The Rocco Lab, part of the OSUCCC – James and the Department of Otolaryngology – Head and Neck Surgery at The Ohio State University, studies the biological basis of two molecular markers that Dr. Rocco and his colleagues have shown to be associated with head and neck cancer outcome: intra-tumor heterogeneity and estrogen-receptor signaling.
Intra-tumor heterogeneity, the differences among cancer cells within a tumor, lies at the core of cancer treatment resistance. Even if only a single cancer cell can escape from the primary tumor site or become resistant to radiation, standard or targeted chemotherapy, or immunotherapy, that cell might regrow a tumor after therapy removes all the other cancer cells. Studies led by Dr. Rocco showed that higher intra-tumor heterogeneity is associated with worse outcome in head and neck cancer. The Rocco Lab thus explores all aspects of intra-tumor heterogeneity in an attempt to develop new approaches that can turn it from a barrier to therapeutic success into a target for therapy.
Dr. Rocco’s group recently showed that higher expression of estrogen receptor alpha in tumors, known to be important in breast cancer, is related to better outcomes in both male and female head and neck cancer patients who are treated with a combination of radiation and chemotherapy. This surprising result has led his laboratory to investigate the roles that estrogen signaling plays in head and neck cancer and whether estrogen-receptor signaling could provide a novel target for therapy.
Dr. Rocco began his translational research laboratory in 1999 at the Massachusetts Eye and Ear Infirmary and Massachusetts General Hospital (MGH). His NIH-supported laboratory there developed the first simple and general way to measure intra-tumor heterogeneity and used it to show that high heterogeneity was 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 Lab have a wide range of 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 unique research opportunities. Current work in the laboratory includes:
- Elucidating the controls on propagation of normal cells that they lose when they become cancerous
- Understanding the early steps in tumor formation and how they lead to development of heterogeneous tumors
- 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
- Investigating the role of estrogen-receptor signaling in head and neck cancer
- Studying the implications of this work for how to provide the best type of therapy for individual patients
To support this work, the Rocco Lab has begun a Head and Neck Tumor Heterogeneity (HNTH) initiative in collaboration with the Total Cancer Care® Program at the OSUCCC – James. After obtaining permission from a head and neck cancer patient, the HNTH group starts with fresh tumor tissue from the operating room and uses several different ways to obtain and propagate living cells from the tumor for research on intra-tumor heterogeneity and personalized cancer therapy.
Graduate students, postdoctoral researchers and medical students interested in the Rocco Lab should contact Gaila Konneker, administrative manager for head and neck cancer research, at Gaila.Konneker@osumc.edu.
Present Lab Members
James W. Rocco, MD, PhD, professor, 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, which 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 Head and Neck Disease Group Leader at the OSUCCC – James, and his work with many groups devoted to improving clinical care of head and neck cancer patients.
Edmund Mroz, PhD, research associate professor, 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 moving to Ohio State, Dr. Mroz has 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 Lab students and staff.
Bin Li, PhD, senior research associate, 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 keratinocytes lines will help to dissect out the roles of CDKN2A and TP53 alterations in initiation and development of SCC and to identify actionable targets for developing novel treatments.
Arti Yadav, MS, research associate, is helping to identify the best ways to process, sort and collect cancer cells from patient tumors for the Head and Neck Tumor Heterogeneity (HNTH) project. She uses the HNTH Flow Cytometer to analyze, characterize and sort different types of cells from patient tumors and patient-derived tumor xenografts (PDX). She also provides highly experienced technical support to other laboratory projects, most recently on developing ways to identify specific strains of human papillomavirus (HPV) in cells from head and neck tumors
Devi M Nair, PhD, research associate, is a member of the Head and Neck Tumor Heterogeneity (HNTH) group. She is helping to establish the best ways to use living cells from patients’ tumors for studies of intra-tumor heterogeneity. Devi processes tumors for live tissue/cell harvest to analyze complex cancer models such as tumorsphere formation from single cells, responses to drug treatments and associations of cellular behaviors with patient clinical characteristics.
Tia Watts, BS, research assistant, is a member of the Head and Neck Tumor Heterogeneity (HNTH) group in the laboratory. Tia procures living tumor and normal tissues, and then processes them in the laboratory in ways designed to keep the cells alive for study: in standard two-dimensional tissue culture, as three-dimensional organoids and tumorspheres, and as tumors growing in mice. Tia also helps characterize these tissues and cells, like preparing fixed tissue for pathology and histology.
Jason Andersen, BS, research assistant, 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. Jason particularly wants to use these tools to help elucidate cellular pathways associated with the p16 and p14 products of the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene and the tumor suppressor p53.
Ernest Duah, PhD, postdoctoral researcher, brings his background in studying targeted anticancer agents in head and neck cancer to the Rocco Lab. Dr. Duah is developing an animal model of head and neck squamous cell carcinoma (HNSCC) in immune-competent mice that will allow study of the role of the immune system in HNSCC progression and how immunotherapy can contribute to HNSCC treatment. He is also characterizing the expression of estrogen receptor expression in HNSCC to see if our recent discoveries about estrogen receptors in HNSCC can lead to better, novel therapies.
Travis Witkowski, BS, graduate student 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 TIC.
Bhavna, Kumar, MS, program director, provides scientific and technical oversight of the Rocco Lab and other groups in the Head and Neck Cancer Research Program at Ohio State while she is engaged in several research projects. She is in charge of the Head and Neck Tumor Heterogeneity (HNTH) group in the Rocco Lab, helping develop the original concept of the HNTH initiative and then taking it through the design and equipping of research space and the hiring and supervision of staff.
Gaila Konneker, MEd, administrative manager, provides budgetary and administrative support to the Rocco Lab and other laboratories in the Head and Neck Cancer Research Program of the Department of Otolaryngology – Head and Neck Surgery. She maintains fiscal accountability, ensuring that resources are efficiently used to reach program goals, and helps plan future initiatives. Gaila also serves as liaison with other departments, programs and offices at Ohio State and assists the department chair, division director and COO with faculty and staff recruitment, travel and hiring.
Former Lab Members
Jharna Datta, PhD, research associate, worked on deciphering how expression of the p16 tumor suppressor product of the CDKN2A gene is regulated. Her primary focus was how loss of the C-terminal binding protein (CtBP) could release the Polycomb–based repression of CDKN2A so that p16 protein is expressed constitutively, thus inhibiting cell proliferation. Targeting CtBP to activate p16-based tumor suppression could then lead to a novel therapeutic strategy to prevent head and neck squamous carcinogenesis.
Caitlin Goodman, MS, research associate, brought a background in the study of genetics, replication stress and disease to the Rocco Lab. She expanded the use of adenoviral delivery of CRISPR technology for genetic editing in cells, in particular to elucidate the cellular pathways associated with the p16 and p14 products of the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene and the tumor suppressor p53. She was also responsible for day-to-day lab functions, ordering supplies and organizing the lab.
Anita Janssen, BS, research associate, played a fundamental role in establishing the Rocco Lab at Ohio State after 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 Lab as the self-described “lab mom,” she took a position in the Clinical Trials Office at the OSUCCC – James.
Satavisha Roy, BS, research associate, investigated the properties of cancer stem cells (CSC) in cell lines derived from head and neck squamous cell carcinoma (HNSCC). She used the ability of single cells to form tumorspheres, 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.
Jorge Toro-Zapata, BS, graduate student, worked 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 investigated a protein complex including 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.
Jun-Ge Yu, MD, MS, senior research associate, provided scientific and technical support in histopathology and immunohistochemistry for the laboratory. Jun-Ge developed patient-derived tumor xenografts (PDX) in mice from human head and neck tumors or cells grown in culture to evaluate intra-tumor heterogeneity and devise preclinical screens for the development of novel cancer therapeutics. He also helped other lab members establish and monitor animal experimental models.