Epithelial cells form sheets of cells that separate body compartments. The epithelial cells are joined together along their lateral membranes by several types of junctions (see figure), the tight junction located at the apicolateral region of the epithelial cell membrane (zonula occludens), the adherens junction located under the tight junction (zonula adherens), and desmosomes located in the basolateral region of the epithelial cell membrane. The tight junctions form a circumferential seal between adjacent epithelial cells. This creates a barrier limiting the movement of molecules from one body compartment to another. Molecules can cross the epithelial cell sheet from one body compartment to the other either by moving through the epithelial cells (Transcellular Pathway), via specific membrane transporters in the apical and basolateral membranes, or by moving between adjacent epithelial cells (Paracellular Pathway), through the tight junctions.
See below for the PI's CV and some of our recent publications. Please look at the subpages for further information about tight junctions, paracellular permeability, and the research activities on-going in our lab.
Amsler CV
Kurt Amsler, Ph.D.
Associate Dean for Research
Professor, Department of Biomedical Sciences
Rockefeller Building, Room 314F
NYIT College of Osteopathic Medicine
New York Institute of Technology
Northern Boulevard
Old Westbury, NY 11568-8000
Phone – (516) 686-3716
email – kamsler@nyit.edu
Academic Appointments
1986-1990 Assistant Professor Department of Physiology and Biophysics
Mt. Sinai School of Medicine
New York, NY
1991-2002 Assistant Professor Department of Physiology and Biophysics
UMDNJ-Robert Wood Johnson Medical School
Piscataway, NJ
2002-2004 Assistant Professor Division of Nephrology
Department of Medicine
Mt. Sinai School of Medicine
New York, NY
2004-2007 Associate Professor Division of Nephrology
Department of Medicine
Mt. Sinai School of Medicine
New York, NY
2007-present Professor Department of Biomedical Sciences
NYIT College of Osteopathic Medicine
Old Westbury, NY
Administrative Appointments
2007-present Associate Dean Office of Research
for Research NYIT College of Osteopathic Medicine
Old Westbury, NY
Employment History
2001-2002 Group Leader Biology Group
TransForm Pharmaceuticals
Waltham, MA
2002-2003 Senior Scientist BioSource
Hopkinton, MA
Education
1971-1975 New College B.A.
1975-1978 University of Toronto M.Sc.
1979-1982 University of Tennessee-Oak Ridge
Graduate School of Biomedical Sciences Ph.D.
Postdoctoral Training
1982-1984 Yale University Medical School; Advisor – Dr. E.A. Adelberg
1984-1986 Max-Planck-Institute for Systemphysiology; Advisor – Dr. R.K.H. Kinne
Grant History
Completed
2012-2016 NIDDK 1 R15 DK091749-01A1 PI – Kurt Amsler
“Src Family Kinases and Control of Epithelial Paracellular Permeability”
2003-2008 NIDDK 1-P01-DK062345-01A1
PPG – “Development of Novel Therapeutics for PKD”
Project 2 – “Signal Transduction by Polycystin-1” PI – Kurt Amsler
2002-2004 NICHD 1-R03-HD40824-01 PI – Kurt Amsler
“ErbB3 Receptor and Renal Development”
2001-2004 accepted position in startup biotech company
2000-2001 UMDNJ Foundation
1998-1999 Charles T. Culpeper Foundation
1995-1997 American Heart Association, New Jersey Affiliate
1994-1997 American Heart Association, National Affiliate
1991-1994 American Heart Association, National Affiliate
1988-1990 Cystic Fibrosis Foundation
1988-1991 Investigatorship, American Heart Association, New York City Affiliate
1988-1990 Young Investigator Award, National Kidney Foundation
1986 Lucille P. Markey Fellowship, Mount Desert Island Biological Laboratory
Patents
US Patent Application #20050233461
Levinson, D, K. Amsler, and M. Peterson. “HIGH-THROUGHPUT METHODS AND SYSTEMS FOR SCREENING OF COMPOUNDS TO TREAT/PREVENT KIDNEY DISORDERS”
Other Professional Activities
Reviewer – Grant Applications
1986-2000 Ad Hoc Reviewer for National Science Foundation grant applications (as requested basis)
1994-1996 Reviewer; Study Section A, American Heart Association, New Jersey
Affiliate
1996 Reviewer; Ad Hoc Study Section for NIH Centers of Excellence in
Pediatric Nephrology and Urology
1996, 1997 Ad Hoc Reviewer for Wellcome Trust grant applications (as
requested basis)
1998-2000 Reviewer; Study Section, National Kidney Foundation of New York/New
Jersey
2003 Reviewer, NIH Special Emphasis Panel (ZRG1 SSS-M (57)) “Research
Opportunities in Tissue Engineering”
2008-2013 Reviewer; American Heart Association, Molecular Signaling Study
Group
Reviewer – Manuscripts
1986-present Reviewer for manuscript submissions to multiple journals including
American Journal of Physiology (Cell Physiology and Renal Physiology),
Journal of Cell Biology, Journal of Cellular Physiology, Journal of
Membrane Biology, Biochimica Biophysica Acta, Journal of
Biological Chemistry, Journal of Experimental Biology and Medicine,
Biochemical Pharmacology
Thesis Committee Member
7/12 Justin Costa, Mt. Sinai School of Medicine
mentor – Basil Hanss, Ph.D.
“Evidence of Nucleic Acid Transport”
7/12-12/2016 Qualifying Exam Committee Member/Thesis Committee Member, Miriam
Fein, Stony Brook University/Cold Spring Harbor Laboratories
Mentor – Mikala Egblad, Ph.D.
“Contributions of CCR2-Expressing Host Cells To Breast Cancer
Metastasis”
Symposium Organizer
1999 Organizer; FASEB Symposium
“Asymmetric Receptor Signaling in Polarized Epithelia”
Committees
2012-2014 American Osteopathic Association, Osteopathic Research Strategic
Plan – member
2012-2016 American Society of Nephrology, Biomedical Research Advisory
Group – member
2013 American Society of Nephrology, PhD Task Force, - member
2013 American Society of Nephrology, Kidney Week Strategic Assessment
Task Force – member
2015 American Society of Nephrology, Blue Ribbon Panel on Career
Development in Nephrology – member
2016 American Society of Nephrology, 2nd PhD Task Force – member
2017-2019 American Society of Nephrology, Career Advancement
Committee – member
2017-2020 Association of Academic Health Centers, Vice Presidents for Research,
VPR meeting planning committee – member
2018-present American Society of Nephrology Pre-Doctoral Fellowship Program
Review Committee – chair
2018-present American Society of Nephrology Kidney Tutored Research and Education
for Kidney Scholars – application review sub-committee
2021-present Association of Medical Schools of New York (AMSNY) Biosciences
Advisory Committee
Administrative Activities
2014-2018 Spearheaded effort to establish dual DO/PhD Program at NYITCOM
- Approved – fall, 2018 for incoming 2019 class
2009-present Coordinates laboratory and animal facility renovation efforts
Service
NYITCOM
2010 NYCOMEC Research Symposium (discussant)
2009-2018 NYITCOM Academic Senate – Senator
2008-2013 NYITCOM Reappointments and Promotions Committee – member
2014-present NYITCOM Reappointments and Promotions Committee – chair
2008-present NYITCOM Student Disciplinary Executive Committee – member
2008-2017 NYITCOM Facilities Committee – member
2008-2016 American Osteopathic Association Research Council – member
2007-present NYITCOM Research Advisory Group – chair
2007-present NYITCOM Summer Student Research Program – organizer
2007-present NYITCOM Fellows/Scholars Research Program – organizer
2012-present Advanced Research Core program – co-Director
Students and Trainees
Graduate Students (rotation/non-degree) 10
Graduate Students (degree) 9
Undergraduate Students (summer and in-term research projects) 26
High School Students (summer) 7
Medical Students (summer intern program and volunteer) 14
Medical Students (Fellows/Scholars Program) 15
Renal Fellows 4
Recent Students and Trainees (previous 5 years)
Daniel Chang Medical student (NYITCOM) 10/19-9/20
Christian Jakobsen Undergraduate student (Vassar) 6/19-8/19
Irene Qazi Undergraduate student (Loyola Marymount Univ) 6/19-8/19
Ashley Monaco Medical student (NYITCOM) 10/18-12/21
Jessica Abruzesse Medical student (NYITCOM) 10/17-9/19
Rhea Sharma Undergraduate student (NYIT) 10/17-1/19
Rania Muhieddine Medical Students (NYITCOM) 10/17-6/18
Sahar Bilar Medical student/M.Sc. (NYITCOM) 1/17-12/18
Shereen Teymour Medical student (NYITCOM) 5/16-7/17
Nileena Johnkutty Undergraduate student (NYIT) 2/16-6/18
Angelina Voronina Medical student (NYITCOM) 9/12-6/18
Teaching Activities
Medical School
1987-1990 Medical Physiology Review Sessions – osmosis and membrane
transport
1990 Medical Physiology Small Group Leader
1991-2000 Medical Physiology – renal physiology, acid-base physiology,
endocrinology, labs and small groups in all areas
2004-2007 Medical Physiology Small Group Leader
2004-2007 Cells and Molecules Small Group Leader
2012-2014 Introduction to Body Fluid and Ion Balance (5 hours)
2012-2014 Electrolyte and Acid-Base Disorders (2 hours)
2011-2014 Mechanisms of Diuretic Actions (2 hour lecture)
2012-present Introduction to Body Fluid Balance (2 hours)
2013-present Introduction to Membrane Transport and Bulk Transport (1 hour)
2015-present Introduction to Acid-Base Balance (1 hour)
Physician’s Assistants Program
1991-2000 Medical Physiology – renal physiology, acid-base physiology,
endocrinology
Graduate School
1993-1996 Cell and Molecular Biology Special Topics Seminar Course – Signal
Transduction Mechanisms
1994-1996 Co-Organizer, Cell and Molecular Biology Core Course
1997 Cell and Molecular Biology Special Topics Seminar Course –
Extracellular Matrix and Basement Membranes
1998-2000 Molecular Pharmacology – transepithelial transport and drug delivery
1999-2000 Member, Qualifying Exam Committee; Molecular Biosciences Graduate
Program
2004-2007 Graduate student journal club
2006 Responsible Conduct in Research, Small Group Leader
2006 Introduction to Journal Club, group leader
2007-present Introduction to Biomedical Research – Scholars Program
Publications
Original peer-reviewed articles
1. Amsler, K. and J.S. Cook. (1982) Development of Na+-dependent hexose transport in a cultured line of porcine kidney cells. Am. J. Physiol. 242: C94-C101. PMID:6277200
2. Amsler, K., C. Shaffer, and J.S. Cook. (1983) Growth-dependent AIB and MeAIB uptake in LLC-PK1 cells: effects of differentiation inducers and TPA. J. Cell. Physiol. 114: 184-190. PMID:6185510
3. Amsler, K. and J.S. Cook. (1985) Linear relationship of phlorizin-binding capacity and hexose uptake during differentiation in a clone of LLC-PK1 cells. J. Cell. Physiol. 122: 254-258. PMID:2578475
4. Amsler, K., J.J. Donahue, C.W. Slayman, and E.A. Adelberg. (1985) Stimulation of bumetanide-sensitive K+ transport in Swiss 3T3K fibroblasts by serum and mitogenic hormones. J. Cell. Physiol. 123: 257-263. PMID:3884636
5. Chaillet, J.R., K. Amsler, and W. Boron. (1986) Optical measurements of intracellular pH in single LLC-PK1 cells: demonstration of Cl--HCO3- exchange. Proc. Natl. Acad. Sci. (USA) 83: 522-526. PMID:3001738
6. Amsler, K. and R. Kinne. (1986) Photoinactivation of sodium-potassium-chloride cotransport in LLC-PK1/Cl 4 cells by bumetanide. Am. J. Physiol. 250: C799-C806. PMID:3010731
7. Wondergem, R. And K. Amsler. (1986) Transmembrane potentials of cultured rectal gland cells of Raja erinacea. MDIBL Bull. 26: 105-107
8. Jans, A.W.H., K. Amsler, B. Griewel, and R.K.H. Kinne. (1987) Regulation of intracellular pH in LLC-PK1 cells: studies using 31P NMR spectroscopy. Biochim. Biophys. Acta 927: 203-212. PMID:3028491
9. Haggerty, J.G., N. Agarwal, K. Amsler, C.W. Slayman, and E.A. Adelberg. (1987) Stimulation by serum of the Na+/H+ antiporter in quiescent pig kidney epithelial (LLC-PK1) cells and the role of the antiporter in the reinitiation of DNA synthesis. J. Cell. Physiol. 132: 173-177. PMID:3036891
10. Amsler, K. (1988) Chloride uptake pathways into primary cultures of Squalus acanthias rectal gland epithelial cells. MDIBL Bull. 28: 42-43
11. Amsler, K. (1990) Cyclic adenosine monophosphate modulates cell morphology and behavior of a cultured renal epithelial cell. Pediatric Nephrol. 4: 378-386.OMID:1698440
12. Amsler, K., S. Ghatani, and B.A. Hemmings. (1991) cAMP-dependent protein kinase regulates renal epithelial cell properties. Am. J. Physiol. 260: C1290-C1299. PMID:1711777
13. Amsler, K. (1993) Cell surface expression of DBA binding sites in LLC-PK1 cells increases at confluence and is enhanced by PKA activation. J. Cell. Physiol. 156: 469-479. PMID:7680571
14. Amsler, K. (1993) cAMP-dependent protein kinase modulates expression and subcellular localization of Dolichos biflorus agglutinin binding sites in renal epithelial cells. J. Cell. Biochem. 52: 486-495. PMID:7693730
15. Amsler, K. (1994) Role of cell density/cell-cell contact and growth state in expression of differentiated functions by the LLC-PK1 cell. J. Cell. Physiol. 159: 331-339. PMID:8163571
16. Chen, J.-L. And K. Amsler. (1995) Expression of gamma-glutamyl transpeptidase by renal epithelial cells occurs on a cell-by-cell basis and is inhibited by chronic TPA treatment. J. Cell. Biochem. 58: 73-82. PMID:7642725
17. Amsler, K., J. Murray, R. Cruz, and J.-L. Chen. (1996) Chronic TPA treatment inhibits expression of proximal tubule-specific properties by LLC-PK1 cells. Am. J. Physiol. 270: C332-C340. PMID:8772461
18. Sun, L., K. Amsler, and E.R. Weiss. (1998) Inhibition of cell differentiation by Gaq in the renal epithelial cell line, LLC-PK1. Am. J. Physiol. 274: C1030-C1039. PMID:9575800
19. Kuwada, S.K., K.A. Lund, X.F. Li, P. Cliften, K. Amsler, L.K. Opresko, and H.S. Wiley. (1998) Differential signaling and regulation of apical versus basolateral EGF receptors in polarized epithelial cells. Am. J. Physiol. 275: C1419-C1428. PMID:9843701
20. Amsler, K. and S.K. Kuwada. (1999) Membrane receptor location defines receptor interaction with signaling proteins in a polarized epithelium. Am. J. Physiol. 276: C91-C101. PMID:9886924
21. Kapadia, R., P.D. Yurchenco, and K. Amsler. (1999) Binding of the renal epithelial cell, LLC-PK1, to laminin is regulated by protein kinase C. J. Am. Soc. Nephrol. 10: 1214-1223. OMID:10361859
22. You, G., K. Kuze, R.A. Kohanski, K. Amsler, and S. Henderson. (2000) Regulation of mOAT-mediated organic anion transport by okadaic acid and protein kinase C in LLC-PK1 cells. J. Biol. Chem. 275: 10278-10284. PMID:10744714
23. Li, X., H.-P. Li, K. Amsler, D. Hyink, P.D. Wilson, and C.R. Burrow. (2002) PRKX, a phylogenetically and functionally distinct cAMP-dependent protein kinase, activates renal epithelial cell migration and morphogenesis. PNAS (USA) 99: 9260-9265. PMID:12082174
24. Qiu, L., W. Gans, D. Hyink, K. Amsler, P. Wilson, and C. Burrow. (2004) Autocrine regulation of nephrogenic mesenchymal cell survival and proliferation by midkine. Organogenesis 1: 14-21. PMID:19521555
25. Wilson, S., K. Amsler, D.P. Hyink, X. Li, W. Lu, J. Zhou, C.R. Burrow, and P.D. Wilson. (2006) Inhibition of HER-2 (neu/ErbB2) restores normal function and structure to polycystic kidney disease (PKD) epithelia. Biochim. Biophys. Acta 1762:647-655. (epub – May 19, 2006) PMID:16797938
http://www.sciencedirect.com/science/article/pii/S0925443906000809
26. Israeli, S., K. Amsler, N. Zheleznova, and P.D. Wilson. (2010) Abnormalities in focal adhesion complex formation, regulation and function in human Autosomal Recessive Polycystic Kidney Disease (ARPKD) epithelial cells. Am. J. Physiol. 298:C831-C846. http://ajpcell.physiology.org/content/298/4/C831.long
27. Caswell, D., S. Jaggi, J. Axis, and K. Amsler. (2013) Src Family Kinases Regulate Renal Epithelial Cell Paracellular Permeability Independent of Occludin Protein. J. Cell. Physiol. 228:1210-1220. doi: 10.1002/jcp.24274. PMID:23129414
28. Loh, M., N. Gevitz, W. Gilliar, M. Hussain, L. Iacono, M.-K. Jung, B. Krishnamachari, K. Amsler. (2015) Effect of training on palpation skills in an osteopathic medical student population. J. Amer. Osteo. Asso. 115:32-40. doi:10.7556/jaoa.2015.005.
29. Janosevic, D., J. Axis, R. Bacallao and K. Amsler. (2016) Occludin content modulates hydrogen peroxide-induced increase in renal epithelial cell paracellular permeability. J. Cell. Biochem. 117:769-779. doi: 10.1002/jcb.25362. PMID:26348235.
30. Bilal S, Jaggi S, Janosevic D, Shah N, Teymour S, Voronina A, Watari J, Axis J, Amsler K. (2018) ZO-1 protein is required for hydrogen peroxide to increase MDCK cell paracellular permeability in an ERK 1/2-dependent manner. Am J Physiol:Cell Physiol 315:C422-C431. doi: 10.1152/ajpcell.00185.2017. PMID:29871407.
31. Monaco A, Ovryn B, Axis J, Amsler K. (2021) The epithelial cell Leak Pathway. Int J Mol Sci 22(14):7677. doi:10.3390/ijms22147677.
32. Monaco A, Axis J, Amsler K. (2022) Simple graphical approach to investigate differences in paracellular Leak Pathway permeability. Physiol Reports doi:10.14814/phy2.15202
33. Rana S, Nasr L, Chang D, Axis J, Amsler K. (2024) Na-caprate-induced increase in MDCK II epithelial cell leak pathway permeability and opening number is associated with disruption of basal F-actin organization. Am J Physiol: Cell Physiol 327(4):C913-C928. doi: 10.1152/ajpcell.00534.2023.
Invited contributions
1. Cook, J.S., K. Amsler, E.R. Weiss, and C. Shaffer. (1982) Development of Na+-dependent hexose transport in vitro. In: Membranes in Growth and Development (Giebisch, G., Hoffman, J., and Bolis, L., eds.) Alan R. Liss, New York, pp. 551-567.
2. Weiss, E.R., K. Amsler, W.D. Dawson, and J.S. Cook. (1985) Development of Na+-dependent hexose transport in cultured renal epithelial cells. In: Membrane Transport Driven by Ion Gradients (Semenza, G., And Kinne, R., eds.) New York Academy Press, New York, Ann. N. Y. Acad. Sci. 456: 420-425. PMID:7146012
3. Amsler, K., and Ince, B.A. (1989) Chloride uptake into high resistance MDCK cells. In: Bicarbonate, Chloride, and Proton Transport Systems (Durham, J.H., and Hardy, M.A., eds.) New York Academy Press, New York, Ann. N. Y. Acad. Sci. 574: 104-105
Books and Book Chapters
1. Amsler, K. (1989) Sodium-coupled transport processes in cultured epithelial cells. In: Functional Epithelial Cells in Culture (Matlin, K.S., Valentich, J.D., and Satir, B.H., eds.) Alan R. Liss, New York, Modern Cell Biology 8: 193-233
Abstracts (last 5 years)
1. Bilal S, Axis J, Jaggi S, Voronina A, Amsler K. ZO-1 protein is required for H2O2-induced, ERK 1/2-dependent increase in MDCK cell paracellular permeability. American Society of Nephrology annual meeting. October 31-November 5, 2017. New Orleans, LA.
2. Bilal S, Voronina A, Axis J, Amsler K. Manipulation of actin cytoskeleton and tight junction protein knockdown differentially interact to modulate basal and H2O2-induced paracellular permeability of renal epithelial cells. EB2018 annual meeting. April 21-25, 2018. San Diego, CA.
3. Axis J, Kolb A, Bacallao R, Amsler K. Lack of correlation between paracellular permeability to large solutes and occludin protein mobility in renal epithelia. American Society of Cell Biology annual meeting. December 8-12, 2018. San Diego, CA.
4. Amsler K, Monaco A, Axis J, Ovryn B. Does the paracellular permeability pathway for large solutes, the Leak Pathway, have a size limit? American Society of Cell Biology annual meeting. December 7-11, 2019. Washington, DC.
5. Amsler K, Axis J. ZO-2 Protein But Not ZO-1 Protein Limits Occludin Lateral Mobility in MDCK Type II Renal Epithelial Cells. EB2022 annual meeting. April 2-5, 2022. Philadelphia, PA.
6. Monaco A, Axis J, Amsler K. ZO-1 Knockdown in MDCK Type II Cells Decreases Leak Pathway Opening Size and Increases Opening Number. EB2022 annual meeting. April 2-5, 2022. Philadelphia, PA.
Invited Seminars and Lectures (partial list)
1999 – FASEB Symposium, “Asymmetric Signaling by EGF Receptor in a Polarized Renal
Epithelium"
2000 – Winthrop Hospital, Division of Nephrology
Mt. Sinai School of Medicine, Division of Nephrology
2005 – Mt. Sinai School of Medicine, Division of Nephrology
Mt. Sinai School of Medicine, Signaling Research Colloquium
2007 – Harvard Medical Institute, Brigham and Women’s Hospital
2008 – Northeast Salt and Water Club
2011 – Northeast Salt and Water Club
2013 – AAHC Vice Presidents for Research Executive Leadership Group
Rana S, Nasr L, Chang D, Axis J, Amsler K. Am J Physiol Cell Physiol. 2024 Oct 1;327(4):C913-C928. doi: 10.1152/ajpcell.00534.2023. Epub 2024 Aug 19.