Thread by @DrTiffanyL

And then he took from chapter 1 and applied it to chapter 2 - found that he could assess for mixed chimerism using restriction length polymorphism. And then.. time to find a job! And he wanted to bring it in to the clinic, so... #ASH22 6/n

Always love showing photos of the researchers earlier in their careers! So then he was able to establish a mouse a model of graft rejection. And tried in vivo cytokine injection to increase graft - tried lots of them, some toxic, some didn't work. 7/n #ASH22

Then tried donor NK cell depletion and CD4 and CD8 depletion -- but then tried L-leucyl-L-leucine methyl ester that worked but.. it couldn't be made in GMP - what a let down for a researcher, but real life. Thanks for sharing this roller coaster. #ASH22 8/n

Look at all the Blazar publications in those years -- and then found rapamycin -- not all of them working but giving them more information. #ASH22 9/n

Now we have this list of T cell costimulatory and co-inhibitory signals -- and you look at the sum total of the positive and negative signals to decide which cells respond, how long it lasts, etc! This is complex! #ASH22 10/n

Look at the time from the original findings published to the final approval - #abatacept got FDA approval in 2021. Way to continue along. #ASH22 11/n

Then thinking about Treg:T cell ratio was used. Was able to go from 200 fold expression to 13000 fold! But then the immune response was not sustained after infusion so then found orthogonal IL-2 ameliorates this. #ASH22 12/n

Four GVHD drugs are now FDA approved. CTAL4-Ig, ibrutinib for chronic GVHD, belumosudil (ton increase Tregs) and ruxolitinib for a and cGVHD! #ASH22 13/n

If any #ASH22 #ASHtrainees wonder why we want you to have a SOC for your fellowship project -- look at these many people listed including research mentors but also clinical physicians, trainees and postdocs. You HAVE to remember this is a team sport. Love it! 14/14