The ability to perturb desired RNA molecules in a cell with high efficiency and specificity is a key technology across biomedical science. Despite rapid progress in effective technologies for genome engineering, analogous systems for transcriptome engineering lag behind their DNA counterparts. We recently identified the RNA-targeting type VI-D CRISPR-Cas family (Cas13d), in particular the engineered Cas13d from R. flavefaciens strain XPD3002 (CasRx) (Konermann et al., 2018), which are the smallest and most efficient Cas13 RNA targeting effectors in mammalian and plant cells reported to date. We are working to further characterize and optimize the Cas13d enzymes as RNA-targeting tools (Wei et al., 2022) to advance the investigation of RNA biology and application in RNA therapeutics.
High-throughput CRISPR perturbation screening has emerged as a powerful approach to interrogate gene expression networks (Konermann et al., 2015; Joung et al., 2017; Biering et al., 2022). We are developing and applying methods for CRISPR screening in stem cell-derived models of the human brain to investigate the cellular and molecular pathways driving genetic risk in neurodegenerative disease. Concurrently, we are developing computational methods for analyzing large-scale perturbation datasets towards the goal of elucidating the genetic architecture of complex disease risk.
Matthew G. Durrant*, Nicholas T. Perry*, James J. Pai, Aditya R. Jangid, Januka S. Athukoralage, Masahiro Hiraizumi, John P. McSpedon, April Pawluk, Hiroshi Nishimasu, Silvana Konermann, Patrick D. Hsu
Jingyi Wei, Peter Lotfy, Kian Faizi, Hannah Slabodkin, Emily Kinnaman, Sita Chandrasekaran, Hugo Kitano, Matthew G. Durrant, Connor V. Duffy, Patrick David Hsu, Silvana Konermann
Scott B. Biering, Sylvia A. Sarnik, Eleanor Wang, James R. Zengel, Sarah R. Leist, Alexandra Schäfer, Varun Sathyan, Padraig Hawkins, Kenichi Okuda, Cyrus Tau, Aditya R. Jangid, Connor V. Duffy, Jin Wei, Rodney C. Gilmore, Mia Madel Alfajaro, Madison S. Strine, Xammy Nguyenla, Erik Van Dis, Carmelle Catamura, Livia H. Yamashiro, Julia A. Belk, Adam Begeman, Jessica C. Stark, D. Judy Shon, Douglas M. Fox, Shahrzad Ezzatpour, Emily Huang, Nico Olegario, Arjun Rustagi, Allison S. Volmer, Alessandra Livraghi-Butrico, Eddie Wehri, Richard R. Behringer, Dong-Joo Cheon, Julia Schaletzky, Hector C. Aguilar, Andreas S. Puschnik, Brian Button, Benjamin A. Pinsky, Catherine A. Blish, Ralph S. Baric, Wanda K. O’Neal, Carolyn R. Bertozzi, Craig B. Wilen, Richard C. Boucher, Jan E. Carette, Sarah A. Stanley, Eva Harris, Silvana Konermann, Patrick D. Hsu
Silvana Konermann, Peter Lotfy, Nicholas J Brideau, Jennifer Oki, Maxim N Shokhirev, Patrick D Hsu
Julia Joung, Silvana Konermann, Jonathan S Gootenberg, Omar O Abudayyeh, Randall J Platt, Mark D Brigham, Neville E Sanjana, Feng Zhang
Omar O Abudayyeh, Jonathan S Gootenberg, Silvana Konermann, Julia Joung, Ian M Slaymaker, David BT Cox, Sergey Shmakov, Kira S Makarova, Ekaterina Semenova, Leonid Minakhin, Konstantin Severinov, Aviv Regev, Eric S Lander, Eugene V Koonin, Feng Zhang
James E Dahlman, Omar O Abudayyeh, Julia Joung, Jonathan S Gootenberg, Feng Zhang & Silvana Konermann
Silvana Konermann, Mark D. Brigham, Alexandro E. Trevino, Patrick D. Hsu, Matthias Heidenreich, Le Cong, Randall J. Platt, David A. Scott, George M. Church, Feng Zhang
Silvana is an Assistant Professor of Biochemistry at Stanford. Her research laboratory aims to understand the molecular pathways that drive the development of Alzheimer’s disease using next-generation functional genomics, with the long-term goal of developing rationally targeted therapeutics for neurodegenerative disorders. She received her Ph.D. in Neuroscience from MIT. Silvana’s pioneering work on tools to directly perturb the transcriptomic landscape of the cell using CRISPR has been recognized by her faculty appointment as a Chan Zuckerberg Biohub Investigator and Hanna Gray Fellow of the Howard Hughes Medical Institute.
Connor Duffy is a graduate student in the Stanford Genetics PhD program. He received his S.B. in Computer Science and Molecular Biology from MIT.
Jayesh Salvi is a Senior Scientist in the Konermann and Hsu labs at the Arc Institute. He received his PhD from the University of Toronto and completed Postdoctoral training in Dr. Thomas Rando’s lab at Stanford University. Jay is broadly interested in modeling CNS disorders and determining important signaling pathways in development and disease.
Kiki Chu is the lab manager for the Konermann and Hsu labs at the Arc Institute. She received her PhD from the University of Wisconsin-Madison and completed her postdoctoral training at Massachusetts General Hospital. Before joining the Arc Institute, she was a lab manager at MIT in a neuroelectrophysiology lab, further adding to her diverse research background in the fields of lipid metabolism and cancer biology.
Alessandra is interested in applying modern functional genomic tools to neuroscience. She received her PhD in Neuroscience from the Open University of London and trained as a postdoctoral fellow with Dr. Thomas C. Südhof at Stanford University.
Januka Athukoralage is a Senior Scientist in the Konermann and Hsu labs. He received his PhD in Biochemistry from the University of St Andrews in Scotland working on the biochemistry of novel CRISPR systems. He then held an EMBO postdoctoral fellowship at UCSF. Just prior to joining Arc, Januka worked as a Discovery Scientist at Arcadia Science.
Seula Shin is a Senior Scientist. She received her PhD in Cancer Biology from UT MD Anderson Cancer Center and completed her postdoctoral training at Denali Therapeutics. Seula is interested in understanding the crosstalk of polygenic risk factors in pathobiology of Alzheimer's Disease using 3D human brain models.
Shivani Pandit a Research Associate. She received her Masters in Medical Biotechnology from the University of Illinois Chicago. She is interested in determining neuron - neuron interaction using the rabies virus for monosynaptic tracing.
Dhruva Katrekar is a Senior Scientist in the Hsu and Konermann labs. He received his PhD in Bioengineering from UC San Diego where he developed a new RNA editing technology. After his PhD, he spent a few years working at Shape Therapeutics before making the transition to Arc. Dhruva has a keen interest in building novel molecular tools and advancing the field of synthetic biology.
Abinaya is a Research Associate, interested in investigating the molecular mechanisms that instruct neural wiring using in vivo techniques. She received her B.S. Physiology and Neuroscience, from the University of California San Diego.
Claudia is a Research Associate interested in the application of stem cell derived brain organoids to recapitulate neural like tissue, architecture, and function to study the molecular mechanisms of neurodegenerative disorders and explore potential genetic therapeutics. Claudia received her BS in Neuroscience from the University of California, Santa Cruz.
Joanna is an Executive Assistant supporting Silvana Konermann. After working at many different finance and tech companies in Silicon Valley, she is very excited to be surrounded by science again. She received her BA in Geology from Hamilton College.
Gwanggyu Sun is a Scientist in the Konermann and Hsu Labs. He received his PhD in Bioengineering from Stanford University, where he worked on building a whole-cell computational model of E. coli. Gwanggyu is interested in computational approaches that aim to understand and demystify complex biological systems.
I received my BSc in Molecular Genetics and Microbiology and my MSc in Medical Science, both from the University of Toronto. For my MSc, I investigated a key transcription factor in the proximal tubular epithelial cells of the kidney and its role in controlling gene expression and cellular metabolism in these cells. Afterwards, and prior to Arc, I was a Life Science Research Professional in the Wernig lab at Stanford, where I worked on developing approaches to prevent gene silencing and enable robust expression of transgenes in iPSC-derived neurons. Broadly speaking, I am interested in utilizing genome engineering and genetic approaches to answer fundamental, disease-relevant questions in iPSC-derived cell types.
