Helmut Zarbl, PhD

Genomic Instability and Cancer Genetics Program

Academic Appointment

Professor
Department of Environmental and Occupational Health
School of Public Health
Rutgers, The State University of New Jersey

Links

• Environmental and Occupational Health Sciences Institute (EOHSI) Profile
• Center for Environmental Exposures and Disease (CEED)

Research Interests

• Research interests include understanding how mutagenic chemicals also induce genetic and epigenetic changes in oncogenes and tumor suppressor genes in vitro and in vivo, and how that these changes contribute to carcinogenesis and tumor progression.
• Research also focuses on the development and use of in vitro assays and genetic linkage analysis to identify tumor suppressor /susceptibility genes that confer susceptibility to mammary carcinogenesis. These studies led to the identification of the FRY mammary carcinogenesis susceptibility gene which is being developed as novel tool for cancer diagnostics and prognosis.
• My laboratory was also among the first to use genomics to study mechanisms of toxicity and carcinogenicity. Our findings helped establish standards in the field and performed mechanistic studies of toxicant exposures.
• We are also investigating the potent endocrine disruptor, zeranol, which is directly introduced into livestock in the USA to promote growth. Our studies investigate the role of this potent myco-estrogen in mammary carcinogenesis and sexual development. Studies included a population based study of zeranol and puberty in prepubescent girls, and a three-generation study of in utero zeranol exposure in rats at doses permitted in the human diet by the FDA.
• Our toxicogenomics studies also led us to discover that Methylseleocysteine (MSC), which is a potent chemopreventive agent, mediates its effects by restoring circadian rhythm disrupted in mammary cells by carcinogen. Our studies were the first to provide a mechanistic link between chemoprevention and circadian rhythm and elucidated the epigenetic mechanisms by which a chemopreventive regimen of MSC restores circadian gene expression. These studies showed that DNA damage response and repair genes are regulated by circadian rhythm, suggesting the proposed link between loss of circadian control of DNA repair, chronic diseases and aging. We further showed that MSC mediates its epigenetic effects by restoring regulation of Sirtuin 1 protein deacetylase activity. More recent studies indicate the disruption of circadian rhythm ablated normal responses of DNA damage response and repair genes the toxicants and stressors. Since shift work and exposure to light-at-night, which also disrupt circadian rhythm, have been classified as probable human mammary carcinogens by IARC, we also initiated an MSC intervention trial to determine if MSC could also restore peripheral cell rhythm is shift workers.