Cell Death and Survival Networks

Cellular sensor’s 3D structure reveals new clues <br> for combating cancer.

Cellular sensor’s 3D structure reveals new clues
for combating cancer.

Scientists have determined the three-dimensional structure of a complete, unmodified G-protein-coupled receptor (GPCR) in its native environment: embedded in a lipid membrane.

How cancer cells rewire their metabolism in order <br>to survive.

How cancer cells rewire their metabolism in order
to survive.

Researchers discover that tumors lacking the protein PKCζ are good at surviving when nutrients are scarce—opening a new therapeutic avenue that targets cancer metabolism.

Mapping a new pathway implicated in cancer and <br> metabolic disorders.

Mapping a new pathway implicated in cancer and
metabolic disorders.

Researchers at Sanford-Burnham now have a more complete picture of one particular pathway that can lead to cancer and diabetes.

What are cell death and survival networks?

These are the pathways and signaling cascades that control the ability of cells to resist or promote cell death under stressful conditions, both during normal tissue development and as consequence of pathological situations, such as cancer or neurodegeneration. Tumor cells can reprogram their metabolism under conditions of nutrient scarcity and chemotherapy making them resistant to death, which correlates with poor patient prognosis.

The program is divided into three themes:
  • Metabolic and Stress Signaling
  • Autophagy and Cell Death
  • Structural and Chemical Biology

What is the focus of our program—What questions are
we asking?

We are identifying and characterizing the signaling molecules that control the interphase between cell survival and death cascades. The main emphasis is to study how cancer cells reprogram their metabolism and protein homeostasis to survive nutrient stress conditions associated to tumor progression and how they might use autophagy to prevent various forms of cell death, including apoptosis and necrosis. We address these fundamental biological questions at the organismal level, utilizing relevant models of human cancer, and at a cellular and detailed structural level. This interdisciplinary approach, together with our capability of drug discovery, positions our program at the leading edge of translating basic discoveries into better medicines.

How will our research help patients?

One of the fundamental weaknesses in the present treatment of cancer is the ability of tumor cells to endure stress. Understanding these pathways, and the identification of the key proteins that control the ability of cancer cells to reprogram their metabolism through biochemical, and epigenetic or genetic alterations that make them resistant to therapies, is of paramount importance for the design of more targeted and therefore less toxic therapies. Our program constitutes a highly interdisciplinary group addressing these important questions, which results in the identification of new and more selective therapeutic targets not only for cancer but also for other pathologies.


Recent Developments

donation

3D look at protein family with a long Sanford-Burnham history

Structural biologists Stefan Riedl, Ph.D. and Peter Mace, Ph.D. recently answered several perplexing questions about the Cas proteins--a family of cancer-related proteins that's long been studied at Sanford-Burnham.  Read More...

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