Axial - Stanford #1
Analysis of exciting Stanford life sciences inventors and their inventions
Stanford is home to a set of great inventors particularly focused on company formation and technology commercialization. Founders and inventors from the university have had an outsized impact on our current world especially in software and computing (i.e. Google, Cisco). In life sciences, Stanford’s impact is no less important (i.e. Sutro, Hexagon Bio, Inflammatix).
Developing and using new biological measurement tools.
Measured, with high-throughput sequencing, B-cell responses in 5 individuals before and after vaccination for influenza - https://www.pnas.org/content/116/4/1261.long- discovering stable B-cell lineages; important to use phylogenetic profiling to identify high affinity antibodies.
Involved in research using single-cell RNA sequencing to study microglia cell - https://www.cell.com/neuron/fulltext/S0896-6273(18)31082-1
Using single-cell RNA sequencing to study IgE B-cells from people with food allergies and surprisingly had the same gene rearrangements in different people - http://science.sciencemag.org/content/362/6420/1306.long
Studied 6 cell types in the endometrium discovering an implantation window based on transcriptomic signatures -https://www.biorxiv.org/content/early/2018/06/19/350538- really exciting work; DotLab recently raised on a liquid biopsy for endometriosis.
Mapping the lineage of cell development.
Using a set of 6 antibodies (Abs) targeting CD47 and targets important for T-cells, NK cells, and HSCs to enable HSC transplants with MHC-mismatches between patient and donor - https://www.sciencedirect.com/science/article/abs/pii/S193459091930222X?via%3Dihub- however, toxicity is a major issue for the approach and will require very specific Abs. There is already a better way.
Important analysis of the recent retractions in the cardiovascular regeneration field to understand what to avoid and a path forward - https://www.nature.com/articles/s41587-019-0042-1
Discovery-driven synthetic biology for human health.
Inventing a CRISPRa platform to systematically map out cause-effect relationships in cell lineages focusing on neuronal fates - http://med.stanford.edu/qilab/publications/_jcr_content/main/panel_builder_1181997808/panel_0/panel_builder/panel_0/download_169312130/file.res/Liu%20Y_Cell%20Stem%20Cell_2018%20full.pdf
A system called CRISPR-GO to localize nuclear bodies to specific genomic positions - http://med.stanford.edu/qilab/publications/_jcr_content/main/panel_builder_924294413/panel_0/panel_builder/panel_0/download_169312130/file.res/Wang_Cell_2018.pdf
Computational tools for biology and medicine.
Invented an at-scale kinase inhibitor profiling method, KinomeFEATURE https://academic.oup.com/bioinformatics/article-abstract/35/2/235/5050788?redirectedFrom=fulltext- analyzing 5K binding pockets to reduce drug cross-reactivities across kinases.
Modeling and visualizing the cell.
Work showing the power of live-cell imaging monitoring MAPK and NF-κB signaling important to sense bacterial infection - https://www.cell.com/cell-systems/pdfExtended/S2405-4712(19)30069-9- discovered the former is responsble to measure insult levels and the latter, the insult itself.
Invented a very useful tool to measure kinase activity in a multiplex format in live-cells - https://docs.wixstatic.com/ugd/f6999c_2f438c0a716b49e0804632cad745d278.pdf
Combining single-cell RNA-seq and live imaging to measure NF-κB activity- https://docs.wixstatic.com/ugd/f6999c_805c931635e74f71b855ab543af1d4bc.pdf
Leading the way characterizing cell surface sugars.
Invented degraders for secreted and membrane proteins called LYTACs - https://chemrxiv.org/articles/Lysosome_Targeting_Chimeras_LYTACs_for_the_Degradation_of_Secreted_and_Membrane_Proteins/7927061- one of the most exciting inventions this year.
Great overview by Abe and Carolyn on MRSA and the role of sugars in resistance - https://pubs.acs.org/doi/10.1021/acs.biochem.9b00170
Engineered new, orthogonal tRNA synthetases to enable cell-specific proteomics - https://pubs.acs.org/doi/10.1021/jacs.8b03074
Creating new tools for conditional control of cells and proteins.
Created a method to create protein aggregates in cells and measure them fluorescently - https://www.nature.com/articles/ncomms11689- useful as a model for Alzheimer’s and other diseases whose hallmark is aggregation.
Overview of methods to control protein activity posttranslationally - https://www.sciencedirect.com/science/article/pii/S1074552114002877?via%3Dihub
Inventing a domain when fused to a protein of interest imbues small molecule conditional degradation when added - https://www.nature.com/articles/nchembio.598
Studying genetic change.
The Fire lab is legendary for the fundamental work around RNAi and how genes are regulated; in worms mapped out the steps in nonsense mRNA suppression (a common mechanism also found in humans to remove mRNAs with errors)- https://elifesciences.org/articles/33292
Using a CRISPR scene to find a common mechanism in worms and humans to destabilize proteins that include amino acids after the stop codon - https://www.nature.com/articles/nature18308- briefly, model organisms are pretty powerful tools and there is value using worms, zebrafish, and yeast in drug development.
Engineering large-scale proteomics to understand complex biological networks.
Developing TagGraph, a computational method to map out post-translational modifications across an entire proteome - https://www.nature.com/articles/s41587-019-0067-5.epdf
Profiled specific immuno-proteomes of certain T-cell populations -https://onlinelibrary.wiley.com/doi/full/10.1002/pmic.201700410
Overview of the potential for proteomics to be applied to the microbiome - http://www.tandfonline.com/doi/full/10.1080/14789450.2017.1311211
Leading the way studying the molecular basis of T- and B-lymphocyte recognition, differentiation, and function.
Using organoids to co-culture primary tumor cells and TILs replicating the TME and native immune cells present - https://www.sciencedirect.com/science/article/pii/S0092867418315137
Part of a paper to develop iPSC cancer vaccines - https://www.sciencedirect.com/science/article/pii/S193459091830016X
One of the most important pieces of work in immunology, a hallmark of any graduate course; characterized on antigen binding effects T-cell activity - http://kendallasmith.com/pdf/Altman_Davis_1996.pdf
Studying the regulation of gene expression.
Linking an RNA helicase to nucleolar homeostasis driving various craniofacial disorders - https://www.nature.com/articles/nature25449
Chromatin profiling to characterize various neural crest cell enhancers - https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(12)00421-3
Creating new molecular and cellular tools to observe, perturb, and re-engineer brain circuits.
Great review on integrating systems neuroscience with optogenetics - https://www.nature.com/articles/nrn.2017.15
An older paper, but one that deserves a Nobel Prize for creating optogenetics - https://www.nature.com/articles/nn1525
Creating new tools to study complex biological systems.
Overview of high-throughput methods to engineer enzymes - https://www.sciencedirect.com/science/article/abs/pii/S0958166917300708?via%3Dihub
Engineering a heterochiral protein - https://pubs.acs.org/doi/10.1021/acs.biochem.7b00722
Review of Knottins, proteins with exceptional stability, and their potential as a therapeutic and diagnostic -https://www.sciencedirect.com/science/article/abs/pii/S1740674911000138
Engineering new epitopes into Knottins to improve drug-like properties and diagnostic capabilities - https://www.sciencedirect.com/science/article/abs/pii/S1367593116301284
Review of the next-generation of cancer protein therapeutics - https://www.sciencedirect.com/science/article/abs/pii/S0165614716301353
Engineering biology and creating tools to cure genetic disease.
The Porteus lab is always pushing the limits on what genetic engineering tools are capable of; developed a method to improve efficiency rates to edit HSPCs with CRISPR - https://www.cell.com/molecular-therapy-family/nucleic-acids/fulltext/S2162-2531(18)30095-7- really important as transplants play a more important role with cell therapies coming through the clinic.
Great review on the role of gene editing to develop new medicines - http://www.nejm.org/doi/full/10.1056/NEJMra1800729
Studying large-scale genetic networks to understand biological coordination.
Howard Chang is an incredibly nice person and great scientist; created a process called EMBLEM to track cell lineage via ATAC-seq - https://cdn.elifesciences.org/articles/45105/elife-45105-v1.pdf
Part of inventing APEX-seq to map RNA and their subcellular localization - https://www.biorxiv.org/content/biorxiv/early/2018/10/30/454470.full.pdf
Mapping out epigenomic variability to cancer cell variability - http://genomebiology.biomedcentral.com/track/pdf/10.1186/s13059-016-1133-7?site=genomebiology.biomedcentral.com
Really important paper to show a function of a long noncoding RNA, HOTAIR and its role in cancer metastasis - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3049919/
Leading the way on engineering organic materials and wearable electronics.
Created a biodegradable sensor to monitor blood flow - https://www.nature.com/articles/s41551-018-0336-5
Invented a hydrogel array to stimulate the sciatic nerve in mice - https://www.nature.com/articles/s41551-018-0335-6
Review on the role of polymers to improve battery chemistry - https://www.nature.com/articles/s41578-019-0103-6
Studying cellular signaling at a single-cell resolution in cancer.
Most of his research ideas probably come from aliens and recently developing CODEX to multiplex stain cells selectively via antibodies -http://www.cell.com/cell/retrieve/pii/S0092867418309048- to map out tissue architecture of the spleen.
Inventing an algorithm, X-shift, to automate cell classification - https://www.nature.com/articles/nmeth.3863
Overview of mass cytometry and its ability to scale up single-cell studies - https://www.cell.com/cell/fulltext/S0092-8674(16)30410-X
Genetics of aging and longevity.
Great overview on the genetics of aging; Gary Ruvkun did pioneering work here - https://web.stanford.edu/group/brunet/Singh,%20Demmitt,%20Nath%20et%20al,%202019.pdf
Overview of rejuvenation methods to increase longevity - https://web.stanford.edu/group/brunet/Mahmoudi,%20Xu,%20and%20Brunet%202019.pdf
Connecting transcriptome/epigenome remodeling in mice to inflammation - https://web.stanford.edu/group/brunet/Benayoun%20et%20al,%202019.pdf- also found African turquoise killifish, an organism the Brunet lab is making an aging model.
Doing a network analysis of FOXO, an important regulator of lifespan, across species and tissues - https://web.stanford.edu/group/brunet/Webb%20et%20al,%20Aging%20Cell%202016.pdf- mapping out the set of targets and the pathways they activate. Laying out an important framework to potential drug FOXO in some way.
Creating a set of reusable biological tools.
Drew Endy is one of the most important synthetic biologists and has led the way on creating the framework to think about the potential outcomes of engineering biology; help create an open source material transfer agreement (MTA) - https://www.nature.com/articles/nbt.4263
Population and computational genomics tools.
Jungla is a really interesting company coming out of the lab; the Bustamante lab helped develop a tool called FIRE to score regions of the genome for their potential to regulate gene expression of nearby regions - https://academic.oup.com/bioinformatics/article/33/24/3895/4093216
Using genetic variation across a population to map out structure-function relationships in β-cardiac myosin - https://www.pnas.org/content/113/24/6701.long
Chemical and optical control of protein function.
The Lin lab is going to put out some great work over the next few years; engineered a synthetic pathway, RASER, to selectively activate a therapeutic response in cancer cells not in normal ones - https://science.sciencemag.org/content/364/6439/eaat6982.full?ijkey=09tG2NV7sI5RY&keytype=ref&siteid=sci