Ty Miller Lab
@tymillerlab.bsky.social
http://tymillerlab.org @CWRUSOM @UHhospitals | Researchers of #braincancer, myeloid cells, epigenetics, #immunotherapy | Dedicated to finding cures for patients
Home cooked meals are the best.
Grateful to have @vrishab_x's mother visit the lab from Seattle and cook us all authentic South Indian food for lunch today 😋❤️
Grateful to have @vrishab_x's mother visit the lab from Seattle and cook us all authentic South Indian food for lunch today 😋❤️
August 12, 2025 at 1:51 AM
Home cooked meals are the best.
Grateful to have @vrishab_x's mother visit the lab from Seattle and cook us all authentic South Indian food for lunch today 😋❤️
Grateful to have @vrishab_x's mother visit the lab from Seattle and cook us all authentic South Indian food for lunch today 😋❤️
Celebrating "UH100", the 100th brain tumor we've collected (in ~10 months!) & processed to learn more about these tumors & make patient organoids to test new therapies @uhreinstitute.bsky.social & @caseccc.bsky.social. Thanks to the patients, @staudtmd.bsky.social & Dr. Tiffany Hodges, & my lab!
August 6, 2025 at 11:16 AM
Celebrating "UH100", the 100th brain tumor we've collected (in ~10 months!) & processed to learn more about these tumors & make patient organoids to test new therapies @uhreinstitute.bsky.social & @caseccc.bsky.social. Thanks to the patients, @staudtmd.bsky.social & Dr. Tiffany Hodges, & my lab!
Our lab @caseccc.bsky.social, CWRU SOM, & University Hospitals is recruiting! We are looking for 2 talented immunotherapy postdocs eager to make an impact for brain tumor patients using cutting edge single-cell & spatial genomics & patient-tissue organoids - join us!
Please share positions below:
Please share positions below:
April 15, 2025 at 1:58 PM
Our lab @caseccc.bsky.social, CWRU SOM, & University Hospitals is recruiting! We are looking for 2 talented immunotherapy postdocs eager to make an impact for brain tumor patients using cutting edge single-cell & spatial genomics & patient-tissue organoids - join us!
Please share positions below:
Please share positions below:
Honored for our lab to be highlighted in the @caseccc.bsky.social annual report - I can't say enough great things about the environment and support for our new lab. 9 months in and so happy to be @CWRUSOM and @caseccc! A couple pictures in the lab that didn't make the report:
March 31, 2025 at 10:40 AM
Honored for our lab to be highlighted in the @caseccc.bsky.social annual report - I can't say enough great things about the environment and support for our new lab. 9 months in and so happy to be @CWRUSOM and @caseccc! A couple pictures in the lab that didn't make the report:
Celebrating two summer fellowships today with ice cream @ Mitchells! Congrats to Kaylie for being awarded the CanSUR fellowship for undergraduates and Medical student Alex Wang the @caseccc.bsky.social Medical Training Award! Both awards will support their work in the lab this summer 🔬
March 22, 2025 at 3:51 AM
Celebrating two summer fellowships today with ice cream @ Mitchells! Congrats to Kaylie for being awarded the CanSUR fellowship for undergraduates and Medical student Alex Wang the @caseccc.bsky.social Medical Training Award! Both awards will support their work in the lab this summer 🔬
Was great to see friends and colleagues in London as part of the @braintumourcharity.bsky.social annual Scientific Advisory Board meeting! There are exciting things happening in brain tumor research around the world and honored to get to help guide it. Views were pretty good toon
March 14, 2025 at 9:15 PM
Was great to see friends and colleagues in London as part of the @braintumourcharity.bsky.social annual Scientific Advisory Board meeting! There are exciting things happening in brain tumor research around the world and honored to get to help guide it. Views were pretty good toon
In summary, we utilized a new analytical tool, cNMF, to define consensus myeloid programs in glioma & revealed 4 dominant immunomodulatory programs that were previously hidden. Being able to study them in isolation reveals their drivers and ways to target them.
February 27, 2025 at 4:05 AM
In summary, we utilized a new analytical tool, cNMF, to define consensus myeloid programs in glioma & revealed 4 dominant immunomodulatory programs that were previously hidden. Being able to study them in isolation reveals their drivers and ways to target them.
The clusters in prior important studies of myeloid cells in glioma (which taught us a lot) end up being composites of our programs – with our cell identity programs being captured well by 1-3 clusters, but the activities programs being shared across many clusters.
February 27, 2025 at 4:05 AM
The clusters in prior important studies of myeloid cells in glioma (which taught us a lot) end up being composites of our programs – with our cell identity programs being captured well by 1-3 clusters, but the activities programs being shared across many clusters.
Notably, we would not have been able to find these important programs and study them in isolation with a traditional clustering/UMAP strategy. Clustering is good for finding cell types, but not activities, which are shared across clusters.
February 27, 2025 at 4:05 AM
Notably, we would not have been able to find these important programs and study them in isolation with a traditional clustering/UMAP strategy. Clustering is good for finding cell types, but not activities, which are shared across clusters.
Taking all this data together, and through many conversations with a lot of really smart people over the last 4+ years, we now think about myeloid cells in glioma through this framework (which is probably applicable to other solid tumors):
February 27, 2025 at 4:05 AM
Taking all this data together, and through many conversations with a lot of really smart people over the last 4+ years, we now think about myeloid cells in glioma through this framework (which is probably applicable to other solid tumors):
These 4 immunomodulatory programs dictate the overall immune state tumor and are very interconnected!
February 27, 2025 at 4:05 AM
These 4 immunomodulatory programs dictate the overall immune state tumor and are very interconnected!
Excitingly, we could reprogram the immunosuppressive macrophages back to their default inflammatory state using a p300 inhibitor from @genentech.bsky.social
February 27, 2025 at 4:05 AM
Excitingly, we could reprogram the immunosuppressive macrophages back to their default inflammatory state using a p300 inhibitor from @genentech.bsky.social
Using clinical data, we found the Complement Suppressive program is specifically & irreversibly driven by dexamethasone, a potent corticosteroid given to most patients for symptom & surgical management. High IFNg only partially rescued. Most IO trials in GBM allow some dex use...
February 27, 2025 at 4:05 AM
Using clinical data, we found the Complement Suppressive program is specifically & irreversibly driven by dexamethasone, a potent corticosteroid given to most patients for symptom & surgical management. High IFNg only partially rescued. Most IO trials in GBM allow some dex use...
We identified IL1B as a major driver of the Scavenger suppressive program, which is being produced by monocytes that enter the tumor expressing the System Inflammatory program. Likely an evolutionary feedback loop to reduce inflammation in the brain!
February 27, 2025 at 4:05 AM
We identified IL1B as a major driver of the Scavenger suppressive program, which is being produced by monocytes that enter the tumor expressing the System Inflammatory program. Likely an evolutionary feedback loop to reduce inflammation in the brain!
Given their apparent importance, we dove in to discover the mechanisms underlying these immunosuppressive programs. We used snATAC-seq data to identify transcription factors at the heart of these programs and then identified upstream regulators of these TFs.
February 27, 2025 at 4:05 AM
Given their apparent importance, we dove in to discover the mechanisms underlying these immunosuppressive programs. We used snATAC-seq data to identify transcription factors at the heart of these programs and then identified upstream regulators of these TFs.
It turns out that it was the Scavenger Suppressive program, not any cell type, that was associated with immunotherapy resistance, higher Tregs in tumors, and overall worse survival in patients – only discoverable because we can now study this program in isolation:
February 27, 2025 at 4:05 AM
It turns out that it was the Scavenger Suppressive program, not any cell type, that was associated with immunotherapy resistance, higher Tregs in tumors, and overall worse survival in patients – only discoverable because we can now study this program in isolation:
The authors found SIGLEC9 is a mediator of resistance. We plotted their cells according to our program usage & then labeled SIGLEC9+ cells. They were quite diverse in our program expression. However, responder/non-responder tumor cells almost perfectly segregated by our programs!
February 27, 2025 at 4:05 AM
The authors found SIGLEC9 is a mediator of resistance. We plotted their cells according to our program usage & then labeled SIGLEC9+ cells. They were quite diverse in our program expression. However, responder/non-responder tumor cells almost perfectly segregated by our programs!
Importantly, do these programs matter clinically? Fortunately, a paper was published this summer with a scRNA-seq dataset of 12 patients w/ neoadjuvant PD1 blockade, categorized as responder or non-responder.
February 27, 2025 at 4:05 AM
Importantly, do these programs matter clinically? Fortunately, a paper was published this summer with a scRNA-seq dataset of 12 patients w/ neoadjuvant PD1 blockade, categorized as responder or non-responder.
Using a new spatial regression model by @CouturierMDPhD & @davidsebfischer.bsky.social, we aggregated the spatial association data of tumor niches & our cellular programs across sections. We created a spatial map from the data - each activity program had a distinct tumor niche.
February 27, 2025 at 4:05 AM
Using a new spatial regression model by @CouturierMDPhD & @davidsebfischer.bsky.social, we aggregated the spatial association data of tumor niches & our cellular programs across sections. We created a spatial map from the data - each activity program had a distinct tumor niche.
Grade = microenvironment under a microscope, so we looked to see what specific environments in the tumor were associated w/specific myeloid activities using 10X Visium data from @milolab.bsky.social .Our Scavenger Suppressive program was only in hypoxia. The Complement Suppressive? Everywhere else
February 27, 2025 at 4:05 AM
Grade = microenvironment under a microscope, so we looked to see what specific environments in the tumor were associated w/specific myeloid activities using 10X Visium data from @milolab.bsky.social .Our Scavenger Suppressive program was only in hypoxia. The Complement Suppressive? Everywhere else
We also looked to see if IDH mutation was a driver of myeloid activity. While the Microglial inflammatory program was very enriched, and the 2 immunosuppressive programs were depleted, this turns out to be entirely driven by tumor GRADE not IDH mutation.
February 27, 2025 at 4:05 AM
We also looked to see if IDH mutation was a driver of myeloid activity. While the Microglial inflammatory program was very enriched, and the 2 immunosuppressive programs were depleted, this turns out to be entirely driven by tumor GRADE not IDH mutation.
Side note, we found that myeloid cells were so plastic that even some cells expressing microglia programs were derived from circulating monocytes. We validated this ex vivo - when we applied peripheral monocytes to patient organoids, they infiltrate & express microglia markers!?
February 27, 2025 at 4:05 AM
Side note, we found that myeloid cells were so plastic that even some cells expressing microglia programs were derived from circulating monocytes. We validated this ex vivo - when we applied peripheral monocytes to patient organoids, they infiltrate & express microglia markers!?
This made us rethink how we should view myeloid cells. Rather than taking a cell type-centric approach, we decided to focus on the immunomodulatory programs and study myeloid cells in that way (in a cell-type agnostic way). This plot becomes very useful to do that.
February 27, 2025 at 4:05 AM
This made us rethink how we should view myeloid cells. Rather than taking a cell type-centric approach, we decided to focus on the immunomodulatory programs and study myeloid cells in that way (in a cell-type agnostic way). This plot becomes very useful to do that.
And they were shared across myeloid cell types = the same activity program was being expressed in different microglia, macrophage, and monocytes.
February 27, 2025 at 4:05 AM
And they were shared across myeloid cell types = the same activity program was being expressed in different microglia, macrophage, and monocytes.
Surprisingly, these 4 immunomodulatory were the most utilized programs across myeloid cells (d). Nearly all (91%) of myeloid cells in our gliomas expressed at least one of these 4 programs
February 27, 2025 at 4:05 AM
Surprisingly, these 4 immunomodulatory were the most utilized programs across myeloid cells (d). Nearly all (91%) of myeloid cells in our gliomas expressed at least one of these 4 programs