20.109 MOD3 Research Proposal

Maryelise Cieslewicz
Kyle Atmore

"Peroxiredoxin 1 PDB image"

Logistics

Prepare a 12 minute powerpoint talk that describes the research question you have identified, how you propose to study the question and what you hope to learn. A general outline your research proposal presentation is:

• a brief project overview
• sufficient background information for everyone to understand your proposal
• a statement of the research problem and goals
• project details and methods
• predicted outcomes if everything goes according to plan and if nothing does
• needed resources to complete the work
• societal impact if all goes well

Topic

• Peroxiredoxin inhibition to facilitate cancer therapy

Topic Background

• Prx's are mostly found in the cytosol (also found in mitochondria, chloroplasts, and peroxisomes).
• Prx's exhibit antioxidant behavior through peroxidase activity, reducing organic hydroperoxides.
• Many cancer cells and tissues show increased expression levels of both Prx1 and Prx2.
• Expression of both Prx's in cancer cells has been associated with increased resistance to standard cancer treatments.
  • Prx1 expression may be used as a predictive indicator of relative risk of death or patient survival among cancer patients.
• Prx1 may be useful as a new therapeutic target in cancer treatments.

Research Ideas

• A specific cysteine residue is important for the Prx function. This cysteine could be modified in vivo to inactivate the enzyme. Cancer cell response to therapeutics could be measured for cells with and without the modifications.
• For overall cancer treatment, cells with increased expression levels of Prx1 could be targeted with therapies that inhibited Prx1 expression.
• DNA-protein binding protocol [1]
• Nuclear related factor 2
  • Upregulated by hypoxia
  • Binds Prx1 promoter and induces Prx1 expression
  • Use phage display to test binding affinities of a library of Nrf mutants
  • Isolate a mutant(how?) that shows decreased levels of Prx1 expression

Publications

1. GOOD"Up-regulation of peroxiredoxin 1 in lung cancer and its implication as a prognostic and therapeutic target."[2]
2. "Structure, mechanism and regulation of peroxiredoxins."[3]
3. "Oxidation of archaeal peroxiredoxin involves a hypervalent sulfur intermediate."[4]
4. "Identification of tumor antigens that elicit a humoral immune response in breast cancer patients' sera by serological proteome analysis (SERPA)"[5]
5. "Taenia solium: antioxidant metabolism enzymes as targets for cestocidal drugs and vaccines."[6]
6. "Presence of cytosolic peroxiredoxin 2 in the erythrocyte membrane of patients with hereditary spherocytosis." [7]
7. "Peroxiredoxins, a novel protein family in lung cancer"[8]
8. GOOD"Involvement of peroxiredoxin IV in the 16alpha-hydroxyestrone-induced proliferation of human MCF-7 breast cancer cells."[9]
9. GOOD"Inhibition of lung tumor growth and augmentation of radiosensitivity by decreasing peroxiredoxin I expression"[10]
10. GOOD"Identification of the functional role of peroxiredoxin 6 in the progression of breast cancer."[11]
11. TASTY"Human prx1 Gene Is a Target of Nrf2 and Is Up-regulated by Hypoxia/Reoxygenation: Implication to Tumor Biology"

[12]

Web Pages

1. Wikipedia - [13]