Laura Attardi

Last updated
Laura Attardi
Education Cornell University
University of California at Berkeley
Father Giuseppe Attardi
Scientific career
Institutions Stanford University
Doctoral advisor Robert Tjian
Website www.med.stanford.edu/attardilab.html
External videos
Nuvola apps kaboodle.svg “Stanford Faculty - Meet Laura Attardi", August 19, 2015

Laura Attardi is the Catharine and Howard Avery Professor of the school of medicine, and professor of radiation oncology and genetics at Stanford University [1] where she leads the Attardi Laboratory. Attardi studies the tumor suppressor protein p53 and the gene that encodes it, TP53, to better understand mechanisms for preventing cancer. [2] [3] [4]

Contents

Early life and education

Laura Donatella Attardi is the daughter of biologists Giuseppe Attardi and Barbara Furman. [5] [6]

Laura Attardi received her BA in biochemistry from Cornell University in 1988. She earned her PhD in molecular and cell biology from the University of California at Berkeley in 1994, [7] working with Robert Tjian. [8] She then did postdoctoral work at Massachusetts Institute of Technology [9] with Tyler Jacks. [8]

Career

In 2000, Attardi joined Stanford University School of Medicine in the departments of radiation oncology and genetics. [10] Attardi is the Catharine and Howard Avery Professor of the school of medicine, and professor of radiation oncology and genetics at Stanford University [1] She serves as a Program Director of the Cancer Biology and Cancer Stem Cells Program at Stanford Cancer Institute. [11]

Attardi is co-editor of the Annual Review of Cancer Biology [12] and a member of the editorial board of the Journal of Cell Biology. [8]

Research

Attardi studies the tumor suppressor protein p53 and the gene that encodes it, [2] [9] TP53. TP53 is the most frequently mutated gene (>50%) in human cancer, suggesting that it has a key role in preventing cancer formation. [13] The cellular mechanisms and transcriptional programs involved in p53 activation are complicated. There is evidence that p53 can suppress tumors, but it can also can cause toxicity in normal tissues. Understanding the activity of p53 and how to restore p53 function may lead to advances in anti-cancer therapeutics. Attardi's goal is to understand the mechanisms of p53 and its actions and effects in different settings. [9]

With Colleen A. Brady and others, Attardi developed knock-in mice with transactivation mutations in the two transactivation domains (TADs) to compromise p53 gene transactivation. The p53 transactivation mutant L25Q:W26S (p5325,26) affected the first TAD, while F53Q;F54S (p5353,54) mutated the second TAD. This model has enabled researchers to study p53's suppression of tumour formation [4]

In 2014, Attardi's research unexpectedly linked p53 with a developmental disorder, CHARGE syndrome. While studying mice with a mutated form of p53, researchers noted that mice with one mutated protein and one normal protein developed symptoms similar to CHARGE and died. Researchers also demonstrated a link between p53 and the CHD7 gene, which often displays mutations in cases of CHARGE. [14]

Attardi uses mice with a predisposition to pancreatic cancer as a model of p53 mutation. In 2017 her group reported that mice with a favorable mutation in the TAD2 transcriptional activation domain remained cancer-free longer than mice with the normal p53 gene. Using human cancer genomic data, Attardi has further suggested that a central mechanism of cancer suppression may involve a pathway, or “axis,” of three proteins, with p53 activating Ptpn14, which then suppresses Yap, which would otherwise promote cancer development. Deficiencies in p53 and Ptpn14 might therefore have similar consequences to Yap activation. [15]

Awards and honors

Related Research Articles

p53 Mammalian protein found in humans

p53, also known as Tumor protein P53, cellular tumor antigen p53, or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins are crucial in vertebrates, where they prevent cancer formation. As such, p53 has been described as "the guardian of the genome" because of its role in conserving stability by preventing genome mutation. Hence TP53 is classified as a tumor suppressor gene.

<span class="mw-page-title-main">Tumor suppressor gene</span> Gene that inhibits expression of the tumorigenic phenotype

A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results in a loss or reduction in its function. In combination with other genetic mutations, this could allow the cell to grow abnormally. The loss of function for these genes may be even more significant in the development of human cancers, compared to the activation of oncogenes.

<span class="mw-page-title-main">Li–Fraumeni syndrome</span> Autosomal dominant cancer syndrome

Li–Fraumeni syndrome (LFS) is a rare, autosomal dominant, hereditary disorder that predisposes carriers to cancer development. It was named after two American physicians, Frederick Pei Li and Joseph F. Fraumeni Jr., who first recognized the syndrome after reviewing the medical records and death certificates of childhood rhabdomyosarcoma patients. The disease is also known as SBLA, for the Sarcoma, Breast, Leukemia, and Adrenal Gland cancers that it is known to cause.

p73 Protein-coding gene in the species Homo sapiens

p73 is a protein related to the p53 tumor protein. Because of its structural resemblance to p53, it has also been considered a tumor suppressor. It is involved in cell cycle regulation, and induction of apoptosis. Like p53, p73 is characterized by the presence of different isoforms of the protein. This is explained by splice variants, and an alternative promoter in the DNA sequence.

<span class="mw-page-title-main">Bert Vogelstein</span> American oncologist (born 1949)

Bert Vogelstein is director of the Ludwig Center, Clayton Professor of Oncology and Pathology and a Howard Hughes Medical Institute investigator at The Johns Hopkins Medical School and Sidney Kimmel Comprehensive Cancer Center. A pioneer in the field of cancer genomics, his studies on colorectal cancers revealed that they result from the sequential accumulation of mutations in oncogenes and tumor suppressor genes. These studies now form the paradigm for modern cancer research and provided the basis for the notion of the somatic evolution of cancer.

<i>PTEN</i> (gene) Tumor suppressor gene

Phosphatase and tensin homolog (PTEN) is a phosphatase in humans and is encoded by the PTEN gene. Mutations of this gene are a step in the development of many cancers, specifically glioblastoma, lung cancer, breast cancer, and prostate cancer. Genes corresponding to PTEN (orthologs) have been identified in most mammals for which complete genome data are available.

<span class="mw-page-title-main">Adenomatous polyposis coli</span> Protein-coding gene in the species Homo sapiens

Adenomatous polyposis coli (APC) also known as deleted in polyposis 2.5 (DP2.5) is a protein that in humans is encoded by the APC gene. The APC protein is a negative regulator that controls beta-catenin concentrations and interacts with E-cadherin, which are involved in cell adhesion. Mutations in the APC gene may result in colorectal cancer and desmoid tumors.

p300-CBP coactivator family Protein family

The p300-CBP coactivator family in humans is composed of two closely related transcriptional co-activating proteins :

  1. p300
  2. CBP
p16 Mammalian protein found in humans

p16, is a protein that slows cell division by slowing the progression of the cell cycle from the G1 phase to the S phase, thereby acting as a tumor suppressor. It is encoded by the CDKN2A gene. A deletion in this gene can result in insufficient or non-functional p16, accelerating the cell cycle and resulting in many types of cancer.

<span class="mw-page-title-main">TP63</span> Protein-coding gene in the species Homo sapiens

Tumor protein p63, typically referred to as p63, also known as transformation-related protein 63 is a protein that in humans is encoded by the TP63 gene.

Caretaker genes encode products that stabilize the genome. Fundamentally, mutations in caretaker genes lead to genomic instability. Tumor cells arise from two distinct classes of genomic instability: mutational instability arising from changes in the nucleotide sequence of DNA and chromosomal instability arising from improper rearrangement of chromosomes.

<span class="mw-page-title-main">STK11</span> Protein-coding gene in the species Homo sapiens

Serine/threonine kinase 11 (STK11) also known as liver kinase B1 (LKB1) or renal carcinoma antigen NY-REN-19 is a protein kinase that in humans is encoded by the STK11 gene.

<span class="mw-page-title-main">ING1</span> Protein-coding gene in the species Homo sapiens

Inhibitor of growth protein 1 is a protein that in humans is encoded by the ING1 gene.

<span class="mw-page-title-main">CDKN2A</span> Protein-coding gene in humans

CDKN2A, also known as cyclin-dependent kinase inhibitor 2A, is a gene which in humans is located at chromosome 9, band p21.3. It is ubiquitously expressed in many tissues and cell types. The gene codes for two proteins, including the INK4 family member p16 and p14arf. Both act as tumor suppressors by regulating the cell cycle. p16 inhibits cyclin dependent kinases 4 and 6 and thereby activates the retinoblastoma (Rb) family of proteins, which block traversal from G1 to S-phase. p14ARF activates the p53 tumor suppressor. Somatic mutations of CDKN2A are common in the majority of human cancers, with estimates that CDKN2A is the second most commonly inactivated gene in cancer after p53. Germline mutations of CDKN2A are associated with familial melanoma, glioblastoma and pancreatic cancer. The CDKN2A gene also contains one of 27 SNPs associated with increased risk of coronary artery disease.

<span class="mw-page-title-main">Retinoblastoma protein</span> Mammalian protein found in humans

The retinoblastoma protein is a tumor suppressor protein that is dysfunctional in several major cancers. One function of pRb is to prevent excessive cell growth by inhibiting cell cycle progression until a cell is ready to divide. When the cell is ready to divide, pRb is phosphorylated, inactivating it, and the cell cycle is allowed to progress. It is also a recruiter of several chromatin remodeling enzymes such as methylases and acetylases.

Peto's paradox is the observation that, at the species level, the incidence of cancer does not appear to correlate with the number of cells in an organism. For example, the incidence of cancer in humans is much higher than the incidence of cancer in whales, despite whales having more cells than humans. If the probability of carcinogenesis were constant across cells, one would expect whales to have a higher incidence of cancer than humans. Peto's paradox is named after English statistician and epidemiologist Richard Peto, who first observed the connection.

Anticancer genes have a special ability to target and kill cancer cells without harming healthy ones. They do this through processes like programmed cell death, known as apoptosis, and other mechanisms like necrosis and autophagy. In the late 1990s, researchers discovered these genes while studying cancer cells. Sometimes, mutations or changes in these genes can occur, which might lead to cancer. These changes can include small alterations in the DNA sequence or larger rearrangements that affect the gene's function. When these anticancer genes are lost or altered, it can disrupt their ability to control cell growth, potentially leading to the development of cancer.

<span class="mw-page-title-main">Hereditary cancer syndrome</span> Inherited genetic condition that predisposes a person to cancer

A hereditary cancer syndrome is a genetic disorder in which inherited genetic mutations in one or more genes predispose the affected individuals to the development of cancer and may also cause early onset of these cancers. Hereditary cancer syndromes often show not only a high lifetime risk of developing cancer, but also the development of multiple independent primary tumors.

<span class="mw-page-title-main">WRAP53</span> Protein-coding gene in the species Homo sapiens

WRAP53 is a gene implicated in cancer development. The name was coined in 2009 to describe the dual role of this gene, encoding both an antisense RNA that regulates the p53 tumor suppressor and a protein involved in DNA repair, telomere elongation and maintenance of nuclear organelles Cajal bodies.

Guillermina 'Gigi' Lozano is an American geneticist. She is a Professor and Hubert L. Olive Stringer Distinguished Chair in Oncology in Honor of Sue Gribble Stringer at the University of Texas MD Anderson Cancer Center, Houston, Texas. Lozano is recognised for her studies of the p53 tumour suppressor pathway, characterising the protein as a regulator of gene expression and that is disturbed in many cancers. She was the first to recognize that the p53 gene encoded a transcriptional activator of other genes Her lab has made significant contributions by developing and analyzing mouse models to study the activities of mutant p53, revealing how these mutations drive tumor development and progression. She also found out how the Mdm2 and Mdm4 proteins work in the body, especially in stopping cancer and controlling p53. This research suggested that blocking Mdm2/4 could be a new way to treat cancer.

References

  1. 1 2 "Laura Attardi's Profile | Stanford Profiles". Stanford University. Archived from the original on 21 July 2022. Retrieved 21 July 2022.
  2. 1 2 3 "Researchers receive outstanding investigator awards from National Cancer Institute". News Center (in Samoan). November 17, 2015. Archived from the original on 27 October 2021. Retrieved 21 July 2022.
  3. ↑ McCarthy, Nicola (July 2008). "Stop start". Nature Reviews Cancer. 8 (7): 485. doi: 10.1038/nrc2421 . S2CID   13129574.
  4. 1 2 McCarthy, Nicola (June 2011). "Unpicking a Gordian knot". Nature Reviews Cancer. 11 (6): 389. doi:10.1038/nrc3075. ISSN   1474-1768. S2CID   32495259. Archived from the original on 21 July 2022. Retrieved 21 July 2022.
  5. ↑ Chomyn, Anne (2015). Biographical Memoires: Giuseppe Attardi 1923–2008 (PDF). National Academy of Sciences. p. 8. Archived (PDF) from the original on 21 July 2022. Retrieved 21 July 2022.
  6. ↑ Wallace, Douglas C. (July 2008). "Giuseppe Attardi 1923–2008". Nature Genetics. 40 (7): 814. doi: 10.1038/ng0708-814 . ISSN   1546-1718. S2CID   44278848.
  7. 1 2 3 "LAURA D. ATTARDI, Ph.D." Stanford University. Archived from the original on 21 July 2022. Retrieved 21 July 2022.
  8. 1 2 3 4 5 Short, B. (23 November 2015). "New editorial board members". Journal of Cell Biology. 211 (4): 723–727. doi: 10.1083/jcb.201511023 . PMC   4657179 . S2CID   30257376.
  9. 1 2 3 "Laura Attardi : Tumor biology". Ludwig Cancer Research. Archived from the original on 4 July 2022. Retrieved 21 July 2022.
  10. ↑ "Spatial Genomics in Cancer Research with Illumina Sequencing and the NanoString GeoMx® Digital Spatial Profiler". Nanostring. Archived from the original on 2 August 2022. Retrieved 21 July 2022.
  11. ↑ "Cancer Biology and Cancer Stem Cells". Stanford Cancer Institute (in Samoan). Archived from the original on 21 July 2022. Retrieved 21 July 2022.
  12. ↑ "Annual Review of Cancer Biology Editorial Committee". Annual Reviews. 2022. Archived from the original on 18 July 2022. Retrieved 18 July 2022.
  13. ↑ Surget S, Khoury MP, Bourdon JC (December 2013). "Uncovering the role of p53 splice variants in human malignancy: a clinical perspective". OncoTargets and Therapy. 7: 57–68. doi: 10.2147/OTT.S53876 . PMC   3872270 . PMID   24379683.
  14. ↑ Bach, Becky (August 3, 2014). "Rare developmental disorder linked to tumor-suppressing protein, researchers find". Stanford News Center (in Samoan). Archived from the original on 21 July 2022. Retrieved 21 July 2022.
  15. ↑ "Stanford-Led Study Uncovers Mutation that Supercharges Tumor-Suppressor". Research & Development World. 11 October 2017. Archived from the original on 29 September 2022. Retrieved 21 July 2022.
  16. ↑ "2015 Recipients of NCI Outstanding Investigator Awards - NCI". National Cancer Institute. 14 October 2015. Archived from the original on 21 July 2022. Retrieved 21 July 2022.
  17. ↑ Bergeron, Louis (25 October 2007). "Five university scholars among fellows newly elected to AAAS". Stanford News Service. Archived from the original on 21 July 2022. Retrieved 21 July 2022.
  18. ↑ "AAAS Fellows" (PDF). American Association for the Advancement of Science. Archived (PDF) from the original on 11 November 2021. Retrieved 21 July 2022.
  19. ↑ "Scholars: Current and Former Awardees". Damon Runyon. Archived from the original on 16 May 2022. Retrieved 21 July 2022.
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