Axial - UCSF #1

Analysis of exciting UCSF life sciences inventors and their inventions

Beyond Berkeley, across the bridge with two main campuses, UCSF supports some of the world’s greatest inventors changing human health and creating incredible businesses in life sciences from Genentech and Exelixis to Cell Design Labs, System1, Akili, Avail Bio, GBT, Pionyr, Voyager, Soteria Biotherapeutics, Bolt Threads, Serotiny, Pivot Bio, and KSQ. With the increasing importance of great inventors, the odds of other great companies emerging from UCSF are pretty high.

Lim Lab

Studying and engineering the logic of cellular signaling pathways.

Recent

• Engineered sender and receiver cells via synthetic ligands - https://science.sciencemag.org/content/361/6398/156.long- enabling self-organizing mammalian cells and possibly tissues.

Past

• Put out one of the most important pieces on immune cell engineering - https://www.ncbi.nlm.nih.gov/pubmed/28187291

• With Bluestone, writing one of the best reviews on engineering T-lymphocytes - http://limlab.ucsf.edu/papers/pdfs/esensten_rev_2017.pdf

Agard Lab

Structural studies of biological function focusing on microtubules and chaperones.

Recent

• With Eva Nogales, Dave Agard is a pioneer in the use of cryo-EM/ET; the Agard lab created a structure framework to understand centriole (important for cell division) biogenesis and assembly - https://elifesciences.org/articles/43434

Past

• Helped map out the interactions between Hsp27 and Tau (the next best target to pursue for Alzheimer’s) - https://www.nature.com/articles/s41467-018-07012-4

• Part of an exciting initiative to map out cellular networks in psychiatric disease - https://www.cell.com/cell/fulltext/S0092-8674(18)30784-0

Weissman Lab

Understanding the molecular machinery involved in protein folding and misfolding.

Recent

• Using Perturb-seq to map out genetic interactions for mechanisms of interest and broad principles - https://www.biorxiv.org/content/10.1101/601096v1

Past

• Expanding the use of Perturb-seq with direct capture of CRISPR guides - https://www.biorxiv.org/content/10.1101/503367v1

• With the Huang lab, invented a way to tag proteins with GFP genome-wide - https://www.pnas.org/content/113/25/E3501.long - that will surely improve our understanding of protein localization and protein–protein interactions.

Shokat Lab

Chemistry to understand and engineer signal transduction.

Recent

• Using chemical biology to create small molecule-sensitive DEAD-box proteins, which are notoriously to selectively drug due to high similarities within the class - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158709/

Past

• Fantastic review on drugging KRAS - http://dx.doi.org/10.1038/nrd.2016.139

Marson Lab

Studying and engineering genetic circuits controlling the human immune system.

Recent

• Non-virally reprogramming T-cells - https://www.nature.com/articles/s41586-018-0326-5.epdf?author_access_token=hTOPYXbVI_zEiZj3d3PwlNRgN0jAjWel9jnR3ZoTv0PJkSBqpqUc27ivPcWBqjm5ofw-5kxKHrta_dUB6FvTY9t_KLUx2qfLfoD4thaDTsluDkI1J4N9CcP39muRRXSxxxHx8VX0Tw7o18py_Z30QA%3D%3D- incredible piece of work that is now on the path to impact patient lives.

• Genome-wide screen to identify regulators of T-cell activators and suppressors - https://www.cell.com/cell/fulltext/S0092-8674(18)31333-3?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867418313333%3Fshowall%3Dtrue- another great piece; now moving toward therapeutics as well.

Past

• Great review on the genetic basis of autoimmunity - https://marsonlab.ucsf.edu/sites/marsonlab.ucsf.edu/files/wysiwyg/JCI78086_0.pdf

• Using CRISPRa to identify functional enhancers of T-cells especially non-coding regions - https://marsonlab.ucsf.edu/sites/marsonlab.ucsf.edu/files/wysiwyg/nature23875.pdf

Julius Lab

Researching sensory  transduction and neurotransmitter action in the mammalian  nervous system.

Recent

• Characterizing sensory systems in sharks and skates - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6101975/- providing an exciting case study of sensory adaptation.

Past

• Using single-particle cryo-EM to determine the structure of TRPA1 (i.e. Wasabi receptor) - https://www.nature.com/articles/nature14367- providing the scaffold for anti-inflammatory drugs.

Altschuler Lab

Combining systems biology and pharmacology to study cellular heterogeneity, tissue development, and homeostasis.

Recent

• Inventing a deep learning framework to analyze single-cell data in order to segment cell compositions - https://www.nature.com/articles/s41592-019-0353-7

Past

• Modeling cell-to-cell communication networks - https://www.cell.com/cell-systems/fulltext/S2405-4712(18)30053-X

• Characterizing morphogenic pathways - http://www.jbc.org/content/early/2016/11/28/jbc.M116.759654.abstract- discovering less crosstalk between TGF-beta and Wnt pathways than expected.

Gartner Lab

Understanding tissue structure and function.

Recent

• Inventing MULTI-seq to barcode single cells via lipids enabling recovery of cells with low amounts of RNA - https://gartnerlab.ucsf.edu/papers/2019_mcginnis_multiseq.pdf

• Showing phosphorylated EGFR dimers are not solely sufficient to activate the Ras pathway - https://gartnerlab.ucsf.edu/papers/Liang%20et%20al%202018.pdf

Past

• Generating tissue curvature for ex vivoengineering - https://gartnerlab.ucsf.edu/papers/2017_hughes_devcell_online_final.pdf

Walter Lab

Using molecular biology to study the endoplasmic reticulum and the unfolded protein response.

Recent

• The Walter lab is legendary; Peter is an incredible person with a great taste in beer and a great family; recently, showed how the 5’ untranslated region of mRNA regulates the stress response - http://walterlab.ucsf.edu/wp-content/uploads/2016/07/aad3867.full_.pdf

Past

• The UPR and ER trafficking converge on the stress sensor IRE1 - http://walterlab.ucsf.edu/wp-content/uploads/2018/12/elife-43036-v1.pdf

DeRisi Lab

Using genomics to understand and treat infectious disease.

Recent

• Using metagenomics to measure the pathogen, microbiome, and host response to diagnose lower respiratory tract infections - http://derisilab.ucsf.edu/pdfs/pnas.pdf

Past

• Really interesting paper using metagenomics to find new drivers for Cache Valley virus - http://derisilab.ucsf.edu/pdfs/AnnNeuro_Wilson_2017.pdf- proving out the method to discover new disease phenotypes and targets.

• Helped map out the ubiquitin fitness landscape - http://derisilab.ucsf.edu/pdfs/article3.pdf

McCormick Lab

Developing drugs against the Ras pathway.

Recent

• Update on drugging Ras with small molecules - http://www.biochemj.org/content/476/2/365

Past

• Showing KRAS suppresses Wnt/calcium signaling cancer cells - https://www.cell.com/cell/fulltext/S0092-8674(15)01396-3

Wells Lab

Studying apoptosis and differentiation.

Past

• Really important paper to develop antibodies against Ras-induced proteins - https://elifesciences.org/articles/31098- discovering an antibody against CDCP1 (discovered through a CRISPRi screen) to drug Ras-transformed cells.

McManus Lab

Characterizing the non-coding genome.

Recent

• Collaborating with the Roose Lab, was part of creating a shRNA synthetic lethality screening platform focused on PI3K signaling - https://www.cell.com/cell-reports/fulltext/S2211-1247(19)30361-4- but more importantly created a searchable database for others to build on top of: https://mmues.shinyapps.io/K7screen/

Turnbaugh Lab

Studying and engineering the role of human gut microbiome on pharmacology.

Recent

• The Turnbaugh Lab is on track to make key breakthroughs in our understanding of the microbiome and its effect on human health; recently, inventing metagenomic toxicology - https://www.nature.com/articles/s41575-018-0028-3- by showing non-antibiotic drugs have collateral damage on the microbiome.

• Review on the effects of drug programs and the microbiome - http://dmd.aspetjournals.org/content/46/11/1588.long

Past

• Review of metagenomic xenobiotic metabolism - https://www.nature.com/articles/nrmicro.2016.17

• Awesome review/reflection on the effects on the microbiome - https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(17)30087-2

• In mice, showing gut microbe respond linearly to dietary changes and after perturbation, remain stable for ~3 days - https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(14)00426-0

Krogan Lab

High-throughput network analysis to understand the cell and disease.

Recent

• Designing a CRISPR screen of CD4+ T-cells to identify essential host factors in HIV infection - https://www.nature.com/articles/s41596-018-0069-7

Past

• For tuberculosis, identifying a switch that determines the antiviral versus antibacterial response in the host - https://www.cell.com/molecular-cell/fulltext/S1097-2765(18)30557-4

Shipman Lab

Engineering new functions in cells.

Past

• Encoded a movie in a living bacteria - https://www.nature.com/articles/nature23017

Floor Lab

Understanding the role of RNA in gene expression and human health.

Past

• An incredible paper characterizing translational remodeling during neuronal differentiation - https://www.cell.com/cell-reports/fulltext/S2211-1247(17)31575-9

Fraser Lab

Defining protein conformational states essential for function.

Recent

• Involved in de novodesign of protein sensors/actuators - https://www.biorxiv.org/content/biorxiv/early/2019/05/24/648485.full.pdf

• Creating a framework to QA cryo-EM data - https://fraserlab.com/static/pdf/herzik_2018.pdf

Past

• Mapping out the relationship between enzymatic catalysis and evolutionary changes in conformation - https://fraserlab.com/static/pdf/otten_liu_2018.pdf

Bluestone Lab

Leading the way to characterize the basic processes that control T-cell activation and immune tolerance.

Recent

• Part of one of the most important clinical results this year showing an anti-CD3 antibody delayed progress of T1D - https://www.nejm.org/doi/full/10.1056/NEJMoa1902226

• Overview of the use of Tregs and their upcoming role in a new generation of cell therapies - https://science.sciencemag.org/content/362/6411/154.long

• Reviewing the relationship between immunotherapies and autoimmunity - http://cancerimmunolres.aacrjournals.org/content/6/12/1445.long

• Review on the next generation of cell therapies - https://www.sciencedirect.com/science/article/pii/S0952791519300019?via%3Dihub

Past

• Developing an anti-IL-2 antibody to selectively expand Treg populations with potential applications in autoimmunity and GvHD - https://www.nature.com/articles/s41591-018-0070-2

Roy Lab

Designing new medical devices and artificial organs.

Past

• Overview of macro-capsules to treat T1D- https://europepmc.org/abstract/med/26615050

• Invented a patch to monitor physiology and hemodynamics for over 48 hours at a time - https://ieeexplore.ieee.org/document/7105963