Korobkova Group - John Jay College

Half a million people in the United States and eight million people worldwide are expected to die from cancer in 2012. Over 11 million people are currently diagnosed with cancer in the United States, and the number is expected to grow from 11 to 15 million in two decades. In our lab we investigate the processes in cells that may lead to carcinogenesis.

A substantial number of experimental evidence collected over the last decade, supports the involvement of mitochondria in the key processes associated with cancer such as cellular apoptosis, growth, metabolism and energy supply.
In the last ten years, extensive proteomic analysis has been performed on the mitochondria of various types of cancerous cells. One of the proteins found consistently overexpressed in the mitochondria of cancerous cells as opposed to the normal cells is chaperone HSP60. This protein is located in the mitochondrial matrix and plays a significant role in protein folding, assembly, transport and degradation of damaged proteins as well as in the regulation of apoptosis. The identification of small molecules specifically targeting the interactions of HSP60 with other proteins is one of the ongoing projects in our lab.

Arylamines (AAs) are widely employed in chemical, cosmetic, pharmaceutical, and food industries. Examples include diphenylamine used in the preservation of apples; 2-naphthylamine, which occurs in nature, utilized to make azo dyes; and paraphenylenediamine, which is applied as a permanent hair dye. Exposure normally occurs through skin contact or inhalation. AAs may be very genotoxic as they are capable of interacting with DNA causing various types of damage.
Complex systems that repair DNA damage are present in almost all organisms including humans. However, the accumulation of unrepairable DNA lesions promotes the development of a number of diseases including cancer. Even though a lot of AAs have been classified as carcinogenic, mechanisms underlying the processes of carcinogenesis caused by these compounds are not comprehensively understood. In our lab we focus on the chemistry of the formation of arylamine radicals and mechanisms of the formation of double strand breaks on DNA caused by these reactive species.

Oxidation-reduction reactions occurring in mitochondria and endoplasmic reticulum generate the flow of electrons. Leaking electrons may interfere with surrounding molecules, producing reactive oxygen species (ROS). ROS react with DNA, which results in the formation of covalent modifications on DNA bases. The repair of the oxidized bases is performed by a Base Excision Repair (BER) mechanism. The first step in this mechanism represents the excision of a damaged base by the hydrolysis of N-glycosidic bond. This task is performed by glycosylases.
The structure and function of these enzymes have been comprehensively described. However, the dynamics of their expression, mechanisms of their translocation to DNA damage sites and the dynamics of the DNA repair performed by glycosylases in living cells are not comprehensively understood. In our lab we study the dynamics of glycosylase expression in response to stress using Western blot technology and fluorescence imaging.