Science, Technology and Engineering

ARC Federation Fellow

Department of Biochemistry

Apoptosis

David Vaux BMedSci (Melb) MBBS (Melb) PhD (Melb) FAA NHMRC Australia Fellow Phone: +61 3 9479 2211 Fax: +613 9479 2467 Email: D.Vaux@latrobe.edu.au Room 408 (office) / 407 (lab), Reid/Agriculture Building

Research

Humans have about a million billion cells. Every second of every day, over a million of them kill themselves. In fact, committing suicide is the ultimate fate of 99% of our cells. If cells fail to die when they should, they accumulate and can turn into cancers. On the other hand, if cells activate their self-destruct mechanisms when they shouldn't, it can cause damage of important tissues such as the heart and brain.

In order to kill themselves, cells activate an inbuilt self-destruct mechanism, and die by a process with a characteristic appearance known as " apoptosis ".

Obviously, it would be wonderful if we had drugs that could get cancer cells to do the right thing and undergo apoptosis, or drugs that could stop neurons dying in strokes, or heart muscle cells dying in a heart attack.

In order to come up with such drugs, it is necessary to understand the mechanisms of cell death at the molecular level. The main goal of the lab is to do just that. We use genetic and biochemical approaches to isolate, identify and characterise components of the cell death mechanism bit by bit.

We are currently looking at these areas:

Bcl-2 family members
Some promote cell death and some inhibit cell death. They funnel signals from many different sources into the core apoptotic mechanism.

IAPs
Inhibitor of Apoptosis (IAP) proteins prevent cell death by countering the activity of caspases, a family of cell death proteases.

TNF superfamily receptors and ligands
Binding of these receptors by their ligands sends signals to the cell that can lead to apoptosis, or activate transcription factors such as NFkB and AP1.

Publications

Vaux DL, Cory S, Adams JM (1988) Bcl-2 gene promotes hematopoietic-cell survival and cooperates with c-myc to immortalize pre-B-cells. Nature 335: 440-442

Verhagen AM, Ekert PG, Pakusch M, et al. (2000) Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins. Cell 102: 43-53

Vaux DL, Strasser A (1996) The molecular biology of apoptosis. Proc. Natl Acad. Sci. USA 93: 2239-2244

Vaux DL, Korsmeyer SJ (1999) Cell death in development. Cell 96: 245-254 1999

Vaux DL (1993) Toward an understanding of the molecular mechanisms of physiological cell-death. Proc. Natl Acad. Sci. USA 90: 786-789

Vaux DL, Hacker G, Strasser A (1994) An evolutionary perspective on apoptosis. Cell 76: 777-779 1994

Vaux DL, Weissman IL, Kim SK (1992) Prevention of programmed cell-death in Caenorhabditis elegans by human bcl-2. Science 258: 1955-1957

Uren AG, Pakusch M, Hawkins CJ, et al. (1996) Cloning and expression of apoptosis inhibitory protein homologs that function to inhibit apoptosis and/or bind tumor necrosis factor receptor-associated factors. Proc. Natl Acad. Sci. USA 93: 4974-4978

Allison J, Georgiou HM, Strasser A, et al. (1997) Transgenic expression of CD95 ligand on islet beta cells induces a granulocytic infiltration but does not confer immune privilege upon islet allografts. Proc. Natl Acad. Sci. USA 94: 3943-3947

Verhagen AM, Silke J, Ekert PG, et al. (2002) HtrA2 promotes cell death through its serine protease activity and its ability to antagonize inhibitor of apoptosis proteins. J. Biol Chem. 277: 445-454

For other publications by this author:

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