Jeroen Roose

Professor
Anatomy
+1 415 476-3977

The Roose lab focuses on understanding cell fate decisions driven by cell-cell interactions and signaling pathways, in the context of cancer, autoimmune diseases, and COVID-19. Our collaborative research programs benefit from many technology platforms, such as organoids, CyTOF, single cell RNAseq, spectral flow, mouse models, and patient samples. Dr. Roose is a co-founder of the Bakar ImmunoX initiative at UCSF and a co-lead investigator on the UCSF Endeavor Program that focuses on cancer metastasis, funded through the Mark Foundation for Cancer Research.

Couple of words about myself; I trained with Profs. Hans Clevers and Art Weiss, obtaining cancer- and immune- expertise. I started my own group at UCSF in 2007, I am now full Professor and also Vice Chair of my Anatomy Department at UCSF. 

Specific to the DSCB program, we are interested in the “fitness” of stem cells and different stem cell niches. Our most recent (unpublished) work has focuses on (1) metabolic programs of hematopoietic stem cells in mouse models of leukemia, (2) fitness and potential of intestinal stem cells receiving cues from resident immune cells in mouse models and organoids. DSCB student Lauren Shechtman joined the lab in 2022 to work on this, and (3) potential and identity of stem cells in the breast and relationship to breast cancer. 

In 2018 I started a “Roose Organoid D2B unit” which now grew into a UCSF Plug-In CoLab. We have developed organoids co-cultured with immune cells (unpublished work), and we are testing hypotheses of the crosstalk in organoids and impact on stem cells, informed by large omics datasets.

Research Summary: 
Our goal is to understand the fitness and potential of stem cells to fuel various cell lineages in different organs. We use organoids to understand how cues from different stem cell niches impact that fitness and potential.

Websites

Publications: 

Abstract A046: nSMase2-generated ceramide promotes PDA aggression through exosome reprogramming of the stroma.

Cancer research

Audrey M. Hendley, Atsushi Urano, Xianlu L. Peng, Sudipta Ashe, Tuan A. Phu, Martin Ng, Natanya R. Kerper, David I. Berrios, Jonghyun Lee, David Jin, Gun H. Jang, Oghenekevwe M. Gbenedio, Jeroen P. Roose, Jen J. Yeh, Steven Gallinger, Andrew V. Biankin, Vasilis Ntranos, David K. Chang, David W. Dawson, Grace E. Kim, Valerie M. Weaver, Robert L. Raffai, Matthias Hebrok

Single cell proteomics characterization of bone marrow hematopoiesis with distinct Ras pathway lesions.

bioRxiv : the preprint server for biology

Karra L, Finger AM, Shechtman L, Krush M, Huang RM, Prinz M, Tennvooren I, Bahl K, Hysienaj L, Gonzalez PG, Combes AJ, Gonzalez H, Argüello RJ, Spitzer MH, Roose JP

Transcriptional-translational conflict is a barrier to cellular transformation and cancer progression.

Cancer cell

Jana S, Brahma S, Arora S, Wladyka CL, Hoang P, Blinka S, Hough R, Horn JL, Liu Y, Wang LJ, Depeille P, Smith E, Montgomery RB, Lee JK, Haffner MC, Vakar-Lopez F, Grivas P, Wright JL, Lam HM, Black PC, Roose JP, Ryazanov AG, Subramaniam AR, Henikoff S, Hsieh AC

SARS-CoV-2 infection of airway organoids reveals conserved use of Tetraspanin-8 by Ancestral, Delta, and Omicron variants.

Stem cell reports

Hysenaj L, Little S, Kulhanek K, Magnen M, Bahl K, Gbenedio OM, Prinz M, Rodriguez L, Andersen C, Rao AA, Shen A, Lone JC, Lupin-Jimenez LC, Bonser LR, Serwas NK, Mick E, Khalid MM, Taha TY, Kumar R, Li JZ, Ding VW, Matsumoto S, Maishan M, Sreekumar B, Simoneau C, Nazarenko I, Tomlinson MG, Khan K, von Gottberg A, Sigal A, Looney MR, Fragiadakis GK, Jablons DM, Langelier CR, Matthay M, Krummel M, Erle DJ, Combes AJ, Sil A, Ott M, Kratz JR, Roose JP

Abstract IA022: Cell archetypes in human brain metastases: Connecting programs in tumor cells with the microenvironment.

Cancer research

Hugo Gonzalez, Wenbin Mei, Isabella Robles, Catharina Hagerling, Breanna Allen, Trine Hauge Okholm, Ankitha Nanjaraj, Tamara Verbeek, Sandhya Kalavacherla, Merel van Gogh, Stephen Georgiou, Mariza Daras, Joanna J. Phillips, Matthew H. Spitzer, Jeroen P. Roose, Zena Werb

NF-κB inhibitor alpha has a cross-variant role during SARS-CoV-2 infection in ACE2-overexpressing human airway organoids.

bioRxiv : the preprint server for biology

Simoneau CR, Chen PY, Xing GK, Khalid MM, Meyers NL, Hayashi JM, Taha TY, Leon KE, Ashuach T, Fontaine KA, Rodriguez L, Joehnk B, Walcott K, Vasudevan S, Fang X, Maishan M, Schultz S, Roose J, Matthay MA, Sil A, Arjomandi M, Yosef N, Ott M

Immediate myeloid depot for SARS-CoV-2 in the human lung.

Research square

Looney M, Magnen M, You R, Rao A, Davis R, Rodriguez L, Simoneau C, Hysenaj L, Hu K, Love C, Woodruff P, Erle D, Hendrickson C, Calfee C, Matthay M, Roose J, Sil A, Ott M, Langelier C, Krummel M

Immediate myeloid depot for SARS-CoV-2 in the human lung.

bioRxiv : the preprint server for biology

Magnen M, You R, Rao AA, Davis RT, Rodriguez L, Simoneau CR, Hysenaj L, Hu KH, UCSF COMET Consortium, Love C, Woodruff PG, Erle DJ, Hendrickson CM, Calfee CS, Matthay MA, Roose JP, Sil A, Ott M, Langelier CR, Krummel MF, Looney MR

Tcof1 haploinsufficiency promotes early T cell precursor-like leukemia in NrasQ61R/+ mice.

Leukemia

Wen Z, Finn R, Gao X, Li L, Hebert A, Ranheim EA, Zhou Y, Yun G, Roose JP, Coon JJ, Shiang R, Wen R, Yu M, Wang D, Zhang J

Cellular architecture of human brain metastases.

Cell

Gonzalez H, Mei W, Robles I, Hagerling C, Allen BM, Hauge Okholm TL, Nanjaraj A, Verbeek T, Kalavacherla S, van Gogh M, Georgiou S, Daras M, Phillips JJ, Spitzer MH, Roose JP, Werb Z

Editorial overview: Communities in immune cell signaling.

Current opinion in immunology

Roose J, Barton G

603 Autoreactivity drives increased metabolism in T cells from SLE patients?.

Lupus Science & Medicine

Kriti Bahl, Darienne Myers, Jeroen Roose

NrasQ61R/+ and Kras-/- cooperate to downregulate Rasgrp1 and promote lympho-myeloid leukemia in early T-cell precursors.

Blood

Wen Z, Yun G, Hebert A, Kong G, Ranheim EA, Finn R, Rajagoplan A, Li S, Zhou Y, Yu M, Damnernsawad A, Roose J, Coon J, Wen R, Wang D, Zhang J

SARS-CoV-2 infection studies in lung organoids identify TSPAN8 as novel mediator.

bioRxiv : the preprint server for biology

Hysenaj L, Little S, Kulhanek K, Gbenedio OM, Rodriguez L, Shen A, Lone JC, Lupin-Jimenez LC, Bonser LR, Serwas NK, Bahl K, Mick E, Li JZ, Ding VW, Matsumoto S, Maishan M, Simoneau C, Fragiadakis G, Jablons DM, Langelier CR, Matthay M, Ott M, Krummel M, Combes AJ, Sil A, Erle DJ, Kratz JR, Roose JP

T cells: a dedicated effector kinase pathways for every trait?

The Biochemical journal

Bahl K, Roose JP

Regulation of the Small GTPase Ras and Its Relevance to Human Disease.

Methods in molecular biology (Clifton, N.J.)

Kulhanek KR, Roose JP, Rubio I

Dysregulated RASGRP1 expression through RUNX1 mediated transcription promotes autoimmunity.

European journal of immunology

Baars MJD, Douma T, Simeonov DR, Myers DR, Kulhanek K, Banerjee S, Zwakenberg S, Baltissen MP, Amini M, de Roock S, van Wijk F, Vermeulen M, Marson A, Roose JP, Vercoulen Y

Increased baseline RASGRP1 signals enhance stem cell fitness during native hematopoiesis.

Oncogene

Karra L, Romero-Moya D, Ksionda O, Krush M, Gu Z, Mues M, Depeille P, Mullighan C, Roose JP

Next-Generation Surrogate Wnts Support Organoid Growth and Deconvolute Frizzled Pleiotropy In Vivo.

Cell stem cell

Miao Y, Ha A, de Lau W, Yuki K, Santos AJM, You C, Geurts MH, Puschhof J, Pleguezuelos-Manzano C, Peng WC, Senlice R, Piani C, Buikema JW, Gbenedio OM, Vallon M, Yuan J, de Haan S, Hemrika W, Rösch K, Dang LT, Baker D, Ott M, Depeille P, Wu SM, Drost J, Nusse R, Roose JP, Piehler J, Boj SF, Janda CY, Clevers H, Kuo CJ, Garcia KC

Protocol for Barcoding T Cells Combined with Timed Stimulations.

STAR protocols

Kulhanek KR, Myers DR, Ksionda O, Vercoulen Y, Romero-Moya D, Roose JP

Protocol for Comprehensive Synthetic Lethality Screens.

STAR protocols

Romero-Moya D, Roose JP

Cryo-EM structure of a dimeric B-Raf:14-3-3 complex reveals asymmetry in the active sites of B-Raf kinases.

Science (New York, N.Y.)

Kondo Y, Ognjenovic J, Banerjee S, Karandur D, Merk A, Kulhanek K, Wong K, Roose JP, Subramaniam S, Kuriyan J

RasGRP1 is a potential biomarker to stratify anti-EGFR therapy response in colorectal cancer.

JCI insight

Gbenedio OM, Bonnans C, Grun D, Wang CY, Hatch AJ, Mahoney MR, Barras D, Matli M, Miao Y, Garcia KC, Tejpar S, Delorenzi M, Venook AP, Nixon AB, Warren RS, Roose JP, Depeille P

Active Tonic mTORC1 Signals Shape Baseline Translation in Naive T Cells.

Cell reports

Myers DR, Norlin E, Vercoulen Y, Roose JP

High-Complexity shRNA Libraries and PI3 Kinase Inhibition in Cancer: High-Fidelity Synthetic Lethality Predictions.

Cell reports

Mues M, Karra L, Romero-Moya D, Wandler A, Hangauer MJ, Ksionda O, Thus Y, Lindenbergh M, Shannon K, McManus MT, Roose JP

Comprehensive analysis of T cell leukemia signals reveals heterogeneity in the PI3 kinase-Akt pathway and limitations of PI3 kinase inhibitors as monotherapy.

PloS one

Ksionda O, Mues M, Wandler AM, Donker L, Tenhagen M, Jun J, Ducker GS, Matlawska-Wasowska K, Shannon K, Shokat KM, Roose JP

A Histidine pH sensor regulates activation of the Ras-specific guanine nucleotide exchange factor RasGRP1.

eLife

Vercoulen Y, Kondo Y, Iwig JS, Janssen AB, White KA, Amini M, Barber DL, Kuriyan J, Roose JP

Tonic Signals: Why Do Lymphocytes Bother?

Trends in immunology

Myers DR, Zikherman J, Roose JP

Tonic LAT-HDAC7 Signals Sustain Nur77 and Irf4 Expression to Tune Naive CD4 T Cells.

Cell reports

Myers DR, Lau T, Markegard E, Lim HW, Kasler H, Zhu M, Barczak A, Huizar JP, Zikherman J, Erle DJ, Zhang W, Verdin E, Roose JP

RasGRP3 Mediates MAPK Pathway Activation in GNAQ Mutant Uveal Melanoma.

Cancer cell

Chen X, Wu Q, Depeille P, Chen P, Thornton S, Kalirai H, Coupland SE, Roose JP, Bastian BC

Lost GRP on cytotoxicity?

Nature immunology

Roose JP

One-way membrane trafficking of SOS in receptor-triggered Ras activation.

Nature structural & molecular biology

Christensen SM, Tu HL, Jun JE, Alvarez S, Triplet MG, Iwig JS, Yadav KK, Bar-Sagi D, Roose JP, Groves JT

Human iPS Cell-Derived Neurons Uncover the Impact of Increased Ras Signaling in Costello Syndrome.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Rooney GE, Goodwin AF, Depeille P, Sharir A, Schofield CM, Yeh E, Roose JP, Klein OD, Rauen KA, Weiss LA, Ullian EM

RasGRP1 overexpression in T-ALL increases basal nucleotide exchange on Ras rendering the Ras/PI3K/Akt pathway responsive to protumorigenic cytokines.

Oncogene

Ksionda O, Melton AA, Bache J, Tenhagen M, Bakker J, Harvey R, Winter SS, Rubio I, Roose JP

Unexpected insights for anti-EGFR cancer therapy.

Oncotarget

Depeille P, Warren RS, Roose JP

RasGRP1 opposes proliferative EGFR-SOS1-Ras signals and restricts intestinal epithelial cell growth.

Nature cell biology

Depeille P, Henricks LM, van de Ven RA, Lemmens E, Wang CY, Matli M, Werb Z, Haigis KM, Donner D, Warren R, Roose JP

Cutting Edge: Codeletion of the Ras GTPase-Activating Proteins (RasGAPs) Neurofibromin 1 and p120 RasGAP in T Cells Results in the Development of T Cell Acute Lymphoblastic Leukemia.

Journal of immunology (Baltimore, Md. : 1950)

Lubeck BA, Lapinski PE, Oliver JA, Ksionda O, Parada LF, Zhu Y, Maillard I, Chiang M, Roose J, King PD

Flavors of EGFR-Ras signals impacting intestinal homeostasis.

Cell cycle (Georgetown, Tex.)

Depeille P, Roose JP

Protein kinase Cd promotes transitional B cell-negative selection and limits proximal B cell receptor signaling to enforce tolerance.

Molecular and cellular biology

Limnander A, Zikherman J, Lau T, Leitges M, Weiss A, Roose JP

Rasgrp1 mutation increases naive T-cell CD44 expression and drives mTOR-dependent accumulation of Helios? T cells and autoantibodies.

eLife

Daley SR, Coakley KM, Hu DY, Randall KL, Jenne CN, Limnander A, Myers DR, Polakos NK, Enders A, Roots C, Balakishnan B, Miosge LA, Sjollema G, Bertram EM, Field MA, Shao Y, Andrews TD, Whittle B, Barnes SW, Walker JR, Cyster JG, Goodnow CC, Roose JP

PLC-? and PI3K link cytokines to ERK activation in hematopoietic cells with normal and oncogenic Kras.

Science signaling

Diaz-Flores E, Goldschmidt H, Depeille P, Ng V, Akutagawa J, Krisman K, Crone M, Burgess MR, Williams O, Houseman B, Shokat K, Sampath D, Bollag G, Roose JP, Braun BS, Shannon K

RasGRP Ras guanine nucleotide exchange factors in cancer.

Frontiers in biology

Ksionda O, Limnander A, Roose JP

Structural analysis of autoinhibition in the Ras-specific exchange factor RasGRP1.

eLife

Iwig JS, Vercoulen Y, Das R, Barros T, Limnander A, Che Y, Pelton JG, Wemmer DE, Roose JP, Kuriyan J

Biochemical heterogeneity and developmental varieties in T-cell leukemia.

Cell cycle (Georgetown, Tex.)

Chakraborty AK, Roose JP

Dysregulated RasGRP1 responds to cytokine receptor input in T cell leukemogenesis.

Science signaling

Hartzell C, Ksionda O, Lemmens E, Coakley K, Yang M, Dail M, Harvey RC, Govern C, Bakker J, Lenstra TL, Ammon K, Boeter A, Winter SS, Loh M, Shannon K, Chakraborty AK, Wabl M, Roose JP

A phospholipase C-?1-independent, RasGRP1-ERK-dependent pathway drives lymphoproliferative disease in linker for activation of T cells-Y136F mutant mice.

Journal of immunology (Baltimore, Md. : 1950)

Kortum RL, Rouquette-Jazdanian AK, Miyaji M, Merrill RK, Markegard E, Pinski JM, Wesselink A, Nath NN, Alexander CP, Li W, Kedei N, Roose JP, Blumberg PM, Samelson LE, Sommers CL

The membrane environment can promote or suppress bistability in cell signaling networks.

The journal of physical chemistry. B

Abel SM, Roose JP, Groves JT, Weiss A, Chakraborty AK

Basal LAT-diacylglycerol-RasGRP1 signals in T cells maintain TCRa gene expression.

PloS one

Markegard E, Trager E, Yang CW, Zhang W, Weiss A, Roose JP

Stim1, PKCd and RasGRP proteins set a threshold for pro-apoptotic Erk signaling during B cell development (109.6).

The Journal of Immunology

Andre Limnander, Philippe Depeille, Tanya Freedman, Jen Liou, Michael Leitges, Tomohiro Kurosaki, Jeroen Roose, Arthur Weiss

STIM1, PKC-d and RasGRP set a threshold for proapoptotic Erk signaling during B cell development.

Nature immunology

Limnander A, Depeille P, Freedman TS, Liou J, Leitges M, Kurosaki T, Roose JP, Weiss A

Response and resistance to MEK inhibition in leukaemias initiated by hyperactive Ras.

Nature

Lauchle JO, Kim D, Le DT, Akagi K, Crone M, Krisman K, Warner K, Bonifas JM, Li Q, Coakley KM, Diaz-Flores E, Gorman M, Przybranowski S, Tran M, Kogan SC, Roose JP, Copeland NG, Jenkins NA, Parada L, Wolff L, Sebolt-Leopold J, Shannon K

Molecular origin and functional consequences of digital signaling and hysteresis during Ras activation in lymphocytes.

Science signaling

Chakraborty AK, Das J, Zikherman J, Yang M, Govern CC, Ho M, Weiss A, Roose J

Digital signaling and hysteresis characterize ras activation in lymphoid cells.

Cell

Das J, Ho M, Zikherman J, Govern C, Yang M, Weiss A, Chakraborty AK, Roose JP

Origin of the sharp boundary that discriminates positive and negative selection of thymocytes.

Proceedings of the National Academy of Sciences of the United States of America

Prasad A, Zikherman J, Das J, Roose JP, Weiss A, Chakraborty AK

Phosphoinositide-dependent kinase 1 targets protein kinase A in a pathway that regulates interleukin 4.

The Journal of experimental medicine

Nirula A, Ho M, Phee H, Roose J, Weiss A

A diacylglycerol-protein kinase C-RasGRP1 pathway directs Ras activation upon antigen receptor stimulation of T cells.

Molecular and cellular biology

Roose JP, Mollenauer M, Gupta VA, Stone J, Weiss A

Intramolecular regulatory switch in ZAP-70: analogy with receptor tyrosine kinases.

Molecular and cellular biology

Brdicka T, Kadlecek TA, Roose JP, Pastuszak AW, Weiss A

T cell receptor-independent basal signaling via Erk and Abl kinases suppresses RAG gene expression.

PLoS biology

Roose JP, Diehn M, Tomlinson MG, Lin J, Alizadeh AA, Botstein D, Brown PO, Weiss A

All Tcf HMG box transcription factors interact with Groucho-related co-repressors.

Nucleic acids research

Brantjes H, Roose J, van De Wetering M, Clevers H

T cells: getting a GRP on Ras.

Nature immunology

Roose J, Weiss A

dTcf antagonises Wingless signalling during the development and patterning of the wing in Drosophila.

The International journal of developmental biology

Lawrence N, Dearden P, Hartley D, Roose J, Clevers H, Arias AM

Differential expression of the Groucho-related genes 4 and 5 during early development of Xenopus laevis.

Mechanisms of development

Molenaar M, Brian E, Roose J, Clevers H, Destrée O

TCF transcription factors: molecular switches in carcinogenesis.

Biochimica et biophysica acta

Roose J, Clevers H

Synergy between tumor suppressor APC and the beta-catenin-Tcf4 target Tcf1.

Science (New York, N.Y.)

Roose J, Huls G, van Beest M, Moerer P, van der Horn K, Goldschmeding R, Logtenberg T, Clevers H

The Sox-13 gene: structure, promoter characterization, and chromosomal localization.

Genomics

Roose J, Korver W, de Boer R, Kuipers J, Hurenkamp J, Clevers H

Drosophila Tcf and Groucho interact to repress Wingless signalling activity.

Nature

Cavallo RA, Cox RT, Moline MM, Roose J, Polevoy GA, Clevers H, Peifer M, Bejsovec A

The Xenopus Wnt effector XTcf-3 interacts with Groucho-related transcriptional repressors.

Nature

Roose J, Molenaar M, Peterson J, Hurenkamp J, Brantjes H, Moerer P, van de Wetering M, Destrée O, Clevers H

Differential expression of the HMG box transcription factors XTcf-3 and XLef-1 during early xenopus development.

Mechanisms of development

Molenaar M, Roose J, Peterson J, Venanzi S, Clevers H, Destrée O

Two members of the Tcf family implicated in Wnt/beta-catenin signaling during embryogenesis in the mouse.

Molecular and cellular biology

Korinek V, Barker N, Willert K, Molenaar M, Roose J, Wagenaar G, Markman M, Lamers W, Destree O, Clevers H

High expression of the HMG box factor sox-13 in arterial walls during embryonic development.

Nucleic acids research

Roose J, Korver W, Oving E, Wilson A, Wagenaar G, Markman M, Lamers W, Clevers H

The human TRIDENT/HFH-11/FKHL16 gene: structure, localization, and promoter characterization.

Genomics

Korver W, Roose J, Heinen K, Weghuis DO, de Bruijn D, van Kessel AG, Clevers H

The winged-helix transcription factor Trident is expressed in cycling cells.

Nucleic acids research

Korver W, Roose J, Clevers H

XTcf-3 transcription factor mediates beta-catenin-induced axis formation in Xenopus embryos.

Cell

Molenaar M, van de Wetering M, Oosterwegel M, Peterson-Maduro J, Godsave S, Korinek V, Roose J, Destrée O, Clevers H

Characterization of the gene encoding the polymorphic immunodominant molecule, a neutralizing antigen of Theileria parva.

Journal of immunology (Baltimore, Md. : 1950)

Toye PG, Metzelaar MJ, Wijngaard PL, Nene V, Iams K, Roose J, Nyanjui JK, Gobright E, Musoke AJ, Clevers HC

Synthetic protease inhibitors: promising compounds to arrest pathobiologic processes.

The Journal of laboratory and clinical medicine

Roose JP, Van Noorden CJ