-differentiation Mediated Treatment Resistance in Thyroid Cancer ”, was selected for funding as one of the Stanford Cancer Institute’s March 2025 SCI Innovation Awards. 

Background and Rationale

While surgery is the mainstay of thyroid cancer treatment, more aggressive cancers are treatable with adjuvant radioactive iodine (RAI). However, a subset of patients develops resistance to RAI due to loss of iodine uptake capability. Furthermore, BRAF-V600E mutation is a common targetable mutation present in up to 70% of thyroid cancers, but about 1/3 do not respond to BRAF inhibitors . This study aims to use CRISPR multi-target screening, novel YFP-derived iodide reporter, and single-cell multi-omics, to identify synergistic targets and combination strategies, focusing on enhancing iodine trapping in de-differentiated tumors.

This study will be conducted by the strong collaborating team of Dr. Le Cong who has CRISPR functional genomics expertise, and Drs. Maya M. Kasowski and Dr. Lisa Orloff, who have deep expertise in thyroid cancer models, assays, and clinical aspects of thyroid cancer management.

Dr. Nathan Reticker-Flynn is a Co-Principal Investigator (MPI) on an Administrative Supplement from the National Institute on Aging (NIA) entitled, “Genetic analysis of aging on immune responses to lung cancer.” Despite the critical influence of both aging and the immune system on carcinogenesis there is little understanding of the interplay between aging and anti-cancer immune responses. In this proposal, he and Stanford Genetics professor Dr. Monte Winslow will use quantitative in vivo genetic approaches to generate tumors with alteration in diverse immune regulators and assess how age impacts the influence of the adaptive and innate immune systems on lung carcinogenesis.

Dr. Reticker-Flynn is the Principal Investigator on a Stanford Cancer Institute Innovation Award entitled, “Uncovering the role of the type I interferon receptor in cancer metastasis.” As tumors metastasize throughout the body they frequently evolve to evade and suppress anti-tumor immunity. One mechanism by which they acquire these capabilities is by colonizing lymph nodes, wherein they are initially exposed to anti-tumor immunity orchestrated by a family of molecules known as interferons. The chronic exposure to these interferons results in epigenetic rewiring of any surviving cancer cells in a manner that enables them to express immunosuppressive mediators. Dr. Reticker-Flynn’s lab previously discovered the importance of the type I interferon receptor in maintaining this signature in cancer cells. In this proposal, his groups will employ a variety of synthetic biology and genetic tools to uncover the mechanisms by which this receptor enables maintenance of the interferon signature and suppression of anti-tumor immunity.

Dr. Reticker-Flynn is the Principal Investigator on a grant from the Robert L. Fine Cancer Research Foundation entitled, “An immune activating cell therapy for the treatment of metastatic pancreatic cancer.” Pancreatic cancer is the deadliest common malignancy, and while cancer immunotherapies have improved outcomes for a range of advanced malignancies, they have yet to demonstrate efficacy in this near uniformly fatal disease. Most patients with pancreatic adenocarcinoma exhibit metastases to the liver and lymph nodes, and liver metastases are associated with poor immunotherapy responses across a range of malignancies. We previously discovered that when tumors spread to sites of immune education, they can induce tumor-specific immune tolerance, which facilitates further disease progression. In this proposal, we seek to develop a cell therapy capable of activating anti-tumor immunity within livers to repolarize immune responses away from tolerance induction and towards activation. This therapy exploits cell engineering and the endogenous machinery of T cells to break immunological tolerance in livers and promote systemic anti-tumor immunity.

Drs. Cheng and Stankovic are Co-Principal Investigators on a U24 extension grant from the NIH-NIDCD and NIA for their project, “Molecular markers of Alzheimer’s disease pathology in the human inner ear.” This study will examine whether the hallmark Alzheimer’s pathology which causes damage in the brain—the accumulation of amyloid-beta protein and phosphorylated tau (p-tau) tangles— may also damage the sensory cells and neurons in the cochlea required for human hearing. Alzheimer’s disease is the most common cause of dementia in the United States and, in addition to the classical symptoms such as memory loss, people with this disease also have abnormal perception and processing of sound. The results of the proposed experiments will help inform the identification of new therapeutic targets for hearing loss as well as potential biomarkers for risk stratification for people with Alzheimer’s disease.

Dr. Andrey Finegersh has received an American Cancer Society-Stanford Cancer Institute (ACS-SCI) IRG Pilot Grant for his project, "Targeting SWI/SNF mediated metabolic reprogramming as a novel treatment strategy for head and neck cancer." Head and neck cancer is the sixth most common cancer worldwide and outcomes remain poor for many patients, with limited treatment gains over the last several decades. Changes in cancer metabolism are common in head and neck cancer but are not exploited for treatment benefit. The Finegersh lab has identified a commonly amplified epigenetic pathway called SWI/SNF as an important mediator of metabolism in head and neck cancer. This proposal develops a new strategy using orally bioavailable drugs to simultaneously target the SWI/SNF pathway and cancer metabolism  for tumors that are resistant to most therapies. The proposal also identifies how this treatment strategy primes the immune system to attack cancers and other pathways regulating metabolism. Together, this data is expected to open a new avenue of research into SWI/SNF inhibition as a therapy for head and neck cancer.

Dr. Anthony Ricci is a Co-Principal Investigator on a grant from Fondation Pour L’Audition for his project, “Deciphering the role of TMIE palmitoylation in the hair cell mechanosensory transduction channel.” This work focuses on the rapidly growing area of biochemical modulation of hair cell mechanotransduction.

Dr. Konstantina Stankovic has received a Clinical Research Award from the Children’s Tumor Foundation for her project “Temporal Trends in Plasma Biomarkers: Implications for Hearing and Tumor Progression in People with Vestibular Schwannoma.” Vestibular schwannoma (VS) is a slow-growing intracranial tumor that causes hearing loss in most (95%) patients. In a prior cross-sectional study, the Stankovic lab identified and validated blood biomarkers associated with the presence of VS, VS-associated hearing loss, and VS tumor size in a large study of patients with VS. In this new longitudinal study, her team will determine whether these molecular biomarkers can predict VS patient outcomes such as progressive hearing loss, the extent of surgical removal of the tumor, or tumor growth. Such blood biomarkers could improve the precision of VS diagnosis, prognosis, and management, opening future possibilities for novel molecular therapeutics.

Dr. Matthew Fitzgerald has received a grant from the Stanford Center for Digital Health for his project, “Automatic scoring of human speech recognition tests.” His team has recently developed a tool which takes advantage of modern speech recognition techniques and artificial intelligence to automatically score any audiologic test of speech recognition in quiet and noise in any language.  Dr. Fitzgerald plans to validate this tool and to the capacity of his algorithm to provide information that is not available with manual scoring, such as the duration of time the participant needs to respond.  This may provide quantifiable estimates of listening effort and cognitive load.  Moreover, this approach also has the potential to provide increased access to care for non-native speakers of English, and to help audiologists with hearing loss who may have difficulty scoring audiologic tests of speech recognition.

Dr. Vasu Divi has received funding from Merck & Co., Inc. for his project, “A Phase 2/3, adaptive, randomized, open-label, clinical study to evaluate neoadjuvant and adjuvant V940 (mRNA-4157) in combination with pembrolizumab (MK-3475) versus standard of care, and pembrolizumab monotherapy in participants with resectable locally advanced cutaneous squamous cell carcinoma (LA cSCC)”. This trial is studying a new cancer therapy called V940 for patients with a type of skin cancer called advanced cutaneous squamous cell carcinoma (cSCC). cSCC is the second most common type of skin cancer. The usual standard of care treatment for cSCC tumors is to remove the cancer with surgery and then radiation therapy if needed. This clinical trial’s new therapy is called V940, which is a personalized cancer vaccine using mRNA technology. The study aims to compare V940, in combination with pembrolizumab immunotherapy, pembrolizumab alone, or the standard of care approach to see if this new type of vaccine is safe and effective. The uniqueness of the V940 approach to treating this disease is in that this is an individualized therapy. The V940 is made specifically for each person based on the mutational characteristics of their specific type of cancer. In other words, it is personalized for each individual. The V940 is designed to stimulate a patient’s own immune system which in turn allows it to target their tumor.

Achintya Bhowmik, Chief Technology Officer at Starkey, has been appointed as an Industry Representative to the U.S. FDA Digital Health Advisory Committee. This prestigious appointment highlights Dr. Bhowmik's leadership in integrating advanced digital technologies, including artificial intelligence, into hearing health solutions. His role on the committee will contribute to shaping policies for the development and regulation of digital health technologies, ensuring they are innovative, safe, and effective. For more details, visit Hearing Mojo and Hearing Health & Technology Matters.