- BBSRB B169
B.Sc. Tel-Aviv University, Israel
Ph.D. Tel-Aviv University, Israel
Postdoctoral fellow, University of Colorado Denver
The major interest of my research is the functional cross-talk between endocytic and signaling cellular machineries and how this applies to normal and cancer development. Endocytosis is a mechanism by which cells remove plasma membrane proteins, ligands, nutrients, lipids and other types of molecules from the cell-surface to the cell interior. One important aspect of endocytosis is that endocytosis provides spatial and temporal control of signaling. However, there are gaps in our knowledge of the mechanisms of endocytosis cross-talk with signaling cascades.
To address these questions, I am currently focusing on the extracellular signal-regulated kinases 1 and 2 (ERK1/2) signaling pathway. This pathway plays an essential role in several critical steps of embryonic development and tumor progression. It also controls critical cellular functions such as apoptosis, motility and differentiation. Although, kinases and phosphatases of this pathway have been extensively studied and targeted therapeutically, the mechanisms that determine the signal specificity and orchestrate the diverse biological outcomes of ERK1/2 signaling are still poorly understood.
Scaffold proteins are key players in the ERK1/2 signaling pathway that are thought to integrate incoming signals and deliver signaling specificity, and yet their role in signal propagation and the mechanisms of their action are still unknown. Our goal is to reveal how scaffold proteins are involved in the biological processes regulated by the ERK1/2 cascade. In this way, new therapeutic strategies can be developed to target this cascade more specifically and without affecting its other essential biological functions.
Current studies in my lab are aiming to determine the mechanisms underlying the ability of the scaffold protein, Shoc2, to accelerate ERK1/2 signals. Shoc2 protein is essential for embryonic development and a critical regulator of ERK1/2 activity. We found that Shoc2 creates a signaling hub that regulates ERK's developmental signals in a spatio-temporal manner. To provide a detailed understanding of how Shoc2 is involved in determining the specificity of ERK1/2 signaling outcomes we employ state-of-the-art innovative microscopy, genetic (zebrafish model), molecular, and cellular approaches.
Our research will contribute to the advancement of novel therapeutic strategies and innovations for treatment of developmental disorders and cancer progression and potentially will result in improved therapies with low toxicity.
- Song, E.S.;Jang, H.;Guo, H.F.;Juliano, M.A.;Juliano, L.;Morris, A.J.;Galperin, E.;Rodgers, D.W.;Hersh, L.B. "Inositol phosphates and phosphoinositides activate insulin-degrading enzyme, while phosphoinositides also mediate binding to endosomes." Proceedings of the National Academy of Sciences of the United States of America 114, 14 (2017): E2826-E2835. [PubMed Link] | [ Full text ]
- Jeoung, M.;Jang, E.R.;Liu, J.;Wang, C.;Rouchka, E.C.;Li, X.;Galperin, E. "Shoc2-tranduced ERK1/2 motility signals--Novel insights from functional genomics." Cellular signalling 28, 5 (2016): 448-59. [PubMed Link] | [ Full text ]
- Rouchka, E.C.;Jeoung, M.;Jang, E.R.;Liu, J.;Wang, C.;Li, X.;Galperin, E. "Data set for transcriptional response to depletion of the Shoc2 scaffolding protein." Data in brief 7, (2016): 770-8. [PubMed Link] | [ Full text ]
- Jang, E.R.;Galperin, E. "The function of Shoc2: A scaffold and beyond." Communicative & integrative biology 9, 4 (2016): e1188241. [PubMed Link] | [ Full text ]
- Jang, E.R.;Jang, H.;Shi, P.;Popa, G.;Jeoung, M.;Galperin, E. "Spatial control of Shoc2-scaffold-mediated ERK1/2 signaling requires remodeling activity of the ATPase PSMC5." Journal of cell science 128, 23 (2015): 4428-41. [PubMed Link] | [ Full text ]
- Jang, E.R.;Shi, P.;Bryant, J.;Chen, J.;Dukhande, V.;Gentry, M.S.;Jang, H.;Jeoung, M.;Galperin, E. "HUWE1 is a molecular link controlling RAF-1 activity supported by the Shoc2 scaffold." Molecular and cellular biology 34, 19 (2014): 3579-93. [PubMed Link] | [ Full text ]
- Hannig, V.;Jeoung, M.;Jang, E.R.;Phillips JA, 3rd;Galperin, E. "A Novel SHOC2 Variant in Rasopathy." Human mutation 35, 11 (2014): 1290-4. [PubMed Link] | [ Full text ]
- Fuqua, J.L.;Littrell, O.M.;Lundblad, M.;Turchan-Cholewo, J.;Abdelmoti, L.G.;Galperin, E.;Bradley, L.H.;Cass, W.A.;Gash, D.M.;Gerhardt, G.A. "Dynamic changes in dopamine neuron function after DNSP-11 treatment: effects in vivo and increased ERK 1/2 phosphorylation in vitro." Peptides 54, (2014): 1-8. [PubMed Link] | [ Full text ]
- Jeoung, M.;Galperin, E. "Visualizing of signaling proteins on endosomes utilizing knockdown and reconstitution approach." Methods in enzymology 534, (2014): 47-63. [PubMed Link] | [ Full text ]
- Jeoung, M.;Abdelmoti, L.;Jang, E.R.;Vander Kooi, C.W.;Galperin, E. "Functional Integration of the Conserved Domains of Shoc2 Scaffold." PloS one 8, 6 (2013): e66067. [PubMed Link] | [ Full text ]
- Galperin, E.;Abdelmoti, L.;Sorkin, A. "Shoc2 is targeted to late endosomes and required for Erk1/2 activation in EGF-stimulated cells." PloS one 7, 5 (2012): e36469. [PubMed Link] | [ Full text ]
- Galperin, E.;Sorkin, A. "Endosomal targeting of MEK2 requires RAF, MEK kinase activity and clathrin-dependent endocytosis." Traffic (Copenhagen, Denmark) 9, 10 (2008): 1776-90. [PubMed Link] | [ Full text ]
- Rapaport, D.;Auerbach, W.;Naslavsky, N.;Pasmanik-Chor, M.;Galperin, E.;Fein, A.;Caplan, S.;Joyner, A.L.;Horowitz, M. "Recycling to the plasma membrane is delayed in EHD1 knockout mice." Traffic (Copenhagen, Denmark) 7, 1 (2006): 52-60. [PubMed Link] | [ Full text ]
- Galperin, E.;Sorkin, A. "Visualization of Rab5 activity in living cells using FRET microscopy." Methods in enzymology 403, (2005): 119-34. [PubMed Link] | [ Full text ]
- Galperin, E.;Verkhusha, V.V.;Sorkin, A. "Three-chromophore FRET microscopy to analyze multiprotein interactions in living cells." Nature methods 1, 3 (2004): 209-17. [PubMed Link] | [ Full text ]
- Sorkina, T.;Doolen, S.;Galperin, E.;Zahniser, N.R.;Sorkin, A. "Oligomerization of dopamine transporters visualized in living cells by fluorescence resonance energy transfer microscopy." The Journal of biological chemistry 278, 30 (2003): 28274-83. [PubMed Link] | [ Full text ]
- Galperin, E.;Sorkin, A. "Visualization of Rab5 activity in living cells by FRET microscopy and influence of plasma-membrane-targeted Rab5 on clathrin-dependent endocytosis." Journal of cell science 116, Pt 23 (2003): 4799-810. [PubMed Link] | [ Full text ]
- Galperin, E.;Benjamin, S.;Rapaport, D.;Rotem-Yehudar, R.;Tolchinsky, S.;Horowitz, M. "EHD3: a protein that resides in recycling tubular and vesicular membrane structures and interacts with EHD1." Traffic (Copenhagen, Denmark) 3, 8 (2002): 575-89. [PubMed Link] | [ Full text ]
- Rotem-Yehudar, R.;Galperin, E.;Horowitz, M. "Association of insulin-like growth factor 1 receptor with EHD1 and SNAP29." The Journal of biological chemistry 276, 35 (2001): 33054-60. [PubMed Link] | [ Full text ]
- Haider, N.B.;Searby, C.;Galperin, E.;Mintz, L.;Horowitz, M.;Stone, E.M.;Sheffield, V.C. "Evaluation and molecular characterization of EHD1, a candidate gene for Bardet-Biedl syndrome 1 (BBS1)." Gene 240, 1 (1999): 227-32. [PubMed Link] | [ Full text ]
- Mintz, L.;Galperin, E.;Pasmanik-Chor, M.;Tulzinsky, S.;Bromberg, Y.;Kozak, C.A.;Joyner, A.;Fein, A.;Horowitz, M. "EHD1--an EH-domain-containing protein with a specific expression pattern." Genomics 59, 1 (1999): 66-76. [PubMed Link] | [ Full text ]
- Moran, D.;Galperin, E.;Horowitz, M. "Identification of factors regulating the expression of the human glucocerebrosidase gene." Gene 194, 2 (1997): 201-13. [PubMed Link] | [ Full text ]