Karam El-Bayoumy, Ph.D., Associate Director for Basic Research, Penn State Cancer Institute
The overall goals of Dr. El-Bayoumy’s research are to understand the causes of select cancers in the United States and develop the means of their prevention. Traditionally, his laboratory takes leads from epidemiologic observations, examines these leads in the laboratory setting, and then translates the findings into cancer prevention initiatives.
Dr. El-Bayoumy’s research is focused on the prevention of tobacco- and environmentally-related cancers by various synthetic and naturally-occurring chemopreventive agents, combined with dietary manipulation. His research has been continuously funded, primarily by the NCI. The most recent funded R01 application is focusing on chemoprevention of oral cancer by black raspberry (BRB) and its active components. Detailed mechanistic studies were initially performed to fully understand the biochemical, pharmacological and molecular basis which can account for the induction of oral squamous cell carcinoma (OSCC) by the environmental pollutant and tobacco smoke component dibenzo[a,l]pyrene (DB[a,l]P). OSCC is the major histological type of head and neck cancer and tobacco smoking is the major etiological factor for the development of this disease. Collectively the results of these studies provided important information on multiple and relevant biomarkers that are currently being examined to determine the effects of BRB and its components in a mouse model that was developed by our team to realistically mimic human exposure to smoking and environmental pollutants such as DB[a,l]P; specifically his laboratory is focusing on the effects of BRB on cellular and molecular targets which are critical in the development of OSCC using rodent and human oral cells in vitro. Of particular significance we have shown that BRB not only inhibits oxidative stress but also showed for the first time that it enhanced the DNA repair of carcinogen-DNA damage. The results of studies aimed at understanding the etiology and prevention of OSCC have been reported in a series of publications (Guttenplan et al, Int. J. Cancer 130:2783-2790, 2012; Chen et al, Int. J. Cancer 133: 1300-1309, 2013: Zhang et al, Chem. Res. Toxicol. 27:1199-1206, 2014; Sun et al, Chem. Res. Toxicol. 28:1427-1433, 2015; Guttenplan et al, Cancer Prev. Res. 9(8); 704-12, 2016)
Dr. El-Bayoumy is actively pursuing studies aimed at developing highly effective chemopreventive agents against tobacco smoke inducing lung cancer and developing biomarkers in noninvasive fluids indicative of cigarette smoking. In a pilot study utilizing the isobaric Tags for Relative and Absolute Quantification (iTRAQ) proteomic methodology, his team identified several proteins, including vitamin D binding protein (VDBP), that may serve as candidate biomarkers of diseases resulting from exposure to cigarette smoke in future molecular epidemiological studies (J. Proteome Res. 10:1151-1159, 2011). In a follow-up collaboration with Dr. Robin Wilson using a large sample size (African American [AA] and European American [EA] [N = 116], smokers matched to nonsmokers on age, race/ethnicity, and sex, we examined the role of gene-environment interaction on plasma VDBP concentration (Wilson et al, Transl. Res. 165:667-676, 2015). In a more recent study we used a proteomics approach (iTRAQ) to identify differentially expressed lung proteins during early stages of the tobacco carcinogen NNK-induced lung tumorigenesis (from hyperplasia/atopia, adenoma, to adenocarcinoma) in the A/J mice. The results demonstrated that the expression of multiple proteins were altered in early lesions which can be used as potential biomarkers for early detection of lung cancer and to monitor the efficacy of preventative agents (Das et al EuPA Open Proteomics 9:23-33, 2015).
Because of his long-term track record on studies aimed at understanding the role of the micronutrient selenium in cancer prevention, Dr. El-Bayoumy is currently collaborating with Dr. Sandeep Prabhu, University Park Campus, on an R01 entitled “Targeting Leukemia Stem Cells with Dietary Selenium.” To enhance translational research at the PSCI, Dr. El-Bayoumy was funded by an NCI R01 that included basic and clinical investigators studying the role of different forms of selenium on biomarkers of prostate cancer risk in both African Americans and Caucasians. This was the only clinical trial in the USA and around the world aimed at comparing these two different forms of selenium on biomarkers of prostate cancer risk. Dr. El-Bayoumy and his team showed for the first time that selenium enriched yeast but not the selenomethionine reduced oxidative stress in healthy men (Richie et al Cancer Prev. Res. 7:796-804, 2014). In an earlier study he used a proteomic approach to demonstrate that selenium inhibits serum α-1 antitrypsin in men (a protein known to be elevated in prostate cancer patients; it is more elevated in African American men than Caucasians and is positively correlated with PSA levels). This novel finding suggests the use of α-1 antitrypsin as a biomarker, in addition to PSA, to monitor disease progression and cancer chemoprevention of the prostate (Cancer Epidemiology, Biomarkers & Prevention 19:2332, 2010). Furthermore, he showed for the first time that selenium inhibits NF-κB via its covalent binding to Cysteine – S62 of the protein; this was confirmed by MALDI/TOF/TOF analysis and further supported by computer modeling (Chen et al, Cancer Res. 67:10475-14083, 2007). Dr. El-Bayoumy was also the first to introduce the term “molecular chemoprevention” as a guiding principle in the design of future clinical intervention chemoprevention trials (Mutation Res. 591, 224, 2005). Because of Dr. El-Bayoumy’s discovery of novel chemopreventive selenium compounds, he was featured on the cover of Cancer Research (Volume 59, 1999).
Furthermore, as a Co-Principal Investigator with Dr. Andrea Manni on a project which was funded by the Susan G. Komen (Promise Grant) examined the role of low dose antiestrogens in combination with Omega-3 fatty acids in the chemoprevention of breast cancer in preclinical animal models and in the clinic. Our results suggest that obese women and not lean women may preferentially experience breast cancer risk reduction from omega-3 fatty acids which emphasize the need for personalized cancer prevention in future clinical chemoprevention trials (Sandhu et al, Cancer Prev. Res. 9:275-282, 2016). In a recent study, his graduate student (Christine Skibinski, now at Johns Hopkins as a postdoctoral fellow), developed for the first time an acid stable liposome formulation that protects the chemopreventive agent DHA from oxidation and pH fluctuations which would be an ideal formulation for breast cancer prevention (Chemico-Biological Interactions 252:1-8, 2016).
In addition to his contribution to the fields of carcinogenesis and cancer chemoprevention, Dr. El-Bayoumy has served on numerous national and international committees (e.g. California Air Resources Board, Environmental Protection Agency, World Health Organization and International Agency for Research on Cancer) and the editorial board of several scientific journals. He has 230 publications including 191 peer-reviewed manuscripts, and 39 books, chapters and reviews. Because of his long track record in the field of carcinogenesis and chemoprevention, he has been invited as a speaker at national and international conferences/symposia, as well as universities and cancer centers across the USA. About 10 years after joining the College of Medicine, four graduate students received their Ph.D. degree under this mentorship (Nicole Facompre, James Bortner, Shang-Min Zhang and Christine Skibinski). In addition, he also served as a committee member of another 4 PhD students; one within the College of Medicine (Sans Emmert) and 3 at the University Park Campus (Jeffrey Coleman, Russell William Smith III, and Ling Tao). He also served as a mentor first a first year medical student (Aaron Baker) under the Medical Student Research (MSR) program. Dr. El-Bayoumy has trained numerous post-doctoral fellows who are currently holding respected positions at academic and industrial settings and he continues to encourage and advise fixed-term faculty members in his laboratory. Dr. El-Bayoumy is committed to continuing his focus on basic and translational research and promoting appropriate strategies for cancer prevention and mentoring the next generation of cancer researchers.
As the Associate Director for Basic Research (see above link to the Penn State Cancer Institute), Dr. El-Bayoumy provides ongoing consultation, advice, and guidance to basic research activities across all programs within PSCI. His experience as the director of basic research at the NCI CCSG designated Institute for Cancer Prevention (formerly the American Health Foundation [AHF], Valhalla, N.Y.) and co-principal investigator of that Center from 2001-2004 has given him the scientific and administrative background needed to lead the Division of Basic Research at PSCI from 2005 to the present. He is responsible for formulating the overall direction and development of basic research, advising the Director of PSCI on promising areas of basic research, encouraging multidisciplinary collaboration and translational research and providing oversight to the basic science shared resources of PSCI such as the Organic Synthesis core. He works with other core directors to maintain high-quality service, identify services that need to be introduced or eliminated and be a “champion” for the Cores in discussions with the College of Medicine.