The Spatial Biology Week™ 2026

This opening-day roundtable introduces the essential steps behind modern high-plex spatial biology. The discussion will cover how markers are transitioned into multiplex panels, how automation improves robustness and scalability, and how image analysis enables biological interpretation. Pannellists will conclude with how spatial data is increasingly used to inform translational research and patient-focused applications.

Researchers experienced with immunohistochemistry and multiplexing in different platforms such as Tyramide Signalling Amplification (TSA/Opal) have a wealth of antibodies and staining panels that can be quickly transferred to the Lunaphore COMET™ platform. This presentation will overview: (1) the fundamental differences in assay chemistries across standard immunohistochemistries, immunofluorescence, TSA, and sequential immunofluorescence (seqIF™) on COMET™, (2) how to apply that knowledge to choosing commercially available antibodies and COMET™ panel design, and (3) options to address low signal. 

The complement system is increasingly implicated in a wide range of diseases, while a growing number of complement inhibitors are being developed but not always successfully translated into clinical practice. This complexity calls for holistic tools to study complement activation in human tissues. We developed an in situ complementomics approach combining highly validated antibodies and a dedicated analysis pipeline to assess multiple complement pathways on a single tissue section and generate therapeutic hypotheses. This talk will first present the methodological development, then illustrate its translational value in cholesterol crystal embolism–associated kidney injury, where it informed the compassionate use of a complement inhibitor.

This talk will focus on the launch of the Lunaphore COMET™ platform at the Africa Health Research Institute (AHRI) and my role in piloting and implementing this technology. I will share my experience with training, pilot runs, and the design and optimization of a spatial biology panel to study macrophage HIV reservoirs in lymph node tissues. Importantly, I will shed light on the challenges to HIV cure, and the role of my lab (The Ndhlovu Lab-AHRI) in advancing HIV cure through the high-plex proteomics and DNA/RNAscope multiplexed ISH approaches in tissues from PLWH subtype C. 

Prostate cancer is a multifocal disease characterized by profound spatial and molecular heterogeneity, with distinct tumor foci often harboring different oncogenic alterations within the same prostate. This complexity poses major challenges for accurate diagnosis, prognosis, and targeted therapy. Traditional biomarker studies typically evaluate genomic alterations in isolation, without considering their spatial relationships or the multifocal nature of the disease. In this talk, I will present our recent work using spatially resolved biomarker analysis to map key oncogenic drivers across prostate cancer foci. By integrating multiplex molecular assays with intact tissue architecture, we demonstrate how distinct molecular subtypes coexist and evolve within localized disease. This spatial perspective provides new insights into clonal diversity and tumor evolution, and highlights the importance of spatial biology approaches for improving molecular classification and advancing precision diagnostics in prostate cancer.

Clear cell renal cell carcinoma (ccRCC) displays extensive immune infiltration yet remains largely immunosuppressed, a paradox whose underlying mechanisms are poorly defined. The contribution of the complement system to this microenvironment is understudied, in part because complement activation cannot be inferred from most omics-based methods. Using an Integrated Complementomics approach combining spatial imaging, single-cell and spatial transcriptomics, plasma profiling, and clinical datasets, we show that malignant cells facilitate complement activation through local C3 production, without formation of cytotoxic membrane attack complexes. This abortive activation reshapes the myeloid compartment by recruiting C5aR1+ macrophages, including C1q-enriched tumor-associated macrophages (TAM) associated with T cell exhaustion. In primary ccRCC, C3 production, C3 deposition, and C5aR1+/C1q+ TAM infiltration mark immune dysfunction and predict poor prognosis.

TDP-43 aggregation is a defining feature of amyotrophic lateral sclerosis (ALS), yet its distribution and cellular context across brain regions remain incompletely mapped. To address this gap, we are constructing a spatial atlas of TDP-43 pathology across motor and non-motor regions of the ALS brain by integrating molecular and imaging-based approaches. Building on our previous work identifying inflammation-associated cellular phenotypes, we will examine how these states relate to regional TDP-43 pathology. Together, this atlas aims to clarify the relationship between TDP-43 aggregation and local cellular environments, providing insight into pathological and clinical heterogeneity in ALS. 

Our knowledge of glioblastoma (GBM) heterogeneity is mostly restricted to the surgically resectable tumor core, while functional characterization of tumor cells at the infiltrating edge remains largely elusive due to the presence of normal functional brain tissue in the peritumoral lesion. Edge-derived cells exhibit a larger capacity for infiltrative expansion and are the main drivers of treatment failure and tumor recurrence, making them action targets for novel treatment approaches. 

In this study, we present a first-of-its-kind integrative spatial investigation of GBM, combining two complementary spatial omics modalities, high-definition spatial transcriptomics (Visium HD) and spatial proteomics (COMET™), to achieve a comprehensive morphological, transcriptomic, and proteomic characterization of invasive tumor edge in situ. This multimodal spatial framework enabled the resolution of the complex molecular landscape of the GBM periphery and the identification of druggable biomarkers specific to edge-derived malignant cell populations. 

The human cerebellum contains more neurons than the rest of the brain combined, yet its development remains poorly understood compared with that of the cerebral cortex. As a result, many prevailing models of cerebellar development and disease are extrapolated from nonhuman systems. In this talk, I will present insights gained from direct interrogation of the developing human cerebellum using molecular, cellular, and transcriptomic approaches. These data reveal human-specific developmental programs and challenge assumptions derived from animal models. I will further discuss how disruptions to these programs contribute to congenital cerebellar malformations, providing a framework for understanding their developmental origins. 

This study explores spatial profiling of epithelial–mesenchymal transition (EMT) and immune–stromal interactions in colorectal polyps and cancer using Lunaphore’s spatial biology tools. We analyzed two cohorts: polyps (n=1256) and CRC resections (n=787). Wnt pathway proteins (E-cadherin, β-catenin, SOX9) were assessed by IHC, with transcriptomic enrichment via Temp-O-Seq® and high-plex seqIF™ on the COMET™. CRC showed low E-cadherin, high β-catenin and SOX9, correlating with poor survival. β-catenin-high tumors enriched EMT and MYC targets while suppressing IFN pathways. Spatial analysis revealed distinct epithelial clusters and immune infiltration patterns, highlighting EMT-immune crosstalk and informing risk stratification and therapeutic strategies. 

Dr. Klimowicz will be presenting a talk on his area of expertise. Abstract will be provided shortly.

Somatic CAG repeat expansion occurs in Huntington’s disease (HD) and is governed by a balance between mismatch repair (MMR) proteins, which promote expansion, and FAN1, which suppresses it. Disruption of this balance, such as elevated MMR activity, accelerates repeat instability, whereas increased FAN1 activity restrains expansion and preserves genomic integrity. Therapeutic strategies to slow somatic expansion are under development, including modulation of MMR proteins and FAN1. Here, we demonstrate that antisense oligonucleotide (ASO)-mediated blocking of miRNA binding sites in the FAN1 3′-UTR upregulates FAN1 and slows CAG expansion in the huntingtin (HTT) gene. We confirm ASO uptake and assess biodistribution in 2D and 3D models and, through the development of a novel ASO-mRNA binding assay, demonstrate in vitro target engagement.

Dr. George will be presenting a talk on her area of expertise. Abstract will be provided shortly.

This talk highlights the use of COMET™ to advance spatially resolved biomarker discovery in renal cancer research. The first section explores how a curated biomarker panel, combined with COMET™ and HORIZON™ clustering, delineates the nephronal origin of SDHB-deficient RCC through Leiden cluster identification and user-defined neighborhood mapping, particularly without computational biologist support. The second part focuses on leveraging COMET™ to uncover rare benign epithelial subtypes in human prostate and their spatial relationships with canonical epithelial populations and the tumor microenvironment (TME). Finally, the discussion emphasizes how COMET™ integrates seamlessly into spatial transcriptomics pipelines, enabling context-aware multimodal analysis for translational pathology.

Dr. Damsky will present laboratory-developed tests (LDTs) developed and analytically validated by his group at Yale and implemented in clinical practice. He will review the clinical rationale, assay design, and validation strategy, and operational considerations for deploying these tests on diagnostic skin biopsies. These biopsy-based assays support real-world decision-making by improving discrimination between psoriasis and atopic dermatitis and by providing clinically meaningful insight into immune heterogeneity that may inform treatment selection and monitoring in both diseases. 

B-cell lymphomas encompass a wide range of malignancies, with clinical features ranging from indolent to aggressive. The diagnosis of these malignancies can routinely entail the evaluation of up to 20 immunohistochemistry markers for complete characterization. An additional challenge is that analysis of these lymphomas requires inferring co-expression patterns from single-plex IHC on serial tissue sections, which leads to significant subjectivity and inaccuracy. Here, we present the development, validation, and evaluation of a 22-marker sequential immunofluorescence (seqIF™) panel for the diagnosis and prognostication of B-cell lymphomas, which can be performed on a single FFPE section using the Lunaphore COMET™ automated staining and imaging platform.