Squamous Cell Carcinoma Tumor Ecology & Microenvironment (STEM) Working Group

Mỹ G. Mahoney, PhD

Principle Investigator (Program), Co-Lead (Core A), Lead (Project 3)

Dr. Mahoney is a molecular and cellular biologist with over 25 years of independent, funded research studying the mechanisms that control skin homeostasis and regeneration during wound healing and carcinogenesis. The goal of the Mahoney lab is to understand how molecular and cellular signaling during normal development is subverted to pathogenic signaling during disease progression. For many years, her lab focused on the roles of desmosomal proteins in autoimmune, infectious, and inherited diseases associated with fragility and abnormality in diverse tissues such as the skin, hair and heart and have generated genetically manipulated animal models to study these human diseases. Outside of the junctions, the cadherin desmoglein 2 (Dsg2) can activate multiple mitogenic signaling pathways regulating epithelial cell growth and survival, and this synergy accelerates skin and oral 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 alters the biogenesis of extracellular vesicles and alters their mitogenic content providing a mechanism by which epithelial cells can modulate their microenvironment. The Mahoney lab now focuses on understanding the critical roles that intercellular communications through cell-cell adhesion, extracellular vesicles, and modulating factors such as cytokines and chemokines play in cancer development and progression.

Adam Luginbuhl, MD

Co-Principle Investigator (Program), Lead (Core A)

Dr. Luginbuhl is a surgical oncologist involved in translational research. He is the director of the Sidney Kimmel Comprehensive Cancer Center’s Squamous cell carcinoma Tumor Ecology and Microenvironment (STEM) programmatic working group where he has brought together clinicians and scientists from six different departments to develop and facilitate four investigational initiated trials (IIT) including two that are multi-institutional.. His focus of inquiry includes biomarker discovery and TME/peripheral phenotyping amongst responders and non-responders to ICI treatment. Dr. Luginbuhl’s laboratory has reported discordant responses to ICI treatment between primary tumors and lymph node metastases in HNSCC and has ongoing investigation into this phenomenon. Dr. Luginbuhl’s leadership of the STEM group and his work in phenotyping tumor micro- and macro-environments will be instrumental in translating clinical reality to experimental design.

George C. Prendergast, PhD

Co-Lead (Core A)

Dr. Prendergast is an international leader in cancer biology, drug discovery and drug mechanism validation, with a breadth of experience gained in academia and pharmaceutical industry. His group pioneered the discovery of small molecule inhibitors of IDO1 and IDO1/TDO as immunometabolism therapy for the treatment of cancer and retinopathies, several of which are presently under study in multiple Phase 2 trials worldwide. Through collaboration with colleagues at the Lankenau Institute for Medical Research (LIMR) and Thomas Jefferson University (LIMR’s academic affiliate), he has also developed several experimental antibodies and genetic nano therapies with relevance to this Program.

Andrew P. South, PhD

Lead (Project 3)

Dr. South will be responsible for overseeing all aspects of the work in Project 1 including i) primary cell culture, colony, and DNA isolation ii) transfection, transduction, and characterization of cells, iii) all 3D culture assays and downstream analysis, and iv) in vivo work, tumor induction, and treatment/ prevention protocols. Dr. South has over 15 years of experience working on Squamous Cell Carcinoma and has extensive knowledge of primary cell culture and routinely isolates viable cells from a number of tissues, including the oral cavity, the skin, cervix, lung, bladder and breast. Thomas Jefferson IACUC protocol approval is in place for aspects of the current work, #02115. As a trained molecular biologist and having worked in hospital departments since 1999, Dr. South is well versed in DNA manipulation, sequencing, RNA analysis, as well as tissue handling, embedding and immunohistochemical processing.

Ubaldo Martinez Outschoorn, MD

Lead (Project 2)

Dr. Martinez Outschoorn has extensive experience in murine models of aggressive cancer. He has studied metabolic coupling in cancer for the past ten years. He has discovered that inflammation and oxidative stress drives metabolic coupling and is modulated by upregulation of stromal MCT4 and increased MCT1 expression in carcinoma cells. In collaboration with Dr. Joseph Curry, he will coordinate this sub-project.

Joseph Curry, MD

Co-Lead (Project 2)

Dr. Curry has expertise in translational research of cancer metabolism and immunology in HNSCC. He has optimized the 4-Nitroquinoline-1-oxide (4NQO) model of chemical carcinogenesis to study the metabolic profile of HNSCC. Dr. Curry will be responsible for all 4NQO chemical carcinogenesis experiments to define determinants of progression from preneoplasia to invasive HNSCC. In a clinical trial using metformin in head and neck cancer, he has established that metformin induces apoptosis of carcinoma cells with modulation of oxidative phosphorylation in these carcinoma cells. Importantly, Dr. Curry is ideally positioned to translate the basic research findings of this project into clinical trials and other clinical applications that target the tumor microenvironment for improved cancer diagnosis (biomarker development) and new treatment options (drug development and testing in patient trials).

Adam Snook, PhD

Co-Lead (Project 3)

Dr. Snook will serve as co-leader of project 3 and will be responsible for the overall administration and direction of the project. He has been developing cancer immunotherapeutics for gastrointestinal and head and neck malignancies for more than 15 years, including vaccine strategies for secondary prevention of metastasis and CAR-T cell therapies. He identified GUCY2C as a novel colorectal cancer immunotherapeutic target, developed a GUCY2C vaccine technology from conception to testing in phase I and II clinical trials he is leading, and he developed CAR-T cell technologies targeting GUCY2C for upcoming clinical testing.

Larry Harshyne, PhD

Lead (Core B)

Dr. Harshyne is an Assistant Professor in the Department of Microbiology & Immunology, Sidney Kimmel Comprehensive Cancer Center, Thomas Jefferson University. He will direct and coordinate the duties (tissue collection and storage, HLA-profiling, and immune analyses) performed by this Core. Dr. Harshyne is an immunologist with over 20 years’ experience monitoring immune responses in patients using a variety of high-throughput technologies including flow cytometry, luminex and genomic-based technologies. He has developed protocols for procuring, processing, and storing patient tissues including fresh-frozen and OCT-imbedded tumor tissue, white blood cells, plasma/sera, and extracellular vesicles. Dr. Harshyne has established tissue-banking programs for multiple departments and is currently managing tissue collection for six clinical trials at Jefferson.

Jennifer Johnson, MD, PhD

Co-Lead (Core B)

Dr. Johnson has expertise in clinical trial design, with a specific focus in novel agents in head and neck cancer. She currently represents the head and neck cancer team within EDDO and leads the Sidney Kimmel Comprehensive Cancer Center enterprise precision medicine program, allowing enhanced access to novel anti-cancer agents and molecular profiling of tumors.

Rajanikanth Vadigepalli, PhD

Lead (Core C)

Dr. Vadigepalli will be responsible for the ongoing supervision of the computational data analysis and network modeling aspects of the collaborative program. He has over two decades of experience in transcriptomic profiling, computational modeling, network biology, pathway analysis, high-dimensional omics analysis, and bioinformatics of transcriptional regulatory networks. 

Benjamin Leiby, PhD

Co-Lead (Core C)

Dr. Leiby will be responsible for supervising the statistical analysis support for the projects. He has significant experience in a wide range of statistical analysis and has been director of the Biostatistics Shared Resource for the Sidney Kimmel Comprehensive Cancer Center and Jefferson since 2014. He will coordinate with the Program MPIs, Project Leads, and the staff in the Biostatistics Service Center to ensure a consistent approach to design and analysis of experiments across projects. He will ensure that the experimental designs are appropriately powered for efficient testing of hypotheses to detect meaningful differences. He will also support the project personnel in conducting rigorous statistical analysis of data including data transformations and testing of assumptions for appropriate use of downstream statistical methods.

Adam Ertel, PhD

Co-Lead (Core C)

Dr. Ertel will be responsible for supporting the bioinformatics analysis aspects of the collaborative projects. He has a PhD in Biomedical Engineering and Postdoctoral training in bioinformatics. Dr. Ertel an expert in a wide range of bioinformatics methods and published on transcriptomics and pathway analysis methods and has long experience in the Jefferson MetaOmics shared resource providing bioinformatics analysis support for numerous projects.