Just in time for #WorldKidneyDay, I'm happy to share our latest work on human kidney endothelial cells published today in BJC Reports. We use single-cell RNA-seq, tissue & cell-based validation studies to study the unique phenotypes of these cells. (1/14) nature.com/articles/s44276-0…

The inherent complexity of the kidney makes it an ideal validation platform for showcasing topographical molecular mapping: Multiscale topology classifies cells in subcellular spatial transcriptomics | Nature nature.com/articles/s41586-0…

⚡️🔬📣 Excited to share our new @Nature article building and evaluating PathChat, a multimodal generative AI copilot and chatbot for human pathology. Article: nature.com/articles/s41586-0… Open Access Link: rdcu.be/dKC0r We leverage our previous success in building foundation models for computational pathology such as UNI / CONCH and combine it with the advancements of large vision language models and generative AI to enable PathChat to answer diverse pathology-related queries. We assessed PathChat using both multiple choice diagnostic questions and open-ended questions. Congratulations to @MYLu97 @chenbowen118 @DFKW_MD @richardjchen and everyone else who contributed to this work. Also see blog post from @MYLu97 about this work: linkedin.com/pulse/towards-m… , also teasing the development and preview of PathChat 2, a successor to PathChat 1 bringing new capabilities and substantially improved performance to the state-of-the-art.

Spatial transcriptomics technologies have great potential for clinical translation. In this commentary, @kelsmith_path, myself and colleagues discuss practical considerations, costs, and challenges in moving these technologies to the clinic: karger.com/gdz/article/4/1/4…

Finally, we studied the functional properties of kidney tumor endos in culture. We asked if various immune cells (isolated from the same patient's tumor, normal adjacent tissue (NAT) or PBMC) could preferentially adhere to their tumor or normal endos (11/14)

Our study is the *deepest* dataset of primary ccRCC tumor endothelial cells (the normal endothelial dataset is pretty deep too). Next we decided to see if tumor endothelial cells from different tumors shared similar gene expression programs... (7/14)

We validated the ex vivo scRNA-seq findings using RNA in situ hybridization (RNA-ISH) on intact normal kidney and kidney tumors. These stains validated our scRNA-seq findings (plus, soooo pretty! 😍) (6/14)

Interestingly, the IGF signaling proteins IGFBP3 and 5 were the most differentially expressed genes between TECs and NECs. Other pathways regulating the matrix, immune cell attachment and cytokine signaling were also different. Hmmm... Any IGFBP experts out there? (5/14)

First, we isolated tumor and normal endothelial cells from n=4 tumor nephrectomy specimens and performed single cell RNA-seq. There was great overlap in the endothelial cells from all 4 donors and the TECs and NECs had distinct phenotypes. (4/14)

❓The most common malignant kidney cancer, clear cell carcinoma (ccRCC) has prominent vasculature. In all tumors, the tumor vessels represent the first barrier for immune cells. We decided to characterize these tumor endos (TECs) and compare them to normal endos (NECs) (3/14)

This opus was primarily driven by Dr. Yuexin Xu & was a collaboration between my lab @uwlabmedpath & Dr. Scott Tykodi's lab with assistance from Dr. Hootie Warren's group @fredhutch, Dr. Ying Zheng & Dr. Chris Miller. Major funding from DOD's KCRP & @kidneycan advocacy! (2/14)