Epigenetics of health and disease

Biology 4110: Advances in Genetics, Molecular and Cell Biology

Olga Kovalchuk's Laboratory - Research

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Selected Research Projects and Outcomes


In vivo radiation exposure effects

Radiation affects males and females in a different way. My laboratory discovered that males and females respond to ionizing radiation in a different way. We analyzed radiation responses in various tissues and organs using a mouse model and proposed some possible mechanisms of the sex-specific radiation responses. Our findings, published in cancer and radiation field journals, may have serious repercussions for development of sex-specific radiation diagnostic and treatment regimes. They also could influence how we design radiation protection protocols.
Chronic exposure is much more dangerous than previously thought. We proved that different exposure regimes can yield different results even if the total radiation dose is the same. Those results have challenged the classical paradigm of radiation biology, which stated that the dose is more dangerous than the delivery regime. We have shown that prolonged/chronic application of the given radiation dose exerts different effects than the single ‘lump-sum' application. We have shown that prolonged exposure to very low doses leads to profound accumulation of DNA and cellular damage, affects DNA recombination, cellular proliferation rates and may in turn pre-dispose cells to tumor transformation.

Molecular mechanisms of radiation-induced bystander effects

Irradiated cells can cross-talk with un-irradiated neighbors predisposing them to tumor formation. We were among the first to uncover the existence of the enigmatic radiation–induced bystander effect in the living organisms. The b ystander effect is a negative complication in radiation oncology whereby directly irradiated cells communicate the damage to the non-irradiated ‘bystander' cells in proximity, thus contributing to their genome destabilization, accumulation of mutations and cancer development. Until recently, all the existing evidence on the induction of a bystander effect came from cell cultures and no solid mechanistic data were proposed for the bystander effect in the living organism. My laboratory showed that bystander effects do exist in the living organisms . We proved that bystander effects are epigenetically mediated.

Epigenetic mechanisms of radiation-induced transgenerational genome instability

Offspring of exposed parents are indeed at risk! Radiation effects can span over generations. Recent studies indicate that children of exposed parents have a 6-8 times higher risk of developing leukemia and other cancers. With cancer rates increasing in people of child-bearing age, the problem of deleterious effects of radiation treatment on the progeny of exposed patients becomes even more dramatic. Children of exposed parents were reported to have high mutation levels possibly leading to cancer. Yet, nothing was known as to why those mutations arise. My laboratory proposed an epigenetic model of transgeneration mutation and cancer induction in the progeny of exposed parents.

 Epigenetic dysregulation in breast carcinogenesis and breast cancer treatment resistance

How do hormonal imbalance and radiation cause breast cancer? Recently we have entered the area of breast cancer research. Breast cancer can be caused by hormonal imbalances and by radiation exposure. Using animal models we have identified the initial, pre-cancerous molecular change that precedes estrogen-induced tumor development . We have identified several novel potential biomarkers that can be used to predict and classify breast cancers. We are currently investigating the mechanisms of radiation-induced breast carcinogenesis. We also study the mechanisms involved in the breast cancer treatment responses and in the breast cancer drug resistance. We specifically focus on the role of epigenetic changes in breast carcinogenesis and breast cancer treatment responses.

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