Research Summary

I obtained my PhD in The Netherlands where I investigated Wnt signaling and cancer in the lab of Dr. Hans Clevers. I subsequently studied Ras signaling in lympohcytes during my postdoc in the lab of Dr. Arthur Weiss at UCSF. Since 2007 I built my own research group as an independent investigator in the department of Anatomy at UCSF. I am currently a tenured Professor with a team of staff members, graduate students, postdoctoral fellows, and Master’s students. Our focus is on Ras-kinase signaling an implications of signal alterations in human disease.

Half of my group currently focuses on various aspects of Ras signaling and cancer. We have published on the leukemic role of the Ras activator Rasgrp1 in both T cell leukemia and in myeloid leukemia. We reported on two biochemically distinct oncogenic Ras signals in T cell leukemia. We continue this research area with the goal of improving molecular therapy for leukemia patients. We expanded our research to carcinomas and reported that the EGFR sends not only growth-stimulatory cues in colorectal cancer but also growth-restricting signals, depending on the use of the SOS1- or RasGRP1- Ras activators.

We are part of the Biomedical Science (BMS) Graduate Program, the Immunology Program, the Helen Diller Family Comprehensive Cancer Center, and the Stem Cell Center. For more information on research directions, projects, and publications, please visit our website at rooselab.ucsf.edu.

Research Funding

  • May 18, 2020 - June 30, 2021 - Defining the Unique Properties of the Distinct Signaling Machinery Used by the TCR, Co-Investigator. Sponsor: NIH/NIAID, Sponsor Award ID: P01AI091580
  • July 1, 2015 - June 30, 2020 - Molecular understanding of cytokine-Ras signals in leukemic bone marrow, Principal Investigator. Sponsor: NIH/NCI, Sponsor Award ID: R01CA187318
  • August 15, 2015 - April 30, 2020 - Balanced signaling cues to guide cell transitions in the blood lineage continuum, Principal Investigator. Sponsor: NIH/NHLBI, Sponsor Award ID: R01HL120724
  • March 1, 2014 - February 28, 2019 - Loss of Intrinsic Control in Autoimmune T Helper Cells with Signaling Variants, Principal Investigator. Sponsor: NIH/NIAID, Sponsor Award ID: R01AI104789

Education

University of Utrecht, The Netherlands, MS, 1993, Medical Biology
University of Utrecht, The Netherlands, PhD, 1999, Immunology/Transcription
University of Utrecht, The Netherlands, Fellowship, 1997-1999, Immunology/Transcription
University of California San Francisco, San Francisco, Fellowship, 1999-2004, Immunology/Signaling

Honors & Awards

Past 5 years:

  • 2012
    Gabrielle's Angel Foundation Award
  • 2013
    9th annual Mentoring award by the UCSF PSA (Postdoctoral Scholar’s Association)
  • 2014
    R01 Award (NIH; NIAID)
  • 2015
    R01 Award (NIH; NCI)
  • 2015
    Alex's Lemonade Stand Foundation Innovator Award
  • 2015
    R01 Award (NIH; NHLBI)
  • 2016
    Renewal P01 Award (NIH; NIAID)

Selected Publications

  1. Wen Z, Yun G, Hebert A, Kong G, Ranheim EA, Finn R, Rajagoplan A, Li S, Zhou Y, Yu M, Damnernsawad A, Roose JP, Coon JJ, Wen R, Wang D, Zhang J. Nras Q61R/+ and Kras-/- cooperate to downregulate Rasgrp1 and promote lympho-myeloid leukemia in early T-cell precursors. Blood. 2021 Jun 10; 137(23):3259-3271.  View on PubMed
  2. 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. SARS-CoV-2 infection studies in lung organoids identify TSPAN8 as novel mediator. bioRxiv. 2021 Jun 02.  View on PubMed
  3. Bahl K, Roose JP. T cells: a dedicated effector kinase pathways for every trait? Biochem J. 2021 03 26; 478(6):1303-1307.  View on PubMed
  4. Karra L, Roose JP. Investigating increased hematopoietic stem cell fitness in a novel mouse model. Small GTPases. 2021 Feb 10; 1-7.  View on PubMed
  5. Li PJ, Roose JP, Jablons DM, Kratz JR. Bioinformatic Approaches to Validation and Functional Analysis of 3D Lung Cancer Models. Cancers (Basel). 2021 Feb 09; 13(4).  View on PubMed
  6. Kulhanek KR, Roose JP, Rubio I. Regulation of the Small GTPase Ras and Its Relevance to Human Disease. Methods Mol Biol. 2021; 2262:19-43.  View on PubMed
  7. 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. Dysregulated RASGRP1 expression through RUNX1 mediated transcription promotes autoimmunity. Eur J Immunol. 2021 02; 51(2):471-482.  View on PubMed
  8. Karra L, Romero-Moya D, Ksionda O, Krush M, Gu Z, Mues M, Depeille P, Mullighan C, Roose JP. Increased baseline RASGRP1 signals enhance stem cell fitness during native hematopoiesis. Oncogene. 2020 11; 39(45):6920-6934.  View on PubMed
  9. 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. Next-Generation Surrogate Wnts Support Organoid Growth and Deconvolute Frizzled Pleiotropy In Vivo. Cell Stem Cell. 2020 11 05; 27(5):840-851.e6.  View on PubMed
  10. Kulhanek KR, Myers DR, Ksionda O, Vercoulen Y, Romero-Moya D, Roose JP. Protocol for Barcoding T Cells Combined with Timed Stimulations. STAR Protoc. 2020 Sep 18; 1(2):100067.  View on PubMed
  11. Romero-Moya D, Roose JP. Protocol for Comprehensive Synthetic Lethality Screens. STAR Protoc. 2020 Jun 19; 1(1).  View on PubMed
  12. Samocha A, Doh H, Kessenbrock K, Roose JP. Unraveling Heterogeneity in Epithelial Cell Fates of the Mammary Gland and Breast Cancer. Cancers (Basel). 2019 Sep 24; 11(10).  View on PubMed
  13. Kondo Y, Ognjenovic J, Banerjee S, Karandur D, Merk A, Kulhanek K, Wong K, Roose JP, Subramaniam S, Kuriyan J. Cryo-EM structure of a dimeric B-Raf:14-3-3 complex reveals asymmetry in the active sites of B-Raf kinases. Science. 2019 10 04; 366(6461):109-115.  View on PubMed
  14. Myers DR, Wheeler B, Roose JP. mTOR and other effector kinase signals that impact T cell function and activity. Immunol Rev. 2019 09; 291(1):134-153.  View on PubMed
  15. Jun JE, Kulhanek KR, Chen H, Chakraborty A, Roose JP. Alternative ZAP70-p38 signals prime a classical p38 pathway through LAT and SOS to support regulatory T cell differentiation. Sci Signal. 2019 07 23; 12(591).  View on PubMed
  16. 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. RasGRP1 is a potential biomarker to stratify anti-EGFR therapy response in colorectal cancer. JCI Insight. 2019 06 25; 5.  View on PubMed
  17. Myers DR, Norlin E, Vercoulen Y, Roose JP. Active Tonic mTORC1 Signals Shape Baseline Translation in Naive T Cells. Cell Rep. 2019 05 07; 27(6):1858-1874.e6.  View on PubMed
  18. Mues M, Karra L, Romero-Moya D, Wandler A, Hangauer MJ, Ksionda O, Thus Y, Lindenbergh M, Shannon K, McManus MT, Roose JP. High-Complexity shRNA Libraries and PI3 Kinase Inhibition in Cancer: High-Fidelity Synthetic Lethality Predictions. Cell Rep. 2019 04 09; 27(2):631-647.e5.  View on PubMed
  19. Ksionda O, Mues M, Wandler AM, Donker L, Tenhagen M, Jun J, Ducker GS, Matlawska-Wasowska K, Shannon K, Shokat KM, 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. 2018; 13(5):e0193849.  View on PubMed
  20. Vercoulen Y, Kondo Y, Iwig JS, Janssen AB, White KA, Amini M, Barber DL, Kuriyan J, Roose JP. A Histidine pH sensor regulates activation of the Ras-specific guanine nucleotide exchange factor RasGRP1. Elife. 2017 09 27; 6.  View on PubMed

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