The Rocco Laboratory, part of The Ohio State University Comprehensive Cancer Center and the Department of Otolaryngology – Head and Neck Surgery at Ohio State, studies the development and consequences of intra-tumor heterogeneity, or the differences among cancer cells within a tumor. Intra-tumor heterogeneity lies at the core of cancer treatment resistance. Even if only a single cancer cell develops the ability to escape from the primary tumor site or becomes resistant to radiation, to standard or targeted chemotherapy, or to immunotherapy, that cell might regrow a tumor after therapy removes all the other cancer cells. The Rocco lab explores all aspects of intra-tumor heterogeneity in an attempt to develop new approaches that can turn it from a therapeutic barrier to a target for therapy.
James Rocco, MD, PhD, began his translational research laboratory in 1999 at the Massachusetts Eye and Ear Infirmary and Massachusetts General Hospital (MGH). His early basic-science work on the regulation of tumor cell death following chemotherapy led him to translational work that identified the protein Bcl2 as a marker of poor response to standard therapy for oropharyngeal cancer. His National Institutes of Health-supported laboratory then developed the first simple and general way to measure intra-tumor heterogeneity and used it to show that high heterogeneity is associated with poor outcome in head and neck cancer. He moved his laboratory to Ohio State in 2015.
The faculty, students and staff of the Rocco laboratory have substantial expertise ranging from cellular and molecular biology to translational and clinical research. Although the laboratory focuses on head and neck cancer, Dr. Rocco’s clinical specialty, its work has already helped to advance research on other types of cancer. The laboratory thus provides a balanced mix of basic and translational science projects that offers many research opportunities. Current work in the laboratory includes:
- Understanding how the functions of tumor-suppressor proteins—especially p16, p14 and p53—can be lost, leading to development of heterogeneous tumors;
- Documenting the differences among cancer cells that allow only some of them, called cancer stem cells (CSC) or tumor-initiating cells (TIC), to re-grow a tumor after therapy;
- Learning how genetic differences develop and are maintained among cancer cells in a tumor, providing a reservoir of cancer cells that might be resistant to particular therapies;
- Finding the best ways to measure these functional and genetic differences among cancer cells in a tumor;
- Studying how these differences influence patients’ responses to therapy for head and neck cancer.
Graduate students, postdoctoral researchers and medical students interested in the Rocco Lab should contact Gaila Sunkle, program manager for head and neck cancer research, at firstname.lastname@example.org.
Present Lab Members:
Professor James W. Rocco, MD, PhD, holds the Mary E. and John W. Alford Research Chair in Head and Neck Cancer. In addition to directing his research laboratory, he has fruitful collaborations with the Getz group at the Broad Institute and the Bernstein lab at MGH that aim to understand the biological basis of intra-tumor heterogeneity. His laboratory research interests synergize with his interests in clinical trials, his roles as a head and neck surgeon and as Head and Neck Disease Group Leader at The James Cancer Hospital and Solove Research Institute, and his work with many groups devoted to improving clinical care of head and neck cancer patients.
Research Associate Professor Edmund Mroz, PhD, worked with Dr. Rocco to develop a measure of genetic differences among cancer cells in a tumor and to show its relation to outcome in head and neck cancer. Researchers studying other types of cancer are now adopting this approach. Since coming to Ohio State, Dr. Mroz had been extending this work to evaluate the relation of intra-tumor heterogeneity to head and neck cancer outcomes following specific types of therapy, with a long-term goal of helping to personalize therapy choices. He is working with colleagues at the Broad Institute to understand the early processes of tumor evolution that lead to intra-tumor heterogeneity, and provides senior-level supervision for Rocco laboratory students and staff.
Research Associate 2 Bin Li, PhD, is studying how loss of tumor-suppressor functions leads to tumor development and heterogeneity. To model the initiating stages of squamous cell carcinoma (SCC), he uses CRISPR/Cas9-mediated genome editing to induce concurrent mutations in the TP53 and CDKN2A genes of primary keratinocytes. These include knockouts and mutations of the p53 protein (which promote heterogeneity) and individual or combined knockouts of the p14 and p16 protein products of the CDKN2A gene. This panel of genetically modified keratinocyte lines will help to dissect the roles of CDKN2A and TP53 alterations in initiation and development of SCC, and to identify targets for developing novel treatments.
Research Associate 1 Satavisha Roy, BS, is investigating the properties of cancer stem cells (CSC) in cell lines derived from head and neck squamous cell carcinoma (HNSCC). She uses the ability of single cells to form tumorspheres, or floating sphere-shaped structures, as a model to understand how CSC differ from other cancer cells and to find ways to target the CSC population.
Research Assistant 1 Jason Andersen, BS, provides skilled technical support for molecular biology studies in the laboratory. He is developing a system to use adenovirus to deliver CRISPR technology for editing genes in cells. The goal is to combine the ease of use and specificity of CRISPR with the advantages of adenoviruses, which unlike retroviruses do not directly alter the genome themselves. He wants to use these tools to elucidate cellular pathways associated with the p16 and p14 products of the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene and the tumor suppressor p53.
Graduate student Jorge Toro-Zapata, BS, who is in the Biomedical Sciences Graduate Program, is working to determine the ways that carcinogenic stimuli normally lead to expression of the p16 tumor suppressor from the CDKN2A gene. This tumor suppression is almost always lost before HNSCC develops. He is investigating a protein complex that includes the C-terminal binding protein (CtBP), which helps determine whether p16 expression is kept off or turned on. Understanding the ways that p16 normally is engaged to prevent tumor development may provide ways to detect and treat disease at an early stage, before dangerous heterogeneity can develop.
Graduate student Travis Witkowski, BS, who is in the Biomedical Sciences Graduate Program, studies tumor-initiating cells (TIC), whose functional differences from other cancer cells in a tumor provide a mechanism of recurrence in HNSCC. He is developing both marker-dependent and functional assays to identify TIC and is investigating drugs that modulate these cells.
Program Director Bhavna, Kumar, MS., provides scientific and technical oversight of the Rocco Laboratory and other laboratories in the Head and Neck Cancer Research Program at Ohio State while she is engaged in several research projects in these laboratories. In the Rocco Laboratory, she is helping to develop tumorsphere assays as a model of CSC.
Program Manager Gaila Sunkle, MEd, provides budgetary and administrative support to the Rocco laboratory and to other laboratories in the Head and Neck Cancer Research Program at Ohio State.
Former Lab Member:
Research Associate 1 Anita Janssen, BS, played a fundamental role in establishing the Rocco Laboratory at Ohio Stateafter its move from Boston in 2015. She was responsible for day-to-day lab functions, overseeing staff training and safety, ordering supplies, and performing equipment maintenance and upkeep. She found, expanded, organized and documented the many cancer cell lines and other reagents that came from Boston, allowing the laboratory’s work to proceed efficiently. After two years in the Rocco Laboratory as the self-described “Lab Mom,” she took a position in the Clinical Trials Office at Ohio State’s Comprehensive Cancer Center.