Maximal Cancer Diagnostics with Sid Sijbrandij and Jacob Stern

Maximal Cancer Diagnostics with Sid Sijbrandij and Jacob Stern

In 2024, Sid Sijbrandij got the news that no cancer patient wants to hear: his tumor was back and his doctors told him they had nothing left to offer.  Sid, a tech entrepreneur who up until that point had been running his company, GitLab, went all in, doing as much testing and as many treatments as he could.  It seems to have worked. Moreover, Sid’s team thinks they’ve been able to figure out what went right, thanks to heaps of molecular data they’ve collected, including single-cell sequencing data. “It's very difficult, if not impossible, to do causative work in an N-of-1 study, but because we have this longitudinal sampling over the course of Sid's case, we can start to build a mechanistic hypothesis,” said Jacob Stern, a single-cell data expert on Sid's team and veteran of 10x Genomics. “Which seems to be that there was a bunch of combination immunotherapy that helped to rev up the immune system over the course of 2024.” Join Sid, Jacob, and I as we discuss the "maximal diagnostics” approach and how Sid plans to bring it to other patients who find themselves in a similar situation.During our chat, Sid mentions that he got a treatment from a company started by a friend he made at the Y Combinator startup accelerator. That company is Shasqi [https://www.shasqi.com/leadership], founded by José Oneto. To see a timeline of Sid’s experience and all the data he and his team collected diagnosing and treating his disease check out osteosarc.com [http://osteosarc.com]. Sid has also written about his experience on his personal Substack. [https://sijbrandij.substack.com/p/im-going-founder-mode-on-my-cancer] For more information about Sid’s policy proposals, check out slide 17 of his embedded PowerPoint at https://sytse.com/cancer/ [https://sytse.com/cancer/] For more information about the cancer “playbooks” offered by the Sijbrandij Foundation’s Future of Cancer Care Today program, see: https://sijbrandijfoundation.org/fcct [https://sijbrandijfoundation.org/fcct] More information about the companies Sid is investing in to bring aspects of his maximal diagnostics approach to market is at Evenone.ventures [http://Evenone.ventures].

Protein Sequencing-by-Subtraction with Pumpkinseed Cofounder/CEO Jen Dionne

“We right now are developing our technology to be able very soon to sequence roughly hundred-length proteins that are on each of those sensors within a 24-hour period. You can think about this as being essentially 10 billion letters per day: 100 million sensors times those 100-mers on each sensor and then sequencing letter by letter.” That’s the scale that Pumpkinseed CEO and Cofounder Jen Dionne thinks her company can reach for analyzing proteins. The technology, developed in her lab at Stanford University, uses Raman spectroscopy to fingerprint molecules and Edman degradation to achieve sequencing-by-subtraction of peptides: 30 amino acids at a time now, possibly up to 300, or full-length proteins, in the future.  The ability to capture 10 billion amino acids per day would represent several orders of magnitude better throughput than the best and fastest proteomics methods available today, whether via mass spectroscopy or other single-molecule technologies being developed by competitors like Quantum-Si or Nautilus.  Remarkably, that’s still a long way from achieving the data acquisition rate that state-of-the-art high-throughput sequencers can achieve, but it’s enough to start thinking about making the type of impact that the first next-generation sequencers had on biological research.  Join us as we discuss the underlying physics behind Pumpkinseed’s technology, Jen’s journey from lab to C-suite, the applications they’re already pursuing, and her love of sports, including the World Cup.  For more information, check out pumpkinseed.bio [http://pumpkinseed.bio] or email Jen.  Links to papers discussed in the episode: Hu et al. Rapid genetic screening with high quality factor metasurfaces [https://www.nature.com/articles/s41467-023-39721-w]. Nature Communications, July 26, 2023. Zhang et al. From Genotype to Phenotype: Raman Spectroscopy and Machine Learning for Label-Free Single-Cell Analysis [https://pubs.acs.org/doi/abs/10.1021/acsnano.4c04282]. ACS Nano, July 1, 2024. Stiber, et al. Dynamic, single-cell monitoring of CAR T cell identity and activation with Raman spectroscopy [https://www.biorxiv.org/content/10.64898/2026.02.22.707331v1]. BioRxiv, February 23, 2026.

Q1 Company News Roundup with Wall Street Analyst Kyle Mikson

What kind of market share can Illumina expect when it launches its own MRD kits and is it worth the risk of annoying customers that also offer those tests?  Why did liquid biopsy company stocks do so well in May? What were his headline takeaways from the recent American Society of Clinical Oncology annual meeting? Where is he going on summer vacation after a hectic several months? Tune in to hear the answers to these questions, and more. If you’re interested in learning more about Kyle’s takes on the life science tools and diagnostics industries, you can reach out to him on LinkedIn to start a conversation.  https://www.linkedin.com/in/kylemiksoncfa/ [https://www.linkedin.com/in/kylemiksoncfa/] For full disclosure, he asked me to note that Seer is an investment banking client of Canaccord Genuity.

Spatial Perturb-seq, so hot right now! With Alexander Nevue

“It's one extra step ahead of a single cell RNA-seq workflow where we can get all the information that we can get from standard Perturb-seq, but we also know the spatial location.” That’s how my guest this week, Arc Institute Senior Scientist Alexander Nevue, describes PerturbSpace, a new method he and his colleagues introduced in a preprint posted to BioRxiv [https://www.biorxiv.org/content/10.64898/2026.05.25.727765v1] May 18.  PerturbSpace is the latest method to marry the power of CRISPR-based perturbation screening, where genes across the genome are systematically targeted and the effects of those perturbations are read out in the transcriptome of the cell in which they were made.  This juncture of CRISPR-based screening and spatial transcriptomics is one of the hottest areas in molecular biology right now, with nearly 10 different methods published in the last two years, from leading scientists including Genentech’s Aviv Regev; Harvard University’s Xiaowei Zhuang, the inventor of MERFISH and cofounder of Vizen; Yale University’s Rong Fan, and the Broad Institute’s Sami Farhi.  Join Alex and me as we discuss the PertubSpace workflow, its advantages and disadvantages compared to other spatial perturb-seq methods, and where he sees the data from these screens making the most impact.  Links to other publications of spatial perturbation screening methods with notable authors:  PerturbView. Aviv Regev and Erik Lubeck of Genentech. https://www.nature.com/articles/s41587-024-02391-0 [https://www.nature.com/articles/s41587-024-02391-0] Large-scale pooled in vivo CRISPR screening. Jonathan Weissman of MIT and Harvard’s Xiaowei Zhuang, inventor of MERFISH and cofounder of Vizgen. https://www.biorxiv.org/content/10.1101/2024.11.18.624217v3 [https://www.biorxiv.org/content/10.1101/2024.11.18.624217v3] SPAtial Cell Exploration (SPACE). Joe Beechem of Bruker/NanoString, in collaboration with Merck. https://www.biorxiv.org/content/10.1101/2025.09.14.675819v2 [https://www.biorxiv.org/content/10.1101/2025.09.14.675819v2] Perturb-DBiT. Rong Fan of Yale University, inventor of DBIT family of methods and cofounder of AtlasXOmics . https://www.researchsquare.com/article/rs-6481967/v1 [https://www.researchsquare.com/article/rs-6481967/v1] CRISPRMap. Jellert Gaublomme of Columbia University, Dan Landau of Weill Cornell Medicine. https://www.nature.com/articles/s41587-024-02386-x [https://www.nature.com/articles/s41587-024-02386-x] Perturb-FISH. Sami Farhi  of the Broad Institute.  https://www.cell.com/cell/fulltext/S0092-8674(25)00197-7 [https://www.cell.com/cell/fulltext/S0092-8674(25)00197-7] NIS-Seq Jonathan L. Schmid-Burgk of University Hospital Bonn. https://www.nature.com/articles/s41587-024-02516-5 [https://www.nature.com/articles/s41587-024-02516-5] Spatial Perturb-Sseq. Wei Leong Chew of A*STAR GIS. https://www.nature.com/articles/s41467-026-69677-6 [https://www.nature.com/articles/s41467-026-69677-6]

Remembering Craig Venter With Jamie Shreeve, Author of 'The Genome War'

Craig Venter, the renegade scientist who tried to beat the publicly-funded Human Genome Project with a private company — and nearly succeeded — died last week at 79. My guest this week, Jamie Shreeve, shadowed Venter for two years as part of his research for The Genome War, a book about the saga that captured not only the best and the worst aspects of Venter, but of human nature itself.  Shreeve and I evaluated Venter’s legacy while also reminiscing about the man who will be remembered both as a good friend and as an “asshole” in equal measure. We also remembered Venter’s longtime colleague and Nobel laureate Hamilton Smith, who died in October. Shreeve is also revealing, for the first time, a James Watson take on Venter so brutal that Shreeve left it out of the book.  I never met Venter, so my conception of him has always been and will forever be based on Shreeve’s portrait of him. The Genome War is one of my all-time favorite books and provides an even fuller picture. Please consider buying a copy through your local bookstore: https://bookshop.org/p/books/the-genome-war-how-craig-venter-tried-to-capture-the-code-of-life-and-save-the-world-james-shreeve/e018f9700a01fcd0?ean=9780345433749&next=t [https://bookshop.org/p/books/the-genome-war-how-craig-venter-tried-to-capture-the-code-of-life-and-save-the-world-james-shreeve/e018f9700a01fcd0?ean=9780345433749&next=t] Shreeve is also the author of The Neandertal Enigma [https://www.goodreads.com/book/show/19447625-the-neandertal-enigma] and co-author of Lucy’s Child: The Discovery of a Human Ancestor. A note: In the interview I say that sequencing-by-synthesis, the dominant method for analyzing whole human genomes today, is similar to the shotgun sequencing method used by Venter at Celera. As I was informed by Adam Phillippy, a leading computational biologist, this is not correct.  “Performing de novo genome assembly, as was required for the first genome project, is nearly impossible from short (~100 bp) reads,” he said in an email. “During the entire short-read era, people were mapping reads to the human reference, rather than re-assembling the genome each time.” Still, Venter's work helped push the field towards assembling a reference genome, which was essential for SBS. “This method of analysis was only possible because a reference sequence already existed,” Phillippy said. “Early SBS would have been nearly worthless without a reference sequence.”