Laura Attardi
Academic Appointments
- Associate Professor, Radiation Oncology - Radiation Biology
- Associate Professor, Genetics
- Member, Bio-X
- Member, Cancer Center
Professional Snapshot
Postdoctoral Advisees
Sylvain Baron , Rachel Dusek , Dadi Jiang , Daniela Kenzelmann Broz , Stephano Spano Mello
Web Site Links
Scientific Focus
Research Interests
The p53 tumor suppressor gene plays a crucial role in protecting organisms from developing cancer. Our research is aimed at dissecting the mechanism of p53 action and the role of target genes it activates in apoptosis and tumor suppression, using the mouse as a model system. Our strategy is to use combination of biochemical, cell biological, and mouse genetic approaches, starting by generating hypotheses about p53 using primary mouse embryo fibroblasts (MEFs), and then testing them using knockout technology in the mouse. An understanding of p53 function in the mouse will ultimately be useful for understanding how inactivation of p53 in humans leads to cancer and for designing therapies for the many tumors disrupted in the p53 pathway.
Specific projects include:
1) Analysis of PERP, a p53 apoptosis-specific target gene
In a screen to identify genes activated during p53-mediated apoptosis but not G1 arrest, we previously isolated a novel gene known as PERP (P53 apoptosis Effector Related to PMP-22). PERP induction correlates with p53-dependent apoptosis and not p53-independent cell death, and PERP overexpression can induce cell death in p53-deficient MEFs, suggesting that it could be a downstream mediator of p53 function in apoptosis. PERP displays sequence similarity to PMP-22/gas3 (Peripheral Myelin Protein 22/growth arrest specific 3), a tetraspan membrane protein that is commonly mutated in human hereditary peripheral neuropathies (i.e. Charcot Marie Tooth), and that appears to function in part by regulating cell proliferation and apoptosis. We are currently characterizing PERP and its encoded protein in two ways. We are constructing a PERP conditional knockout mouse to examine the function of PERP in development and tumorigenesis. We are also dissecting the mechanism by which overexpression of PERP induces cell death. PERP is a multipass transmembrane protein that could act potentially either as a signalling molecule or as an ion channel....
Publications
- Differential PERP regulation by TP63 mutants provides insight into AEC pathogenesis. Am J Med Genet A. 2009; (9): 1952-7
- SKP-ing TAp63: stem cell depletion, senescence, and premature aging. Cell Stem Cell. 2009; (1): 1-2
- Loss of the desmosomal protein perp enhances the phenotypic effects of pemphigus vulgaris autoantibodies. J Invest Dermatol. 2009; (7): 1710-8
- Knockin mice expressing a chimeric p53 protein reveal mechanistic differences in how p53 triggers apoptosis and senescence. Proc Natl Acad Sci U S A. 2008; (4): 1215-20
- The metastasis-associated gene Prl-3 is a p53 target involved in cell-cycle regulation. Mol Cell. 2008; (3): 303-14
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