Jane Buchanan, M6G
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MSTP Learning Community: Bean MSTP Entry Date: June 6, 2016 |
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PhD Program: Molecular Medicine |
Mentor: Eric Taylor, PhD |
| Graduate Profile | Lab Website |
Disruption of the mitochondrial pyruvate carrier drives non-essential amino acid synthesis and growth in cancer cells
In order to sustain rapid proliferation, cancer cells undergo metabolic reprogramming to increase protein, nucleotide, and lipid synthesis. A classic example of this is the Warburg effect, a phenomenon in which certain cancer types upregulate glycolysis at the expense of oxidative phosphorylation in order to channel glycolytic intermediates into biosynthetic substrates. We predict that the deletion or downregulation of the mitochondrial pyruvate carrier (MPC) is also a type of metabolic reprogramming used to drive cancer cell proliferation. The MPC facilitates the transport of pyruvate from the cytoplasm into the mitochondria, linking glycolysis and the TCA cycle. Downregulation of the MPC is correlated with metastasis and poor survival in certain cancer types. Studies have also shown that MPC disruption increases cell proliferation. Research groups have proposed that MPC disruption increases cellular proliferation by promoting the Warburg effect or by altering stem cell fate. However, our preliminary studies suggest that MPC inhibition drives ammonia into the mitochondria in the form of alanine, which the cell then recycles into non-essential amino acids that are critical for protein synthesis and growth.
Committees:
2016-2017 - MSTP Retreat & I Heart Science Committee
2018-2021 - MSTP Wellness Committee (Co-chair for 2020-2021)
Awards:
2020 - Graduate College Post-Comprehensive Research Fellowship for Fall 2020
Individual Funding Awards:
06/08/2021 - 06/07/2024
F30 DK127845 - (National Institute of Diabetes & Digestive Kidney Disease)
Muscle Mitochondrial Pyruvate Carrier Disruption Alters Amino Acid Metabolism to Maintain Muscle Mass During Recovery from Obesity
Education:
2014 - BA, Biochemistry - University of Colorado at Boulder
2008 - BA, Fine Arts - College of Charleston
Publications:
Tompkins S, Sheldon R, Raukhorst A, Noterman M, Solst S, Buchanan J, Mapuskar K, Gray L, Oonthanpan L, Sharma A, Scerbo D, Dupuy A, Spitz D, Taylor E. Disrupting mitochondrial pyruvate uptake directs glutamine into the TCA cycle away from glutathione synthesis and impairs hepatocellular tumogenesis. Cell Reports. 2019 September. 28, 2608-2619. PMID: 31484072.
Buchanan JL, Taylor EB. Mitochondrial Pyruvate Carrier Function in Health and Disease across the Lifespan. Biomolecules. 2020 Aug 8;10(8):1162. doi: 10.3390/biom10081162. PMID: 32784379; PMCID: PMC7464753.
Sun M, Hines N, Scerbo D, Buchanan J, Wu C, Ten Eyck P, Zepeda-Orozco D, Taylor EB, Jalal DI. Allopurinol Lowers Serum Urate but Does Not Reduce Oxidative Stress in CKD. Antioxidants (Basel). 2022 Jun 29;11(7):1297. doi: 10.3390/antiox11071297. PMID: 35883787; PMCID: PMC9312025.
Brashears CB, Prudner BC, Rathore R, Caldwell KE, Dehner CA, Buchanan JL, Lange SES, Poulin N, Sehn JK, Roszik J, Spitzer D, Jones KB, O'Keefe R, Nielsen TO, Taylor EB, Held JM, Hawkins W, Van Tine BA. Malic Enzyme 1 Absence in Synovial Sarcoma Shifts Antioxidant System Dependence and Increases Sensitivity to Ferroptosis Induction with ACXT-3102. Clin Cancer Res. 2022 Aug 15;28(16):3573-3589. doi: 10.1158/1078-0432.CCR-22-0470. PMID: 35421237; PMCID: PMC9378556.
Dong Q, Xiu Y, Wang Y, Hodgson C, Borcherding N, Jordan C, Buchanan J, Taylor E, Wagner B, Leidinger M, Holman C, Thiele D, O'Brien S, Xue H, Zhao J, Li Q, Meyerson H, Boyce B, Zhao C. HSF1 is a Driver of Leukemia Stem Cell Self-Renewal in Acute Myeloid Leukemia. Nature Communications. (Accepted 10-5-2022)