About This Project

Women with the BRCA gene mutation have an 80% risk of developing breast or ovarian cancer. Most research focuses on how to treat cancer once it has developed. This research aims to provide a non-invasive way to prevent transmission of this gene mutation by selectively targeting the sperm that carry it.

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What is the context of this research?

The fundamental question I am trying to answer is whether PARP inhibitors can be used to prevent the production of BRCA mutant gametes. This may provide a mechanism to prevent transmission of BRCA mutations to offspring.

To test the hypothesis that BRCA mutation transmission can be prevented with PARP inhibitors, an animal model that is highly relevant to human BRCA mutation carriers will be used. Brca mutant mice develop breast tumors that histologically resemble human BRCA mutant cancers and Brca deficient cells from these mice are exquisitely sensitive to PARP inhibition, similarly to humans. The Mendelian ratio of inheritance of Brca mutations is identical to that of human BRCA carriers. Therefore heterozygous mutant mice can be used to determine whether PARP inhibitor administration during conception can prevent transmission of BRCA mutations to offspring.

What is the significance of this project?

This project matters to me because I strongly believe that it could really help BRCA mutation carriers. Currently carriers of BRCA mutations are faced with a difficult choice when they are planning to have children. They can take the risk that their children will inherit the BRCA mutation from them (a 50% chance), resulting in an 80% chance that they will develop breast or ovarian cancer if they are female. The only other options are adoption, selective termination, or pre-implantation genetic diagnosis /IVF. All of which have significant drawbacks. If this project is successful, PARP inhibitors could be used by male BRCA mutation carriers during conception to selectively deplete BRCA mutant sperm, and thereby prevent the transmission of BRCA mutations to offspring. This would provide a cost effective and non-invasive way to prevent transmission of BRCA mutations to offspring.

Importantly this study will provide proof of principle that drugs can be used to prevent transmission of mutations to offspring. This approach could then be broadly applied to prevent genetically inherited diseases.

What are the goals of the project?

The total cost for this experiment is $15,000. The animal experiments will be conducted by Dale Cowley, Ph.D. from the University of North Carolina Animal Models Core via Science Exchange.

Male Brca1+/- heterozygous mutant mice will be treated with olaparib (a PARP inhibitor) or vehicle control and bred with wild type female mice. The resultant pups will be genotyped to determine whether PARP inhibitor treatment prevents the transmission of Brca1 mutations, resulting in fewer Brca1 mutant carrier pups being born (50% of pups are expected to carry the mutation).

Details of the experimental design are available in the lab notes tab.

Budget

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This project is being conducted very efficiently by using an expert, Dr Dale Cowley from the University of North Carolina Animal Models Core. Dr Cowley has all the expertise, experience, equipment and protocols set up to conduct the experiment so all funds are used for conducting the experiments.

Meet the Team

Dr. Elizabeth Iorns
Dr. Elizabeth Iorns
Co-Founder & CEO at Science Exchange

Affiliates

Education:
Postdoctoral Associate, Cancer Biology; University of Miami
Ph.D., Cancer Biology; The Institute of Cancer Research, University of London
B.Sc (Hons), Biomedical Science; University of Auckland
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Team Bio

I am currently the co-founder and CEO of Science Exchange, the online marketplace for science experiments.

I am also Adjunct Professor at the University of Miami. I am a breast cancer biologist with a PhD in Cancer Biology from the Institute of Cancer Research (London, UK).

My research has focused on understanding the causes of breast cancer development and metastasis with a focus on ideas that can applied to benefit breast cancer patients.

My publications are available at pubmed

Dr. Elizabeth Iorns

I am currently the co-founder and CEO of Science Exchange, the online marketplace for science experiments.

I am also Adjunct Professor at the University of Miami. I am a breast cancer biologist with a PhD in Cancer Biology from the Institute of Cancer Research (London, UK).

My research has focused on understanding the causes of breast cancer development and metastasis with a focus on ideas that can applied to benefit breast cancer patients.

My publications are available at pubmed

Additional Information

One of the exciting aspects of this project is the ability for me to conduct a really exciting research project outside the traditional research system. This is only possible because of the recent development of Microryza and Science Exchange. Microryza allows me to raise the funding required to conduct the project, and Science Exchange provides me with access to an expert scientist to conduct the lab experiments required. It is exciting to think of the potential for all kinds of people to begin to conduct research projects using a strategy like this.

Relevant references:

Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB, Santarosa M, Dillon KJ, Hickson I, Knights C, Martin NM, Jackson SP, Smith GC, Ashworth A. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005; 434(7035):917-21.

Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E, Kyle S, Meuth M, Curtin NJ, Helleday T. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature. 2005; 434(7035):913-7.

Kummar S, Chen A, Parchment RE, Kinders RJ, Ji J, Tomaszewski JE, Doroshow JH. Advances in using PARP inhibitors to treat cancer. BMC Med. 2012; 10:25.

Cobb J, Handel MA. Dynamics of meiotic prophase I during spermatogenesis: from pairing to division. Semin Cell Dev Biol. 1998; 9(4):445-50.

Heller CG, Clermont Y. Spermatogenesis in man: an estimate of its duration. Science. 1963; 140(3563):184-6.

Graziani G, Szabó C. Clinical perspectives of PARP inhibitors. Pharmacol Res. 2005; 52(1):109-18.

Project Backers

  • 46Backers
  • 100%Funded
  • $10,077Total Donations
  • $219.07Average Donation
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