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William Michael Oldham, M.D., Ph.D.

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Mentoring
Available: 09/21/18, Expires: 09/20/19

Accumulating data suggests that pulmonary artery endothelial cells in patients with pulmonary arterial hypertension operate a hypoxia-like metabolic program. It is unclear how this metabolic program supports the dysregulated cell growth characteristic of this disease. In order to address this question, we will develop maps of intracellular metabolic pathways in pulmonary artery endothelial cells cultured in normoxic and hypoxic conditions utilizing cutting-edge technologies including stable isotope tracing liquid chromatography-mass spectrometry. The interested student will take full responsibility for this project, including learning cell culture techniques, approaches to metabolic labeling, sample preparation, fundamentals of LC-MS, and data analysis.


Research
The research activities and funding listed below are automatically derived from NIH ExPORTER and other sources, which might result in incorrect or missing items. Faculty can login to make corrections and additions.
  1. K08HL128802 (OLDHAM, WILLIAM MICHAEL) Apr 1, 2016 - Mar 31, 2021
    NIH/NHLBI
    Regulation of pulmonary vascular cell redox state by L-2-hydroxyglutarate
    Role: Principal Investigator
This researcher has shared information about their research resources in the eagle-i Network. To update or add resource records, contact eagle-i@hms.harvard.edu.
Seahorse Core Facility (BWH) - Core services (3) and Instruments (1)

Bibliographic
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
  1. Singh I, Oliveira RKF, Naeije R, Rahaghi FN, Oldham W, Systrom DM, Waxman AB. Pulmonary Vascular Distensibility and Early Pulmonary Vascular Remodeling in Pulmonary Hypertension. Chest. 2019 May 20. PMID: 31121149.
    Citations:    
  2. Sternschein RM, Oldham WM. Paradoxical Embolization via Large Pulmonary Arteriovenous Malformation. Am J Respir Crit Care Med. 2019 Apr 19. PMID: 31002526.
    Citations:    
  3. Kim EY, Oldham WM. Innate T cells in the intensive care unit. Mol Immunol. 2019 01; 105:213-223. PMID: 30554082.
    Citations:    Fields:    
  4. Bertero T, Oldham WM, Grasset EM, Bourget I, Boulter E, Pisano S, Hofman P, Bellvert F, Meneguzzi G, Bulavin DV, Estrach S, Feral CC, Chan SY, Bozec A, Gaggioli C. Tumor-Stroma Mechanics Coordinate Amino Acid Availability to Sustain Tumor Growth and Malignancy. Cell Metab. 2019 Jan 08; 29(1):124-140.e10. PMID: 30293773.
    Citations:    Fields:    
  5. Musri MM, Coll-Bonfill N, Maron BA, Peinado VI, Wang RS, Altirriba J, Blanco I, Oldham WM, Tura-Ceide O, García-Lucio J, de la Cruz-Thea B, Meister G, Loscalzo J, Barberà JA. MicroRNA Dysregulation in Pulmonary Arteries from Chronic Obstructive Pulmonary Disease. Relationships with Vascular Remodeling. Am J Respir Cell Mol Biol. 2018 10; 59(4):490-499. PMID: 29757677.
    Citations:    Fields:    
  6. Yang JS, Hsu JW, Park SY, Li J, Oldham WM, Beznoussenko GV, Mironov AA, Loscalzo J, Hsu VW. GAPDH inhibits intracellular pathways during starvation for cellular energy homeostasis. Nature. 2018 09; 561(7722):263-267. PMID: 30209366.
    Citations:    Fields:    
  7. Verwer EE, Kavanagh TR, Mischler WJ, Feng Y, Takahashi K, Wang S, Shoup TM, Neelamegam R, Yang J, Guehl NJ, Ran C, Massefski W, Cui Y, El-Chemaly S, Sadow PM, Oldham WM, Kijewski MF, El Fakhri G, Normandin MD, Priolo C. [18F]Fluorocholine and [18F]Fluoroacetate PET as Imaging Biomarkers to Assess Phosphatidylcholine and Mitochondrial Metabolism in Preclinical Models of TSC and LAM. Clin Cancer Res. 2018 Dec 01; 24(23):5925-5938. PMID: 30054282.
    Citations:    Fields:    
  8. Samokhin AO, Stephens T, Wertheim BM, Wang RS, Vargas SO, Yung LM, Cao M, Brown M, Arons E, Dieffenbach PB, Fewell JG, Matar M, Bowman FP, Haley KJ, Alba GA, Marino SM, Kumar R, Rosas IO, Waxman AB, Oldham WM, Khanna D, Graham BB, Seo S, Gladyshev VN, Yu PB, Fredenburgh LE, Loscalzo J, Leopold JA, Maron BA. NEDD9 targets COL3A1 to promote endothelial fibrosis and pulmonary arterial hypertension. Sci Transl Med. 2018 Jun 13; 10(445). PMID: 29899023.
    Citations:    
  9. Oldham WM, Oliveira RKF, Wang RS, Opotowsky AR, Rubins DM, Hainer J, Wertheim BM, Alba GA, Choudhary G, Tornyos A, MacRae CA, Loscalzo J, Leopold JA, Waxman AB, Olschewski H, Kovacs G, Systrom DM, Maron BA. Network Analysis to Risk Stratify Patients With Exercise Intolerance. Circ Res. 2018 Mar 16; 122(6):864-876. PMID: 29437835.
    Citations:    Fields:    
  10. Oldham WM. The Long Noncoding RNA LnRPT Puts the Brakes on Pulmonary Artery Smooth Muscle Cell Proliferation. Am J Respir Cell Mol Biol. 2018 02; 58(2):138-139. PMID: 29388834.
    Citations:    Fields:    Translation:HumansCells
  11. Fessel JP, Oldham WM. Nicotine Adenine Dinucleotides: The Redox Currency of the Cell. Antioxid Redox Signal. 2018 Jan 20; 28(3):165-166. PMID: 29113451.
    Citations:    Fields:    Translation:HumansCells
  12. Wang RS, Oldham WM, Maron BA, Loscalzo J. Systems Biology Approaches to Redox Metabolism in Stress and Disease States. Antioxid Redox Signal. 2018 10 01; 29(10):953-972. PMID: 29121773.
    Citations:    Fields:    
  13. Lam HC, Liu HJ, Baglini CV, Filippakis H, Alesi N, Nijmeh J, Du H, Lope AL, Cottrill KA, Handen A, Asara JM, Kwiatkowski DJ, Ben-Sahra I, Oldham WM, Chan SY, Henske EP. Rapamycin-induced miR-21 promotes mitochondrial homeostasis and adaptation in mTORC1 activated cells. Oncotarget. 2017 Sep 12; 8(39):64714-64727. PMID: 29029388.
    Citations: 4     Fields:    
  14. Fessel JP, Oldham WM. Pyridine Dinucleotides from Molecules to Man. Antioxid Redox Signal. 2018 Jan 20; 28(3):180-212. PMID: 28635300.
    Citations:    Fields:    Translation:HumansCells
  15. Lam HC, Baglini CV, Lope AL, Parkhitko AA, Liu HJ, Alesi N, Malinowska IA, Ebrahimi-Fakhari D, Saffari A, Yu JJ, Pereira A, Khabibullin D, Ogorek B, Nijmeh J, Kavanagh T, Handen A, Chan SY, Asara JM, Oldham WM, Diaz-Meco MT, Moscat J, Sahin M, Priolo C, Henske EP. p62/SQSTM1 Cooperates with Hyperactive mTORC1 to Regulate Glutathione Production, Maintain Mitochondrial Integrity, and Promote Tumorigenesis. Cancer Res. 2017 06 15; 77(12):3255-3267. PMID: 28512249.
    Citations: 2     Fields:    Translation:AnimalsCells
  16. Bertero T, Oldham WM, Cottrill KA, Pisano S, Vanderpool RR, Yu Q, Zhao J, Tai Y, Tang Y, Zhang YY, Rehman S, Sugahara M, Qi Z, Gorcsan J, Vargas SO, Saggar R, Saggar R, Wallace WD, Ross DJ, Haley KJ, Waxman AB, Parikh VN, De Marco T, Hsue PY, Morris A, Simon MA, Norris KA, Gaggioli C, Loscalzo J, Fessel J, Chan SY. Vascular stiffness mechanoactivates YAP/TAZ-dependent glutaminolysis to drive pulmonary hypertension. J Clin Invest. 2016 09 01; 126(9):3313-35. PMID: 27548520.
    Citations: 32     Fields:    Translation:HumansAnimalsCells
  17. Oldham WM, Loscalzo J. Quantification of 2-Hydroxyglutarate Enantiomers by Liquid Chromatography-mass Spectrometry. Bio Protoc. 2016 Aug 20; 6(16). PMID: 28573160.
    Citations:    
  18. Oldham WM, Lewis GD, Opotowsky AR, Waxman AB, Systrom DM. Unexplained exertional dyspnea caused by low ventricular filling pressures: results from clinical invasive cardiopulmonary exercise testing. Pulm Circ. 2016 Mar; 6(1):55-62. PMID: 27162614.
    Citations: 4     
  19. Berry NC, Manyoo A, Oldham WM, Stephens TE, Goldstein RH, Waxman AB, Tracy JA, Leary PJ, Leopold JA, Kinlay S, Opotowsky AR, Systrom DM, Maron BA. Protocol for exercise hemodynamic assessment: performing an invasive cardiopulmonary exercise test in clinical practice. Pulm Circ. 2015 Dec; 5(4):610-8. PMID: 26697168.
    Citations: 6     
  20. Maron BA, Stephens TE, Farrell LA, Oldham WM, Loscalzo J, Leopold JA, Lewis GD. Elevated pulmonary arterial and systemic plasma aldosterone levels associate with impaired cardiac reserve capacity during exercise in left ventricular systolic heart failure patients: A pilot study. J Heart Lung Transplant. 2016 Mar; 35(3):342-351. PMID: 26586488.
    Citations: 4     Fields:    Translation:Humans
  21. Oldham WM, Clish CB, Yang Y, Loscalzo J. Hypoxia-Mediated Increases in L-2-hydroxyglutarate Coordinate the Metabolic Response to Reductive Stress. Cell Metab. 2015 Aug 04; 22(2):291-303. PMID: 26212716.
    Citations: 60     Fields:    Translation:HumansCells
  22. Wang RS, Oldham WM, Loscalzo J. Network-based association of hypoxia-responsive genes with cardiovascular diseases. New J Phys. 2014 Oct 24; 16(10):105014. PMID: 25530704.
    Citations: 4     
  23. Maron BA, Oldham WM, Chan SY, Vargas SO, Arons E, Zhang YY, Loscalzo J, Leopold JA. Upregulation of steroidogenic acute regulatory protein by hypoxia stimulates aldosterone synthesis in pulmonary artery endothelial cells to promote pulmonary vascular fibrosis. Circulation. 2014 Jul 08; 130(2):168-79. PMID: 25001622.
    Citations: 14     Fields:    Translation:HumansAnimalsCells
  24. Ciampa EJ, Hunt AA, Arneson KO, Mordes DA, Oldham WM, Vin Woo K, Owens DA, Cannon MD, Dermody TS. A workshop on leadership for MD/PhD students. Med Educ Online. 2011; 16. PMID: 21841905.
    Citations: 3     Fields:    Translation:Humans
  25. Jernigan KK, Cselenyi CS, Thorne CA, Hanson AJ, Tahinci E, Hajicek N, Oldham WM, Lee LA, Hamm HE, Hepler JR, Kozasa T, Linder ME, Lee E. Gbetagamma activates GSK3 to promote LRP6-mediated beta-catenin transcriptional activity. Sci Signal. 2010 May 11; 3(121):ra37. PMID: 20460648.
    Citations: 16     Fields:    Translation:HumansAnimalsCells
  26. Preininger AM, Funk MA, Oldham WM, Meier SM, Johnston CA, Adhikary S, Kimple AJ, Siderovski DP, Hamm HE, Iverson TM. Helix dipole movement and conformational variability contribute to allosteric GDP release in Galphai subunits. Biochemistry. 2009 Mar 31; 48(12):2630-42. PMID: 19222191.
    Citations: 14     Fields:    Translation:Cells
  27. Oldham WM, Hamm HE. Heterotrimeric G protein activation by G-protein-coupled receptors. Nat Rev Mol Cell Biol. 2008 Jan; 9(1):60-71. PMID: 18043707.
    Citations: 318     Fields:    Translation:HumansAnimalsCells
  28. Oldham WM, Van Eps N, Preininger AM, Hubbell WL, Hamm HE. Mapping allosteric connections from the receptor to the nucleotide-binding pocket of heterotrimeric G proteins. Proc Natl Acad Sci U S A. 2007 May 08; 104(19):7927-32. PMID: 17463080.
    Citations: 26     Fields:    Translation:Cells
  29. Oldham WM, Hamm HE. How do receptors activate G proteins? Adv Protein Chem. 2007; 74:67-93. PMID: 17854655.
    Citations: 21     Fields:    Translation:Cells
  30. Van Eps N, Oldham WM, Hamm HE, Hubbell WL. Structural and dynamical changes in an alpha-subunit of a heterotrimeric G protein along the activation pathway. Proc Natl Acad Sci U S A. 2006 Oct 31; 103(44):16194-9. PMID: 17053066.
    Citations: 29     Fields:    Translation:Cells
  31. Oldham WM, Hamm HE. Structural basis of function in heterotrimeric G proteins. Q Rev Biophys. 2006 May; 39(2):117-66. PMID: 16923326.
    Citations: 69     Fields:    Translation:Cells
  32. Holinstat M, Oldham WM, Hamm HE. G-protein-coupled receptors: evolving views on physiological signalling: symposium on G-protein-coupled receptors: evolving concepts and new techniques. EMBO Rep. 2006 Sep; 7(9):866-9. PMID: 16906127.
    Citations: 4     Fields:    Translation:HumansCells
  33. Oldham WM, Van Eps N, Preininger AM, Hubbell WL, Hamm HE. Mechanism of the receptor-catalyzed activation of heterotrimeric G proteins. Nat Struct Mol Biol. 2006 Sep; 13(9):772-7. PMID: 16892066.
    Citations: 66     Fields:    Translation:AnimalsCells
  34. Preininger AM, Henage LG, Oldham WM, Yoon EJ, Hamm HE, Brown HA. Direct modulation of phospholipase D activity by Gbetagamma. Mol Pharmacol. 2006 Jul; 70(1):311-8. PMID: 16638972.
    Citations: 11     Fields:    Translation:HumansCells
  35. Kwong J, Roundabush FL, Hutton Moore P, Montague M, Oldham W, Li Y, Chin LS, Li L. Hrs interacts with SNAP-25 and regulates Ca(2+)-dependent exocytosis. J Cell Sci. 2000 Jun; 113 ( Pt 12):2273-84. PMID: 10825299.
    Citations: 11     Fields:    Translation:AnimalsCells
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Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.