Research
Fighting traffic
Protein trafficking is an essential process required for the health and proper functioning of all cells, tissues and systems of the human body. Dysfunction of the trafficking machinery leads to cellular traffic jams, a hallmark of many devastating diseases, such as diabetes, cancer, Alzheimer’s disease, cystic fibrosis and more.
Our lab studies the extensive and highly regulated protein trafficking network and addressing major enigmas in the field such as:
- How are billions of proteins shuttled from their site of origin to their final destination?
- How is the system regulated to ensure proper recognition and elimination of defective proteins?
- How do these pathways go awry in human diseases?
- And finally, how can we fix these defective pathways?
Using state-of-the-art imaging technology, the lab conducts high content screening (through genetic CRISPR manipulations, pharmacological perturbations, small molecule libraries, etc.) in complex biological systems, including: mammalian cells, 3D cultures, organoids and mouse models. Our aim is to better understand basic protein trafficking processes and develop therapeutic strategies to combat diseases that result from trafficking malfunction.
Publications
Articles
- Dvela-Levitt M, Kost-Alimova M, Emani M, Kohnert E, Thompson R, Sidhom EH, Rivadeneira A, Sahakian N, Roignot J, Papagregoriou G, Montesinos MS, Clark AR, McKinney D, Gutierrez J, Roth M, Ronco L, Elonga E, Carter T, Gnirke A, Melanson M, Hartland K, Wieder N, Hsu JCH, Deltas C, Hughey R, Bleyer AJ, Kmoch S, Živná M, Barešova V, Kota S, Schlondorff J, Heiman M, Alper SL, Wagner F, Weins A, Golub TR, Lander ES, Greka A. (2019)
Small molecule targets TMED9 and promotes lysosomal degradation to reverse proteinopathy.
- . 178(3):521-535.
https://www.sciencedirect.com/science/article/pii/S009286741930741X?dgcid=coauthor
Also highlighted in:
- https://www.sciencedirect.com/science/article/abs/pii/S1471491419302345
- https://www.nature.com/articles/s41581-019-0194-8
- https://www.nature.com/articles/d41573-019-00133-5
- Was awarded by NapJC for the best nephrology story of 2019 http://www.nephjc.com/news/2020/1/7/the-top-nephorogy-stories-of-2019
- Zhou Y, Castonguay P, Sidhom EH, Clark AR, Dvela-Levitt M, Kim S, Sieber J, Wieder N, Jung JY, Andreeva S, Reichardt J, Dubois F, Hoffmann SC, Basgen JM, Montesinos MS, Weins A, Johnson AC, Lander ES, Garrett MR, Hopkins CR, Greka A. (2017)
A small-molecule inhibitor of TRPC5 ion channels suppresses progressive kidney disease in animal models.
- . 8;358(6368):1332-1336.
https://www.ncbi.nlm.nih.gov/pubmed/29217578
Also highlighted in:
- https://science.sciencemag.org/content/358/6368/1256
- https://www.nature.com/articles/nrneph.2018.4?draft=journal
- Sieber J, Wieder N, Ostrosky-Frid M, Dvela-Levitt M, Aygün O, Udeshi ND, Carr SA, Greka A. (2017)
Lysine trimethylation regulates 78-kDa glucose-regulated protein proteostasis during endoplasmic reticulum stress.
J Biol Chem. 17;292(46):18878-18885.
https://www.ncbi.nlm.nih.gov/pubmed/28912266
- Dvela-Levitt M, Cohen-Ben Ami H, Rosen H, Ornoy A, Hochner-Celnikier D, Granat M and Lichtstein D. (2015)
Reduction in maternal circulating ouabain impairs offspring growth and kidney development.
J. Am. Soc. Nephrol. 26(5):1103-1.
- Dvela-Levitt M, Cohen-Ben Ami H, Rosen H, Shohami E and Lichtstein D. (2014)
Ouabain improves functional recovery following traumatic brain injury.
J Neurotrauma. 1;31(23):1942-7.
- Lichtstein D, Rosen H and Dvela M. (2012)
Cardenolides and bufadienolides as hormones: What is missing?
Am. J. Physiol. Renal Physiol. 302(8):F957-8. *Commentary
http://www.ncbi.nlm.nih.gov/pubmed/22301627
- Dvela M, Rosen H, Cohen-Ben Ami H and Lichtstein D. (2012)
Endogenous ouabain regulates cell viability.
Am J Physiol Cell Physiol. 302(2):C442-52.
http://www.ncbi.nlm.nih.gov/pubmed/22031604
- Jaiswal M, Dvela M, Lichtstein D and Mallick B. (2010)
Endogenous Ouabain-Like Compounds in Locus Coeruleus Modulate Rapid Eye Movement Sleep in Rats.
J. Sleep Res. 19(1 Pt 2):183-91.
http://www.ncbi.nlm.nih.gov/pubmed/19878449
- Nesher M, Shpolansky U, Viola N, Dvela M, Buzaglo N, Cohen Ben-Ami H, Rosen H and Lichtstein D. (2010)
Ouabain attenuates cardiotoxicity induced by other cardiac steroids.
Br. J. Pharmacol. 160(2):346-54.
http://www.ncbi.nlm.nih.gov/pubmed/20423344
- Nesher M, Dvela M, Igbokwe VU, Rosen H, and Lichtstein D. (2009)
Physiological roles of endogenous ouabain in normal rat.
Am. J. Physiol. Heart Circ Physiol. 297(6):H2026-34.
http://www.ncbi.nlm.nih.gov/pubmed/19837951
- Dvela M, Rosen H, Feldmann T, Nesher M and Lichtstein D. (2007)
Diverse biological responses to different cardiotonic steroids.
Pathophysiology. 14: 159-66. *Review article
Last Updated Date : 11/11/2020
