X-Git-Url: https://git.donarmstrong.com/?a=blobdiff_plain;f=resume%2Fresearch_statement.mdwn;h=a2c382a409f7a98e5ec00ed3bb75d7f60b4667b8;hb=HEAD;hp=078bbe96abea73baddae92a07e0f7981d225d739;hpb=a0098b3f8e4b4f14a29add0886045cf0b1ea760c;p=don.git diff --git a/resume/research_statement.mdwn b/resume/research_statement.mdwn index 078bbe9..a2c382a 100644 --- a/resume/research_statement.mdwn +++ b/resume/research_statement.mdwn @@ -51,18 +51,18 @@ I developed novel bioinformatic methods which increase likelihood of identifying reproducible genetic associations using prior knowledge from publicly available databases and expert -information [#Armstrong2008:function2gene]. Using these methods, I -was able to identify genes previously unassociated with SLE in a -trio-based study [#Jacob2007:ar_lupus]. These genes were then +information [^Armstrong2008:function2gene]. Using these methods, I was +able to identify genes previously unassociated with SLE in a +trio-based study [^Jacob2007:ar_lupus]. These genes were then replicated in a larger case-control study which was funded by the NIH -on the basis of the original findings -[#Jacob2009:sle_irak1],[#Armstrong2009:sle_gi]. Among other findings, -this larger study identified a missense allele in NCF2 (H389Q, -rs17849502) which was associated with SLE. Collaborative work -indicated that H389Q altered the binding energy of NCF2 with VAV1 -using docking simulations, and in vitro experiments confirmed that -H389Q altered NADPH oxidase function [#Jacob2012:sle_ncf2], thus -identifying it as a causative SLE mutation. +on the basis of the original findings [^Jacob2009:sle_irak1],[^Armstrong2009:sle_gi]. +Among other findings, this larger study +identified a missense allele in NCF2 (H389Q, rs17849502) which was +associated with SLE. Collaborative work indicated that H389Q altered +the binding energy of NCF2 with VAV1 using docking simulations, and in +vitro experiments confirmed that H389Q altered NADPH oxidase function +[^Jacob2012:sle_ncf2], thus identifying it as a causative SLE +mutation. ## Cancer Stem Cells in Glioblastoma @@ -86,7 +86,7 @@ indentified multiple gene regulation pathways, many of them novel, including the Id1/Thsb1 inhibitory pathway. Additional experiments indicated that the *in vitro* pathology of endothelial cells could be partially rescued using extracellular Thsb1 -[#Stapleton2011:thbs1]. +[^Stapleton2011:thbs1]. # Future research directions @@ -204,39 +204,41 @@ be able to build upon and improve my tools without being forced to reinvent them. -[#Armstrong2009:sle_gi]: D L Armstrong et al. “Identification of new SLE-associated genes with a two-step +[^Armstrong2009:sle_gi]: D L Armstrong et al. “Identification of new SLE-associated genes with a two-step Bayesian study design”. In: Genes Immun. 10.5 (July 2009), pp. 446–456. doi: - 10.1038/gene.2009.38. + [10.1038/gene.2009.38](http://dx.doi.org/10.1038/gene.2009.38). -[#Armstrong2008:function2gene]: Don L Armstrong, Chaim O Jacob, and Raphael Zidovetzki. “Function2Gene: a +[^Armstrong2008:function2gene]: Don L Armstrong, Chaim O Jacob, and Raphael Zidovetzki. “Function2Gene: a gene selection tool to increase the power of genetic association studies by utilizing public databases and expert knowledge”. In: BMC Bioinformatics 9 (2008), p. 311. - doi: 10.1186/1471-2105-9-311. + doi: [10.1186/1471-2105-9-311](http://dx.doi.org/10.1186/1471-2105-9-311). -[#Jacob2009:sle_irak1]: Chaim O Jacob et al. “Identification of IRAK1 as a risk gene with critical role - in the pathogenesis of systemic lupus erythematosus”. In: Proc. Natl. Acad. Sci. - U.S.A. 106.15 (Apr. 2009), pp. 6256–6261. doi: 10.1073/pnas.0901181106. +[^Jacob2009:sle_irak1]: Chaim O Jacob et al. “Identification of IRAK1 as a risk gene with critical role + in the pathogenesis of systemic lupus erythematosus”. In: Proc. Natl. Acad. Sci. + U.S.A. 106.15 (Apr. 2009), pp. 6256–6261. doi: [10.1073/pnas.0901181106](http://dx.doi.org/10.1073/pnas.0901181106). -[#Jacob2007:ar_lupus]: Chaim O Jacob et al. “Identification of novel susceptibility genes in childhood- +[^Jacob2007:ar_lupus]: Chaim O Jacob et al. “Identification of novel susceptibility genes in childhood- onset systemic lupus erythematosus using a uniquely designed candidate gene pathway platform”. In: Arthritis Rheum. 56.12 (Dec. 2007), pp. 4164–4173. doi: - 10.1002/art.23060. + [10.1002/art.23060](http://dx.doi.org/10.1002/art.23060). -[#Jacob2012:sle_ncf2]: Chaim O Jacob et al. “Lupus-associated causal mutation in neutrophil cytosolic +[^Jacob2012:sle_ncf2]: Chaim O Jacob et al. “Lupus-associated causal mutation in neutrophil cytosolic factor 2 (NCF2) brings unique insights to the structure and function of NADPH oxidase”. In: Proc. Natl. Acad. Sci. U.S.A. 109.2 (Jan. 2012), pp. 59–67. doi: - 10.1073/pnas.1113251108. + [10.1073/pnas.1113251108](http://dx.doi.org/10.1073/pnas.1113251108). -[#Stapleton2011:thbs1]: Christopher J Stapleton et al. “Thrombospondin-1 modulates the angiogenic phe- - notype of human cerebral arteriovenous malformation endothelial cells”. In: Neu- - rosurgery 68.5 (May 2011), pp. 1342–1353. doi: 10.1227/NEU.0b013e31820c0a68. +[^Stapleton2011:thbs1]: Christopher J Stapleton et al. + “Thrombospondin-1 modulates the angiogenic phe- notype of human + cerebral arteriovenous malformation endothelial cells”. In: + Neurosurgery 68.5 (May 2011), pp. 1342–1353. + doi: [10.1227/NEU.0b013e31820c0a68](http://dx.doi.org/10.1227/NEU.0b013e31820c0a68). -[survival_rate]: Only 4% of patients survive to 5 years after diagnosis +[^survival_rate]: Only 4% of patients survive to 5 years after diagnosis -[avm_definition]: Direct artery to vein connection without an +[^avm_definition]: Direct artery to vein connection without an intervening capilary bed; leads to high pressure arterial flow in venous tissue and can lead to hemmorrhage and death. -[extending_note]: and extending existing open source tools where they +[^extending_note]: and extending existing open source tools where they exist