Principal Investigator
Edison Biotechnology Institute

Assistant Professor
Department of Chemistry and Biochemistry
College of Arts and Sciences

Education

1986
B.S., Biochemistry, Texas A&M University, College Station, TX

1994
Ph.D., Biological Sciences, University of Texas Graduate School of Biomedical Science, Houston, TX

Research associates

Graduate Students
Bernard Ayanga
Chrisanne Dias
Yan Liu
Pooja Madjumar
Ahmed Malki
Martin Schmerr

Past Graduate Students
Radhika Iyer
Saidiwakar Kuchibhotla, M.S.
Min Liang
Swapna Vemula Sri

Research interests

My primary research interest focuses on the scientific understanding of what influences an individual's risk of cancer. One hypothesis suggests that the risk of cancer is determined by the inheritance of cancer resistance or susceptibility genes, which are referred to as "genetic modifiers." My goal is to identify these cancer-modifying genes.

The tumor suppressor gene, p53, is mutated in over 60% of all human tumors. My research focuses on the p53 tumor suppressor pathway in cancer and development, in particular how p53 function is affected by genetic modifiers or DNA damage. The identification of p53 risk modifiers as well as the essential players in its pathway will have important implications - not only for the fundamental biology of cancer and development, but also for preventing, diagnosing and treating malignant tumors.

My laboratory colleagues and I pursue many related research projects, including:

Discovering the gene responsible for an embryonic lethal phenotype. We are using mice as a model system to discover genetic modifiers of the tumor suppressor p53. In CE/129 mice with a p53 mutant allele, approximately a third of them die during gestation. The embryos have brain malformations and are smaller in size than their littermates. We have mapped to loci linked to the phenotype and are in the process of determining the gene within these loci that cause the lethal event. This study will give information as to human development and birth defects.

Discovering novel tumor suppressors. Using mice as a model, we are searching for genes involved in predisposition to cancer, tumor onset, and metastasis using simple sequence length polymorphism analysis of tumors. We have identified a candidate locus and are now in the process of discovering the gene. The identified tumor suppressor could be used as a target for gene therapy.

Discovering novel synthetic compounds. We are testing synthetic compounds for radiosensitivity of tumor and normal cells. These could be used as a therapeutic in conjunction with radiation for the treatment of cancer.

Determining molecules that cause proliferation of stem cells for the regeneration of intestine after radiation. Using a proteomic and genomic approach, we will identify genes and proteins that help to regenerate normal mucosa which have been highly damaged after radiation treatment of tumors. These molecules may be used to protect the normal cells from radiation damage during therapy.

Characterizing an alternative splice product of HDM2. HDM2 is the negative regulator of the tumor suppressor p53. Recently we have found that it is spliced after DNA damage. We also have discovered that the spliced form (ALT) binds full-length HDM2 and prevents its negative regulation of p53. We are further characterizing this molecule using transgenic mice and performing in vitro studies. It has the potential to be used as a therapeutic in cancer treatment to keep p53 active so that it can cause cell cycle arrest and cell death, and also as a diagnostic marker for cancer.

Selected publications

Evans, S.C ., Gu, J., Strong, L.C., Amos, C., and Lozano, G. A novel modifier of the tumor suppressor p53, mop1, results in embryonic lethality. Mammalian Genome, 15:1-9, 2004.

Iyer, R., Thames, H.D., Tealer, J., Mason, K.A. and Evans, S.C. Effect of reduced EGFR function on the radiosensitivity and proliferative capacity of mouse jejunal crypt clonogens. Radiotherapy and Oncology, 72:283-289, 2004.

Evans, S.C., Mack, D., Mason, K., and Thames, H. Repopulation in jejunal crypts is not uniquely determined by TGFa expression. Radiation Research 155:866-869, 2001.

Evans, S.C. , El-Naggar, A.K., and Lozano, G. An alternatively spliced HDM2 product increases p53 activity by inhibiting HDM2. Oncogene, 20:4041-4049, 2001.

Evans, S.C. , Foster, C.J., El-Naggar, A.K., and Lozano, G. Mapping and mutational analysis of the hTAF2G gene encoding a p53 cofactor. Genomics, 57:182-183, 1999.

Evans, S.C. , Mims, B., McMasters, K.M., Foster, C.J., deAndrade, M., Amos, C.I., Strong, L.C., and Lozano, G. Exclusion of a p53 germline mutation in a classic Li-Fraumeni Syndrome family. Human Genetics, 102:681-686, 1998.

Evans, S.C. and Lozano, G. The Li-Fraumeni syndrome: an inherited susceptibility to cancer. Mol Med Today, 3:390-395, 1997.

Montes de Oca Luna, R., Amelse, L.L., Chavez-Reyes, A., Evans, S.C., Brugarolas, J., Jacks, T., and Lozano, G. Deletion of p21 cannot substitute for p53 loss in rescue of mdm2 null lethality. Nature Genetics, 16:336-337, 1997.