{"678582":{"#nid":"678582","#data":{"type":"news","title":"Mapping Protein Interactions to Fight Lung Cancer: Coskun Pioneering New Field of Research","body":[{"value":"\u003Cp\u003EAs Ahmet F. Coskun and his team of researchers continue their mission to create a 3D atlas of the human body, mapping cells and tissues, they\u2019re making discoveries that could lead to better treatments for the most common type of lung cancer.\u003C\/p\u003E\u003Cp\u003EWhile they\u2019re at it, they\u2019re pioneering new fields of research, and possibly spinning the work into a new commercial venture.\u003C\/p\u003E\u003Cp\u003ELast year, Coskun and his team introduced a new study in \u003Ca href=\u0022https:\/\/news.gatech.edu\/news\/2023\/12\/20\/coskun-lab-pioneering-new-field-research-single-cell-spatial-metabolomics\u0022\u003E\u201csingle cell spatial metabolomics,\u201d\u003C\/a\u003E which explores the distribution of small molecules \u2014 metabolites \u2014 within tissues and organs. Now they\u2019re spearheading \u201cspatial interactomics,\u201d a research area concerned with interactions between various biomolecules inside of individual cells.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003ETo study these interactions, they\u2019ve developed an innovative technique, or tool, to better understand why non-small cell lung cancer, or NSCLC, resists treatment in so many patients. They call it the \u201cintelligent sequential proximity ligation assay,\u201d or iseqPLA.\u003C\/p\u003E\u003Cp\u003E\u201cIt\u2019s a smart test that can look at proteins and how they interact with each other in space,\u201d said Coskun, Bernie Marcus Early Career Professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.\u003C\/p\u003E\u003Cp\u003E\u201cBasically, we\u2019re the first to create a new research area on spatial protein-protein interactions, which can tell us more about cell types and their functions,\u201d said Coskun. \u201cWith spatial interactomics, we can validate how cells physically touch, sense, and regulate nearby cells through the interaction of pairs of proteins.\u201d\u003C\/p\u003E\u003Cp\u003ESo, the immediate goal of spatial interactomics is to investigate how protein-protein interactions drive drug resistance in NSCLC. And iseqPLA allows researchers to visualize how it\u2019s all happening at the subcellular level. Coskun\u2019s team described its work recently in the journal \u003Ca href=\u0022https:\/\/www.nature.com\/articles\/s41551-024-01271-x\u0022\u003E\u003Cem\u003ENature Biomedical Engineering\u003C\/em\u003E\u003C\/a\u003E. He\u2019s also forming a company to commercialize the technology.\u003C\/p\u003E\u003Ch4\u003E\u003Cstrong\u003ESmarter Tools\u003C\/strong\u003E\u003C\/h4\u003E\u003Cp\u003EDrugs called tyrosine kinase inhibitors (TKIs, like Osimertinib) have been successful in treating people with NSCLC. But many patients who initially respond well to the regimen, eventually develop a resistance. Protein interactions, a molecular kind of crosstalk, are a prime suspect in causing this resistance.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003EProteins interact with each other all the time, and this mingling controls how cells grow, divide, or survive. Coskun and his team want to see how these interactions change in response to cancer treatment, and iseqPLA shows them, essentially attaching glowing tags to proteins, lighting up their locations and interactions under a microscope.\u003C\/p\u003E\u003Cp\u003E\u201cThink of it like a super detailed map showing how different proteins in a cell are connected,\u201d Coskun said.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003EThe iseqPLA can examine 47 protein interactions in a single sample, which saves a lot of time (and resources) when compared to older methods, which look at two to three interactions at a time.\u003C\/p\u003E\u003Cp\u003EThe researchers also created a computer model to analyze the spatial data they collected from iseqPLA, identifying patterns in protein interactions to help predict whether a cell was responding to a treatment or developing resistance.\u003C\/p\u003E\u003Cp\u003E\u201cWe showed that the test works not only in lab-grown cells but also in tissues from mice and humans,\u201d Coskun said. \u201cIt can really help us understand how patients respond to certain treatments.\u201d\u003C\/p\u003E\u003Ch4\u003E\u003Cstrong\u003EBuilding a Spatial Omics Market\u003C\/strong\u003E\u003C\/h4\u003E\u003Cp\u003EGoing forward, Coskun aims to enhance iseqPLA to study interactions among RNA, proteins, and metabolites, as well as the RNA, proteins, metabolites, etc., and other subcellular dynamics. He also hopes to get the technology into the hands of other researchers.\u003C\/p\u003E\u003Cp\u003E\u201cWe believe it will be a groundbreaking tool,\u201d he said.\u003C\/p\u003E\u003Cp\u003EWith that in mind, Coskun is planning to form a startup company called SpatAllize. He\u2019s working with VentureLab, the nonprofit organization at Georgia Tech that provides entrepreneurship programs for students and faculty.\u003C\/p\u003E\u003Cp\u003E\u201cWe are currently performing customer interviews and forming a strategy for a viable plan towards the marketplace,\u201d he said.\u003C\/p\u003E\u003Cp\u003EHe also plans to expand iseqPLA\u2019s utility into other areas of research, focusing on how protein interactions influence the immune system, the heart, and brain health. His team is also developing a spatial interactomics robot that integrates iseqPLA with advanced imaging and automated deep learning.\u003C\/p\u003E\u003Cp\u003E\u201cThis will allow us to map all molecules within cells and tissues for an even better understanding of drug-cell interactions, particularly in cancer treatment planning,\u201d Coskun said.\u003C\/p\u003E\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003ECITATION:\u003C\/strong\u003E Shuangyi Cai, Thomas Hu, Abhijeet Venkataraman, Felix G. Rivera Moctezuma, Efe Ozturk, Nicholas Zhang, Mingshuang Wang, Tatenda Zvidzai, Sandip Das, Adithya Pillai, Frank Schneider, Suresh S. Ramalingam, YouTake Oh, Shi-Yong Sun, and Ahmet F. Coskun. \u201cSpatially resolved subcellular protein\u2013protein interactomics in drug-perturbed lung-cancer cultures and tissues.\u201d \u003Cem\u003ENature Biomedical Engineering.\u003C\/em\u003E\u003C\/p\u003E\u003Cp\u003E\u003Ca href=\u0022https:\/\/doi.org\/10.1038\/s41551-024-01271-x\u0022\u003E\u003Cem\u003Ehttps:\/\/doi.org\/10.1038\/s41551-024-01271-x\u003C\/em\u003E\u003C\/a\u003E\u003C\/p\u003E\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EFUNDING:\u003C\/strong\u003E\u0026nbsp;This research was supported by the National Institutes of Health, grant Nos. P50CA217691, P30CA138292, and R33CA291197; and the National Science Foundation, grant No. R35GM151028. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of any funding agency.\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003ECOMPETING INTERESTS:\u003C\/strong\u003E Coskun, Cai, and Hu declare a patent application related to the spatial-signaling interactomics assay (U.S. Provisional 63\/399,427 and U.S. Application No. 18\/452,178).\u0026nbsp;\u003C\/p\u003E","summary":"","format":"limited_html"}],"field_subtitle":"","field_summary":[{"value":"\u003Cp\u003EAhmet Coskun\u2019s team developed new tool for mapping protein interactions in cells to study drug resistance in the most common form of lung cancer and its part of a new research area called \u0022spatial interactomics.\u0022\u003C\/p\u003E","format":"limited_html"}],"field_summary_sentence":[{"value":"Spatial Interactomics: Mapping Protein Interactions to Fight Lung Cancer Coskun pioneering new research area and building a company around iseqPLA technology "}],"uid":"28153","created_gmt":"2024-11-21 14:15:54","changed_gmt":"2024-11-21 15:13:42","author":"Jerry Grillo","boilerplate_text":"","field_publication":"","field_article_url":"","location":"Atlanta, GA","dateline":{"date":"2024-11-21T00:00:00-05:00","iso_date":"2024-11-21T00:00:00-05:00","tz":"America\/New_York"},"extras":[],"hg_media":{"675691":{"id":"675691","type":"image","title":"Ahmet in lab","body":"\u003Cp\u003EAhmet Coskun\u0027s lab has developed iseqPLA to map protein interactions.\u003C\/p\u003E","created":"1732198211","gmt_created":"2024-11-21 14:10:11","changed":"1732198270","gmt_changed":"2024-11-21 14:11:10","alt":"Ahmet in lab with iseqPLA","file":{"fid":"259343","name":"ahmet robot4.jpg","image_path":"\/sites\/default\/files\/2024\/11\/21\/ahmet%20robot4.jpg","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/2024\/11\/21\/ahmet%20robot4.jpg","mime":"image\/jpeg","size":3061812,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/2024\/11\/21\/ahmet%20robot4.jpg?itok=0DMsSbGA"}},"675690":{"id":"675690","type":"image","title":"Cell activity","body":"\u003Cdiv\u003E\u003Cdiv\u003E\u003Cdiv\u003E\u003Cdiv\u003E\u003Cp\u003EAn artistic rendering of sub-cellular activity: The cell membrane is seen at the top, nucleus on the bottom\/right. Protein pairs are being targeted by antibodies (sets of two). Then antibodies are linked to DNA pieces that glow when proteins were found to be closely interacting with each other. The glowing fluorescence DNA signal is then imaged by a microscope indicating the spatial locations of protein interactions as dots, which researchers use to generate graph models. The straight lines connecting the antibody and protein pairs indicate their graph wiring that gets altered in drug resistance. \u0026nbsp;\u003C\/p\u003E\u003C\/div\u003E\u003Cdiv\u003E\u0026nbsp;\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp\u003E\u003Cbr\u003E\u003Cbr\u003E\u0026nbsp;\u003C\/p\u003E","created":"1732198084","gmt_created":"2024-11-21 14:08:04","changed":"1732198196","gmt_changed":"2024-11-21 14:09:56","alt":"An artistic rendering of sub-cellular activity","file":{"fid":"259342","name":"cell world.jpg","image_path":"\/sites\/default\/files\/2024\/11\/21\/cell%20world.jpg","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/2024\/11\/21\/cell%20world.jpg","mime":"image\/jpeg","size":5629141,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/2024\/11\/21\/cell%20world.jpg?itok=mc1snlho"}}},"media_ids":["675691","675690"],"groups":[{"id":"1292","name":"Parker H. Petit Institute for Bioengineering and Bioscience (IBB)"},{"id":"1188","name":"Research Horizons"}],"categories":[{"id":"138","name":"Biotechnology, Health, Bioengineering, Genetics"},{"id":"145","name":"Engineering"},{"id":"146","name":"Life Sciences and Biology"}],"keywords":[{"id":"187423","name":"go-bio"},{"id":"14906","name":"lung cancer"},{"id":"168013","name":"spatial"},{"id":"184359","name":"Omics"},{"id":"14641","name":"protein-protein interactions"},{"id":"187915","name":"go-researchnews"}],"core_research_areas":[{"id":"39441","name":"Bioengineering and Bioscience"}],"news_room_topics":[{"id":"71891","name":"Health and Medicine"},{"id":"71881","name":"Science and Technology"}],"event_categories":[],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cp\u003E\u003Ca href=\u0022mailto:jerry.grillo@ibb.gatech.edu\u0022\u003EJerry Grillo\u003C\/a\u003E\u003C\/p\u003E","format":"limited_html"}],"email":["jerry.grillo@ibb.gatech.edu"],"slides":[],"orientation":[],"userdata":""}}}