The Rocco Laboratory, part of the OSUCCC – James and the Department of Otolaryngology-Head and Neck Surgery at Ohio State, studies the development and consequences of intra-tumor heterogeneity, 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 barrier to therapeutic success into a 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 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 NIH-supported laboratory then 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 laboratory 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:
- 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 types of differences influence patients’ responses to therapy for head and neck cancer; and
- Developing better ways to collect and process cancer cells from patients' tumors to support these studies.
Graduate students, postdoctoral researchers and medical students interested in the Rocco Lab should contact Gaila Sunkle, administrative manager for head and neck cancer research, at email@example.com.
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 moving 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 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.
Research Associate 2 Jharna Datta, PhD, is deciphering how expression of the p16 tumor suppressor product of the CDKN2A gene is regulated. Her primary focus is 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.
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, 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 Associate 1 Devi M Nair, PhD is helping to develop the Head and Neck Tumor Heterogeneity project that will establish the best ways to use living cells from patients’ tumors for studies of 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.
Research Associate 1 Caitlin Goodman, MS who recently completed a Master’s of Science degree, brings a background in the study of genetics, replication stress and disease to the Rocco lab. She is expanding 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 also is responsible for day-to-day lab functions, ordering supplies, and organizing the lab.
Research Assistant 2 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. 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.
Graduate student Jorge Toro-Zapata, BS, 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 develop. He is investigating 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.
Graduate student Travis Witkowski, BS, 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.
Senior Research Associate Jun-Ge Yu, MD, MS, provides scientific and technical support in histopathology and immunohistochemistry for the laboratory. Jun-Ge develops 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 helps other lab members establish and monitor animal experimental models.
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 particularly helping to develop tumorsphere assays as a model of CSC.
Administrative Manager Gaila Sunkle, MEd provides budgetary and administrative support to the Rocco Laboratory 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 Member:
Research Associate 1 Anita Janssen, BS played a fundamental role in establishing the Rocco Laboratory 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 Laboratory as the self-described “Lab Mom,” she took a position in the Clinical Trials Office at the OSUCCC – James.
ROCCO LABORATORY PUBLICATIONS
Mroz EA, Rocco JW. The challenges of tumor genetic diversity. Cancer. 2017 May 15;123(6):917-927. doi: 10.1002/cncr.30430. Epub 2016 Nov 8. Review. PubMed PMID: 27861749; PubMed Central PMCID: PMC5370554.
Ryan J, Montero J, Rocco J, Letai A. iBH3: simple, fixable BH3 profiling to determine apoptotic priming in primary tissue by flow cytometry. Biol Chem. 2016 Jul 1;397(7):671-8. doi: 10.1515/hsz-2016-0107. PubMed PMID: 26910743.
Puram SV, Rocco JW. Molecular Aspects of Head and Neck Cancer Therapy. Hematol Oncol Clin North Am. 2015 Dec;29(6):971-92. doi: 10.1016/j.hoc.2015.07.003. Epub 2015 Oct 17. Review. PubMed PMID: 26568543; PubMed Central PMCID: PMC4648693.
Keenan T, Moy B, Mroz EA, Ross K, Niemierko A, Rocco JW, Isakoff S, Ellisen LW, Bardia A. Comparison of the Genomic Landscape Between Primary Breast Cancer in African American Versus White Women and the Association of Racial Differences With Tumor Recurrence. J Clin Oncol. 2015 Nov 1;33(31):3621-7. doi: 10.1200/JCO.2015.62.2126. Epub 2015 Sep 14. PubMed PMID: 26371147; PubMed Central PMCID: PMC4979243.
Rocco JW. Mutant allele tumor heterogeneity (MATH) and head and neck squamous cell carcinoma. Head Neck Pathol. 2015 Mar;9(1):1-5. doi: 10.1007/s12105-015-0617-1. Epub 2015 Mar 25. PubMed PMID: 25804377; PubMed Central PMCID: PMC4382477.
Mroz EA, Tward AD, Hammon RJ, Ren Y, Rocco JW. Intra-tumor genetic heterogeneity and mortality in head and neck cancer: analysis of data from the Cancer Genome Atlas. PLoS Med. 2015 Feb 10;12(2):e1001786. doi: 10.1371/journal.pmed.1001786. eCollection 2015 FebPubMed PMID: 25668320; PubMed Central PMCID: PMC4323109.
Akagi K, Li J, Broutian TR, Padilla-Nash H, Xiao W, Jiang B, Rocco JW, Teknos TN, Kumar B, Wangsa D, He D, Ried T, Symer DE, Gillison ML. Genome-wide analysis of HPV integration in human cancers reveals recurrent, focal genomic instability. Genome Res. 2014 Feb;24(2):185-99. doi: 10.1101/gr.164806.113. Epub 2013 Nov 7. PubMed PMID: 24201445; PubMed Central PMCID: PMC3912410.
Mroz EA, Tward AD, Pickering CR, Myers JN, Ferris RL, Rocco JW. High intratumor genetic heterogeneity is related to worse outcome in patients with head and neck squamous cell carcinoma. Cancer. 2013 Aug 15;119(16):3034-42. doi: 10.1002/cncr.28150. Epub 2013 May 20. PubMed PMID: 23696076; PubMed Central PMCID: PMC3735618.
Bonilla-Velez J, Mroz EA, Hammon RJ, Rocco JW. Impact of human papillomavirus on oropharyngeal cancer biology and response to therapy: implications for treatment. Otolaryngol Clin North Am. 2013 Aug;46(4):521-43. doi: 10.1016/j.otc.2013.04.009. Epub 2013 Jun 27. Review. PubMed PMID: 23910468; PubMed Central PMCID: PMC3740406.
Mroz EA, Rocco JW. MATH, a novel measure of intratumor genetic heterogeneity, is high in poor-outcome classes of head and neck squamous cell carcinoma. Oral Oncol. 2013 Mar;49(3):211-5. doi: 10.1016/j.oraloncology.2012.09.007. Epub 2012 Oct 15. PubMed PMID: 23079694; PubMed Central PMCID: PMC3570658.
Mroz EA, Rocco JW. Gene expression analysis as a tool in early-stage oral cancer management. J Clin Oncol. 2012 Nov 20;30(33):4053-5. doi: 10.1200/JCO.2012.44.8050. Epub 2012 Oct 8. PubMed PMID: 23045572; PubMed Central PMCID: PMC3607710.
Mroz EA, Forastiere AA, Rocco JW. Implications of the oropharyngeal cancer epidemic. J Clin Oncol. 2011 Nov 10;29(32):4222-3. doi: 10.1200/JCO.2011.37.8893. Epub 2011 Oct 3. PubMed PMID: 21969506; PubMed Central PMCID: PMC3607743.
Nichols AC, Kneuertz PJ, Deschler DG, Lin DT, Emerick KS, Clark JR, Busse PW, Rocco JW. Surgical salvage of the oropharynx after failure of organ-sparing therapy. Head Neck. 2011 Apr;33(4):516-24. doi: 10.1002/hed.21480. PubMed PMID: 20652974.
Ory B, Ramsey MR, Wilson C, Vadysirisack DD, Forster N, Rocco JW, Rothenberg SM, Ellisen LW. A microRNA-dependent program controls p53-independent survival and chemosensitivity in human and murine squamous cell carcinoma. J Clin Invest. 2011 Feb;121(2):809-20. doi: 10.1172/JCI43897. PubMed PMID: 21293058; PubMed Central PMCID: PMC3026726.
Nichols AC, Finkelstein DM, Faquin WC, Westra WH, Mroz EA, Kneuertz P, Begum S, Michaud WA, Busse PM, Clark JR, Rocco JW. Bcl2 and human papilloma virus 16 as predictors of outcome following concurrent chemoradiation for advanced oropharyngeal cancer. Clin Cancer Res. 2010 Apr 1;16(7):2138-46. doi: 10.1158/1078-0432.CCR-09-3185. Epub 2010 Mar 16. PubMed PMID: 20233885.
Rothenberg SM, Mohapatra G, Rivera MN, Winokur D, Greninger P, Nitta M, Sadow PM, Sooriyakumar G, Brannigan BW, Ulman MJ, Perera RM, Wang R, Tam A, Ma XJ, Erlander M, Sgroi DC, Rocco JW, Lingen MW, Cohen EE, Louis DN, Settleman J, Haber DA. A genome-wide screen for microdeletions reveals disruption of polarity complex genes in diverse human cancers. Cancer Res. 2010 Mar 15;70(6):2158-64. doi: 10.1158/0008-5472.CAN-09-3458. Epub 2010 Mar 9. PubMed PMID: 20215515; PubMed Central PMCID: PMC2881662.
Mroz EA, Rocco JW. Functional p53 status as a biomarker for chemotherapy response in oral-cavity cancer. J Clin Oncol. 2010 Feb 10;28(5):715-7. doi: 10.1200/JCO.2009.26.3475. Epub 2010 Jan 4. PubMed PMID: 20048171.
Michaud WA, Nichols AC, Mroz EA, Faquin WC, Clark JR, Begum S, Westra WH, Wada H, Busse PM, Ellisen LW, Rocco JW. Bcl-2 blocks cisplatin-induced apoptosis and predicts poor outcome following chemoradiation treatment in advanced oropharyngeal squamous cell carcinoma. Clin Cancer Res. 2009 Mar 1;15(5):1645-54. doi: 10.1158/1078-0432.CCR-08-2581. Epub 2009 Feb 24. PubMed PMID: 19240170; PubMed Central PMCID: PMC2745309.
Nichols AC, Faquin WC, Westra WH, Mroz EA, Begum S, Clark JR, Rocco JW. HPV-16 infection predicts treatment outcome in oropharyngeal squamous cell carcinoma. Otolaryngol Head Neck Surg. 2009 Feb;140(2):228-34. doi: 10.1016/j.otohns.2008.11.025. PubMed PMID: 19201294.
Mroz EA, Baird AH, Michaud WA, Rocco JW. COOH-terminal binding protein regulates expression of the p16INK4A tumor suppressor and senescence in primary human cells. Cancer Res. 2008 Aug 1;68(15):6049-53. doi: 10.1158/0008-5472.CAN-08-1279. PubMed PMID: 18676825.
Mroz EA, Rocco JW. RNA interference: natural, experimental, and clinical roles in cancer biology. Head Neck. 2006 Dec;28(12):1132-41. Review. PubMed PMID: 16823868.
Morris EJ, Michaud WA, Ji JY, Moon NS, Rocco JW, Dyson NJ. Functional identification of Api5 as a suppressor of E2F-dependent apoptosis in vivo. PLoS Genet. 2006 Nov 17;2(11):e196. PubMed PMID: 17112319; PubMed Central PMCID: PMC1636698.
DeYoung MP, Johannessen CM, Leong CO, Faquin W, Rocco JW, Ellisen LW. Tumor-specific p73 up-regulation mediates p63 dependence in squamous cell carcinoma. Cancer Res. 2006 Oct 1;66(19):9362-8. PubMed PMID: 17018588.
Rocco JW, Ellisen LW. p63 and p73: life and death in squamous cell carcinoma. Cell Cycle. 2006 May;5(9):936-40. Epub 2006 May 1. PubMed PMID: 16687923.
Rocco JW, Leong CO, Kuperwasser N, DeYoung MP, Ellisen LW. p63 mediates survival in squamous cell carcinoma by suppression of p73-dependent apoptosis. Cancer Cell. 2006 Jan;9(1):45-56. PubMed PMID: 16413471.
Cohen EE, Lingen MW, Martin LE, Harris PL, Brannigan BW, Haserlat SM, Okimoto RA, Sgroi DC, Dahiya S, Muir B, Clark JR, Rocco JW, Vokes EE, Haber DA, Bell DW. Response of some head and neck cancers to epidermal growth factor receptor tyrosine kinase inhibitors may be linked to mutation of ERBB2 rather than EGFR. Clin Cancer Res. 2005 Nov 15;11(22):8105-8. PubMed PMID: 16299242.
Amrein PC, Clark JR, Supko JG, Fabian RL, Wang CC, Colevas AD, Posner MR, Deschler DG, Rocco JW, Finkelstein DM, McIntyre JF. Phase I trial and pharmacokinetics of escalating doses of paclitaxel and concurrent hyperfractionated radiotherapy with or without amifostine in patients with advanced head and neck carcinoma. Cancer. 2005 Oct 1;104(7):1418-27. PubMed PMID: 16116597.
Shin JJ, Katayama T, Michaud WA, Rocco JW. Short hairpin RNA system to inhibit human p16 in squamous cell carcinoma. Arch Otolaryngol Head Neck Surg. 2004 Jan;130(1):68-73. PubMed PMID: 14732771.
Rocco JW, Sidransky D. p16(MTS-1/CDKN2/INK4a) in cancer progression. Exp Cell Res. 2001 Mar 10;264(1):42-55. Review. PubMed PMID: 11237522.