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Andres Lebensohn, Ph.D.

Andres M. Lebensohn, Ph.D.

  • Center for Cancer Research
  • National Cancer Institute

RESEARCH SUMMARY

Our lab studies regulatory mechanisms that enable cell signaling pathways to produce distinct cellular outcomes in different biological contexts, such as during embryonic development and in adult tissue homeostasis. We believe this context-specific regulation of cell signaling can also be targeted therapeutically to selectively reduce hyperactive signaling in disease states like cancer, while retaining the physiological level of pathway activity necessary for normal tissue homeostasis and regeneration. We focus on WNT signaling, a fundamental pathway that orchestrates patterning and morphogenesis during embryonic development, promotes tissue renewal and regeneration in adults, and can be a potent cancer driver when it becomes dysregulated. We use powerful genetic screens in human cells to discover new regulatory mechanisms, and probe their molecular underpinning through biochemistry and cell biology.

Areas of Expertise

WNT/R-spondin Pathway
Stem Cells/Tissue Homeostasis
Haploid Genetic Screens/Functional Genomics
Biochemical Dissection/Reconstitution

Publications

Selected Key Publications

Receptor control by membrane-tethered ubiquitin ligases in development and tissue homeostasis

Lebensohn AM†, Bazan JF†, Rohatgi R†. †Corresponding authors.
Current Topics in Developmental Biology. Volume 150: 25-89, 2022.
Full-Text Article
[ Book Chapter ]

R-spondins engage heparan sulfate proteoglycans to potentiate WNT signaling

Dubey R*, van Kerkhof P, Jordens I, Malinauskas T, Pusapati GV, McKenna JK, Li D, Carette JE, Ho M, Siebold C, Maurice M, Lebensohn AM*†, Rohatgi R†. *Contributed equally; †Corresponding authors.
eLife. 9: e54469, 2020.
Full-Text Article
[ Journal Article ]

Discovery of gene regulatory elements through a new bioinformatics analysis of haploid genetic screens

Patel BB*, Lebensohn AM*†, Pusapati GV, Carette JE, Salzman J†, Rohatgi, R†. *Contributed equally; †Corresponding authors.
PLoS ONE. 14(1): e0198463, 2019.
Full-Text Article
[ Journal Article ]

R-spondins can potentiate WNT signaling without LGRs

Lebensohn AM†, Rohatgi R†. †Corresponding authors.
eLife. 7: e33126, 2018.
Full-Text Article
[ Journal Article ]

Comparative genetic screens in human cells reveal new regulatory mechanisms in WNT signaling

Lebensohn AM, Dubey R, Neitzel LR, Tacchelly-Benites O, Yang E, Marceau CD, Davis EM, Patel BB, Bahrami-Nejad Z, Travaglini KJ, Ahmed Y, Lee E, Carette JE, Rohatgi R.
eLife. 5: e21459, 2016.
Full-Text Article
[ Journal Article ]

Job Vacancies

There are no open positions at this time. Check back again later, or take a look at CCR's Careers page.

Team

Myungjoo headshot
Postdoctoral Fellow (Visiting)
Myungjoo Shin, Ph.D.
Praveen headshot
Postdoctoral Fellow (Visiting)
Praveen Sonkusre, Ph.D.
Yalan headshot
Postbaccalaureate Fellow (CRTA)
Yalan Wu, B.A.
Sara headshot
Postdoctoral Fellow (CRTA)
Sara Konopelski Snavely, Ph.D.
Caleb headshot
Postdoctoral Fellow (Visiting)
Caleb Sinclear, Ph.D.

News

September 19, 2022 - Caleb Sinclear joined the lab as a post-doc. He is originally from Ghana and obtained his Ph.D. from Tokyo Medical and Dental University in Japan. Welcome Caleb!

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Caleb headshot

September 7, 2021 - Noa left the lab to gain clinical experience with the group of Dr. Leighton Chan in the Rehabilitation Medicine Department of the NIH Clinical Center. It was great having you in the lab and we wish you all the best in your future endeavors!

August 15, 2022 - Sara Konopelski Snavely joined the lab as a post-doc. She is originally from northern California and obtained her Ph.D. from University of California, Davis, where she did her dissertation in the lab of Dr. Henry Ho. Welcome Sara!

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Sara Headshot

July 26, 2022 - Andres was a judge in the "Genes in Space" contest, which invites students in grades 7 through 12 to design biology experiments that address real-world challenges in space exploration. The five finalists presented their proposals at the International Space Station (ISS) Research and Development Conference in Washington, D.C. Student Pristine Onuoha from Chapel Hill High School in Chapel Hill, NC, was this year's winner. Her experiment seeks to understand the mechanism behind telomere lengthening, a chromosomal change that has been observed in space travelers. Her experiment will be performed by astronauts aboard the International Space Station (ISS) next year.

Andres also delivered the Genes in Space Reception Keynote Address at the Planet Word Museum, in honor of The John Hatch Memorial Prize in Mentorship: "Mentoring: above all, it’s about caring"

June 11, 2022 - Our book chapter entitled "Receptor control by membrane-tethered ubiquitin ligases in development and tissue homeostasis" was published in Volume 150 of Current Topics in Developmental Biology, a volume about "Cell-Cell Signaling in Development" edited by Thomas Kornberg. See the online version here, or download the PDF from the publications section of our website. This chapter explores in great depth an emerging concept in cell signaling: how membrane-tethered ubiquitin ligases control the sensitivity of target cells to secreted ligands by regulating the abundance of signaling receptors at the cell surface. We focus on two examples of this concept: (1) the transmembrane ubiquitin ligases ZNRF3 and RNF43 that regulate WNT and BMP receptor abundance in response to R-spondin ligands and (2) the membrane-recruited ubiquitin ligase MGRN1 that controls Hedgehog and melanocortin receptor abundance. The mechanisms presented in the chapter are illustrated by beautiful structural and protein interaction models enabled by AlphaFold.

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Figure 4

September 8, 2021 - Noa Sasson joined the lab as a post-bac.  She comes from University of California, Santa Barbara. Welcome Noa!

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Noa Sasson

August 31, 2021 - Saskia finished her Fulbright Scholarship and went back to The Netherlands, where she will start her new Scientist position at OcellO, a biotech company in Leiden. It was awesome having you in the lab! We wish you all the best in your future endeavors.

August 4, 2021 - An interview with Saskia about coming to the NIH as a Visiting Fulbright Scholar - and other thoughts on being a scientist - is featured in Elsevier Connect. Congratulations Saskia!

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Saskia Elsevier article image

June 3, 2021 - Joey left us to start his Ph.D. in the Department of Molecular and Cell Biology at UC Berkeley. He will travel cross-country before settling in sunny California. It was fantastic having you in the lab (and fishing monster rock fish together) and we wish you all the best in your future endeavors!

April 5, 2021 - Saskia de Man is visiting the lab as a Fulbright Scholar. She is a Ph.D. student in the lab of Dr. Renée van Amerongen at the University of Amsterdam. Welcome Saskia!

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Saskia de Man

October 13, 2020 - Myungjoo Shin joined the lab as a post-doc. He is originally from Seoul, South Korea and obtained his Ph.D. from Cornell University. Welcome Myungjoo!

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Myungjoo Shin

June 29, 2020 - Yalan Wu joined the lab as a post-bac.  She comes from Boston University. Welcome Yalan!

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Yalan Wu

May 20, 2020 - Our latest paper was published as a Research Advance in eLife! Check it out: https://elifesciences.org/articles/54469. This work builds upon our 2018 eLife Research Article (https://elifesciences.org/articles/33126) to show that interactions between the TSP/BR domain of R-spondin 3 and the heparan sulfate chains of heparan sulfate proteoglycans, such as glypicans and syndecans, are necessary and sufficient to promote LGR-independent potentiation of WNT signaling. Surprisingly, these interactions also contribute substantially to the LGR-dependent signaling by R-spondins necessary to promote the growth of small intestinal organoids. These findings further our understanding of how R-spondins enhance WNT signaling during embryonic development and adult stem cell self-renewal. Any @NCIResearchCtr tweeter followers out there, feel free to retweet :) https://twitter.com/NCIResearchCtr/status/1263904972107726851?s=20

May 14, 2020 - Joey was recognized as a recipient of the "Outstanding Poster Awards" during the first virtual NIH Postbac Poster Day 2020. From the Director of the Office of Intramural Training & Education: "On behalf of the Office of Intramural Training & Education, I want to congratulate you on presenting an outstanding poster at NIH Postbac Poster Day 2020! The judging process was highly competitive, and you should be proud of your accomplishment. This year 839 posters were presented on Poster Day. Of those, 170 were recognized as outstanding, based on the high scores they received during the judging process." Congratulations Joey!

February 3, 2020 - Praveen Sonkusre joined the lab as a post-doc.  He comes from CSIR-Institute of Microbial Technology, Chandigarh, India. Welcome Praveen!

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Praveen Sonkusre

January 27, 2020 - Courtney left us to join the lab of Dr. Kathleen Merikangas at the National Institute of Mental Health. She will spend a year doing research on mood disorders before applying to graduate school in public health. It was a pleasure having you as the first post-bac in the lab and we wish you all the best in your future endeavors!

August 19, 2019 - Joey McKenna joined the lab as a post-bac.  He comes from UC Berkeley (Andres' Alma Mater). Welcome Joey!

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Joey McKenna

August 10-16, 2019 - Andres and Courtney attended the Gordon Research Conference "Wnt Signaling Networks in Development, Disease and Regeneration" in Mount Snow, West Dover, VT. Andres gave a talk entitled "The Ubiquitin Ligase HUWE1 Regulates Canonical WNT Signaling Independently of Changes in Beta-Catenin Abundance"

July 31, 2019 - Andres was a judge in the "Genes in Space" contest, which invites students in grades 7 through 12 to design biology experiments that address real-world challenges in space exploration. The five finalists presented their proposals at the International Space Station (ISS) Research and Development Conference in Atlanta, GA, and the winning team's experiment will be performed by astronauts aboard the ISS U.S. National Laboratory in 2020.

Check out the Genes in Space website: https://www.genesinspace.org/

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The judges with Astronaut Serena Auñón-Chancellor

January 28, 2019 - Courtney Quick joined the lab as the first post-bac. She comes from UNC Asheville. Welcome Courtney!

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Courtney Quick

December 8, 2018 - Andres presented one of the two talks selected as top abstracts at the ASCB Doorstep Meeting "Beyond Homeostasis - Stem Cells Under Stress" in San Diego, CA: “Mechanisms and physiological implications of LGR-dependent and LGR-independent potentiation of WNT signaling by R-spondins”

October 1, 2018 - Andres joined the Laboratory of Cellular and Molecular Biology.  He is very excited to begin studies on new regulatory mechanisms of WNT signaling!