Description of Research Expertise

Research Interests
Molecular mechanisms of apoptosis and how they may relate to cancer and other diseases.
Regulation of apoptosis and immune responses by tumor necrosis factor receptor (TNFR) family proteins.

Key words: Apoptosis, Caspases, Death receptors, Tumor Necrosis Factor Receptor Superfamily, Inhibitors of Apoptosis (IAPs).

Description of Research
Programmed cell death or apoptosis is a physiological process of cell auto-destruction critical for the maintenance of homeostasis in multicellular organisms. Dysregulation of apoptosis is associated with some of the most ravaging diseases such as cancer, neurodegenerative diseases, stroke, and immunodeficiency. Our research goal is to understand the molecular mechanisms of apoptosis in the hope that this insight may lead to new directions for therapeutic interventions. Our current projects are focused on three areas: the regulation of caspases, mechanisms of the inhibitors of apoptosis (IAPs), and the signaling pathways of death receptors.

Caspases are the central executioners of apoptosis, and during apoptosis, they cleave a wide range of cellular proteins to dismantle cells. The activation of caspases is intricately regulated. We are investigating the mechanism for caspase activation and the regulation of this process by various cellular factors.

IAPs are a major group of apoptosis regulators. They inhibit apoptosis in part by directly binding to and inhibiting caspases. Some IAPs are E3 ubiquitin ligases and regulate the expression levels of pro- as well as anti-apoptotic proteins. We are investigating the diverse functions of IAPs by identifying and characterizing the substrates for the IAPs’ E3 activity.

Death receptors--such as Fas, TNFR1, and TRAIL receptors--in the TNFR superfamily mediate apoptosis in a wide range of cells, especially in lymphocytes. These receptors can also activate genes involved in the regulation of immune responses and promote cell proliferation under certain conditions. We are studying the downstream signaling events of these receptors that underlie their ability to dictate cell life and death.

Rotation Projects for 2006-2007
Rotation projects are available in each of the three main research areas of the lab. Students are encouraged to discuss their interests with Dr. Yang to come up with possibilities. Sample projects include:

1. Identify novel caspase regulatory proteins, IAP substrates, and downstream components of the TNFR family proteins through biochemical purification and/or the yeast two-hybrid system;
2. Assess functions of putative apoptotic proteins using various approaches including the siRNA gene knock-down technique;
3. Study global changes in the expression levels of proteins in response to apoptosis induction and the engagement of TNFR family proteins; and
4. Determine genetic alterations in tumor cells that render them resistant to apoptosis.

Lab personnel:
Natalie Howe, Research Specialist
Holli Kawadler, Graduate Student
Hongtu Liu, Postdoctoral Fellow
LiKe Qu, Postdoctoral Fellow
Jun Tang, Postdoctoral Fellow
Wensheng Xie, Postdoctoral Fellow