Jeroen Roose, PhD

TitleAssociate Professor
SchoolUCSF School of Medicine
Address513 Parnassus Ave
San Francisco CA 94143
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    Collapse Biography 
    Collapse Education and Training
    University of California, San FranciscoPostdoctoral StudiesGraduate Division
    University of UtrechtPhDImmunology

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    Research Interests:

    Our laboratory is interested in genetic lesions that lead to abnormal Ras signal transduction events and development of diseases such as autoimmunity and cancer. Active Ras communicates to many downstream targets and affects many cell biological responses. Our goal is to understand the mechanism of activation of the small GTPase Ras by Ras exchange factors and its role in normal physiology as well as understand how alterations in Ras-kinase signals underlie pathology.

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    Collapse Research Activities and Funding
    Balanced signaling cues to guide cell transitions in the blood lineage continuum
    NIH/NHLBI R01HL120724Aug 15, 2015 - Apr 30, 2020
    Role: Principal Investigator
    Molecular understanding of cytokine-Ras signals in leukemic bone marrow
    NIH/NCI R01CA187318Jul 1, 2015 - Jun 30, 2020
    Role: Principal Investigator
    Loss of Intrinsic Control in Autoimmune T Helper Cells with Signaling Variants
    NIH/NIAID R01AI104789Mar 1, 2014 - Feb 28, 2019
    Role: Principal Investigator
    Mechanistic Studies of Ras-MAPK Signals: Specialzed Cues for the T cell Lineage?
    NIH/NIAID R56AI095292Sep 1, 2011 - Aug 31, 2012
    Role: Principal Investigator
    Defining the Unique Properties of the Distinct Signaling Machinery Used by the TCR
    NIH/NIAID P01AI091580Jul 15, 2011 - Jun 30, 2021
    Role: Co-Investigator
    The role of tonic signal-input in stable gene profiles
    NIH/NCI K01CA113367Aug 11, 2006 - Jul 31, 2011
    Role: Principal Investigator
    Bio-Organic Biomedical Mass Spectrometry Resource
    NIH P41RR001614Mar 1, 1982 - May 31, 2015
    Role: Co-Investigator

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    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
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    1. Vercoulen Y, Kondo Y, Iwig JS, Janssen AB, White KA, Amini M, Barber DL, Kuriyan J, Roose J. A Histidine pH sensor regulates activation of the Ras-specific guanine nucleotide exchange factor RasGRP1. Elife. 2017 Sep 27; 6. PMID: 28952923.
      View in: PubMed
    2. Myers DR, Zikherman J, Roose JP. Tonic Signals: Why Do Lymphocytes Bother? Trends Immunol. 2017 Jul 25. PMID: 28754596.
      View in: PubMed
    3. 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 J. Tonic LAT-HDAC7 Signals Sustain Nur77 and Irf4 Expression to Tune Naive CD4 T Cells. Cell Rep. 2017 May 23; 19(8):1558-1571. PMID: 28538176.
      View in: PubMed
    4. Chen X, Wu Q, Depeille P, Chen P, Thornton S, Kalirai H, Coupland SE, Roose J, Bastian BC. RasGRP3 Mediates MAPK Pathway Activation in GNAQ Mutant Uveal Melanoma. Cancer Cell. 2017 May 08; 31(5):685-696.e6. PMID: 28486107.
      View in: PubMed
    5. Roose JP. Lost GRP on cytotoxicity? Nat Immunol. 2016 Nov 16; 17(12):1339-1340. PMID: 27849207.
      View in: PubMed
    6. Christensen SM, Tu HL, Jun JE, Alvarez S, Triplet MG, Iwig JS, Yadav KK, Bar-Sagi D, Roose JP, Groves JT. One-way membrane trafficking of SOS in receptor-triggered Ras activation. Nat Struct Mol Biol. 2016 Sep; 23(9):838-46. PMID: 27501536; PMCID: PMC5016256 [Available on 03/01/17].
    7. Mues M, Roose J, et al. Distinct oncogenic Ras signals characterized by profound differences in flux through the RasGDP/RasGTP cycle. Small GTPases. 2017 Jan 02; 8(1):20-25. PMID: 27159504.
      View in: PubMed
    8. Rooney GE, Goodwin AF, Depeille P, Sharir A, Schofield CM, Yeh E, Roose JP, Klein OD, Rauen KA, Weiss LA, Ullian EM. Human iPS Cell-Derived Neurons Uncover the Impact of Increased Ras Signaling in Costello Syndrome. J Neurosci. 2016 Jan 06; 36(1):142-52. PMID: 26740656; PMCID: PMC4701956.
    9. Ksionda O, Melton AA, Bache J, Tenhagen M, Bakker J, Harvey R, Winter SS, Rubio I, Roose JP. RasGRP1 overexpression in T-ALL increases basal nucleotide exchange on Ras rendering the Ras/PI3K/Akt pathway responsive to protumorigenic cytokines. Oncogene. 2016 Jul 14; 35(28):3658-68. PMID: 26549032; PMCID: PMC4868787.
    10. Depeille P, Warren RS, Roose JP. Unexpected insights for anti-EGFR cancer therapy. Oncotarget. 2015 Aug 07; 6(22):18746-7. PMID: 26300054; PMCID: PMC4662453.
    11. Depeille P, Henricks LM, van de Ven RA, Lemmens E, Wang CY, Matli M, Werb Z, Haigis KM, Donner D, Warren R, Roose JP. RasGRP1 opposes proliferative EGFR-SOS1-Ras signals and restricts intestinal epithelial cell growth. Nat Cell Biol. 2015 Jun; 17(6):804-15. PMID: 26005835; PMCID: PMC4652934.
    12. Lubeck BA, Lapinski PE, Oliver JA, Ksionda O, Parada LF, Zhu Y, Maillard I, Chiang M, Roose J, King PD. 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. J Immunol. 2015 Jul 01; 195(1):31-5. PMID: 26002977; PMCID: PMC4475412.
    13. Roose J, Fagarasan S. Editorial overview: lymphocyte development and activation: lymphocytes, integrators of information. Curr Opin Immunol. 2015 Apr; 33:v-vii. PMID: 25776004; PMCID: PMC4868092.
    14. Depeille P, Roose JP. Flavors of EGFR-Ras signals impacting intestinal homeostasis. Cell Cycle. 2015; 14(20):3205-6. PMID: 26292152; PMCID: PMC4825600.
    15. Limnander A, Zikherman J, Lau T, Leitges M, Weiss A, Roose JP. Protein kinase Cd promotes transitional B cell-negative selection and limits proximal B cell receptor signaling to enforce tolerance. Mol Cell Biol. 2014 Apr; 34(8):1474-85. PMID: 24515435; PMCID: PMC3993585.
    16. 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. Rasgrp1 mutation increases naive T-cell CD44 expression and drives mTOR-dependent accumulation of Helios? T cells and autoantibodies. Elife. 2013 Dec 12; 2:e01020. PMID: 24336796; PMCID: PMC3858598.
    17. 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. PLC-? and PI3K link cytokines to ERK activation in hematopoietic cells with normal and oncogenic Kras. Sci Signal. 2013 Dec 03; 6(304):ra105. PMID: 24300897; PMCID: PMC4117477.
    18. Ksionda O, Limnander A, Roose J, et al. RasGRP Ras guanine nucleotide exchange factors in cancer. Front Biol (Beijing). 2013 Oct 01; 8(5):508-532. PMID: 24744772.
      View in: PubMed
    19. Jun JE, Rubio I, Roose JP. Regulation of ras exchange factors and cellular localization of ras activation by lipid messengers in T cells. Front Immunol. 2013 Sep 04; 4:239. PMID: 24027568; PMCID: PMC3762125.
    20. Iwig JS, Vercoulen Y, Das R, Barros T, Limnander A, Che Y, Pelton JG, Wemmer DE, Roose JP, Kuriyan J. Structural analysis of autoinhibition in the Ras-specific exchange factor RasGRP1. Elife. 2013 Jul 30; 2:e00813. PMID: 23908768; PMCID: PMC3728621.
    21. Chakraborty AK, Roose JP. Biochemical heterogeneity and developmental varieties in T-cell leukemia. Cell Cycle. 2013 May 15; 12(10):1480-1. PMID: 23652920; PMCID: PMC3680523.
    22. Jun JE, Yang M, Chen H, 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. Mol Cell Biol. 2013 Jun; 33(12):2470-84. PMID: 23589333; PMCID: PMC3700092.
    23. 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. Dysregulated RasGRP1 responds to cytokine receptor input in T cell leukemogenesis. Sci Signal. 2013 Mar 26; 6(268):ra21. PMID: 23532335; PMCID: PMC3737252.
    24. 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. A phospholipase C-?1-independent, RasGRP1-ERK-dependent pathway drives lymphoproliferative disease in linker for activation of T cells-Y136F mutant mice. J Immunol. 2013 Jan 01; 190(1):147-58. PMID: 23209318; PMCID: PMC3529846.
    25. Abel SM, Roose JP, Groves JT, Weiss A, Chakraborty AK. The membrane environment can promote or suppress bistability in cell signaling networks. J Phys Chem B. 2012 Mar 22; 116(11):3630-40. PMID: 22332778; PMCID: PMC3321252.
    26. Markegard E, Trager E, Yang CW, Zhang W, Weiss A, Roose JP. Basal LAT-diacylglycerol-RasGRP1 signals in T cells maintain TCRa gene expression. PLoS One. 2011; 6(9):e25540. PMID: 21966541; PMCID: PMC3180458.
    27. Limnander A, Depeille P, Freedman TS, Liou J, Leitges M, Kurosaki T, Roose JP, Weiss A. STIM1, PKC-d and RasGRP set a threshold for proapoptotic Erk signaling during B cell development. Nat Immunol. 2011 May; 12(5):425-33. PMID: 21441934; PMCID: PMC3623929.
    28. 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. Response and resistance to MEK inhibition in leukaemias initiated by hyperactive Ras. Nature. 2009 Sep 17; 461(7262):411-4. PMID: 19727076; PMCID: PMC4119783.
    29. Chakraborty AK, Das J, Zikherman J, Yang M, Govern CC, Ho M, Weiss A, Roose J. Molecular origin and functional consequences of digital signaling and hysteresis during Ras activation in lymphocytes. Sci Signal. 2009 Apr 14; 2(66):pt2. PMID: 19366993; PMCID: PMC2755093.
    30. Das J, Ho M, Zikherman J, Govern C, Yang M, Weiss A, Chakraborty AK, Roose JP. Digital signaling and hysteresis characterize ras activation in lymphoid cells. Cell. 2009 Jan 23; 136(2):337-51. PMID: 19167334; PMCID: PMC2662698.
    31. Prasad A, Zikherman J, Das J, Roose JP, Weiss A, Chakraborty AK. Origin of the sharp boundary that discriminates positive and negative selection of thymocytes. Proc Natl Acad Sci U S A. 2009 Jan 13; 106(2):528-33. PMID: 19098101; PMCID: PMC2626737.
    32. Roose JP, Mollenauer M, Ho M, Kurosaki T, Weiss A. Unusual interplay of two types of Ras activators, RasGRP and SOS, establishes sensitive and robust Ras activation in lymphocytes. Mol Cell Biol. 2007 Apr; 27(7):2732-45. PMID: 17283063; PMCID: PMC1899892.
    33. Nirula A, Ho M, Phee H, Roose J, Weiss A. Phosphoinositide-dependent kinase 1 targets protein kinase A in a pathway that regulates interleukin 4. J Exp Med. 2006 Jul 10; 203(7):1733-44. PMID: 16785309; PMCID: PMC2118337.
    34. Roose JP, Mollenauer M, Gupta VA, Stone J, Weiss A. A diacylglycerol-protein kinase C-RasGRP1 pathway directs Ras activation upon antigen receptor stimulation of T cells. Mol Cell Biol. 2005 Jun; 25(11):4426-41. PMID: 15899849; PMCID: PMC1140631.
    35. Brdicka T, Kadlecek TA, Roose JP, Pastuszak AW, Weiss A. Intramolecular regulatory switch in ZAP-70: analogy with receptor tyrosine kinases. Mol Cell Biol. 2005 Jun; 25(12):4924-33. PMID: 15923611; PMCID: PMC1140569.
    36. Roose JP, Diehn M, Tomlinson MG, Lin J, Alizadeh AA, Botstein D, Brown PO, Weiss A. T cell receptor-independent basal signaling via Erk and Abl kinases suppresses RAG gene expression. PLoS Biol. 2003 Nov; 1(2):E53. PMID: 14624253; PMCID: PMC261890.
    37. Brantjes H, Roose J, van De Wetering M, Clevers H. All Tcf HMG box transcription factors interact with Groucho-related co-repressors. Nucleic Acids Res. 2001 Apr 01; 29(7):1410-9. PMID: 11266540; PMCID: PMC31284.
    38. Roose J, Weiss A. T cells: getting a GRP on Ras. Nat Immunol. 2000 Oct; 1(4):275-6. PMID: 11017094.
      View in: PubMed
    39. Lawrence N, Dearden P, Hartley D, Roose J, Clevers H, Arias AM. dTcf antagonises Wingless signalling during the development and patterning of the wing in Drosophila. Int J Dev Biol. 2000 Oct; 44(7):749-56. PMID: 11128568.
      View in: PubMed
    40. Molenaar M, Brian E, Roose J, Clevers H, Destrée O. Differential expression of the Groucho-related genes 4 and 5 during early development of Xenopus laevis. Mech Dev. 2000 Mar 01; 91(1-2):311-5. PMID: 10704855.
      View in: PubMed
    41. Roose J, Clevers H. TCF transcription factors: molecular switches in carcinogenesis. Biochim Biophys Acta. 1999 Oct 29; 1424(2-3):M23-37. PMID: 10528152.
      View in: PubMed
    42. Roose J, Huls G, van Beest M, Moerer P, van der Horn K, Goldschmeding R, Logtenberg T, Clevers H. Synergy between tumor suppressor APC and the beta-catenin-Tcf4 target Tcf1. Science. 1999 Sep 17; 285(5435):1923-6. PMID: 10489374.
      View in: PubMed
    43. Roose J, Korver W, de Boer R, Kuipers J, Hurenkamp J, Clevers H. The Sox-13 gene: structure, promoter characterization, and chromosomal localization. Genomics. 1999 Apr 15; 57(2):301-5. PMID: 10198172.
      View in: PubMed
    44. Roose J, Molenaar M, Peterson J, Hurenkamp J, Brantjes H, Moerer P, van de Wetering M, Destrée O, Clevers H. The Xenopus Wnt effector XTcf-3 interacts with Groucho-related transcriptional repressors. Nature. 1998 Oct 08; 395(6702):608-12. PMID: 9783587.
      View in: PubMed
    45. Cavallo RA, Cox RT, Moline MM, Roose J, Polevoy GA, Clevers H, Peifer M, Bejsovec A. Drosophila Tcf and Groucho interact to repress Wingless signalling activity. Nature. 1998 Oct 08; 395(6702):604-8. PMID: 9783586.
      View in: PubMed
    46. Molenaar M, Roose J, Peterson J, Venanzi S, Clevers H, Destrée O. Differential expression of the HMG box transcription factors XTcf-3 and XLef-1 during early xenopus development. Mech Dev. 1998 Jul; 75(1-2):151-4. PMID: 9739131.
      View in: PubMed
    47. Korinek V, Barker N, Willert K, Molenaar M, Roose J, Wagenaar G, Markman M, Lamers W, Destree O, Clevers H. Two members of the Tcf family implicated in Wnt/beta-catenin signaling during embryogenesis in the mouse. Mol Cell Biol. 1998 Mar; 18(3):1248-56. PMID: 9488439; PMCID: PMC108837.
    48. Roose J, Korver W, Oving E, Wilson A, Wagenaar G, Markman M, Lamers W, Clevers H. High expression of the HMG box factor sox-13 in arterial walls during embryonic development. Nucleic Acids Res. 1998 Jan 15; 26(2):469-76. PMID: 9421502; PMCID: PMC147262.
    49. Korver W, Roose J, Heinen K, Weghuis DO, de Bruijn D, van Kessel AG, Clevers H. The human TRIDENT/HFH-11/FKHL16 gene: structure, localization, and promoter characterization. Genomics. 1997 Dec 15; 46(3):435-42. PMID: 9441747.
      View in: PubMed
    50. Korver W, Roose J, Wilson A, Clevers H. The winged-helix transcription factor Trident is expressed in actively dividing lymphocytes. Immunobiology. 1997 Dec; 198(1-3):157-61. PMID: 9442387.
      View in: PubMed
    51. Korver W, Roose J, Clevers H. The winged-helix transcription factor Trident is expressed in cycling cells. Nucleic Acids Res. 1997 May 01; 25(9):1715-9. PMID: 9108152; PMCID: PMC146663.
    52. Molenaar M, van de Wetering M, Oosterwegel M, Peterson-Maduro J, Godsave S, Korinek V, Roose J, Destrée O, Clevers H. XTcf-3 transcription factor mediates beta-catenin-induced axis formation in Xenopus embryos. Cell. 1996 Aug 09; 86(3):391-9. PMID: 8756721.
      View in: PubMed
    53. Toye PG, Metzelaar MJ, Wijngaard PL, Nene V, Iams K, Roose J, Nyanjui JK, Gobright E, Musoke AJ, Clevers HC. Characterization of the gene encoding the polymorphic immunodominant molecule, a neutralizing antigen of Theileria parva. J Immunol. 1995 Aug 01; 155(3):1370-81. PMID: 7636202.
      View in: PubMed
    54. Roose JP, Van Noorden CJ. Synthetic protease inhibitors: promising compounds to arrest pathobiologic processes. J Lab Clin Med. 1995 Apr; 125(4):433-41. PMID: 7706897.
      View in: PubMed
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