Taher Jamali
Target: mFGF8b
Pool: N71
Specific Aim 1: Selection of RNA aptamers against mFGF8b
First Progress Report:
https://docs.google.com/file/d/0B8agoD1PeGsSY2pOUlpRYkNtZVU/edit?usp=sharing
Second Progress Report:
https://drive.google.com/file/d/0B8agoD1PeGsScmxSUnlLOFJiZUE/edit?usp=sharing
Final Report:
https://drive.google.com/file/d/0B8agoD1PeGsSMWxsa3Budk55djQ/edit?usp=sharing
Target: mFGF8b
Pool: N71
Abstract:
Breast
and prostate cancer(Jemal et al. 2009). Nasopharyngeal carcinoma. Structure of
the midbrain and cerebellum. What do these three seemingly unrelated phenomena
of the body have in common? Mammalian fibroblast growth factor 8b (mFGF8b).
This unique protein has been found to be involved in the cell signaling pathway
that can lead to uncontrolled growth in hormonal cancers, such as breast and
prostate(Tanaka et al. 1998; Mattila and Harkonen, 2007), as well as
nasopharyngeal cancer. mFGF8b is also interestingly involved with other
isoforms and receptors to control the structure of midbrain and cerebellum
during development(Olsen et al. 2006).
An intricate approach to dealing
with many of these possibly fatal cancerous diseases involves detection, and
conceivably, inhibition of the mFGF8b protein using aptamers. Aptamers are
small nucleic acid strands made up of DNA or RNA that can be selected against a
protein of interest for utilization in a specific purpose. In this case, the
aptamer selected against mFGF8b can attach to the protein of interest, and-
with the proper detection signal such as radioactivity or fluorescence- help to
identify overexpression of the oncoprotein. After finding overexpressed proteins
in specific cells in the body, further action can be taken to remove the cells
before the cancer can progress. The aptamer may also be utilized
therapeutically if allowed to attach to mFGF8b in its cellular pathways, and
hopefully, block any unnecessary effects of the protein in cells showing
uncontrolled growth by inhibiting the entire protein. A representation of this
therapeutic inhibition can be seen in Figure
1.
Figure 1: By preventing mFGF8b from
binding to FGFR with the use of aptamers in cells such as prostate cells, we
can prevent the oncoprotein’s effect in cellular pathways affecting
uncontrolled cancerous growth.
Specific Aim 1: Selection of RNA aptamers against mFGF8b
The first major goal is to complete rounds of
selection to find a specific aptamer that can bind to the mFGF8b protein.
Specific Aim 2:
Perform Binding Assay to Test Binding Affinity of mFGF8b aptamers
The second major
goal is to test the binding affinity of the selected aptamer to the mFGF8b
protein so that it can be possible to see how effectively the aptamer will bind
and inhibit the protein in its cellular pathways in the future.
Target Order Information:
Keatinge-Clay Lab
mFGF8b is currently available in the lab (Purified by Shawn Piasecki)
Lab Info is as follows-
Office: WEL 4.230B
Office Phone: (512) 471-2977
E-mail: adriankc@utexas.edu
Lab: WEL 4.234
Website: http://keatinge-clay.cm.utexas.edu/research/index.html
Target Cost: $0
Cost Per Round: $0
Target Order Information:
Keatinge-Clay Lab
mFGF8b is currently available in the lab (Purified by Shawn Piasecki)
Lab Info is as follows-
Office: WEL 4.230B
Office Phone: (512) 471-2977
E-mail: adriankc@utexas.edu
Lab: WEL 4.234
Website: http://keatinge-clay.cm.utexas.edu/research/index.html
Target Cost: $0
Cost Per Round: $0
References:
1.
"His-Tagged
Protein Isolation & Pulldown Using Dynabeads®." His-Tagged Protein
Isolation & Pulldown Using Dynabeads. Life Technologies Corportation,
2013. Web. 21 Apr. 2013.
2.
Jemal
A, Siegel R, Ward E, Yongping H, Xu Jiaquan, Thun, Michael. (2009). Cancer
Statistics, 2009. A Cancer Journal for
Clinicians. 59, 4. pp 215- 275
3.
Mattila
MM, Harkonen PL. (2007). Role of fibroblast growth factor 8 in growth and
progression of hormonal cancer. Cytokine Growth Factor Rev 18: 257–266.
4.
Olsen
S, Li J, Bromleigh C, et al. (2006) Structural basis by which alternative
splicing modulates the organizer activity of FGF8 in the brain. Genes
Dev. 20: 185-198.
5.
Tanaka
A, Furuya A, Yamasaki M, Hanai N, Kuriki K, Kamiakito T et al. (1998).
High frequency of fibroblast growth factor (FGF) 8 expression in clinical
prostate cancers and breast tissues, immunohistochemically demonstrated by a
newly established neutralizing monoclonal antibody against FGF 8. Cancer Res
58: 2053–2056.
6.
V W
Y Lui, D M-S Yau, C S-F Cheung, S C C Wong, A K-C Chan, et al. (2010). FGF8b
oncogene mediates proliferation and invasion of Espstein-Barr virus-associated
nasopharyngeal carcinoma cells: implication for viral-mediated FGF8b
upregulation. Nature Publishing Group. Oncogene (2011) 30, pp 1518-1530
Proposal:
https://docs.google.com/file/d/0B8agoD1PeGsSNHlCMWN6VUhWbG8/edit?usp=sharingFirst Progress Report:
https://docs.google.com/file/d/0B8agoD1PeGsSY2pOUlpRYkNtZVU/edit?usp=sharing
Second Progress Report:
https://drive.google.com/file/d/0B8agoD1PeGsScmxSUnlLOFJiZUE/edit?usp=sharing
Final Report:
https://drive.google.com/file/d/0B8agoD1PeGsSMWxsa3Budk55djQ/edit?usp=sharing
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