Axial - Harvard #1

Analysis of exciting Harvard life sciences inventors and their inventions

Boston is an epicenter of life sciences creativity. With the right mixture of talent, cold weather, and capital, Harvard is an incredible source of great businesses.

Cowan Lab

Building tools to engineer stem cells.

Recent

• Chad Cowan and his lab has done the work to set the upper limit of gene editing tools in stem cells. Some of the lab’s work was licensed to Mustang Bio. Excitedly, his work helped form the basis of Sanato develop off-the-shelf cell therapies. Developed a method to generate hypoimmunogenic human pluripotent stem cells to minimize GvHDfor cellular therapeutics - https://www.pnas.org/content/116/21/10441.long

Past

• Review on the power of induced pluripotent stem cells (iPSC) to functionalize population genetics - https://www.cell.com/trends/cell-biology/fulltext/S0962-8924(17)30180-0

  

• Using iPSCs to validate genetic variants from large-scale population genetic studies for metabolic disorders - https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(17)30032-2

  

Mooney Lab

Designing new biomaterials to control cell therapies and delivery.

Recent

• Really exciting paper to invent a cryogel scaffold to mimic a bone marrow transplant - https://www.nature.com/articles/s41587-019-0017-2

  

• Overview of the use of immunomaterials for cancer therapeutics - https://www.nature.com/articles/s41563-018-0147-9

Past

• Engineering scaffolds to selectively expand T-cells - https://www.nature.com/articles/nbt.4047- important move forward toward in vivocell therapies:

  

Arlotta Lab

Modeling the mammalian cerebral cortex.

Recent

• One of the most exciting papers of 2019 to create a organoid replicating the diversity of the human cerebral cortex - https://www.nature.com/articles/s41586-019-1289-x- relying on single-cell RNA sequencing to monitor/validate cellular diversity within the model:

  

• Review on using organdies to model the human cerebral cortex - https://www.sciencedirect.com/science/article/abs/pii/S095943881930025X?via%3Dihub

Past

• Mapping out the potential of using organdies to study neurodegeneration - https://www.sciencedirect.com/science/article/pii/S0955067417301096?via%3Dihub

  

Hung Lab

Characterizing host-pathogen interactions.

Recent

• Doing incredible work to understand infectious disease and discover new strategies to respond to them; developing a single-pot assay relying on fluorescent hybridization for a rapid bacterial identification system - https://www.nature.com/articles/s41598-019-40792-3

• Creating a pooled chemical screening method to discover drugs against Mycobacterium tuberculosis - https://www.biorxiv.org/content/10.1101/396440v1- characterizing millions of chemical/target combinations to find tens of new compound leads.

Past

• Using single-cell RNA sequencing to discover cell-specific lipopolysaccharide modifications driving host-pathogen interactions - 

• https://www.cell.com/cell/fulltext/S0092-8674(15)01041-7

  

Melton Lab

Making functional islets that secrete insulin to study and cure type I diabetes.

Recent

• On a mission to cure type I diabetes (T1D) for his children; overview on regenerating the pancreas to treat T1D - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168194/

• Using single-cell RNA sequencing to characterize β cell (insulin producer) development - https://www.cell.com/cell-reports/fulltext/S2211-1247(19)30563-7

• Led by Adrian Veres (a great math TF), to profile thousands of human cells undergoing in vitro β-cell differentiation - https://www.nature.com/articles/s41586-019-1168-5- discovering a new β-cell specific marker:

  

Past

• In vitrogeneration of stem cell derived β cells - https://www.cell.com/cell/fulltext/S0092-8674(14)01228-8

  

Buenrostro Lab

Inventing single-cell tools to study genetic variation.

Recent

• Characterizing chromatin accessibility of 10Ks of cells in the mouse brain (below) - https://www.nature.com/articles/s41587-019-0147-6- and ~100K of human bone marrow-derived cells:

  

• Overview of using single-cell tools to study epigenetic variation - https://www.nature.com/articles/s41588-018-0290-x

Past

• Invented ATAC-seq, an important method to measure chromatin accessibility - https://currentprotocols.onlinelibrary.wiley.com/doi/full/10.1002/0471142727.mb2129s109- reliant on the transposase Tn5 to insert barcodes into open-regions of the genome.

• Using ATAC-seq to measure chromatin accessibility at a single-cell level - https://www.nature.com/articles/nature14590

  

Kleckner Lab

Characterizing the biophysics of chromosomes.

Past

• Overview of Nancy’s legendary career - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5161267/- did pioneering work to study transposition that ended up enabling ATAC-seq.

• Overview of using chromosome capture to study the 3D genome - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4095847/

• Invented 3C, the first tool setting off the study of the 3D genome - https://pdfs.semanticscholar.org/2b0a/db74dc6d9a2dd3e9978dae07e86e70f730b6.pdf

• Mapping out how mechanical forces influences chromosome dynamics - https://www.pnas.org/content/pnas/101/34/12592.full.pdf

Schreiber Lab

Using chemical genetics to study biology and disease.

Recent

• Helped define chemical genetics- screening small molecules for their ability to modulate a pathway not just a certain target; the career of Stuart Schreiber - https://www.princeton.edu/chemistry/macmillan/group-meetings/BDH_Schreiber.pdf

• Generating functional group and stereochemical diversity from an azetidinescaffold - https://pubs.acs.org/doi/10.1021/jacs.8b07319- to screen 100Ks of molecules against hundreds of cellular features (i.e. morphology):

  

• Review of the power of synthetic chemistry to study biology - https://www.nature.com/articles/nrd.2018.53- example of compounds generated by diversity-oriented synthesis(as opposed to target-oriented synthesis):

  

Past

• An incredibly important paper to use diversity-oriented synthesis to identify modulators of TOR proteins important in nutrient sensing - http://www.columbia.edu/itc/gsas/g9600/2002/misc/Dissecting_Glucose.pdf

• Review comparing diversity-oriented synthesis (DOS) and target-oriented synthesis (TOS) - https://science.sciencemag.org/content/287/5460/1964.long

  

• Overview of using DOS to generate chemical diversity to screen for valuable molecular matter - https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.200300626?sid=nlm%3Apubmed