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Andres Lebensohn, Ph.D.

Andres M. Lebensohn, Ph.D.

  • Center for Cancer Research
  • National Cancer Institute
Howard University (HU) - CCR Cancer Track Program Co-Director

RESEARCH SUMMARY

We are interested in understanding how a relatively small number of cell signaling pathways can orchestrate the thousands of cellular events that give rise to complex organisms during embryonic development, and that maintain tissues and organs in adults. To answer this question, we focus on the WNT pathway, a fundamental signaling system that controls patterning and morphogenesis, promotes tissue renewal and regeneration, 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 underpinnings through biochemistry and cell biology. We use organoids and mouse models to understand how these new regulatory mechanisms enable the WNT pathway to generate distinct physiological outcomes during embryonic development and tissue homeostasis.

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 ]

Job Vacancies

We have no open positions in our group at this time, please check back later.

To see all available positions at CCR, take a look at our Careers page. You can also subscribe to receive CCR's latest job and training opportunities in your inbox.

Team

Praveen headshot
Postdoctoral Fellow (Visiting)
Praveen Sonkusre, Ph.D.
Myungjoo headshot
Postdoctoral Fellow (Visiting)
Myungjoo Shin, Ph.D.
Caleb headshot
Postdoctoral Fellow (Visiting)
Caleb Sinclear, Ph.D.
Rebecca Kim headshot
Postbaccalaureate Fellow (CRTA)
Rebecca Kim, B.S.

News

April 3, 2024 - As a member and Chair of The Tenure Track Investigator Representatives Committee, Andres received an NCI Director's Award for Emerging Leader-NCI Champions in recognition of "Significant and numerous contributions to improving the experience of Tenure Track Investigators in the NCI Center for Cancer Research." Take a look!

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Andres and Alex TTIRC NCI Directors Award

March 17, 2024 - Our preprint entitled "The ubiquitin ligase HUWE1 enhances WNT signaling by antagonizing destruction complex-mediated β-catenin degradation and through a mechanism independent of β-catenin stability" is on bioRxiv. In this manuscript we demonstrate that the ubiquitin ligase HUWE1 enhances WNT signaling through two distinct mechanisms. First, HUWE1 antagonizes the phosphorylation and degradation of β-catenin by the destruction complex. Second, HUWE1 enhances WNT signaling through a mechanism independent from control of β-catenin stability. The effects of HUWE1 on WNT signaling require its ubiquitin ligase activity and are mediated by a subset of destruction complex components, including APC, AXIN1 and GSK3A/B. Regulation of β-catenin abundance and a downstream step in the pathway by HUWE1, mediated by the destruction complex, would be an efficient way to coordinately control multiple processes that determine WNT signaling output. Congratulations Joey and Yalan, co-first authors, for a beautiful and thorough genetic analysis of the role of HUWE1 in WNT signaling!

September 26, 2023 - Andres was featured in the 'Celebrating Hispanic Heritage Month' installment of the "Aligned Blog" dedicated to DEIA matters. This installment highlights the contributions of Hispanic scientists to the field of biomedicine, including two scientists at CCR. Take a look!

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Andres picture from Aligned Blog

September 15, 2023 - After many months of working together with Howard University (HU), we launched the HU-CCR Cancer Track! This is a new partnership between four graduate programs at HU and CCR, aimed at promoting collaboration between HU faculty and CCR PIs through the recruitment and training of HU graduate students in CCR labs. Doctoral candidates admitted to HU Ph.D. or M.D./Ph.D. programs in Biomedical Sciences, Pharmaceutical Sciences, Biology or Chemistry will be able to rotate through CCR labs and perform all or part of their dissertation research in CCR labs as collaborative projects or co-mentorships between HU and CCR PIs. This program is a wonderful opportunity to forge new collaborations with our colleagues at HU and to bring outstanding Ph.D. students to CCR labs. Andres is the Program Co-Director for CCR.

September 11, 2023 - Rebecca Kim joined the lab as a post-bac.  She comes from Brown University. Welcome Rebecca!

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Rebecca Kim headshot

July 30, 2023 - Caleb presented a poster at the Wnt Gordon Research Seminar and Conference in Castelldefels, Spain!

June 28, 2023 - Yalan left the lab to start her M.D./Ph.D. in the Medical Scientist Training Program (MSTP) at University of Maryland School of Medicine in Baltimore. It was a real pleasure having you in the lab (and exploring Japan together!) and we wish you all the best in your future endeavors!

May 22, 2023 - Yalan was recognized as a recipient of the "Outstanding Poster Awards" during NIH Postbac Poster Day 2023. Congratulations Yalan!

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Yalan at NIH poster day 2023

March 14, 2023 - Andres presented a seminar at the Swammerdam Institute for Life SciencesUniversity of Amsterdam in The Netherlands.

March 13, 2023 - Saskia defended her thesis at the University of Amsterdam, including a chapter on the work she did in the lab. Congratulations Saskia!

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Saskia defense 1

December 6, 2022 - Andres presented a talk at the Minisimposium on "Mechanisms of intracellular signaling: from receptor to effector" during the Cell Bio 2022 ASCB/EMBO meeting in Washington, D.C.

November 18, 2022 - Yalan presented a poster at the Wnt 2022 EMBO Workshop in Awaji, Japan!

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Yalan poster in Awaji Japan

November 7, 2022 - Sara was awarded the competitive NCI Sallie Rosen Kaplan (SRK) Postdoctoral Fellowship for Women Scientists. Congratulations Sara!

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, 2022 - 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!