# Ben Margolis
**Ben Margolis** (Benjamin Lewis Margolis) is a physician-scientist who grew up in Canada and studies cell signaling and epithelial polarity. He is Professor Emeritus of Internal Medicine in the Division of [Nephrology](https://www.edgepedia.org/nephrology) at the University of Michigan, and he was an investigator of the [Howard Hughes Medical Institute](https://www.edgepedia.org/howard-hughes-medical-institute) (HHMI) from 1995 to 2005.[1](https://www.uofmhealth.org/profile/1013099928/benjamin-lewis-margolis) • [2](https://www.hhmi.org/scientists/ben-margolis)
| Key facts | |
|---|---|
| Full name and role | Benjamin Lewis Margolis, MD; Professor Emeritus, Internal Medicine (Nephrology), University of Michigan[1](https://www.uofmhealth.org/profile/1013099928/benjamin-lewis-margolis) • [3](https://experts.umich.edu/3301-benjamin-margolis) |
| HHMI appointment | Howard Hughes Medical Institute investigator, 1995–2005[2](https://www.hhmi.org/scientists/ben-margolis) |
| Medical training | MD, University of Manitoba, Winnipeg; internal medicine residency, University of Texas, San Antonio; nephrology training, University of Toronto[1](https://www.uofmhealth.org/profile/1013099928/benjamin-lewis-margolis) |
| Research career | Research training and faculty position at New York University, then University of Michigan from 1995[1](https://www.uofmhealth.org/profile/1013099928/benjamin-lewis-margolis) |
| Signature work | "EGF induces tyrosine phosphorylation of phospholipase C-II: a potential mechanism for EGF receptor signaling", *Cell*, 1989[4](https://pmc.ncbi.nlm.nih.gov/) |
| Research interests | Biology of epithelial cells, mechanism of kidney cyst formation, polycystic kidney disease, kidney stones[1](https://www.uofmhealth.org/profile/1013099928/benjamin-lewis-margolis) |
| Shared resources | Laboratory plasmids deposited at Addgene, the nonprofit plasmid repository, for distribution to the research community[5](https://www.addgene.org/Ben_Margolis/) |
## Education and training
Margolis grew up in Canada and attended medical school at the [University of Manitoba](https://www.edgepedia.org/university-of-manitoba) in Winnipeg.[1](https://www.uofmhealth.org/profile/1013099928/benjamin-lewis-margolis) He trained in internal medicine at the University of Texas, San Antonio, and then completed nephrology training at the [University of Toronto](https://www.edgepedia.org/university-of-toronto).[1](https://www.uofmhealth.org/profile/1013099928/benjamin-lewis-margolis) After his clinical training, he did research training and was a faculty member at New York University before coming to Michigan in 1995.[1](https://www.uofmhealth.org/profile/1013099928/benjamin-lewis-margolis)
## Career record
After clinical training in the United States and Canada, Margolis did research training and served as a faculty member at New York University.[1](https://www.uofmhealth.org/profile/1013099928/benjamin-lewis-margolis) In 1995 he moved to the University of Michigan and in the same year became an HHMI investigator, an appointment that ran until 2005.[1](https://www.uofmhealth.org/profile/1013099928/benjamin-lewis-margolis) • [2](https://www.hhmi.org/scientists/ben-margolis) At Michigan he holds the title of Professor Emeritus in Internal Medicine, Nephrology.[1](https://www.uofmhealth.org/profile/1013099928/benjamin-lewis-margolis) • [3](https://experts.umich.edu/3301-benjamin-margolis) His laboratory's plasmid reagents are distributed through Addgene.[5](https://www.addgene.org/Ben_Margolis/) His stated research interests at Michigan are the biology of epithelial cells and the mechanism of kidney cyst formation, with polycystic kidney disease and kidney stones as clinical targets.[1](https://www.uofmhealth.org/profile/1013099928/benjamin-lewis-margolis)
## Representative work
According to the PMC archive record, his 1989 *Cell* paper, "EGF induces tyrosine phosphorylation of phospholipase C-II: a potential mechanism for EGF receptor signaling", showed as its title states that epidermal growth factor triggers tyrosine phosphorylation of phospholipase C-II, proposing this modification as a potential mechanism by which the EGF receptor transmits its signal into the cell.[4](https://pmc.ncbi.nlm.nih.gov/)
## Tight junctions and the Crumbs complex
A tight junction is the belt-like seal between neighboring epithelial cells. Tight junctions control paracellular permeability across epithelial cell sheets and also serve as a barrier to intramembrane diffusion of components between a cell's apical and basolateral membrane domains.[6](https://ohsu.elsevierpure.com/en/publications/tight-junctions-and-cell-polarity-2/) Proteins involved in epithelial cell polarization form evolutionarily conserved multiprotein complexes at the tight junction, and these complexes regulate epithelial architecture throughout the polarization process.[6](https://ohsu.elsevierpure.com/en/publications/tight-junctions-and-cell-polarity-2/) One of these complexes centers on Pals1, a membrane-associated guanylate kinase (Maguk) scaffold protein. Work on Pals1 showed that its L27N domain targets it to tight junctions by binding the PDZ-domain protein PATJ through a unique Maguk recruitment domain.[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC2173254/) PATJ is a homologue of the *Drosophila* protein Discs Lost, which is crucial for epithelial polarity and exists in a complex with the apical polarity determinant Crumbs; the *Drosophila* Pals1 homologue corresponds to the crucial polarity gene *stardust*.[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC2173254/) *Drosophila* Crumbs was discovered through its crucial role in epithelial development. Mammals have three Crumbs genes, and Crumbs3 is the major isoform expressed in mammalian epithelial cells.[8](https://cshperspectives.cshlp.org/content/10/3/a027961) The Crumbs–PALS1–PATJ complex is conserved across metazoans and acts as a master regulator of cell growth and polarity at apical membranes of polarized epithelia; it is vital for the development and maintenance of the polarity of diverse tissues, and defects in its formation are known to cause diseases such as cancer and blindness.[9](https://www.pnas.org/doi/abs/10.1073/pnas.1416515111) Structural work has since shown that the PALS1 PDZ–SH3–GK tandem binds the Crumbs cytoplasmic tail with a dissociation constant of 70 nM, about 100-fold stronger than the PALS1 PDZ domain alone, and that mutations disrupting this supramodule compromise PALS1-mediated polarity establishment in MDCK cysts.[9](https://www.pnas.org/doi/abs/10.1073/pnas.1416515111)
Margolis synthesized this field in a 2006 article, "Tight Junctions and Cell Polarity", in the *Annual Review of Cell and Developmental Biology* (volume 22, pages 207–235),[6](https://ohsu.elsevierpure.com/en/publications/tight-junctions-and-cell-polarity-2/) and in the 2006 *Cell* review "ZOning out Tight Junctions", on which he was the corresponding author.[10](https://doi.org/10.1016/j.cell.2006.08.005)
## References
1. [Benjamin Lewis Margolis MD | University of Michigan Health](https://www.uofmhealth.org/profile/1013099928/benjamin-lewis-margolis)
2. [Ben Margolis, MD | Former Investigator Profile | 1995-2005 | HHMI](https://www.hhmi.org/scientists/ben-margolis)
3. [Benjamin Margolis | University of Michigan Experts](https://experts.umich.edu/3301-benjamin-margolis)
4. [EGF induces tyrosine phosphorylation of phospholipase C-II (Cell, 1989), PMC archive record](https://pmc.ncbi.nlm.nih.gov/)
5. [Addgene: Ben Margolis Lab Materials](https://www.addgene.org/Ben_Margolis/)
6. [Tight Junctions and Cell Polarity (Annual Review of Cell and Developmental Biology, 2006)](https://ohsu.elsevierpure.com/en/publications/tight-junctions-and-cell-polarity-2/)
7. [The Maguk protein, Pals1, functions as an adapter, linking mammalian homologues of Crumbs and Discs Lost (Journal of Cell Biology)](https://pmc.ncbi.nlm.nih.gov/articles/PMC2173254/)
8. [The Crumbs3 Polarity Protein (Cold Spring Harbor Perspectives)](https://cshperspectives.cshlp.org/content/10/3/a027961)
9. [Structure of Crumbs tail in complex with the PALS1 PDZ–SH3–GK tandem (PNAS)](https://www.pnas.org/doi/abs/10.1073/pnas.1416515111)
10. [ZOning out Tight Junctions (Cell, 2006)](https://doi.org/10.1016/j.cell.2006.08.005)
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*Topic: Encyclopedia › Life and health › Life and health scientists › Life scientists › Researchers in molecular and cell biology › Molecular biology of the cell / cell signaling › Second messenger and calcium signaling researchers*
*Initially written Sep 21, 2026 · Reviewed: Sep 25, 2026 · Edited: Sep 25, 2026 · Last review: Sep 25, 2026*
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License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license