Jason Walther

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== Contact Information ==
== Contact Information ==
:Jason Walther
:Jason Walther
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:Laboratory for Bioinformatics and Metabolic Engineering<br>
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:waltherj@gmail.com
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:Department of Chemical Engineering<br>
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:Building 56, Room 422<br>
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:77 Massachusetts Avenue<br>
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:Cambridge, MA 02139<br>
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:Phone: (617) 253-6591<br>
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:Fax: (617) 253-7181
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== Research Interests ==
== Research Interests ==
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:The goal of metabolic flux analysis (MFA) is the quantitative determination of all intracellular fluxes in a system of interest.  Results are obtained by introducing a labeled substrate (usually a labeled carbon source) into a cell culture, measuring relative labeling in metabolic byproducts, and computationally processing these measurements to arrive at fluxes.  Various computational techniques have been developed for flux analysis of isotopically stationary systems (Wiechert <i>et al</i>., 1999; Antoniewicz <i>et al</i>., 2006).  These methods require that enough time elapse following the introduction of labeled substrate so that metabolites of the cells under study reach a constant state of isotopic labeling.
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:The goal of metabolic flux analysis (MFA) is the quantitative determination of all intracellular fluxes in a system of interest.  Results are obtained by introducing a labeled substrate (usually a labeled carbon source) into a cell culture, measuring relative labeling in metabolic byproducts, and computationally processing these measurements to arrive at fluxes.
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:I aim to (1) adapt one of these previous models such that it can generate fluxes for  isotopically instationary systems and (2) apply this new instationary model to an engineered strain of <i>E</i>. <i>coli</i>.  Instationary metabolic flux analysis (IMFA), though computationally more complex, claims several advantages over its stationary analog.  First, the amount of prohibitively expensive labeled substrate required for an experiment is greatly reduced.  Second, the duration of such an experiment is considerably shortened, adding credibility to the metabolic steady-state assumption necessary for all flux analyses.  Third, instationary flux analysis allows the pool sizes of all metabolites, including intracellular intermediates, to be estimated in addition to the fluxes themselves.
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:Nonstationary metabolic flux analysis (NMFA) is similar to MFA with the provision that metabolite labeling is sampled and measured before the system reaches an isotopic steady state. NMFA, though computationally more complex, claims several advantages over its stationary analog.  First, the amount of prohibitively expensive labeled substrate required for an experiment is greatly reduced.  Second, the duration of such an experiment is considerably shortened, adding credibility to the metabolic steady-state assumption necessary for all flux analyses.  Third, nonstationary flux analysis allows the pool sizes of metabolites, including intracellular intermediates, to be estimated in addition to the fluxes themselves.
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:I am working with the theoretical, computational, and experimental aspects of NMFA.  In particular, I have developed computational tools for MFA tracer evaluation, I have created a rapid sampling apparatus for automated sampling and quenching, and I have used MFA to study metabolism in the oleaginous yeast ''Yarrowia lipolytica''.
== Education==
== Education==
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:2010 Ph.D. Chemical Engineering, Massachusetts Institute of Technology<br>
:2004 M.Eng. Chemical Engineering, Stanford University<br>
:2004 M.Eng. Chemical Engineering, Stanford University<br>
:2004 B.S. Chemical Engineering, Stanford University
:2004 B.S. Chemical Engineering, Stanford University
== Publications ==
== Publications ==
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:Walther JL, Bartlett DW, Chew W, Robertson CR, Hostetter TH, and Meyer TW. <i>Downloadable computer models for renal replacement therapy</i>. Kidney Int 2006 Mar; 69(6) 1056-63. doi:10.1038/sj.ki.5000196 pmid:16528255. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16528255 PubMed] [http://www.hubmed.org/display.cgi?uids=16528255,16014068 HubMed] [1]<br>
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:Metallo CM*, Walther JL*, and Stephanopoulos G. Evaluation of 13C isotopic tracers for metabolic flux analysis in mammalian cells. 2009. J Biotechnol 144(3):167-174.
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:Young JD*, Walther JL*, Antoniewicz MR, Yoo H, and Stephanopoulos G. An elementary metabolite unit (EMU) based method of nonstationary flux analysis. 2007. Biotechnol Bioeng 99(3):686-699.
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:Styczynski MP, Moxley JF, Tong LV, Walther JL, Jensen KL, and Stephanopoulos, G. Systematic identification of conserved metabolites in GC/MS data for metabolomics and biomarker discovery. 2007. Anal Chem 79(3):966-973.
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:Meyer TW, Peattie JW, Miller JD, Dinh DC, Recht NS, Walther JL, and Hostetter TH. Increasing the clearance of protein-bound solutes by addition of a sorbent to the dialysate. 2007. J Am Soc Nephrol 18(3):868-874.
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:Walther JL, Bartlett DW, Chew W, Robertson CR, Hostetter TH, and Meyer TW. 2006. Downloadable computer models for renal replacement therapy. Kidney Int 69(6):1056-1063.
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:Meyer TW, Walther JL, Pagtalunan ME, Martinez AW, Torkamani A, Fong PD, Recht NS, Robertson CR, and Hostetter TH. <i>The clearance of protein-bound solutes by hemofiltration and hemodiafiltration</i>. Kidney Int 2005 Aug; 68(2) 867-77. doi:10.1111/j.1523-1755.2005.00469.x pmid:16014068. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16014068 PubMed] [http://www.hubmed.org/display.cgi?uids=16014068 HubMed] [2]<br>
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:Meyer TW, Walther JL, Pagtalunan ME, Martinez AW, Torkamani A, Fong PD, Recht NS, Robertson CR, and Hostetter TH. The clearance of protein-bound solutes by hemofiltration and hemodiafiltration. 2005. Kidney Int 68(2):867-877.
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:All Medline abstracts: [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16528255,16014068 PubMed] [http://www.hubmed.org/display.cgi?uids=16528255,16014068 HubMed]
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:<nowiki>*</nowiki>These authors contributed equally to the work

Current revision

Contents

Contact Information

Jason Walther
waltherj@gmail.com

Research Interests

The goal of metabolic flux analysis (MFA) is the quantitative determination of all intracellular fluxes in a system of interest. Results are obtained by introducing a labeled substrate (usually a labeled carbon source) into a cell culture, measuring relative labeling in metabolic byproducts, and computationally processing these measurements to arrive at fluxes.
Nonstationary metabolic flux analysis (NMFA) is similar to MFA with the provision that metabolite labeling is sampled and measured before the system reaches an isotopic steady state. NMFA, though computationally more complex, claims several advantages over its stationary analog. First, the amount of prohibitively expensive labeled substrate required for an experiment is greatly reduced. Second, the duration of such an experiment is considerably shortened, adding credibility to the metabolic steady-state assumption necessary for all flux analyses. Third, nonstationary flux analysis allows the pool sizes of metabolites, including intracellular intermediates, to be estimated in addition to the fluxes themselves.
I am working with the theoretical, computational, and experimental aspects of NMFA. In particular, I have developed computational tools for MFA tracer evaluation, I have created a rapid sampling apparatus for automated sampling and quenching, and I have used MFA to study metabolism in the oleaginous yeast Yarrowia lipolytica.

Education

2010 Ph.D. Chemical Engineering, Massachusetts Institute of Technology
2004 M.Eng. Chemical Engineering, Stanford University
2004 B.S. Chemical Engineering, Stanford University

Publications

Metallo CM*, Walther JL*, and Stephanopoulos G. Evaluation of 13C isotopic tracers for metabolic flux analysis in mammalian cells. 2009. J Biotechnol 144(3):167-174.
Young JD*, Walther JL*, Antoniewicz MR, Yoo H, and Stephanopoulos G. An elementary metabolite unit (EMU) based method of nonstationary flux analysis. 2007. Biotechnol Bioeng 99(3):686-699.
Styczynski MP, Moxley JF, Tong LV, Walther JL, Jensen KL, and Stephanopoulos, G. Systematic identification of conserved metabolites in GC/MS data for metabolomics and biomarker discovery. 2007. Anal Chem 79(3):966-973.
Meyer TW, Peattie JW, Miller JD, Dinh DC, Recht NS, Walther JL, and Hostetter TH. Increasing the clearance of protein-bound solutes by addition of a sorbent to the dialysate. 2007. J Am Soc Nephrol 18(3):868-874.
Walther JL, Bartlett DW, Chew W, Robertson CR, Hostetter TH, and Meyer TW. 2006. Downloadable computer models for renal replacement therapy. Kidney Int 69(6):1056-1063.
Meyer TW, Walther JL, Pagtalunan ME, Martinez AW, Torkamani A, Fong PD, Recht NS, Robertson CR, and Hostetter TH. The clearance of protein-bound solutes by hemofiltration and hemodiafiltration. 2005. Kidney Int 68(2):867-877.
*These authors contributed equally to the work
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