Illuminating Druggable Dark Matter

Contacts

• Michael McManus' Lab: https://mcmanuslab.ucsf.edu/
• Lily Jan’s Lab: https://physio.ucsf.edu/Jan/
• Bin Chen’s Lab: http://binchenlab.org/
• Robinson’s Lab: https://robinsongroup.github.io/
• Monarch Initiative: https://monarchinitiative.org/
• Mouse Biology Program: www.mousebiology.org
• International Mouse Phenotyping Consortium: https://www.mousephenotype.org/
• Mutant Mouse Resource & Research Center: www.mmrrc.org
• NeuroMab: https://neuromab.ucdavis.edu/

Mouse Biology Program: @mousebiology
International Mouse Phenotyping: @IMPC
Monarch Initiative: @monarchinit

Overview

Dr. Michael T. McManus together with Dr. Lily Jan leads a group researchers from UCSF to UCSD focused illuminating Ion Channels by utilizing CRISPR technology to map expression profiles, assess channel activities, develop antibodies and generate new mouse lines.

NIH grant number: 1U24 DK116214-01

Progress on IDG project as tracked by Protein Illumination Timeline: Ion Channels:

https://druggablegenome.net/ProteinTimelineIonChannels

Co-Investigators:

• Allan Basbaum, Ph.D., FRS

Professor and Chair in Department of Anatomy at UCSF School of Medicine
University of California, San Francisco (UCSF)

• Louis Ptacek, Ph.D.

Professor in Department of Neurology at UCSF School of Medicine
University of California, San Francisco (UCSF)

• Allan Balmain, Ph.D., FRS

Barbara Bass Bakar Distinguished Professorship in Cancer Genetics
Co-leader of Cancer Genetics Program
Director of Genome Analysis Core Facility at UCSF Helen Diller Family Comprehensive Cancer Center
University of California, San Francisco (UCSF)

Bioinformaticists:

• Zicheng Hu, Ph.D.

Bioinformaticist, University of California, San Francisco (UCSF)

• Atul Butte, M.D., Ph.D.

Priscilla Chan and Mark Zuckerberg Distinguished Professor at UCSF School of Medicine
Department of Pediatrics
University of California, San Francisco (UCSF)

• Melissa Haendel, Ph.D.

Interim Co-Director of the OHSU Library
Associate Professor in Department of Medical Informatics & Clinical Epidemiology
Oregon Health Science University (OHSU)

• Christopher Mungall, Ph.D.

Computer Research Scientist
Lawrence Berkeley National Laboratory (LBNL)

• Peter Robinson, M.D. MSC.

Professor of Computational Biology
Jackson Labs (JAX)
Production Core Team:

• Nevan Krogan, Ph.D.

Professor in Department of Cellular Molecular Pharmacology at UCSF School of Medicine
University of California, San Francisco (UCSF)

• Kent Lloyd, DVM, Ph.D.

Professor,
Director of Mouse Biology Program
University of California, Davis (UC Davis)

• Allison Xu, Ph.D.

Professor in Department of Surgery at UC Davis Comprehensive Cancer Center
University of California, San Francisco (UCSF)

• Christian Vaisse, M.D., Ph.D.

Professor in Diabetes Center at UCSF School of Medicine
University of California, San Francisco (UCSF)

• Scott Kogan, M.D.

Professor in Department of Laboratory Medicine at UCSF School of Medicine
University of California, San Francisco (UCSF)

• Scott VandenBerg, M.D., Ph.D.

Professor in Department of Pathology at UCSF School of Medicine
University of California, San Francisco (UCSF)

• Jim Trimmer

Director, NeuroMab
University of California, Davis (UC Davis)

• Belvin Gong

Assistant Director of NeuroMab,
University of California, Davis (UC Davis)
Other Contributors:

• Stephen Altschuler, Ph.D.

Professor in Department of Pharmaceutical Chemistry at UCSF School of Pharmacy
University of California, San Francisco (UCSF)

• Lani Wu, Ph.D.

Professor in Department of Pharmaceutical Chemistry at UCSF School of Pharmacy
University of California, San Francisco (UCSF)

• James Wilkerson, JD, DVM

Director of Laboratory Animal Resource Center (LARC)
University of California, San Francisco (UCSF)

• Oliver Fiehn, Ph.D.

Director of Metabolomics at UC Davis Genome Center
University of California, Davis (UC Davis)

• Bo Huang, Ph.D.

Professor in Department of Pharmaceutical Chemistry at UCSF School of Pharmacy
University of California, San Francisco (UCSF)

• Nadav Ahituv, Ph.D.

Professor in Department of Bioengineering at UCSF School of Pharmacy
University of California, San Francisco (UCSF)

• Christophe Borchers, Ph.D.

Genome British Columbia Proteomics Center
University of Victoria (UVic)

• Henry A. Lester, Ph.D.

Bren Professor in the Division of Biology and Biological Engineering
California Institute of Technology (Caltech)

• Vikass Sohal, M.D., Ph.D.

Associate Professor in Department of Psychiatry at UCSF School of Medicine
University of California, San Francisco (UCSF)

DRGC-Ion Channel Publications:

1. ARS-CoV-2 ORF3A interacts with the Clic-like chloride channel-1 (CLCC1) and triggers an unfolded protein response.
   Gruner HN, Zhang Y, Shariati K, Yiv N, Hu Z, Wang Y, Hejtmancik JF, McManus MT, Tharp K, Ku G. S PeerJ. 2023 Apr 3;11:e15077. doi: 10.7717/peerj.15077. PMID: 37033725; PMCID: PMC10078464.
2. Systematic identification of ACE2 expression modulators reveals cardiomyopathy as a risk factor for mortality in COVID-19 patients.
   Kaur N, Oskotsky B, Butte AJ, Hu Z. Genome Biol. 2022 Jan 10;23(1):15. doi: 10.1186/s13059-021-02589-4. PMID: 35012625; PMCID: PMC8743438.
3. TMEM16C is involved in thermoregulation and protects rodent pups from febrile seizures.
   Wang TA, Chen C, Huang F, Feng S, Tien J, Braz JM, Basbaum AI, Jan YN, Jan LY. Proc Natl Acad Sci U S A. 2021 May 18;118(20):e2023342118. doi: 10.1073/pnas.2023342118. PMID: 33972431; PMCID: PMC8157992.
4. Leveraging Big Data to Transform Drug Discovery.
   Glicksberg BS, Li L, Chen R, Dudley J, Chen B. Methods Mol Biol. 2019;1939:91-118. doi: 10.1007/978-1-4939-9089-4_6. PMID: 30848458
5. Far away from the lamppost.
   Oprea TI, Jan L, Johnson GL, Roth BL, Ma'ayan A, Schürer S, Shoichet BK, Sklar LA, McManus MT. PLoS Biol. 2018 Dec 11;16(12):e3000067. doi: 10.1371/journal.pbio.3000067. eCollection 2018 Dec.  PMID: 30532236, PMCID: PMC6289406
6. Unexplored therapeutic opportunities in the human genome.
   Oprea TI, Bologa CG, Brunak S, Campbell A, Gan GN, Gaulton A, Gomez SM, Guha R, Hersey A, Holmes J, Jadhav A, Jensen LJ, Johnson GL, Karlson A, Leach AR, Ma'ayan A, Malovannaya A, Mani S, Mathias SL, McManus MT, Meehan TF, von Mering C, Muthas D, Nguyen DT, Overington JP, Papadatos G, Qin J, Reich C, Roth BL, Schürer SC, Simeonov A, Sklar LA, Southall N, Tomita S, Tudose I, Ursu O, Vidovic D, Waller A, Westergaard D, Yang JJ, Zahoránszky-Köhalmi G., Nat Rev Drug Discov. 2018 May;17(5):317-332. doi: 10.1038/nrd.2018.14. Epub 2018 Mar 23. Review. Erratum in: Nat Rev Drug Discov. 2018 Mar 23. PMID: 29472638, PMCID: PMC6339563
7. Dual gene activation and knockout screen reveals directional dependencies in genetic networks.
   Michael Boettcher, Ruilin Tian, James A Blau, Evan Markegard, Ryan T Wagner, David Wu, Xiulei Mo, Anne Biton, Noah Zaitlen, Haian Fu, Frank McCormick, Martin Kampmann & Michael T McManus. Nature Biotechnology, doi:10.1038/nbt.4062. Published online: 15 January 2018
8. Reversal of cancer gene expression correlates with drug efficacy and reveals therapeutic targets.
   Chen B, Ma L, Paik H, Sirota M, Wei W, Chua MS, So S, Butte AJ. Nat Commun. 2017 Jul 12;8:16022. doi: 10.1038/ncomms16022. PMID: 28699633, PMCID: PMC5510182
9. Choosing the Right Tool for the Job: RNAi, TALEN, or CRISPR.
   Boettcher M, McManus MT. Mol Cell. 2015 May 21;58(4):575-85. doi: 10.1016/j.molcel.2015.04.028. PMID: 26000843, PMCID: PMC4441801.

Page reviewed March 11, 2024