Laboratory of Systems Pharmacology @Harvard Medical School

Upcoming sessions during #AACR25 will highlight advances in cancer early detection and interception. Learn more in AACR Annual Meeting News: www.aacrmeetingnews.org/news/session... @daniel-decarvalho.bsky.social @leciasequist.bsky.social

Legitmately thrilled to share our latest work, in which @fernpizza.bsky.social solved an experimental challenge in plasmid biology as old as the field: measuring how plasmids compete and evolve within individual cells!

Intracellular competition shapes plasmid population dynamics Conflicts between levels of biological organization are central to evolution, from populations of multicellular organisms to selfish genetic elements in microbes. Plasmids are extrachromosomal, self-r...

I'm so happy that I can finally share the results of my first postdoc paper with @baym.lol!!! Turns out plasmids are an amazing system to study multi-scale evolution and we can track within-cell and between-cell dynamics!
(1/n) www.biorxiv.org/content/earl...

Congrats to @tuuliavallius.bsky.social on receiving an American Cancer Society Postdoctoral Fellowship! 🎉

Tuulia’s project aims to understand the earliest stages of melanoma development, which will provide insights into new biomarkers to improve melanoma diagnosis and treatment.

We are so grateful for the passion and insight that Jerry Lin brings to our team!

Our support from @ludwigcancer.bsky.social enables us to collaborate with scientists and clinicians across the globe on the most challenging problems in cancer. 🤝

Human kidney biopsy exhibiting glomerular deposition disease. 🔎 Image courtesy of Jia-Yun Chen and Yilin Xu, Harvard Program in Therapeutic Science, @harvardmed.bsky.social.

Image Details: 18-channel imaging of human kidney acquired in a single scan using the Orion #spatialbiology platform.

Meet Daniel Lu, one of the latest additions to the Sorger Lab!

Daniel aims to blend biology with math, physics, and AI to transform cancer diagnostics. 🔬✨

Read more: labsyspharm.org/press-releas...

Making space for spatial biology in the clinic
Spatial transcriptomics methods have been slow to move into clinical practice, but spatial proteomics are cheaper and more scalable, and could progress faster go.nature.com/3PoWPkz

This paper is the result of an incredibly fun collaboration with Sandro Santagata and Peter Sorger. Led by an amazing postdoc @tanjinakader.bsky.social and JiaRen Lin, we provide a pre-cancer atlas of Fallopian tube precursors to High-Grade Serous Ovarian Cancer. The data is also on cbioportal!

Schematic representation of HGSCO progression, emphasizing the temporal development of hallmark cancer features and the dynamic interplay and interactions between immune cells and precancer/cancer cells. Cancer often starts with oncogenic changes (mutations, aneuploidy, and other cancer hallmarks), under selective pressure. These cells may remain latent for decades. Only a subset of these “phenotypically normal” but mutated clones undergo clonal expansion and acquire additional mutations, ultimately developing into cancer. Early on, despite limited genomic instability, innate immune responses, including the NK-cDC1-CTL axis and tissue-resident memory T cells (TRM), help contain p53 signature cells. Increasing aneuploidy or extrinsic factors can enhance immune surveillance, potentially eliminating precancer clones before significant proliferation occurs. During early STIC expansion, there is pronounced IFN response activation, with activated cDC1 and APCs, and NK cell-secreted chemokines, further attracting cDC1. This environment suggests active immune surveillance and is accompanied by interactions among APCs, activated CD4+, and CD8+ T cells. However, immunosuppressive cells, such as M2-like macrophages and Tregs, also emerge, indicating a complex equilibrium where cytotoxic and suppressive forces coexist. As STIC lesions advance, there is a reduction in CD8+ T cells and the interactions between APCs and CD4 T cells, along with an increase in exhausted CD8+ CTL and CD4+ cells expressing LAG3, almost no NK and cDC1 cells, and more suppressive APCs. The transition from STIC to overt cancer involves hallmark mechanisms such as TGF-β signaling, which excludes CTLs, changes in cytokine and fibroblast profiles, and induction of EMT and migratory programs. Dotted arrows indicate the hypothetical timing of these events, suggesting a prolonged interval from p53 signature to early STIC, followed by a more rapid progression from early to late STIC.

Now online in Cancer Discovery: Multimodal Spatial Profiling Reveals Immune Suppression and Microenvironment Remodeling in Fallopian Tube Precursors to High-Grade Serous Ovarian Carcinoma - by Tanjina Kader, Jia-Ren Lin, Clemens Hug, Ronny Drapkin, Sandro Santagata, et al. doi.org/10.1158/2159...

Lab coats branded with the Lab of Systems pharmacology hung up on hooks.

And with that.... 2024 is a wrap! 🎉 We are grateful for our incredible members and the hard work and dedication they bring to our lab every day.

Wishing you all a happy, restful holiday season and a bright New Year ahead. ✨

Chemotherapy induces myeloid-driven spatially confined T cell exhaustion in ovarian cancer Anti-tumor immunity is crucial for high-grade serous ovarian cancer (HGSC) prognosis, yet its adaptation upon standard chemotherapy remains poorly und…

1/n New paper alert 🚨 We're thrilled to share our just published paper in #CancerCell
Do you ever wonder how the #TME in #HGSC changes during chemotherapy? Check it here: www.sciencedirect.com/science/arti... and let’s dive into the highlights together #spatialbiology #ovariancancer #cancerresarch

We're honored to see work from Peter Sorger and
Greg Baker featured in this article!

We're optimistic that spatial proteomics will advance our understanding of disease biology. Stay tuned: we have several exciting papers on the way for 2025! 🎉

LSP | Sandro Santagata aims to translate research insights to the clinic New Laboratory of Systems Pharmacology Associate Director Sandro Santagata aims to help translate research insights to the clinic

Excited to announce Sandro Santagata as the new Associate Director of the Lab of Systems Pharmacology @harvardmed.bsky.social!
As a pathologist and cell biologist, Sandro brings a clinical perspective to our research.

Read about his journey & vision for the future: labsyspharm.org/press-releas...

Multiplexed 3D Analysis of Immune States and Niches in Human Tissue Tissue homeostasis and the emergence of disease are controlled by changes in the proportions of resident and recruited cells, their organization into cellular neighbourhoods, and their interactions wi...

Read the pre-print that describes this sample here: www.biorxiv.org/content/10.1...

Long orange collagen fibrils at bottom of image. Blue ovals (nuclei) throughout image. Middle layer of tumor cells with green scale-like appearance (MART1) and white ovals (SOX10). Top layer of magenta scales and fibrils (pan-cytokeratin). Scale bar is 100 microns.

Here’s a fluorescent #microscopy image of human skin with early-stage melanoma. 🔬🎨

We study human #cancer tissue to uncover the molecular changes that drive cancer development and ultimately improve how it is diagnosed and treated.

Explore the image: www.cycif.org/data/mel-3d-...

We're curating a list of our current members and alumni! ✨

👇 Follow these folks if you want to hear about science that uses diverse methods to improve how diseases are understood, diagnosed, and treated.

📣 Let us know if you're missing from the list!

go.bsky.app/QBnMu4A

We are looking for a postdoc (Please share 🙏)!
Are you passionate about spatial biology, proteomics, and the TME? Join our culturally diverse, multidisciplinary, and friendly team in 🇫🇮 to make impactful discoveries in ovarian cancer
🧬Details: farkkilab.org/careers/job-...
📅Apply by Dec 11

Please add our group!

A list of science journals (mostly biomed) to be updated as more join Bluesky

go.bsky.app/5kmzyLp

Get ready to dance, our paper – Phage DisCo: targeted discovery of bacteriophages by co-culture – has been pre-printed! 🪩 This has been a really fun project to work on with @sianowen.bsky.social, @baym.lol, @nquinoneso.bsky.social, and our two talented undergrads Kesther and Carmen!

We've long been able to find new phages and figure out what they interact with. But what about the other direction: if you have a gene, like an antibiotic resistance efflux pump, or a phage defense system, and you want to find phages that do or do not interact with it?

Now you can!

Several people working inside of the Laboratory of Systems Pharmacology (LSP) office. On the left, two stand and talk. On the right, three people work alone and two others discuss an image on a computer screen. A lab space is visible through a window in the background. Bottom banner includes LSP logo and branding: a component of HiTS, Harvard Program in Therapeutic Science

Nice to meet you @bsky.app! 👋

🤝 Our lab unites interdisciplinary teams of physicians & scientists to improve how diseases are diagnosed and treated

We use quantitative, #AI, & #SpatialBiology 🔬 methods to study #Cancer 👩‍⚕️, #Immunology, #InfectiousDisease🦠, and #Pharmacology 💊

🦋 Excited to connect!

No matter how you distinguish background from foreground in multiplexed imaging, always verify visually. Errors are surprisingly common, even in published papers. This is especially critical when using publicly available image derived data without access to the actual images. #spatialbiology 🧪