Cancer Research, Drug Discovery, Biochemistry, Pharmaceutical Science
80
Scopus Publications
4576
Scholar Citations
34
Scholar h-index
63
Scholar i10-index
Scopus Publications
Klebsiella pneumoniae LPS drives stromal-mediated repression of p53 and colorectal cancer chemoresistance Konstantinos Fragkoulis, Barbara Łasut-Szyszka, Ákos Végvári, Diyoly Ayona, Amir Ata Saei, et al. Cell Death and Disease, 2026 The gut bacterial microbiota is increasingly recognized as a key modulator of colorectal cancer (CRC) initiation, progression and response to therapy. However, the mechanisms by which bacteria influence the response to anticancer drugs remain poorly understood. Here, we investigate the effects of microbiota-driven signaling on the tumor suppressor p53 and its impact on chemotherapy. We uncover a mechanism by which lipopolysaccharide (LPS) from Klebsiella pneumoniae and other Enterobacteria impairs p53 activity and promotes chemoresistance via paracrine signaling from the tumor microenvironment. While direct exposure to LPS did not alter the drug response of CRC cells, conditioned media from LPS-stimulated macrophages or fibroblasts suppressed p53 accumulation and attenuated the response to chemotherapeutic agents. Deep quantitative proteomics further revealed selective inhibition of a subset of p53 targets by inflammation. This same subset negatively correlated with inflammatory signature and immune infiltration in patients and was associated with improved survival following chemotherapy. Mechanistically, our data suggest that macrophage-derived extracellular vesicles contribute to p53 degradation in cancer cells. Overall, our findings reveal a microbiota-driven mechanism of p53 suppression via the microenvironment that contributes to chemoresistance, highlighting the impact of bacteria on tumor cell fate and therapeutic efficacy in CRC.
A ginsenoside metabolite and its derivative target PRELID3B against lung cancer cells Jilin He, Chun-Nam Lok, Guanya Yang, Ying He, Yungen Liu, et al. Proceedings of the National Academy of Sciences of the United States of America, 2026 Ginseng is widely praised for its benefits on cancer patients, often attributed to its metabolite compound K ( CK ). Here, we synthesized a derivative ( CKD-4 ) that, compared with CK , exhibited enhanced cellular uptake, threefold greater cytotoxicity, and improved pharmacokinetics. CKD-4 induced significant growth inhibition on lung cancer patient-derived organoids, and on cell line-derived xenografts with minimal systemic toxicity. CKD-4 also suppressed orthotopic lung tumor growth in immunocompetent mice with enhanced antitumor immune infiltration. Using proteome integral solubility alteration and ProTargetMiner analyses, the mitochondrial phospholipid transfer protein PRELID3B was unbiasedly identified as a shared anticancer target of CK and CKD-4 . PRELID3B is a potential pancancer therapeutic target and prognostic biomarker supported by cancer genetics and transcriptomics evidence. Both CK and CKD-4 stabilize PRELID3B in cellular thermal shift assay and bind PRELID3B with K d of 23 µM and 5 µM, respectively, measured by biolayer interferometry. Multiomics analyses revealed that CK and CKD-4 share similar anticancer mechanisms, involving mitochondrial phospholipid depletion, integrated stress response activation, and immunomodulatory pathways induction associated with PRELID3B inhibition. This study provides the basis for the immunomodulatory and anticancer effects of ginseng metabolites through targeting PRELID3B, and illustrates the application of orthogonal proteomics in target identification of natural compounds.
Toward a Species Search Engine: KISSE Offers a Rigorous Statistical Framework for Bone Collagen Tandem Mass Spectrometry Data Hassan Gharibi, Amir Ata Saei, Alexey L. Chernobrovkin, Susanna L. Lundstrom, Hezheng Lyu, et al. Advanced Science, 2025 DNA and bone collagen are two key sources of resilient molecular markers used to identify species from their remains. Collagen is more stable than DNA, and thus it is preferred for ancient and degraded samples. Current mass spectrometry‐based collagen sequencing approaches are empirical and lack a rigorous statistical framework. Based on the well‐developed approaches to protein identification in shotgun proteomics, a first approximation of the species search engine (SSE) is introduced. SSE named KISSE is based on a species‐specific library of collagenous peptides that uses both peptide sequences and their relative abundances. The developed statistical model can identify the species and the probability of correct identification, as well as determine the likelihood of the analyzed species not being in the library. The advantages and limitations of the proposed approach, and the possibility of extending it to other tissues is discussed.
Beyond the known cuts: trypsin specificity in native proteins Marcelo Gaspar, Bohdana Sokolova, Amir Ata Saei, José C. Marques, Roman A. Zubarev Chemical Communications, 2025 Peptides from trypsin digestion of native proteomes reveal that size, charge and local sequence motifs influence cleavage speed.
Small Molecule Inhibition of VDAC1 Reroutes Mitochondrial Metabolite Flux SM Modaresi, L Zhang, AA Saei, M Degen, M Khavani, H Gharibi, ... Molecules and Cells, 100369 , 2026 2026
A ginsenoside metabolite and its derivative target PRELID3B against lung cancer cells J He, CN Lok, G Yang, Y He, Y Liu, AA Saei, Y Zhang, C Zhang, Y Zhu, ... Proceedings of the National Academy of Sciences 123 (19), e2533505123 , 2026 2026
Ligand-Mediated Proteome Remodeling Shapes Nanoparticle Protein Corona Composition for Deep Plasma Profiling M Mahmoudi, B Ghaffari, L Han, A Alpaydin, N Wills, S Grumelot, ... 2026
Klebsiella pneumoniae LPS drives stromal-mediated repression of p53 and colorectal cancer chemoresistance K Fragkoulis, B Łasut-Szyszka, Á Végvári, D Ayona, AA Saei, ... Cell Death & Disease 17 (1), 395 , 2026 2026
Solubility based mechanistic profiling of combinatorial drug therapy E Gholizadeh, E Zangene, U Vadadokhau, D Ritz, JJ Miettinen, ... Nature Communications 17 (1), 2744 , 2026 2026 Citations: 5
CoPISA: Combinatorial Proteome Integral Solubility/Stability Alteration analysis E Zangene, E Gholizadeh, U Vadadokhau, D Ritz, AA Saei, M Jafari bioRxiv, 2026.03. 20.713131 , 2026 2026
A systemic circadian nicotinic acid riboside (NaR) signal engages the unfolded protein response and adipogenesis via the prefoldin complex I Vlassakev, C Savva, L Zhou, D Ritz, A Schmidt, C Jang, AA Saei, ... bioRxiv, 2026.03. 04.709493 , 2026 2026
Mass spectrometry-based top-down proteomics for proteoform profiling of protein coronas SA Sadeghi, F Fang, R Tabatabaeian Nimavard, Q Wang, G Zhu, AA Saei, ... Nature protocols 21 (3), 1092-1125 , 2026 2026 Citations: 16
Recalibrating Nanoparticle Protein Corona Analysis for Accurate Biological Identity and Soluble Plasma Proteome Profiling B Ghaffari, S Grumelot, SA Sadeghi, A Alpaydin, K Hilsen, B Shango, ... bioRxiv, 2026.02. 19.706828 , 2026 2026
Above-Filter Digestion Proteomics reveals drug targets and localizes ligand binding site B Sokolova, H Gharibi, M Jafari, H Lyu, S Lovera, M Gaetani, AA Saei, ... Journal of Proteome Research 25 (3), 1556-1570 , 2026 2026 Citations: 2
Preventing Proteomics Data Tombs Through Collective Responsibility and Community Engagement U Vadadokhau, M Soliman, L Castillon, P Pastor Muñoz, L Id, ... Scientific data , 2026 2026 Citations: 2
Multi-omics uncovers interaction in the vaginal microbiome and a type II secretion/Tad pilus system in Gardnerella vaginalis F Romero Garcia, V Dovhalyuk, SL Kuilboer, KJ van Dijk, C Forsstrom, ... bioRxiv, 2026.05. 09.724037 , 2026 2026
Multi-omics uncovers interaction in the vaginal microbiome and a type II secretion/Tad pilus system in Gardnerella vaginalis FR García, V Dovhalyuk, S Kuilboer, KJ van Dijk, C Forsström, H Gharibi, ... 2026
Lipid nanoparticle protein coronas form via lipoprotein fusion rather than shell-like adsorption S Grumelot, N Mohammed, J Colonrosado, SA Sadeghi, F Fang, K Hilsen, ... bioRxiv, 2025.12. 21.695162 , 2025 2025 Citations: 2
A generative deep learning approach to de novo antibiotic design A Krishnan, JA Valeri, W Jin, NM Donghia, L Sieben, A Luttens, Y Zhang, ... Cell 188 (21), 5962-5979. e22 , 2025 2025 Citations: 53
Toward a Species Search Engine: KISSE Offers a Rigorous Statistical Framework for Bone Collagen Tandem Mass Spectrometry Data H Gharibi, AA Saei, AL Chernobrovkin, SL Lundstrom, H Lyu, Z Meng, ... Advanced Science 12 (40), e03963 , 2025 2025
Integrated top-down and bottom-up mass spectrometry enables precise characterization of proteoforms and their post-translational modifications within the protein corona M Mahmoudi, S Sadeghi, K Li, Y Yue, RT Nimavard, S Grumelot, A Saei, ... Research Square, rs. 3. rs-7593385 , 2025 2025 Citations: 2
HigH-ratiO partiaL proteolysiS with carriER proteome (HOLSER) Enables Global Structure Profiling and Site-resolved Elucidation of Ligand-Protein Interactions X Zhang, B Sokolova, Z Meng, H Gharibi, H Lyu, A Ata Saei, M Gaetani, ... bioRxiv, 2025.07. 11.664381 , 2025 2025 Citations: 1
Deciphering the complexity of combinatorial therapies through advanced target engagement deconvolution assays in acute myeloid leukemia E Gholizadeh, E Zangene, U Vadadokhau, D Ritz, JJ Miettinen, ... EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY 81 (1), S21-S21 , 2025 2025
Beyond correlation: establishing causality in protein corona formation for nanomedicine A Rafieioskouei, K Rogale, AA Saei, M Mahmoudi, B Bonakdarpour Molecular Pharmaceutics 22 (5), 2723-2730 , 2025 2025 Citations: 6
MOST CITED SCHOLAR PUBLICATIONS
Superparamagnetic iron oxide nanoparticles for delivery of therapeutic agents: opportunities and challenges S Laurent, AA Saei, S Behzadi, A Panahifar, M Mahmoudi Expert opinion on drug delivery 11 (9), 1449-1470 , 2014 2014 Citations: 558
Proteome integral solubility alteration: a high-throughput proteomics assay for target deconvolution M Gaetani, P Sabatier, AA Saei, CM Beusch, Z Yang, SL Lundstrom, ... Journal of proteome research 18 (11), 4027-4037 , 2019 2019 Citations: 324
Targeted superparamagnetic iron oxide nanoparticles for early detection of cancer: Possibilities and challenges Z Bakhtiary, AA Saei, MJ Hajipour, M Raoufi, O Vermesh, M Mahmoudi Nanomedicine: Nanotechnology, Biology and Medicine 12 (2), 287-307 , 2016 2016 Citations: 249
Electrochemical biosensors for glucose based on metal nanoparticles AA Saei, JE NazhadDolatabadi, P Najafi-Marandi, A Abhari, M Guardia TrAC Trends in Analytical Chemistry , 2013 2013 Citations: 223
Repurposing of auranofin: Thioredoxin reductase remains a primary target of the drug X Zhang, K Selvaraju, AA Saei, P D'Arcy, RA Zubarev, ESJ Arnér, ... Biochimie 162, 46-54 , 2019 2019 Citations: 196
Theranostic MUC-1 aptamer targeted gold coated superparamagnetic iron oxide nanoparticles for magnetic resonance imaging and photothermal therapy of colon cancer M Azhdarzadeh, F Atyabi, AA Saei, BS Varnamkhasti, Y Omidi, M Fateh, ... Colloids and Surfaces B: Biointerfaces 143, 224-232 , 2016 2016 Citations: 183
Superparamagnetic iron oxide nanoparticles for in vivo molecular and cellular imaging S Sharifi, H Seyednejad, S Laurent, F Atyabi, AA Saei, M Mahmoudi Contrast media & molecular imaging 10 (5), 329-355 , 2015 2015 Citations: 155
Microparticles containing erlotinib-loaded solid lipid nanoparticles for treatment of non-small cell lung cancer Z Bakhtiary, J Barar, A Aghanejad, AA Saei, E Nemati, ... Drug development and industrial pharmacy 43 (8), 1244-1253 , 2017 2017 Citations: 153
Nanoparticle surface functionality dictates cellular and systemic toxicity AA Saei, M Yazdani, SE Lohse, Z Bakhtiary, V Serpooshan, M Ghavami, ... Chemistry of Materials 29 (16), 6578-6595 , 2017 2017 Citations: 125
Cellular toxicity of nanogenomedicine in MCF-7 cell line: MTT assay S Ahmadian, J Barar, AA Saei, MAA Fakhree, Y Omidi Journal of visualized experiments: JoVE, 1191 , 2009 2009 Citations: 113
Nanotechnology for targeted detection and removal of bacteria: opportunities and challenges MJ Hajipour, AA Saei, ED Walker, B Conley, Y Omidi, KB Lee, ... Advanced Science 8 (21), 2100556 , 2021 2021 Citations: 111
Nanotoxicology: advances and pitfalls in research methodology M Azhdarzadeh, AA Saei, S Sharifi, MJ Hajipour, AM Alkilany, ... Nanomedicine 10 (18), 2931-2952 , 2015 2015 Citations: 108
Comprehensive chemical proteomics for target deconvolution of the redox active drug auranofin AA Saei, H Gullberg, P Sabatier, CM Beusch, K Johansson, B Lundgren, ... Redox biology 32, 101491 , 2020 2020 Citations: 107
Measurements of heterogeneity in proteomics analysis of the nanoparticle protein corona across core facilities AA Ashkarran, H Gharibi, E Voke, MP Landry, AA Saei, M Mahmoudi Nature Communications 13 (1), 6610 , 2022 2022 Citations: 96
An update to space biomedical research: tissue engineering in microgravity bioreactors A Barzegari, AA Saei BioImpacts: BI 2 (1), 23 , 2012 2012 Citations: 92
ProTargetMiner as a proteome signature library of anticancer molecules for functional discovery AA Saei, CM Beusch, A Chernobrovkin, P Sabatier, B Zhang, ÜG Tokat, ... Nature communications 10 (1), 5715 , 2019 2019 Citations: 90
Breathomics: review of sample collection and analysis, data modeling and clinical applications M Khoubnasabjafari, MRA Mogaddam, E Rahimpour, J Soleymani, ... Critical Reviews in Analytical Chemistry 52 (7), 1461-1487 , 2022 2022 Citations: 85
System-wide identification and prioritization of enzyme substrates by thermal analysis AA Saei, CM Beusch, P Sabatier, JA Wells, H Gharibi, Z Meng, ... Nature communications 12 (1), 1296 , 2021 2021 Citations: 77
The Microbiome: The Forgotten Organ of the Astronaut‘s Body–Probiotics beyond Terrestrial Limits AA Saei, A Barzegari Future microbiology 7 (9), 1037-1046 , 2012 2012 Citations: 76
DNA damage response and repair in ovarian cancer: Potential targets for therapeutic strategies M Mirza-Aghazadeh-Attari, C Ostadian, AA Saei, A Mihanfar, SG Darband, ... DNA repair 80, 59-84 , 2019 2019 Citations: 66