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 Our most recent (unpublished) work has focuses on (1) metabolic programs of hematopoietic stem cells in mouse models of leukemia, (2) fitness and potential of intestinal stem cells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 We have developed organoids co-cultured with immune cells (unpublished work), and we are testing hypotheses of the crosstalk in organoids and impact on stem cells, informed by large omics datasets.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:

nSMase2-mediated exosome secretion shapes the tumor microenvironment to immunologically support pancreatic cancer.

bioRxiv : the preprint server for biology

Hendley AM, Ashe S, Urano A, Ng M, Phu TA, Peng XL, Luan C, Finger AM, Jang GH, Kerper NR, Berrios DI, Jin D, Lee J, Riahi IR, Gbenedio OM, Chung C, Roose JP, Yeh JJ, Gallinger S, Biankin AV, O'Kane GM, Ntranos V, Chang DK, Dawson DW, Kim GE, Weaver VM, Raffai RL, Hebrok M

Abstract A066: nSMase2-mediated exosome secretion shapes the tumor microenvironment to immunologically support pancreatic cancer.

Cancer research

Audrey M Hendley, Sudipta Ashe, Atsushi Urano, Martin Ng, Tuan A Phu, Xianlu Laura Peng, Changfei Luan, Anna-Marie Finger, Gun Ho Jang, Natanya R Kerper, David I Berrios, David Jin, Jonghyun Lee, Irene R Riahi, Oghenekevwe M Gbenedio, Christina Chung, Jeroen P Roose, Jen Jen Yeh, Steven Gallinger, Andrew V Biankin, Grainne M O’Kane, Vasilis Ntranos, David K Chang, David W Dawson, Grace E Kim, Valerie M Weaver, Robert L Raffai, Matthias Hebrok

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

Science advances

Magnen M, You R, Rao AA, Davis RT, Rodriguez L, Bernard O, Simoneau CR, Hysenaj L, Hu KH, Maishan M, Conrad C, Gbenedio OM, Samad B, Consortium TUC, Love C, Woodruff PG, Erle DJ, Hendrickson CM, Calfee CS, Matthay MA, Roose JP, Sil A, Ott M, Langelier CR, Krummel MF, Looney MR

NF-κB inhibitor alpha controls SARS-CoV-2 infection in ACE2-overexpressing human airway organoids.

Scientific reports

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

Focal adhesion kinase-YAP signaling axis drives drug-tolerant persister cells and residual disease in lung cancer.

Nature communications

Haderk F, Chou YT, Cech L, Fernández-Méndez C, Yu J, Olivas V, Meraz IM, Barbosa Rabago D, Kerr DL, Gomez C, Allegakoen DV, Guan J, Shah KN, Herrington KA, Gbenedio OM, Nanjo S, Majidi M, Tamaki W, Pourmoghadam YK, Rotow JK, McCoach CE, Riess JW, Gutkind JS, Tang TT, Post L, Huang B, Santisteban P, Goodarzi H, Bandyopadhyay S, Kuo CJ, Roose JP, Wu W, Blakely CM, Roth JA, Bivona TG

Abstract 7465: Leukemia inhibitory factor creates an immune suppressive tumor microenvironment and fosters tumor growth in KRAS-driven pancreatic ductal adenocarcinoma.

Cancer research

Lisa Miller-Phillips, Imene Boukhalfa Hanafi, Alexis J. Combes, Shabana Bano, Lisiena Hysenaj, Jeroen P. Roose, Adam Olshen, Ashley Kiemen, Sarah Umetsu, Man-Tzu Wang, Eric A. Collisson

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

Cutting Edge: Induced Loss of Rasgrp1 in Peripheral CD4+ T Cells of Conditional Rasgrp1-Deficient Mice Reveals an Essential Role for Rasgrp1 in TCR/CD28-Induced Ras-MAPK Signaling.

Journal of immunology (Baltimore, Md. : 1950)

Chang Y, Manivannan P, Doosti A, Lapinski PE, Chen D, Roose JP, King PD

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

Investigating increased hematopoietic stem cell fitness in a novel mouse model.

Small GTPases

Karra L, Roose JP

Bioinformatic Approaches to Validation and Functional Analysis of 3D Lung Cancer Models.

Cancers

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

Unraveling Heterogeneity in Epithelial Cell Fates of the Mammary Gland and Breast Cancer.

Cancers

Samocha A, Doh H, Kessenbrock K, 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

mTOR and other effector kinase signals that impact T cell function and activity.

Immunological reviews

Myers DR, Wheeler B, Roose JP

Alternative ZAP70-p38 signals prime a classical p38 pathway through LAT and SOS to support regulatory T cell differentiation.

Science signaling

Jun JE, Kulhanek KR, Chen H, Chakraborty A, Roose JP

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

Distinct oncogenic Ras signals characterized by profound differences in flux through the RasGDP/RasGTP cycle.

Small GTPases

Mues M, Roose JP

Abstract B22: Screening and validation of combination therapy in T cell leukemia.

Suppressive signals in colorectal cancer: RasGRP1 a new marker for anti-EGFR therapy?.

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

Kinase and Phosphatase Effector Pathways in T Cells.

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

Editorial overview: lymphocyte development and activation: lymphocytes, integrators of information.

Current opinion in immunology

Roose J, Fagarasan S

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

Regulation of ras exchange factors and cellular localization of ras activation by lipid messengers in T cells.

Frontiers in immunology

Jun JE, Rubio I, 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

Activation of extracellular signal-regulated kinase but not of p38 mitogen-activated protein kinase pathways in lymphocytes requires allosteric activation of SOS.

Molecular and cellular biology

Jun JE, Yang M, Chen H, 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

Abstract 3837: PI-3 kinase acts upstream of oncogenic Ras in hematopoietic cells through a cytokine-PLC?-RasGRP pathway.

PI3 Kinase, Phospholipase C (PLC)-?, and RasGRPs Act Cooperatively to Activate the Ras-Extracellular-Related Kinase (ERK) Pathway in Response to Cytokines in Normal and Kras Mutant Myeloid Cells.

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