Martinez-Outschoorn / Curry Lab
The lab of Ubaldo Martinez-Outschoorn, MD and Joseph Curry, MD focuses on the study of head and neck squamous cell cancer metabolism in the microenvironment of head and neck squamous cell carcinomas (HNSCC). To date, Drs. Martinez-Outschoorn and Curry have jointly published 20 articles. Dr. Martinez-Outschoorn has secured funding including a prior K award, Margaret Q. Landenberger Foundation Award, an R01 for his work in tumor metabolism, and an NIH COVID supplement award. Dr. Curry has been awarded external funding through the American Head and Neck Society and numerous internal grants and has designed and led 5 investigator-initiated trials, including industry sponsored trials in immunotherapy for HNSCC. Their research has generated impactful work including data presented at the American Society of Clinical Oncology, European Society of Medical Oncology, Society for Immunotherapy in Cancer and the American Head and Neck Society. This laboratory has mentored medical students, residents, master's students and PhD students and T32 postdoctoral student every year for the past 10 years. One of our residents received an American Academy of Otolaryngolgoy CORE grant for work in a tobacco smoke HNSCC carcinogenesis model and one of our medical student trainees was awarded the SKCC Population Health grant with the translational component provided.
The lab of My Mahoney, PhD seeks to understand how molecular and cellular signaling during normal development is subverted to pathogenic signaling during disease progression. Her laboratory uses cutting edge technology and multi-disciplinary approaches in cultured cells and animal models to identify molecular targets for translational applications. Dr. Mahoney’s work has shown that intercellular communication through cell-cell adhesion, cytokine release, and secretion of extracellular vesicles are coordinated and can serve as surrogate prognostic markers to inform treatment options.
Her lab has identified desmoglein 2 (Dsg2) as a novel biomarker for epithelial-derived malignancies and that Dsg2 increases cell proliferation and malignant transformation. Dsg2 modulates multiple mitogenic signaling pathways including MEK/Erk1/2 and Gli/Patch, and this synergy accelerates both tumor development. Molecular profiling has shown that Dsg2 can induce profound changes in cellular transcriptome and secretome, critical for neoplasia. An exciting paradigm shift is the recent discovery that Dsg2 modulates the biogenesis of extracellular vesicles and alters their mitogenic content including specific miRNAs and cytokines, providing a mechanism by which epithelial cells can modulate their microenvironment. This creates a window of opportunity for specific elimination of highly malignant cancers by engineering stable vesicles that are loaded with specific miRNAs and use in therapy without toxicity.
The laboratory of Andrew South, PhD researches squamous cell carcinoma (SCC) arising in the skin and oral mucosa. Researchers study rare familial prone disorders that can inform on more common cancer, principally aggressive SCC occurring in patients with the rare genetic skin blistering disease recessive dystrophic epidermolysis bullosa (RDEB), and how mechanisms that lead to this cancer relate to sporadic SCC of the head and neck (HNSCC). Recent work has identified APOBEC mutagenesis and the tumor microenvironment as key drivers of SCC in both RDEB and HNSCC with relevance to all SCC.
Dr. Harshyne’s lab focuses on understanding the interplay between the tumor and host immune response. Researchers interrogate the tumor microenvironment and blood for changes in lymphocyte and macrophage populations or their activation status, metabolic factors, cytokines/chemokines, and extracellular vesicles. They perform a wide range of routine immunological assays including phenotypic and functional flow cytometry, multiplex luminex, and digital spatial transcriptional profiling of blood and tumor.
Researchers in Dr. Harshyne’s lab use these data to ask mechanistic questions as to how inappropriate immune activation drives cancer and metastases. In the context of immunotherapy, we search for predictive and prognostic biomarkers as we seek to increase the number of individuals who benefit from novel therapeutic paradigms. This lab has performed a number of studies with Drs. Luginbuhl and Curry including monitoring the immune status of patients enrolled in one of their window-of-opportunity trials. We have performed a number of projects with Dr. Luginbuhl to investigate the various roles M2 macrophages play in facilitating growth within the primary tumor and metastatic lymph nodes.
More recently, we have begun collaborating with Drs. Toskala and Rabinowitz of Otolaryngology to measure inflammatory factors and cells within the nasal cavity to investigate immune-mediate mechanisms of chronic sinusitis.
Fibrotic diseases constitute a world-wide major health problem, but no completely effective therapies exist. It is universally appreciated that a particular cell type with unique characteristics, the myofibroblast, is responsible for replacement of functioning tissue with non-functional scar tissue. The Joan and Joel Research Center for Fibrotic Diseases was established at Thomas Jefferson University to investigate the complex interactions and signaling pathways stimulating myofibroblast activity with the primary goal of identifying effective pharmacologic targets and therapies. We have collaborated with the Otolaryngology Department in studies on radiation-induced fibrosis and the effect of hypoxia on fibrotic matrix formation.
During the past several years, collaborating with oncologists in the Department of Otolaryngology – Head & Neck Surgery, we have established an ongoing cohort to conduct liquid biopsy research in patients with head and neck cancers. Our research focuses on identification of genomic variants in ctDNAs as makers for minimal residual disease, treatment response, and patient survival. The non-invasive markers identified in ctDNA have the potential to be used in real-time monitoring and precision management of head and neck cancer patients.