Address
UNMC
College of Medicine
984525 UNMC
Omaha, NE 681984525

Nebraska Center for Cellular Signaling

Telephone: (402) 559-7556
Fax: (402) 559-6550
Email: scaplan@unmc.edu  

Education:

• B.S./M.S. Hebrew University, Jerusalem
• Ph.D. Hebrew University, Jerusalem

• The primary research interests of this lab focus on studying the molecular mechanisms regulating the recycling of receptors back to the plasma membrane. Integrins are the major eukaryote receptors for cell adhesion to the extracellular matrix (ECM). Upon ligand binding, integrin receptors cluster to cytoskeleton-linked focal adhesion complexes and play significant roles in cancer cells, affecting signal transduction, gene expression, proliferation, apoptosis regulation, invasion, metastasis, and angiogenesis as well as neovascularization of tumors. To properly function and transmit signals, integrins must localize to the plasma membrane and be able to relocate to focal adhesions. Our laboratory is studying the mechanisms by which receptors, such as integrins, are internalized and recycled to the plasma membrane. We have recently identified the proteins EHD1 and Rabenosyn-5 as critical components of the recycling pathway, and are now utilizing this knowledge to define the role of recycling in integrin-mediated signal transduction and downstream events. These studies are expected to have important ramifications for cancer, because a clear understanding of the elements controlling signaling via focal adhesions is essential for the development of tools to impair aberrant cell growth.

• National Institutes of Health 1R01GM074876 (PI: Caplan) 5/1/06 - 4/30/11 Molecular Mechanisms Controlling Endocytic Recycling The overall objectives of this proposal are to better understand the molecular mechanisms that regulate the recycling of cell surface receptors to the plasma membrane, particularly in defining the role of EHD proteins in regulating transport between early endosomes to the recycling compartment.
• American Heart Association- 0465342z (PI: Caplan) 07/01/04-06/30/06 Beginning Grant-in-Aid Role of endocytic recycling regulatory proteins and their impact on cholesterol trafficking The overall objective of this project is to understand the impact of recycling on cholesterol trafficking.
• National Institutes of Health 1R01CA113903-01- (PI: Mehta) 4/1/05 - 3/31/10 Co-investigator: Caplan (2%) Cell-Cell Communication and Chemoprevention of Prostate Cancer The overall objective is to assess the role of retinoids and vitamin D3 on gap junctions.
• Nebraska Departent of Health LB506 (Caplan: PI) 7/1/07-30/6/08 Role of EHD4 in Endocytic Transport and Signaling
• UNMC Eppley Cancer Center Translational Collaborative Research Award (PI: Caplan, Co-investigator: Sorgen) 02/01/07-31/01/08 A Structural Approach to EHD1-mediated Regulation of ? 1 Integrin Function
• Source: National Institutes of Health, National Cancer Institute (R01) Title: Role of hyaluronan matrix in prostate cancer progression Role: Principal investigator Period of support: 7/1/05-4/30/10
• Source: National Institutes of Health (R01) Title: Structure/function studies of the HA receptor for endocytosis Role: Subcontracted collaborator (PI: Paul H. Weigel, University of Oklahoma) Period of support: 7/1/04-6/30/08
• Source: American Heart Association Title: Characterization of disrupted multi-subunit enzyme interactions that impair cardiac valve development and function Role: Principal investigator Period of support: 7/01/07-6/30/09

• Steve Caplan, Osnat Almogi-Hazan, Analia Ezernitchi, Efrat Manaster., Aviv Gazit, and Michal Baniyash. The cytoskeleton-associated TCR zeta chain is constitutively phosphorylated in the absence of an active p56(lck) form. Eur. J. Immunol., 2001, 31:580-589.
• Steve Caplan and Juan S. Bonifacino. Book chapter entitled: "Lysosomes" in: Intracellular pathogens in membrane interactions and vacuole biogenesis. Ed. Jean-Pierre Gorvel, Landes Bioscience, (ISBN: 0-306-47833-1) 2002.
• Steve Caplan and Michal Baniyash. Protein labeling by iodination. Current Protocols in Cell Biology. In Press.
• Steve Caplan, Lisa M. Hartnell, Ruben C. Aguilar, Naava Naslavsky and Juan S. Bonifacino. Human Vam6p promotes lysosome clustering and fusion in vivo. J. Cell Biol., 2001, 154:109-122.
• Theresa H. Ward, Roman S. Polishchuk, Steve Caplan, Koret Hirschberg, and Jennifer Lippincott-Schwartz. Maintenance of Golgi structure and function depends on the integrity of ER export machinery. J. Cell. Biol., 2001, 155:557-570.
• Steve Caplan, Naava Naslavsky, Lisa M. Hartnell, Robert Lodge, Roman S. Polishchuk, Julie G. Donaldson and Juan S. Bonifacino. A tubular EHD1-containing compartment involved in the recycling of Major histocompatibility complex class I molecules to the plasma membrane. EMBO J, 2002, 21:2557-2567.
• Naava Naslavsky, Markus Boehm, Peter Backlund, Jr. and Steve Caplan*. Rabenosyn-5 and EHD1 interact and sequentially regulate recycling to the plasma membrane. Mol. Biol. Cell, 2004, 15: 2410-2422.
• Naava Naslavsky and Steve Caplan*. C-terminal EH-domain containing proteins: Consensus for a role in endocytic trafficking, EH? J. Cell Sci., 2005, 18:4093-4101.
• Naava Naslavsky, Juliati Rahajeng, Mahak Sharma, Marko Jovic and Steve Caplan*. A novel interaction between EHD3 and Rab11-FIP2 links EHD-family proteins to Rab11-mediated transport. Mol. Biol. Cell, 2006, 17:163-177.
• Deborah Rapaport, Wojtek Auerbach, Naava Naslavsky, Metsada Pasmanik-Chor, Emilia Galperin, Amos Fein, Steve Caplan, Alexandra L. Joyner, and Mia Horowitz. Recycling to the plasma membrane is delayed in EHD1 knockout mice. Traffic, 2006, 7:52-60.
• Masato Maeda, Emhonta Johnson, Shymali Mandal, Kathryn R. Lawson, Robert A. Svoboda, Steve Caplan, Keith R. Johnson and Margaret J. Wheelock. Expression of inappropriate cadherins by epithelial timor cells promotes endocytosis and degradation of E-cadherin via competition for p120ctn. Published online, Oncogene, 2006.
• Marko Jovic, Naava Naslavsky, Debora Rapaport, Mia Horowitz and Steve Caplan * . EHD1 regulates ? 1 integrin endosomal transport: effects on focal adhesions, cell spreading and migration . J. Cell Sci., 2007, 120:802-814.
• Naava Naslavsky, Juliati Rahajeng, Debora Rapaport, Mia Horowitz and Steve Caplan. Steve Caplan * . EHD1 regulates cholesterol homeostasis and lipid droplet storage. Biochem. Biophys. Res. Comm., 2007, 357:792-799.
• Naava Naslavsky, Juliati Rahajeng, Sylvie Chenavas, Paul L. Sorgen * and Steve Caplan * . EHD1 and Eps15 interact with phosphatidylinositols via their EH-domains . J. Biol. Chem., 2007, J. Biol. Chem., 2007, 282:16612-16622.
• Joseph T. Roland, Anne K. Kenworthy, Johan Peranen, Steve Caplan and James R. Goldenring. Rab8a interacts with Myosin Vb on a tubular network containing EHD1 and EHD3 . Mol. Biol. Cell, 2007, 18:2828-2837.
• Mahak Sharma, Marko Jovic and Steve Caplan * . Epidermal Growth Factor receptor Tyrosine Kinase Substrate (Eps15) . Targeted Protein Database, 2007.
• Fabien Kieken, Marko Jovic, Naava Naslavsky, Steve Caplan * and Paul L. Sorgen * . NMR structure note: EH domain of EHD1 . Accepted pending minor revision, J. Biomolecular NMR.