Biology subjects

Suh, K.

Publications and source records attributed to Suh, K..

4 recordsLinked to original sources

bioRxiv2026

Somatic variants activating the RAS-MAPK pathway confer susceptibility to hippocampal sclerosis in drug-resistant epilepsy

Hippocampal sclerosis is a frequent finding in pediatric epilepsy surgery and has traditionally been regarded as an acquired lesion. It commonly co-occurs with focal cortical dysplasia (FCD IIIa), yet whether hippocampal injury is secondary to seizures or reflects a shared underlying etiology remains unresolved. Here we identified somatic variants activating the RAS-MAPK pathway in 40% of patients with hippocampal sclerosis, but in none with non-sclerotic hippocampus. Gain-of-function variants in PTPN11 were the most common finding, with mutations present in both cortex and hippocampus and enriched in hippocampal neurons, consistent with a shared developmental origin. In mice, Ptpn11D61Y mutants developed profound hippocampal degeneration and gliosis following subthreshold kainic acid exposure, whereas wild-type controls were unaffected. p38-dependent stress pathways were upregulated in patients and mice, suggesting a mechanism through which ERK-p38 crosstalk lowers the threshold for seizure-induced injury. These results provide a genetic explanation for FCD IIIa, elucidate the role of somatic mutations within the RAS-MAPK pathway in driving hippocampal sclerosis, and provide a target for pathway-specific interventions for intractable seizures.

neuroscience↗

bioRxiv2024

Large-scale control over collective cell migration using light-controlled epidermal growth factor receptors

Receptor tyrosine kinases (RTKs) are thought to play key roles in coordinating cell movement at single-cell and tissue scales. The recent development of optogenetic tools for controlling RTKs and their downstream signaling pathways suggested these responses may be amenable to engineering-based control for sculpting tissue shape and function. Here, we report that a light-controlled EGF receptor (OptoEGFR) can be deployed in epithelial cell lines for precise, programmable control of long-range tissue movements. We show that in OptoEGFR-expressing tissues, light can drive millimeter-scale cell rearrangements to densify interior regions or produce rapid outgrowth at tissue edges. Light-controlled tissue movements are driven primarily by PI 3-kinase signaling, rather than diffusible signals, tissue contractility, or ERK kinase signaling as seen in other RTK-driven migration contexts. Our study suggests that synthetic, light-controlled RTKs could serve as a powerful platform for controlling cell positions and densities for diverse applications including wound healing and tissue morphogenesis.

bioengineering↗

bioRxiv2023

E-cadherin biointerfaces reprogram collective cell migration and cell cycling by forcing homeostatic conditions

Cells attach to the world around them in two ways--cell:extracellular-matrix adhesion and cell:cell adhesion--and conventional biomaterials are made to resemble the matrix to encourage integrin-based cell adhesion. However, interest is growing for cell-mimetic interfaces that mimic cell-cell interactions using cadherin proteins, as this offers a new way to program cell behavior and design synthetic implants and objects that can integrate directly into living tissues. Here, we explore how these cadherin-based materials affect collective cell behaviors, focusing specifically on collective migration and cell cycle regulation in cm-scale epithelia. We built culture substrates where half of the culture area was functionalized with matrix proteins and the contiguous half was functionalized with E-cadherin proteins, and we grew large epithelia across this Janus interface. Parts of the tissues in contact with the matrix side of the Janus interface exhibited normal collective dynamics, but an abrupt shift in behaviors happened immediately across the Janus boundary onto the E-cadherin side, where cells formed hybrid E-cadherin junctions with the substrate, migration effectively froze in place, and cell-cycling significantly decreased. E-cadherin materials suppressed long-range mechanical correlations in the tissue and mechanical information reflected off the substrate interface. These effects could not be explained by conventional density, shape index, or contact inhibition explanations. E-cadherin surfaces nearly doubled the length of the G0/G1 phase of the cell cycle, which we ultimately connected to the exclusion of matrix focal adhesions induced by the E-cadherin culture surface.

bioengineering↗

bioRxiv2021

Learning the rules of collective cell migration using deep attention networks

Collective, coordinated cellular motions underpin key processes in all multicellular organisms, yet it has been difficult to express the rules behind these motions in clear, interpretable forms. Here we apply deep attention networks to analyze several canonical living tissues systems and present the underlying collective migration rules for each tissue type using only cell migration trajectory data. We use these networks to learn the behaviors of key tissue types with distinct collective behaviors--epithelial, endothelial, and metastatic breast cancer cells--and show how the results complement traditional biophysical approaches. In particular, we present attention maps indicating the relative influence of neighboring cells to the learned turning decisions of a focal cell. These attention networks reveal distinct patterns of influence and attention unique to each model tissue. Endothelial cells exhibit tightly focused attention on their immediate forward-most neighbors, while cells in more expansile epithelial tissues are more broadly influenced by neighbors in a relatively large forward sector. Attention maps of ensembles of more mesenchymal, metastatic cells reveal completely symmetric attention patterns, indicating the lack of any particular coordination or direction of interest. Moreover, we show how attention networks are capable of detecting and learning how these rules changes based on biophysical context, such as location within the tissue and cellular crowding. That these results require only cellular trajectories and no modeling assumptions highlights the potential of attention networks for providing further biological insights into complex cellular systems. Author SummaryCollective behaviors are crucial to the function of multicellular life, with large-scale, coordinated cell migration enabling processes spanning organ formation to coordinated skin healing. However, we lack effective tools to discover and cleanly express collective rules at the level of an individual cell. Here, we employ a carefully structured neural network to extract collective information directly from cell trajectory data. The network is trained on data from various systems, including well-studied cell types (HUVEC and MDCK cells) which display visually distinct forms of collective motion, and metastatic cancer cells (MDA-MB-231) which are highly uncoordinated. Using these trained networks, we can produce attention maps for each system, which indicate how a cell within a tissue takes in information from its surrounding neighbors, as a function of weights assigned to those neighbors. Thus for a cell type in which cells tend to follow the path of the cell in front, the attention maps will display high weights for cells spatially forward of the focal cell. We present results in terms of additional metrics, such as accuracy plots and number of interacting cells, and encourage future development of improved metrics.

systems biology↗