Jolanda van Leeuwen performed her PhD research in the lab of Dr. Nico Vermeulen at VU University Amsterdam (the Netherlands), where she discovered genetic factors that affect the toxicity of non-steroidal anti-inflammatory drugs. After obtaining her PhD in 2011, she joined the labs of Drs. Charlie Boone and Brenda Andrews at the University of Toronto (Canada), where she mapped networks of genetic interactions in yeast. She is joining the Center for Integrative Genomics in April 2018 as Assistant Professor.
The sequencing of thousands of humans has led to the identification of people that are healthy despite carrying mutations that have been directly associated with severe early-onset Mendelian diseases, such as cystic fibrosis. A plausible explanation is that these individuals carry secondary mutations elsewhere in the genome that can compensate for the deleterious effect of the disease-associated mutation, a phenomenon referred to as genetic suppression. However, we currently lack the expertise to identify these suppressor mutations among the millions of variants scattered across the genomes of these resilient individuals.
The main research mission of the Van Leeuwen lab is to use functional genomics tools to improve our understanding of how mutations can interact to produce unexpected phenotypes, and how this determines the severity of genetic traits. Our research specifically focusses on suppression interactions, in which the accumulation of secondary mutations elsewhere in the genome can compensate for the deleterious effects of the primary mutation. Understanding the general mechanisms of suppression will aid the identification of the genes in which suppressing mutations can occur, which in turn can define molecular mechanisms of disease and identify potential drug targets to guide the development of therapeutics.
To study suppression interactions, we use high-throughput genetic analysis in both yeast and human cells. Current projects include:
Expanding the suppressor network in yeast and decipher general rules of suppression to allow us to predict these interactions in human genomes.
Investigating the role of suppressor mutations in tumor development and chemotherapy resistance.
Technology development for high-throughput analysis of suppression interactions in cultured mammalian cells.
Exploring suppression phenotypes involving more than two genes, to understand how multiple mutations can combine to yield phenotypes.
For more information on our lab, please visit http://www.vanleeuwenlab.com.
Jolanda van Leeuwen, Charles Boone, and Brenda J. Andrews (2017) Mapping a diversity of genetic interactions in yeast. Curr Opin Syst Biol, 6, 14-21. URL
Traver Hart, Amy H.Y. Tong, Katie Chan, Jolanda van Leeuwen, Ashwin Seetharaman, Michael Aregger, Megha Chandrashekhar, Nicole Hustedt, Sahil Seth, Avery Noonan, Andrea Habsid, Olga Sizova, Lyudmilla Nedyalkova, Ryan Climie, Leanne Tworzyanski, Keith Lawson, Maria Augusta Sartori, Sabriyeh Alibeh, David Tieu, Sanna Masud, Patricia Mero, Alexander Weiss, Kevin R. Brown, Matej Ušaj, Maximilian Billmann, Mahfuzur Rahman, Michael Costanzo, Chad L. Myers, Brenda J. Andrews, Charles Boone, Daniel Durocher, and Jason Moffat (2017) Evaluation and design of genome-wide CRISPR/Cas9 knockout screens. G3 (Bethesda), 7, 2719-2727. URL
Jolanda van Leeuwen, Carles Pons, Charles Boone, and Brenda J. Andrews (2017) Mechanisms of suppression: the wiring of genetic resilience. BioEssays, 39, 1700042. URL
Jolanda van Leeuwen*, Carles Pons*, Joseph C. Mellor, Takafumi N. Yamaguchi, Helena Friesen, John Koschwanez, Mojca Mattiazzi Ušaj, Maria Pechlaner, Mehmet Takar, Matej Ušaj, Benjamin VanderSluis, Kerry Andrusiak, Pritpal Bansal, Anastasia Baryshnikova, Claire Boone, Jessica Cao, Atina Cote, Marinella Gebbia, Gene Horecka, Ira Horecka, Elena Kuzmin, Nicole Legro, Wendy Liang, Natascha van Lieshout, Margaret McNee, Bryan-Joseph San Luis, Fatemeh Shaeri, Ermira Shuteriqi, Song Sun, Lu Yang, Ji-Young Youn, Michael Yuen, Michael Costanzo, Anne-Claude Gingras, Patrick Aloy, Chris Oostenbrink, Andrew Murray, Todd R. Graham, Chad L. Myers, Brenda J. Andrews, Frederick P. Roth, and Charles Boone (2016) Exploring genetic suppression interactions on a global scale. Science 354, 599. URL
Michael Costanzo*, Benjamin VanderSluis*, Elizabeth N. Koch*, Anastasia Baryshnikova*, Carles Pons*, Guihong Tan*, Wen Wang, Matej Ušaj, Julia Hanchard, Susan D. Lee, Vicent Pelechano, Erin B. Styles, Maximilian Billmann, Jolanda van Leeuwen, Nydia van Dyk, Zhen-Yuan Lin, Elena Kuzmin, Justin Nelson, Jeff S. Piotrowski, Tharan Srikumar, Sondra Bahr, Yiqun Chen, Raamesh Deshpande, Christoph F. Kurat, Sheena C. Li, Zhijian Li, Mojca Mattiazzi Ušaj, Hiroki Okada, Natasha Pascoe, Bryan-Joseph San Luis, Sara Sharifpoor, Emira Shuteriqi, Scott W. Simpkins, Jamie Snider, Harsha Garadi Suresh, Yizhao Tan, Hongwei Zhu, Noel Malod-Dognin, Vuk Janjic, Natasa Przulj, Olga G. Troyanskaya, Igor Stagljar, Tian Xia, Yoshikazu Ohya, Anne-Claude Gingras, Brian Raught, Michael Boutros, Lars M. Steinmetz, Claire L. Moore, Adam P. Rosebrock, Amy A. Caudy, Chad L. Myers, Brenda Andrews, and Charles Boone (2016) A global genetic interaction network maps a wiring diagram of cellular function. Science 353, 1381. URL
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