Carla Finkielstein

Synopsis:

Dr. Finkielstein seeks to understand the molecular basis by which environmental factors influence sporadic breast cancer incidence with focus in circadian disruption as toxic agent.  She also seeks to understand the mechanisms by which tumors develop resistance to conventional therapies and interfere with those processes using nano-based technologies.

Description:

Every 13 minutes a woman dies of breast cancer and, although the etiology of the disease is primarily unknown, it is estimated that one quarter of breast cancer cases are due to heritable factors. Another proportion is due to established environmental risk factors. Interestingly, this proportion rises dramatically when work-habits in modern societies are taken into consideration, suggesting that disturbance of our daily physiology, named “circadian disruption”, impacts breast cancer incidence.

Circadian rhythms are mechanisms that measure time on a scale of about 24 hours and adjust our bodies to external environmental signals. Core circadian clock genes are defined as genes whose protein products are necessary components for the generation and regulation of circadian rhythms. Circadian proteins regulate genes involved in either cell division or death; a perturbation of the balance among these processes leads to cancer development and progression.

The emerging field of chronotherapy, in which treatments for cancer and other diseases are administered at times of the day most likely to yield the greatest efficacy, will rely on deciphering the regulatory systems to which all circadian components connect, and most importantly, will depend on an understanding of the links between circadian and cell cycle mechanisms. Today, the administration of cancer therapy based on circadian timing has shown encouraging results, but, it still lacks a strong mechanistic foundation.

Our novel research aims to identify the pathways by which circadian components directly control cell fate. It will contribute to the development of new therapeutic strategies, optimization of the effectiveness of current therapies, and possibly provide an explanation for the high incidence of breast cancer in modern societies.