Angelique Whitehurst Ph.D.

This grant is being fully funded by the Thomas G. Labrecque Foundation, through the Uniting Against Lung Cancer Grant Program.

Lay Description

The cells that constitute normal tissues carry out elaborate mechanisms to ensure proper function and growth. These mechanisms include checkpoints that prevent uncontrolled cell division. Normal cells do not divide quickly, but instead become specialized to carry out specific physiological functions, such as the production of breast milk. Cancer cells are different from normal cells in many ways, in particular they have lost their ability to regulate how fast they grow and divide. This loss leads to rapid cell division resulting in a mass of cells that has no physiological function. Part of understanding cancer development and progression is identifying genes that cancer cells rely on for survival. Through a number of technological advances, we have been able to develop a method to determine which genes in the human genome are required for tumor cell viability. We have performed this analysis in lung cancer cells and identified a number of genes that allow cancer cells to grow uncontrollably. In particular, we have identified a gene, LAS1, which appears to be required for multiple different types of lung tumor cells, but not normal cells, to grow. Because this gene may not be required for normal cells it is an excellent targets for therapeutic intervention since normal cells will not be impacted. The studies proposed here will determine how this protein functions in the cancer cell.

Scientific Abstract

The overarching objective of our research is to identify the most effective molecular entry-points for the development of novel chemotherapeutic lung cancer intervention strategies. Given the known combination of promise and limitation in the application of paclitaxel for management of lung cancer progression, we have elected to focus on the comprehensive identification of genetic loci that can be exploited to enhance the therapeutic benefit of taxol exposure. We have performed multiple functional genomics screens using paclitaxel as a sensitizer and revealed a tumor specific dependency on the LAS1 protein, a member of the pulmonary adenoma susceptibility locus. It is a rare event that multiple functional genomics screens in diverse genetic backgrounds reveal a common dependency on a single gene, thus we hypothesize that LAS1 is supporting core machinery that drives tumorigenesis, specifically LAS1 has recently been characterized as a contributor to mitosis[1]. The focus of this proposal is to characterize how LAS1 contributes to tumorigenesis by defining its role during the cell cycle and identifying the network of proteins that supports its function.