Professor, Biochemistry and Molecular Biology, Vice Chair for Administration, Director of the UNMC Advanced Microscopy Core Facility
Phone: 402-559-7556 (Office)
Current Lab Members:
Naava Naslavsky, Ph.D. (Hebrew University), Co-investigator
Shuwei Xie, Ph.D. (UNMC), Post-doctoral fellow
Kriti Bahl, Doctoral graduate student
Trey Farmer, Doctoral graduate student
Former Lab Members (graduate students):
Mahak Sharma, Ph.D., Assistant Professor (tenured), Indian Institute of Science
Education and Research, Mohali, India
Marko Jovic, Ph.D., Biochemistry Course Mentor at Western Governors University
Juliati Rahajeng, Ph.D., Post-doctoral fellow, UCSD
Sai Srinivas Panapakkam Giridharan, Post-doctoral fellow, Univ. of Michigan, Ann Arbor,
Bishuang Cai, Ph.D., Post-doctoral fellow, Columbia University
James Reinecke, MD/Ph.D., Resident-fellow, University of Iowa
Cali Reiling, M.Sc., Ph.D. student, UNMC
Former Lab Members (Post-doctoral fellows):
Jing Zhang, PhD., Assistant Professor of Practice of Biochemistry, Univ. of Nebraska at
Laura Simone, Ph.D., Senior Medical Writer, PRIME Education LLC
Dawn Katafiasz, B.Sc.
Linda Kelsey, B.Sc.
Dr. Caplan is a recipient of the 2008 UNMC Distinguished/New Investigator Award and a 2010 recipient of the UNMC Distinguished Investigator Award. He also received UNMC's Outstanding Faculty Mentor of Graduate Students Award in 2011, and the Thomas Maciag Award in 2012, a national award for combined research excellence and mentorship. He serves on the editorial board of The Journal of Biological Chemistry PLoS One, and Frontiers in Cell and Developmental Biology, is a regular member of the NIH Nuclear Cytoplasmic Structure function Dynamics (NCSD) study-section, and previously chaired a review committee at the American Heart Association.
The Caplan laboratory prides itself on the success of its graduate students and lab members. Of the 9 Ph.D. students that have graduated, 4 have received the very top UNMC honor, the Thomas Jefferson Award for ingenuity and extensive productivity (Marko, Mahak, Sai and James). All students have graduated with a minimum of 5 strong publications in the course of their dissertation research, with some as many as 12 and 6 first-author papers and reviews. More importantly, Caplan laboratory alumni have made important scientific contributions that have been recognized nationally and internationally. Students from the lab have gone on to the very top laboratories at elite institutions (Harvard, Columbia, UCSD, U Michigan, NIH, etc.), have received prestigious fellowships, and have moved on to academic positions.
In our laboratory, we believe that basic research driven by curious and dedicated researchers will lead to significant biomedical discoveries. Our philosophy is that research should be driven by the questions that are asked, and not by the techniques that are commonly used. For these reasons, students in the Caplan laboratory will be exposed to a wide range of new and evolving techniques in biochemistry, molecular, structural, cell biology and biophysics, and will likely have opportunities to collaborate with multiple laboratories on campus, in the US and abroad.
Ph.D., Hebrew University, Jerusalem, 1998
Student Rotation Opportunities Available
Rotation opportunities are available for highly motivated students. Contact Dr. Caplan for additional information (email@example.com).
The Caplan laboratory is interested in understanding the basic mechanisms and pathways that control the movement of receptors, proteins and lipids from point to point within the cell—a process known as “MEMBRANE TRAFFICKING,” or “VESICULAR TRANSPORT.”
This schematic diagram illustrates some of the endocytic pathways in which receptors travel, once they have been internalized from the cell membrane, and it depicts key proteins that regulate these processes. Rab GTP-binding proteins and Eps15 homology Domain (EHD) proteins are among some of the proteins we study. Multiple studies from our lab and others have implicated these proteins in the steps needed to move proteins from organelle to organelle within the cell, or to recycle receptors back to the plasma membrane.
The internalization of cell surface molecules from the plasma membrane is a critical event for all eukaryotic cells. While many internalized molecules are degraded in the endo-lysosomal pathway, many receptors, proteins and other molecules undergo sequential rounds of recycling back to the plasma membrane. Endocytic recycling is key for the control of cell surface receptors on the plasma membrane. Since most receptors generally transduce signals only when bind ligands at the plasma membrane (PM), this means that regulation of their localization to the PM may have a critical impact on signal transduction, and cell proliferation, which is directly related to cancer. Endocytic recycling also governs the flow of nutrients into the cell, and can compensate for the loss of membrane lipids incurred during the process of internalization. Other specialized recycling functions include: synaptic vesicle recycling, iron homeostasis in liver, MHC Class II and MHC Class I molecules, transcytosis of Transferrin receptor and Immunoglobulin A (IgA) across polarized epithelial cells, and insulin-dependent glucose transport in muscle and adipose cells.
Since our laboratory follows our discoveries wherever they lead, research in the lab has expanded to studying the actin cytoskeleton and regulation of actin polymerization, the process of cytokinesis and cell division, the study of primary cilia and their biogenesis, centrosome biology, and most recently, mitochondrial dynamics and their continual fusion and fission.
Recent Papers (last 5 years):
45. Naava Naslavsky and Steve Caplan*. EHD proteins: Key conductors of endocytic transport. Trends Cell Biol. 2011, 21(2):122-31.
46. Sai Srinivas Panapakkam Giridharan, Jennifer L. Rohn, Naava Naslavsky and Steve Caplan*. Differential regulation of actin microfilaments by human MICAL proteins. J. Cell Sci., 2012, 125:614-624.
47. Juliati Rahajeng, Sai Srinivas Panapakkam Giridharan, Bishuang Cai, Naava Naslavsky, Steve Caplan*. MICAL-L1 is a tubular endosomal membrane hub that connects Rab35 and Arf6 with Rab8a. Traffic, 2012, 13:82-93.
48. Jing Zhang, Naava Naslavsky and Steve Caplan*. Rabs and EHDs: alternate modes for traffic control. Biosci. Rep., 2012, 32:17-23.
49. Hayley L. Peters, Amit Tuli , Mahak Sharma, Naava Naslavsky , Steve Caplan, Richard G. Macdonald, and Joyce C. Solheim. Regulation of major histocompatibility complex class I molecule expression on cancer cells by amyloid precursor-like protein 2. Immunologic Research, 2011, 51:39-44.
50. Jing Zhang, Calliste Reiling, James B. Reinecke, Iztok Prislan, Luis A. Marky, Paul L. Sorgen,
Naava Naslavsky* and Steve Caplan*. Rabankyrin-5 interacts with EHD1 and Vps26 to regulate
endocytic trafficking and retromer function. Traffic, 2012, 13:745-57.
51. Bishuang Cai, Steve Caplan and Naava Naslavsky. cPLA2a and EHD1 interact and regulate the vesiculation of cholesterol-rich GPI-anchored protein-containing endosomes. Mol. Biol. Cell, 2012, 23:1874-1888.
52. Sai Srinivas Panapakkam Giridharan, Bishuang Cai, Naava Naslavsky and Steve Caplan*. Trafficking cascades mediated by Rab35 and its membrane hub effector, MICAL-L1. Communicative and Integrative Biology, 2012, 1;5(4):384-387.
53. Jenna E. McKenzie, Brent Raisley, Xin Zhou, Naava Naslavsky, Tomohiko Taguchi, Steve Caplan and David Sheff. Retromer guides STxB and CD8-M6PR from early to recycling endosomes, EHD1 guides STxB from recycling endosome to Golgi. Traffic, 2012, 13:1140-59.
54. Jing Zhang, Naava Naslavsky and Steve Caplan*. EHDs meet the retromer: complex regulation of retrograde transport. Cellular Logistics, 2012, 2:161-165.
Caplan*. Cooperation of MICAL-L1, Syndapin2 and phosphatidic acid in tubular recycling endosome biogenesis@. Mol. Biol. Cell, 2013, 24:1776-1790.
56. Gaelle Spagnol, Calliste Reiling, Fabien Kieken, Steve Caplan*, and Paul L. Sorgen*.
Chemical Shift Assignments of the C-terminal Eps15 Homology Domain-3 EH Domain. Biomolecular NMR Assignments, 2013 Jun 11. [Epub ahead of print]
57. Sai Panapakkam Giridharan and Steve Caplan*. MICAL-Family Proteins: Complex Regulators of the Actin Cytoskeleton. Antioxid. Redox Signal. 2014 May 1;20(13):2059-73. doi: 10.1089/ars.2013.5487. Epub 2013 Aug 17.
58. Bishuang Cai, Sai Panapakkam Giridharan, Jing Zhang, Sugandha Saxena, Kriti Bahl, John Schmidt, Wei Guo, Naava Naslavsky, and Steve Caplan*. Differential roles of C-terminal Eps15 Homology Domain proteins as vesiculators and tubulators of recycling endosomes. J. Biol. Chem. 2013, 8;288(42):30172-80. doi: 10.1074/jbc.M113.488627
59. Laura C. Simone, Steve Caplan* and Naava Naslavsky. Role of phosphatidylinositol 4,5-bisphosphate in regulating EHD2 plasma membrane localization. In press, PloS ONE, 2013, Sep 10;8(9):e74519. doi: 10.1371/journal.pone.0074519. eCollection 2013.
60. Laura C. Simone, Naava Naslavsky and Steve Caplan*. Scratching the Surface: Actin’ and other roles for the C-Terminal Eps15 Homology Domain Protein, EHD2. Histol Histopath, 2014, 29(3):285-292.
61. James B. Reinecke, Dawn Katafiasz, Naava Naslavsky, and Steve Caplan*. Regulation of Src trafficking and activation by the endocytic regulatory proteins, MICAL-L1 and EHD1. J Cell Sci. 2014 Apr 15;127(Pt 8):1684-98. doi: 10.1242/jcs.133892. Epub 2014 Jan 30. PMID: 24481818 [PubMed – in process].
62. James B. Reinecke and Steve Caplan*. Endocytosis and the Src family of non-receptor tyrosine kinases. Biomol Concepts, 2014 May 31;5(2):143-55. doi: 10.1515/bmc-2014-0003.
63. Bishuang Cai, Shuwei Xie, Fengming Liu, Laura C. Simone, Steve Caplan*, Xuebin Qin and Naava Naslavsky. Rapid degradation of the complement regulator, CD59, by a novel inhibitor. J Biol Chem. 2014 Apr 25;289(17):12109-25. doi: 10.1074/jbc.M113.547083. Epub 2014 Mar 10. PMID:24616098 [PubMed - in process].
64. Bishuang Cai, Shuwei Xie, Steve Caplan* and Naava Naslavsky. GRAF1 forms a complex with MICAL-L1 and EHD1 to cooperate in tubular recycling endosome vesiculation. Frontiers in Cell and Developmental Biology, 2014 May 27;2:22. doi: 10.3389/fcell.2014.00022. eCollection 2014.
65. Hanjun Li, Gaelle Spagnol, Naava Naslavsky, Steve Caplan and Paul L. Sorgen. Tyrosine phosphatase TC-PTP directly interacts with connexin43 to regulate gap junction intercellular communication. J Cell Sci. 2014 Aug 1;127(Pt 15):3269-79. pii: jcs.145193. [Epub ahead of print].
66. Shuwei Xie, Naava Naslavsky and Steve Caplan*. Diacylglycerol kinase alpha regulates tubular recycling endosome biogenesis and major histocompatibility complex class I recycling. J. Biol. Chem. 2014 Nov 14;289(46):31914-26. pii: jbc.M114.594291. [Epub ahead of print].
67. James B. Reinecke, Dawn Katafiasz, Naava Naslavsky, and Steve Caplan*. Novel functions for the endocytic regulatory proteins MICAL-L1 and EHD1 in mitosis. Traffic, 2014 Oct 7. doi: 10.1111/tra.12234. [Epub ahead of print] &
68. Quanlong Lu, Christine Insinn, Carolyn Ott, Jimmy Stauffer, Petra Pintado, Juliati Rahajeng, Ulrich Baxa, Vijay Wali, Adrian Cuenca, Yoo-Seok Hwang, Ira O. Daar, Susana Lopes, Jennifer Lippincott-Schwartz, Peter K. Jackson, Steve Caplan, Christopher J. Westlake. Early steps in primary cilium assembly require EHD1/EHD3-dependent ciliary vesicle formation. Nature Cell Biology, 2015 Mar;17(3):228-40. doi: 10.1038/ncb3109. Epub 2015 Feb 16.
69. Poomy Pandey, Satyanarayana Rachagani, Srustidhar Das, Parthasarathy Seshacharyulu, Yuri Sheinin, Naava Naslavsky, Zenggang Pan, Brittney L. Smith, Haley L. Peter, Prakash Radhakrishnan, Nicole R. McKenna, Sai Srinivas Panapakkam Giridharan, Danya Haridas, Sukwinder Kaur, Michael A. Hollingsworth, Richard G. MacDonald, Jane L. Meza, Steve Caplan, Surinder K. Batra, and Joyce C. Solheim. Amyloid precursor-like protein 2 (APLP2) affects the actin cytoskeleton and increases pancreatic cancer growth and metastasis. Oncotarget, 2015 Feb 10;6(4):2064-75.
70. Kriti Bahl, Naava Naslavsky and Steve Caplan*. Role of the EHD2 unstructured loop in dimerization, protein binding and subcellular localization. PLoS One. 2015 Apr 15;10(4):e0123710. doi: 10.1371/journal.pone.0123710. eCollection 2015.
71. Caitlin O. McAtee, Abigail R. Berkebile, Christian G. Elowsky, Teresa Fangman, Joseph J. Barycki, James K. Wahl 3rd, Oleh Khalimonchuk, Naava Naslavsky, Steve Caplan, and Melanie A. Simpson. Hyaluronidase Hyal1 increases tumor cell proliferation and motility through accelerated vesicle trafficking. J. Biol. Chem. 2015, 290(21):13144-56, Apr 8. pii: jbc.M115.647446. [Epub ahead of print] PMID: 25855794.
72. James B. Reineke, Shuwei Xie, Naava Naslavsky and Steve Caplan*. Qualitative and quantitative analysis of endocytic recycling. Methods in Cell Biology, 2015, 130:139-55.
73. Shuwei Xie, Naava Naslavsky and Steve Caplan*. Novel endocytic functions for diacylglycerol kinases. In press, Cellular Logistics, 2015.
74. Shuwei Xie, Kriti Bahl, James B. Reinecke, Gerald R.V. Hammond, Naava Naslavsky and Steve Caplan*. The endocytic recycling compartment maintains cargo segregation acquired upon exit from the sorting endosome. Mol. Biol. Cell, 2016, 7:108-26.
75. Kriti Bahl, Shuwei Xie, Gaelle Spagnol, Paul Sorgen, Naava Naslavsky, and Steve Caplan*. EHD3 Protein Is Required for Tubular Recycling Endosome Stabilization, and an Asparagine-Glutamic Acid Residue Pair within Its Eps15 Homology (EH) Domain Dictates Its Selective Binding to NPF Peptides. J. Biol Chem. 2016 Jun 24;291(26):13465-78. doi: 10.1074/jbc.M116.716407. Epub 2016 May 4.
76. Steve Caplan*. Into the linker’s DENN: A tyrosine’s control of autophagy. J. Biol Chem. 2017, 292(17): 7283-7284. DOI 10.1074/jbc.H116.772434 .
77. Trey Farmer, James B. Reinecke, Shuwei Xie, Kriti Bahl, Naava Naslavsky and Steve Caplan*. Control of Mitochondrial Homeostasis by Endocytic Regulatory Proteins. J Cell Sci. 2017 Jun 8. pii: jcs.204537. doi: 10.1242/jcs.204537. [Epub ahead of print] PMID: 28596240