Personal tools
Document Actions

2004/2S - Abstract

Grant Information

Aging - Fellowship
Mechanism of Endoplasmic Reticulum Stress-induced Cell Death
David Madden, PhD
The Buck Institute
Funding Status
  • Completed
  • 3 years, $60,000 per year
  • 9/1/2004 to 8/31/2007


2004/2S - Abstract
Brief Summary
"Mechanism of Endoplasmic Reticulum Stress-induced Cell Death"

How do cells die? Cells use their own energy to destroy themselves; dysregulation of the signals that govern cell death has been linked to both neurodegenerative diseases and cancer. Therefore, developing a complete description of programmed cell death (PCD) pathways is paramount to our understanding of aging-associated diseases.

There are multiple forms of PCD, including: (1) apoptosis, (2) autophagic cell death, (3) paraptosis, (4) PARP-mediated, and (5) calcium-mediated PCD. Apoptosis has been the most extensively studied pathway and, as a result, relatively little is known about other forms of PCD. To better understand how cells regulate entry into apoptosis versus autophagic cell death, I tested the response of a mouse cell line (L929) to an apoptosis-blocking drug. I showed that cells dying from both apoptosis and autophagic cell death can be recognized by immune cells for removal - important for the prevention of inflammation. I also determined that autophagic cell death is regulated by two classes of proteases: caspases and calpains. This finding suggests that caspases and calpains may be key regulators of autophagic cell death in other biological settings (e.g. neurodegeneration).

I am now applying my research to detail PCD pathways in human embryonic stem cells (hESCs). One of the major challenges facing the growth of hESCs is the abundance of cell death that occurs during culturing; describing the mechanisms of PCD in hESCs will make it possible to limit the loss of cells during propagation and, therefore, deliver hESC-based therapies to greater numbers of patients.

online help

You are currently browsing the grant area of the website, where you have access to abstracts from research projects funded by LLHF.

The Funded Research area has a complete list of active and completed grants.


Powered by Plone CMS, the Open Source Content Management System

This site conforms to the following standards: