Assistant Professor, Department of Anatomy, UCSF
Research SummaryI 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. Beginning in 2007, I have built my own research group as an independent investigator in the department of Anatomy at UCSF. I am currently a tenured Associate Professor, and my research group consists of a team of twelve staff members, graduate students, postdoctoral fellows, and Master’s students.
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. The potency of active Ras is illustrated by the fact that activating mutations in the Ras genes are among the most common genetic lesions leading to cancer.
Our goal is to understand the mechanism of activation of the small GTPase Ras by Ras exchange factors, comparing normal physiology with pathology. We collaborate with many different groups and benefit from these collaborations by tapping into computational models, biophysical approaches, structural insights, and patient samples. We combined these collaborative efforts with our own expertise in the biochemistry of Ras signal transduction, cell line approaches, and various mouse models.
There are four main directions in the lab:
1. Mechanistic understanding of Ras activation by Ras exchange factors.
2. Altered Ras-kinase signaling in autoimmune T cells.
3. Interfering with oncogenic Ras signals in leukemia.
4. Ras exchange factors in epithelial cells and carcinoma.
My lab is part of the Biomedical Science (BMS) Graduate Program, the Immunology Program, the Helen Diller Family Comprehensive Cancer Center, and the Stem Cell Center at UCSF. For more information on research directions, projects, and publications, please visit our website @ http://rooselab.ucsf.edu.
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
Adjunct Instructor, Div. of Rheumatology, Dept. of Medicine, UCSF, San Francisco
Assistant Adjunct Professor, Div. of Rheumatology, Dept. of Medicine, UCSF, San Francisco
Assistant Professor, Dept. of Anatomy, School of Medicine, UCSF, San Francisco
Honors & Awards
Arthritis Investigator Award
Howard Temin Career Development Award (K01; NCI)
Kimmel Foundation Award
Stewart Trust Award
Arthritis Investigator Award (2-year renewal)
UCSF Shared Equipment Award
Physical Science - Oncology Center Award (U54; NCI)
ARRA Award (K01; NCI)
ACS Individual Researcher Award (UCSF)
Trans Physical Science – Oncology Center Award (NIH; NCI)
Pilot Physical Science – Oncology Center Award (NIH; NCI)
P01 Award (NIH; NIAID)
R56 Award (NIH; NIAID)
Gabrielle’s Angel Foundation Award
UCSF Research Allocation Program (RAP) Award
UCSF PBBR/Sanofi Leap to Innovation for Therapeutics and Technology (LIFTT) Program Award
Pilot Physical Science – Oncology Center Award (NIH; NCI)
UCSF PBBR TMC (Technologies, Methodologies, and Cores)
- 1.Molenaar M, van de Wetering M, Oosterwegel M, Peterson-Maduro J, Godsave S, Korinek V, Roose J, Destree O, Clevers H. XTcf-3 transcription factor mediates beta-catenin-induced axis formation in Xenopus embryos. Cell. 1996 Aug 9;86(3):391-9.
- 2.Roose J, Molenaar M, Peterson J, Hurenkamp J, Brantjes H, Moerer P, van de Wetering M, Destree O, Clevers H. The Xenopus Wnt effector XTcf-3 interacts with Groucho-related transcriptional repressors. Nature. 1998 Oct 8;395(6702):608-12.
- 3.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.
- 4.Roose J, Diehn M, Tomlinson M, Lin J, Alizadeh A, Botstein D, Brown P, Weiss A. T cell Receptor-Independent Basal Signaling via Erk and Abl Kinases Suppresses RAG gene Expression. PLOS Biology. 2003 1(2):271-287.
- 5.Roose J, Mollenauer M, Gupta V, Stone J, and Weiss A. A Diacylglycerol-Protein Kinase C-RasGRP1 Pathway Directs Ras Activation Upon Antigen Receptor Stimulation of T cells. Mol. Cell Biol. 2005 25(11);4426-41.
- 6.Roose J, Mollenauer M, Ho M, Kurosaki T, and Weiss A. Unusual Interplay of Two Types of Ras Activators, RasGRP and SOS, Establishes Robust and Controlled Ras Activation in Lymphocytes. Mol Cell Biol. 2007 27(7):2732-45
- 7.Ashok Prasad, Julie Zikherman, Jayajit Das, Jeroen Roose, Arthur Weiss, Arup K. Chakraborty. Origin of the sharp boundary that discriminates positive and negative selection of thymocytes. PNAS. 2009 Jan 13;106(2):528-33.
- 8.Jayajit Das, Mary Ho, Julie Zikherman, Christopher Gover, Ming Yang, Arthur Weiss, Arup K. Chakraborty, and Jeroen P. Roose. Digital signaling and hysteresis characterize Ras activation in lymphoid cells. Cell. 2009 136, 337-351.
- 9.Chakraborty AK, Das J, Zikherman J, Yang M, Govern CC, Ho M, Weiss A, and Roose J. Molecular origin and functional consequences of digital signaling and hysteresis during Ras activation in lymphocytes. Science Signaling. 2009 2, 66:pt2.
- 10.Jennifer O. Lauchle, Doris Ki, Doan T. Le, Keiko Akagi, Michael Crone, Kimberly Krisman, Kegan Warner, Jeannette M. Bonifas, Qing Li, Kristin M. Coakley, Ernesto Diaz-Flores, Matthew Gorman, Sally Przybranowski, Mary Tran, Scott C. Kogan, Jeroen P. Roose, Neal Copeland, Nancy Jenkins, Luis Parada, Linda Wolff, Judith Sebolt-Leopold, and Kevin Shannon. Response and resistance to MEK inhibition in leukaemias initiated by hyperactive Ras. Nature, 2009 Sep 17;461(7262):411-4.
- 11.Andre Limnander, Philippe Depeille, Jen Liou, Michael Leitges, Tomohiro Kurosaki, Jeroen P. Roose and Arthur Weiss. Stim1, PKCŒ¥ and RasGRP Proteins Set a Threshold for Pro-Apoptotic Erk Signaling During B cell Development. Nature Immunology, 2011 May;12(5):425-33.
- 12.Evan Markegard, Evan Trager, Chih-wen Ou Yang, Weiguo Zhang, Arthur Weiss, and Jeroen P. Roose. Basal LAT-diacylglycerol-RasGRP1 Signals in T cells Maintain TCR-alpha Gene Expression. PLoS ONE, 2011;6(9):e25540. Epub 2011 Sep 26.
- 13.Hartzell, C., Ksionda, O. , Lemmens, E., Coakley, K., Yang M., Harvey, R., Govern C., Bakker, J., Lenstra, T., Dail, M., Ammon, K., Boeter, A., Loh, M., Winter, S., Chakraborty, A., Shannon, K., Wabl, M., Roose, J. Deregulated RasGRP1 Responds to Cytokine Receptor-input in T cell leukemogenesis. Science signaling , 2013 March.
- 14.Chakraborty, A. and Roose, J.. Biochemical Heterogeneity and Developmental Varieties in T cell Leukemia. Cell Cycle, 2013 May.
- 15.Activation of ERK but not of P38 MAP kinase Pathways in Lymphocytes Requires Allosteric Activation of SOS. Jun, J., Yang, M., Chen, H., Chakraborty, A., and Roose, J. MCB, 2013 June.
- 16.The Structural Basis for Autoinhibition of the Ras-specific exchange factor RasGRP1. Jeffrey S. Iwig, Yvonne Vercoulen, Rahul Das, Tiago Barros, Andre Limnander, Yan Che, Jeffrey G. Pelton, David E. Wemmer, Jeroen P. Roose# and John Kuriyan#. eLIFE, 2013 July.
- 17.Regulation of Ras Exchange Factors and Cellular Localization of Ras Activation by Lipid Messengers in T cells. Jesse E. Jun, Ignacio Rubio, and Jeroen Roose. Frontiers in Immunology, September 2013
- 18.Rasgrp Ras Guanine Nucleotide Exchange Factors in Cancer. Olga Ksionda, Andre Limnander, and Jeroen Roose Frontiers in Biology, October 2013.
- 19.PLCgamma and PI3 Kinase Link Cytokine Stimulation to ERK Activation in Primary Hematopoietic Cells Expressing Normal and Oncogenic Kras. Ernesto Diaz-Flores, Hana Goldschmidt, Philippe Depeille, Victor Ng, Kimberly Krisman, Michael Crone, Olusegun Williams, Benjamin Houseman, Kevan Shokat, Deepak Sampath, Gideon Bollag, Jeroen P. Roose, Benjamin S. Braun, and Kevin Shannon. Science Signaling, in press.
- 20.Rasgrp1 mutation increases naive T-cell CD44 expression and drives mTOR-dependent accumulation of Helios+ CD44hi CD4+ T cells and autoantibodies. Stephen R. Daley, Kristen M. Coakley, Daniel Hu, Katrina L. Randall, Craig N. Jenne, Andre Limnander, Darienne R. Myers, Noelle K. Polakos, Anselm Enders, Carla Roots, Bhavani Balakishnan, Lisa A. Miosge, Geoff Sjollema, Edward M Bertram, Matthew A Field, Yunli Shao, T. Daniel Andrews, Belinda Whittle, S. Whitney Barnes, John R. Walker, Jason G. Cyster, Christopher C. Goodnow, and Jeroen P. Roose. eLIFE, in press.