Sherif Abdel-Rahman, Ph.D.

Associate Professor,  Department of Preventive Medicine and Community Health, Division of Environmental Toxicology

Investigator, UTMB-NIEHS Center

Education:      B.S. University of Alexandria
                        M.S. University of Alexandria
                        Ph.D. University of Alexandria

Post-doctoral: University of Texas Medical Branch     

Research program

The focus of my research is on understanding how inherited genetic characteristics influence the susceptibility of individuals to environmental agents and affect the response to drug therapy. Understanding of these processes will ultimately help identify individuals who may be highly susceptible to the adverse health effects resulting from environmental or occupational exposures. In clinical settings, this will help to better predict individuals’ response to drug therapy.

 Three complementary lines of research are being pursued in my laboratory.  The first involves population studies and focuses on developing methods to better identify individuals at high risk of cancer and other adverse health effects associated with environmental and occupational exposures using a battery of biological markers for susceptibility, exposure and effect.  The second involves mechanistic studies using cell culture systems and laboratory animals to understand the functional significance of human genetic polymorphisms in susceptibility genes, and to study the mechanisms of toxicity and carcinogenicity of environmental chemicals. The third line of research emphasizes the need to better understand the safety and the mechanism(s) of action of potential cancer chemopreventive agents before massive chemoprevention clinical trials are conducted. Chemoprevention, defined as the use of natural or synthetic agents to reverse, prevent, or delay carcinogenic progression to invasive cancer, is a promising approach that can be applied to susceptible individuals with high-risk of cancer. Effective, and safe, chemopreventive agents can thus avoid many clinical complications associated with malignancy and can prevent the need for treatment of advanced malignancies that are less responsive than early neoplastic lesions to therapeutic interventions. 

Examples of Currently funded Research Activities:

Cytochrome P450 2C9 (CYP2C9) Genotype and Long Term Warfarin Dose Requirements. Activity of the CYP2C9 enzyme plays a major role in the metabolism and clearance of warfarin, the drug of choice prescribed to millions of patients to treat or prevent thrombosis. A number of polymorphisms (inherited genetic variations) in the CYP2C9 gene have been recently identified, and are associated with substantial differences in enzyme activity. Our objective is to determine whether these polymorphisms affect the dose of warfarin required to maintain stable anticoagulation in ambulatory patients. The results generated from this pharmacogenomic translational research would have great utility for clinicians. By conducting a simple molecular genetic test before initiating therapy, this would greatly improve patient safety by eliminating the most serious consequences of excess dosing or under-dosing (such as bleeding or thrombosis). These studies are funded by a grant from the Doris Duke Charitable Foundation. The investigators involved are Drs. Sherif Abdel-Rahman (P.I.), Hans vonMarrensdorf, Karl Anderson, Chul Lee, Csilla Hallberg and graduate student Kevin Wolfe.

Effect of genetic variation in DNA repair genes on sensitivity to cigarette smoke constituents. We are investigating the roles of several functional polymorphisms in genes controlling DNA repair functions on the sensitivity of cigarette smokers to cytogenetic and mutagenic effects. In addition to studies of populations of smokers and non-smokers, experimental in vitro studies using molecular techniques are being conducted to study the sensitivity of lymphocytes from individuals with selected genotypes to the genotoxic effects of several tobacco smoke carcinogens. The investigators involved are Drs. Sherif Abdel-Rahman (P.I.), Marinel Ammenheuser, Jeffery Wickliffe, Judah Rosenblath and Jonathan Ward assisted by Kevin Wolfe, Alessandra Affatato and Lori Galbert.

Human sensitivity to the genotoxic effects of 1,3-butadiene. Butadiene is a widely used industrial chemical, a common air pollutant, and a useful model compound for several other chemicals. We are investigating the ability of occupational exposure to butadiene to induce mutations in the HPRT gene in the lymphocytes of exposed workers. In addition, we are studying the roles of polymorphic genes involved in the metabolism of butadiene in relation to human sensitivity. We have found that workers experience a dose-responsive increase in the frequency of HPRT mutations and that individuals with a polymorphic form of the gene for microsomal epoxide hydrolase that reduces its activity by 40% are more sensitive to the mutagenic effects of butadiene than individuals with higher levels of enzyme activity (Abdel-Rahman et al., 2001, 2003). These studies are funded by a grant from the National Institute of Environmental Health Sciences. The investigators involved in these studies are Jonathan Ward (P.I), Marinel Ammenheuser, Sherif Abdel-Rahman. and Jeffrey Wickliffe.

Chromosomal and sensitivity studies to determine the presence of increased risk for cancer in children exposed to Ritalin. The purpose of this project is to determine the safety or increased risk for cancer of Ritalin, a widely used drug for treatment of attention deficit hyperactivity disorder, especially in children between the ages of 5-12. The investigation also seeks to identify a possible sensitive sub-set of children receiving Ritalin therapy. The PI on this grant is Dr. Marvin Legator, with Dr. Abdel-Rahman serving as Co-investigator.
 

Selected Publications (from 1999-2003):

Paolini, M., Cantelli-Forti, G., Perocco, P., Pedulli, G.F., Abdel-Rahman, S.Z.
         and Legator, M.L. (1999) The nature of the co-carcinogenic property of
         beta carotene discovered. Nature, 398, 760-761.

Abdel-Rahman, S.Z. Soliman, A., Bondy, M.L., Khaled, H.M. and  Levin, B. (2000). Polymorphism in DNA repair gene XRCC1 increases the risk of colorectal cancer in Egypt. Cancer Lett. 159, 79-86.

Abdel-Rahman, S.Z. and El-Zein, R.A. (2000) The 399Gln polymorphism in the DNA repair gene XRCC1 modulates the genotoxic response induced in human lymphocytes by the tobacco-specific nitrosamine NNK. Cancer Lett. 159, 63-71.

 Rossit, A.R., Cabral, I.R., Hackel, C., da Silva, R.A., Conforti Froes, N. and Abdel-Rahman, S.Z. (2002). Association between polymorphisms in the DNA repair gene XRCC1 and susceptibility to alcoholic liver cirrhosis in Southeastern Brazil. Cancer Lett. 180,173-182.

 Abdel-Rahman, S.Z., El-Zein, R.A., Ammenheuser, M.M., Yang, Z., Stock, T., Morandi, M. and Ward, J.B. (2003) Variability in Human sensitivity to 1,3-butadiene: influence of the allelic variants of the microsomal epoxide hydrolase gene. Environ. Mol. Mutagen. 41, 140-146.

Paolini, M., Perocco, P., Donatella C., Valgimigli, L., Pedulli, G.F., Iori, R., Croce, C., Cantelli-Forti, G., Legator, M.S. and  Abdel-Rahman, S.Z. (2003). Induction of cytochrome P450, generation of oxidative stress and in vitro cell-transforming and DNA-damaging activities by glucoraphanin, the bioprecursor of the chemopreventive agent sulforaphane found in broccoli. Carcinogenesis (in press).