Dr. Cullen graduated from Harvard Medical School in 1983 and completed an internal medicine residency there, moving on to fellowship training in medical oncology at the National Cancer Institute (NCI) in Bethesda, MD. His first faculty appointment was Georgetown University, where I established successful, funded lab programs—first in the molecular biology of breast cancer and later in head and neck malignancies. He established and maintained a busy clinical referral practice in head and neck cancer and helped to direct the clinical head and neck program. Dr. Cullen maintains an active clinical practice to this day.
From 2000 to 2002, Dr. Cullen served as interim director of the Lombardi Cancer Center at Georgetown after having been appointed by the dean of the School of Medicine. During this time, he oversaw the successful recompetition of Lombardi’s NCI Cancer Center Support Grant. In January 2004, after having been recruited as part of a strategic effort to be recognized as an NCI-designated Cancer Center, Dr. Cullen became director of the University of Maryland Marlene and Stewart Greenebaum Cancer Center (UMGCC).
At UMGCC, Dr. Cullen directed a complete reorganization of the clinical and research programs and supervised an investment of more than $125 million in new faculty, lab space, and capital equipment. As a result, UMGCC was recognized as an NCI Cancer Center in 2008, and the designation was renewed in 2011. Throughout his tenure as director, UMGCC has continued to make strong scientific and clinical contributions and is now ranked among the top Cancer Centers in the country.
Dr. Cullen has served on the scientific advisory boards or as a special consultant for Cancer Centers at Brown University, Howard University, University of Louisiana, and University of West Virginia. Dr. Cullen is currently on the scientific advisory committees for the Cancer Centers of University of Minnesota, Case Western Reserve University, and Johns Hopkins University.
Dr. Cullen was appointed to the board of directors of the South Atlantic Division of the American Cancer Society (ACS) in 2007. He moved to the National Board of Directors of ACS in 2009. In that capacity, he served as a liaison between ACS and the White House as part of ACS’s efforts to support the passage of the Affordable Care Act.
In service to NCI, Dr. Cullen co-chaired the NCI Operational Efficiency Working Group and the Clinical Trials Reporting Program Strategic Subcommittee, both leading to important components of the reorganization of NCI’s National Clinical Trials Network.
In 2011, President Obama appointed Dr. Cullen to a 6-year term as a member of the National Cancer Advisory Board (NCAB). In that capacity, he worked extensively with the President’s Cancer Panel to prepare its 2013 report on strategies to increase vaccination for human papillomavirus (HPV) in the United States. Having been appointed by NCI Director Harold Varmus, he also served on a working group tasked with making recommendations for revising the budgeting processes of NCI’s Office of Cancer Centers. NCAB accepted the recommendations, and NCI leadership is developing an implementation plan and schedule for this new funding scheme.
In 2012, Dr. Cullen was elected to the Board of the Association of American Cancer Institutes.
1. The Role of Insulin-Like Growth Factor II (IGF-II) in Breast Cancer
After completing clinical training at NCI, Dr. Cullen began lab studies on the role of IGFs in the breast cancer section of Dr. Marc Lippman’s lab. Dr. Cullen moved with Dr. Lippman to Georgetown in 1988, where he established his own lab to continue studies on peptide growth factors in breast cancer. Dr. Cullen has been continuously funded through NIH and other sources since 1989. His lab characterized important genotypic and phenotypic differences in the stroma of normal and malignant breast and demonstrated that expression of potent mitogens, including IGF-II, could be induced in tumor stroma following exposure to malignant breast epithelium. He also demonstrated that IGF-II exerts its mitogenic signal in breast cancer by binding the IGF-I receptor. Additionally, Dr. Cullen showed autocrine IGF-II expression results in an aggressive, hormone-independent phenotype.
2. Cisplatin Action and Resistance in Head and Neck Cancer
After moving to Georgetown University in 1988, as an extension of his clinical care of patients with head and neck cancer, his lab began a series of collaborations with the Department of Otolaryngology. For the past 20 years, his research efforts have shifted to molecular studies in head and neck cancer. Specifically, his lab has focused on the development of predictive and prognostic indicators in squamous cell carcinoma of the head and neck (SCCHN). Dr. Cullen’s group has also analyzed molecular targets and mechanisms of resistance for cisplatin and related drugs in SCCHN. We have demonstrated that overexpression of enzymes in the glutathione pathway, specifically glutathione s-transferase-p (GST-p), is associated with resistance to platinum-based chemotherapy and poor prognosis. Furthermore, his group was the first to demonstrate that overexpression of GST-p in head and neck cancers is frequently the result of gene amplification. As part of his lab’s studies of cisplatin resistance in head and neck cancer, we showed that a significant portion of the antitumor activity of cisplatin in the head and neck may be due to direct interactions of this class of chemotherapy drugs with mitochondrial membrane proteins, specifically isoforms of the voltage-dependent anion channel. Although the preponderance of literature has studied the effects of platinum adducts with nuclear DNA, we demonstrated that cisplatin can induce tumor cell apoptosis by direct action on mitochondrial membrane proteins.
3. Prognostic and Predictive Biomarkers in Head and Neck Cancer
Our group has extended its work in predictive and prognostic markers to a number of cooperative group-sponsored (Radiation Therapy Oncology Group) and industry-sponsored (TAX-324) trials in head and neck cancer, again demonstrating that important predictive and prognostic information can guide treatment selection for patients with head and neck cancer. In our analysis of the TAX-324 trial, we developed a prognostic marker model that differentiates patients into three risk groups: high risk (24-month survival: 29 percent survival), intermediate risk (24-month survival: 67 percent survival), and low risk (24-month survival: 89 percent) (p<0.0001).
4. Disparities in Head and Neck Cancer
Since his move to the University of Maryland in 2004, Dr. Cullen has focused increasingly on the issue of health disparities, specifically survival disparities in head and neck cancer associated with race and ethnicity. Compared with Whites, Blacks have poor survival of head and neck cancer. We demonstrated that this survival disparity is not generalized among all head and neck cancers but arises in large part from a significant survival disparity in the subset of patients with oropharyngeal cancer. Further investigation demonstrated that this difference in survival among patients with oropharyngeal cancer is attributable to a large but unexpected difference in the rate of HPV-positive tumors by race. Whites are four to nine times more likely to have favorable prognosis of HPV tumors compared with Blacks. This finding was cited as one of the most important cancer research discoveries of 2009 by the Journal of Clinical Oncology (Petrelli et al., J Clin Oncol, 2009) and received significant coverage in the national lay and scientific press. We have demonstrated that the prevalence of HPV-positive oropharyngeal cancer is increasing rapidly in Whites. Although it has emerged more recently in Blacks, it is now increasing rapidly in that population as well. His most recent work has extended these observations on disparities in head and neck cancer and has helped to characterize an emerging disparity due to a recent, unexplained increase in the incidence of oral tongue cancer among young White females.
Dr. Cullen specializes in head and neck cancer.