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Jonathan W. Lowery, Ph.D.

Investigator Page

Background:

  • Postdoctoral Fellowship, Harvard University (2010-14)

  • Ph.D. in cell and developmental biology, Vanderbilt University (2010)

  • B.S. in biology, Freed-Hardeman University (2004)

Research Interests and Current Projects:

My research interests center on the cell-to-cell communication pathways underlying human physiology with an eye toward developing translational modalities. My particular expertise is in the BMP and Activin/TGF-beta signaling pathways, which are essential to human development and health and are dys-regulated in numerous diseases. During my PhD work, I showed for the first time that BMP signaling plays a direct role in the regulation of pulmonary microvascular tone. And, during my postdoc, I described how competition between BMP and related pathways regulates postnatal bone mass. Current projects in my lab use cell biology, biochemistry, and mouse genetics approaches to examine the mechanics of the BMP pathway in several physiological contexts, such as bone, skeletal muscle, and the vasculature. Additionally, in collaboration with my post-doc advisor, Dr. Rosen, at Harvard, I am engineering a novel set of tools which will allow investigators to directly determine the relative balance of two signaling pathways and equate this to cellular behavior in vivo, which is impossible to do at present. More detailed information about ongoing projects is available on my lab’s website (https://sites.google.com/site/jlowerylab). Student initiated project ideas in the broad area of cellular physiology, signal transduction, and cell biology are also welcome.

Research Investigations

  1. Kokabu S, Lowery JW, Toyono T, Seta Y, Hitomi S, Sato T, Enoki Y, Okubo M, Fukushima Y, Yoda T. “Muscle regulatory factors regulate T1R3 taste receptor expression.” Biochemical and Biophysical Research Communications. 2015 Dec 25;468(4):568-73. PMC In Process. PMID: 26545778.

  2. Lowery JW, Intini G, Gamer L, Lotinun S, Salazar V, Ote S, Cox K, Baron R, Rosen V. “Loss of BMPR2 leads to high bone mass due to increased osteoblast activity.” J Cell Sci. 2015 Apr 1;128(7):1308-15. PMC4379725. PMID: 25663702.

  3. Lowery JW, Amich JM, Andonian A, Rosen V. “N-linked glycosylation of the Bone Morphogenetic Protein Type 2 Receptor (BMPR2) enhances ligand binding.” Cell Mol Life Sci. 2014; 71:3165-3172. PMC4058410. PMID: 24337809.

  4. Frump AL, Lowery JW, Hamid R, Austin ED, de Caestecker M. “Abnormal trafficking of endogenously expressed BMPR2 mutant allelic products in patients with Heritable Pulmonary Arterial Hypertension.” PLoS One. 2013 Nov;8(11):e80319. PMC3818254. PMID: 24224048.

  5. Lowery JW, LaVigne AW, Kokabu S, Rosen V. “Comparative genomics identifies the mouse Bmp3 promoter and an upstream evolutionary conserved region (ECR) in mammals.” PLoS One. 2013 Feb;8(2):e57840. PMC3579780. PMID: 23451274.

  6. Chappuis V, Gamer L, Cox K, Lowery JW, Bosshardt D, Rosen V. “Periosteal BMP2 activity drives bone graft healing.” Bone. 2012 Oct;51(4):800-809. PMID: 22846673.

  7. Kokabu S, Gamer L, Cox K, Lowery JW, Kunikazu T, Econimedes A, Katagiri T, Rosen V. “BMP3 suppresses osteoblast differentiation of bone marrow stromal cells via interaction with Acvr2b.” Mol Endocrinol. 2012;26(1):87-94. PMC3248326. PMID: 22074949.

  8. Gamer LW, Tsuji K, Cox K, Capelo LP, Lowery J, Beppu H, Rosen V. “BMPR-II is dispensable for formation of the limb skeleton.” Genesis. 2011 Sep;49(9):719-24. PMID: 21538804.

  9. Lowery JW, Frump AL, Anderson LA, diCarlo GE, Jones MT, de Caestecker M. “ID family protein expression and regulation in hypoxic pulmonary hypertension.” Am J Physiol Regul Integr Comp Physiol. 2010 Dec;299(6):R1463-77. PMC3007180. PMID: 20881097.

  10. Anderson LA* & Lowery JW*, Frank DB, Jones MT, Mortlock DP, Chandler RL, de Caestecker M. “Bmp2 and Bmp4 exert opposing effects in hypoxic pulmonary hypertension.” Am J Phsyiol Regul Integr Comp Physiol. 2010 Mar;298(3):R833-42. PMC2838658. PMID: 20042692.

    * denotes equal contribution

  11. Frank DB, Lowery J, Anderson L, Brink M, Reese J, de Caestecker M. “Increased susceptibility to hypoxic pulmonary hypertension in Bmpr2 mutant mice is associated with endothelial dysfunction in the pulmonary vasculature.” Am J Physiol Lung Cell Mol Physiol. 2008 Jan;294(1):L98-L109. PMID: 18024717.

Reviews and Editorials

  1. Lowery JW, Brookshire B, Rosen V. "A survey of strategies to modulate the Bone Morphogenetic Protein (BMP) signaling pathway: current and future perspectives." Stem Cells International. In Press.

  2. Kokabu S, Lowery JW, Jimi E. "Cell fate and differentiation of bone marrow mesenchymal stem cells." Stem Cells International. In Press.

  3. Hudnall AM, Arthur JW, Lowery JW. “Clinical relevance and mechanisms of antagonism between the BMP and Activin/TGFβ signaling pathways” Journal of the American Osteopathic Association. In Press..

  4. Kokabu S, Sughiyama G, Tsuchiya-Hirata S, Lowery JW, Jimi E. “Inhibition of BMP-induced osteoblast differentiation.” Journal of Oral Biosciences. 2015 Nov;57(4):179-184.

  5. Lowery JW and Rosen V. “Allele-specific RNA interference in FOP: Silencing the FOP gene.” Gene Ther. 2012 Jul;19(7):701-702. PMID: 22130446.

  6. Lowery JW, Pazin D, Intini G, Kokabu S, Chappuis V, Capelo LP, Rosen V. “The role of BMP2 signaling in the skeleton.” Crit Rev Eukaryot Gene Expr. 2011;21(2):177-85. PMID: 22077155.

  7. Lowery JW, de Caestecker M. “BMP signaling in vascular development and disease.” Cytokine & Growth Factor Reviews. 2010 Aug;21(4):287-298. PMC2939258. PMID: 20674464.

Books and Book Chapters

  1. Lowery JW, de Caestecker M. “Bmp signaling and vascular disease.” Encyclopedia of Biological Chemistry, 2nd edition. ISBN: 9780123786302. 2013(1):229-239.

  2. Lowery JW. Bmp signaling in pulmonary vascular homeostasis and disease. Vanderbilt University Dissertation. 2010. Available at http://etd.library.vanderbilt.edu/available/etd-04212010-083626/.

Published Conference Proceedings

  1. Eaton MS, Newby JB, Plattes M, Foster H, Wauson EM, Dewar B, Arthur J, Lowery JW. “Loss of the nutrient sensor Tas1R3 leads to reduced bone resorption.” Accepted to the American Society for Bone and Mineral Research (ASBMR) Annual Meeting, Seattle, WA, 2015.

  2. Lowery J, Intini G, Gamer L, Cox K, Rosen V. “Type 2 receptor-level competition between BMP and Activin ligands regulates postnatal bone mass.” Presented at the American Society for Bone and Mineral Research (ASBMR) Annual Meeting, Baltimore, MD, 2013. J Bone Miner Res 28 (Suppl 1). Available at http://www.asbmr.org/asbmr-2013-abstract-detail?aid=ab41aadf-1af0-4172-a5ac-46068de11ca5.

  3. Kokabu S, Gamer L, Lowery J, Sato T, Yoda T, Katagiri T, Rosen V. “BMP3 expression by osteoblasts is regulated by canonical Wnt signaling.” Presented at the American Society for Bone and Mineral Research (ASBMR) Annual Meeting, Baltimore, MD, 2013. J Bone Miner Res 28 (Suppl 1). Available at http://www.asbmr.org/asbmr-2013-abstract-detail?aid=31e0c776-ac4f-4e62-b571-4f1f9e7d6586.

  4. Lowery JW, LaVigne AW, Kokabu S, Rosen V. “Comparative genomics identifies the mouse Bmp3 promoter and an upstream evolutionary conserved region (ECR) in mammals.” Presented at the American Physiological Society Annual Meeting (Experimental Biology 2013). FASEB J April 9, 2013 27:1212.10.

  5. Smith EA, Lowery JW, Gamer LW, Cox KA, Rosen V. “Spatial expression of Bone Morphogenetic Protein-2 (BMP2) in the pulmonary vasculature.” Presented at the International Association for Dental Research General Session 2013. J Dent Res 92(Spec Iss A):2595, 2013.

  6. Lowery JW, Intini G, Cox K, Gamer L, Lotinun S, Tsuji K, Baron R, Rosen V. “Loss of BMPR2 leads to high bone mass due to increased osteoblast activity.” Presented at the American Society for Bone and Mineral Research (ASBMR) Annual Meeting, Minneapolis, MN, 2012. J Bone Miner Res 27 (Suppl 1). Available at http://www.asbmr.org/Meetings/AnnualMeeting/AbstractDetail.aspx?aid=b6c706ac-d4ae-429b-b046-b316bdaac6c2.

  7. Frump A, Lowery J, de Caestecker M. “Effects of different BMPR2 mutations on pulmonary endothelial cells from patients with hereditary arterial pulmonary hypertension.” American Thoracic Society (ATS) International Conference, Denver, CO, 2011. Am J Respir Crit Care Med 183;2011:A5011.

  8. Lowery JW, Anderson L, Jones M, de Caestecker MP. “The role and regulation of Inhibitor of Differentiation (Id) family members in hypoxic pulmonary hypertension.” Presented at the American Physiological Society Annual Meeting (Experimental Biology 2010). FASEB J April 6, 2010 24:1023.7.

  9. de Caestecker MP, Anderson L, Jones M, Lowery J. “Bmp2 and Bmp4 exert opposing effects in hypoxic pulmonary hypertension.” Presented at the American Physiological Society Annual Meeting (Experimental Biology 2010). FASEB J 2010 April 6, 2010 24:1023.3.

  10. Moore M, Edwards JR, Lwin S, Lowery J, Zhao M, Garrett R, Gutierrez GE, Mundy GR. “BMP2-eNOS axis is essential for normal skeletal development and statin-induced bone formation.” American Society for Bone and Mineral Research (ASBMR) Annual Meeting, Denver, CO, 2009. J Bone Miner Res 24 (Suppl 1). Available at http://www.asbmr.org/Meetings/AnnualMeeting/AbstractDetail.aspx?aid=df42a0eb-834c-4a1b-9588-c838c72b3519.

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