T. Mamie Lih
A5086436405- Advanced Proteomics Techniques and Applications
- Glycosylation and Glycoproteins Research
- Ubiquitin and proteasome pathways
- Machine Learning in Bioinformatics
- Ferroptosis and cancer prognosis
- Genomics and Phylogenetic Studies
- Mass Spectrometry Techniques and Applications
- Prostate Cancer Treatment and Research
- Metabolomics and Mass Spectrometry Studies
- Molecular Biology Techniques and Applications
- Renal cell carcinoma treatment
- Cancer, Hypoxia, and Metabolism
- Cancer Genomics and Diagnostics
- Cancer, Lipids, and Metabolism
- Cancer Research and Treatments
- Advanced biosensing and bioanalysis techniques
- Wnt/β-catenin signaling in development and cancer
- Cancer Cells and Metastasis
- Biotin and Related Studies
- Carbohydrate Chemistry and Synthesis
- Cancer-related Molecular Pathways
- RNA modifications and cancer
- Biosensors and Analytical Detection
- Isotope Analysis in Ecology
- Immunotherapy and Immune Responses
Johns Hopkins University
2019-2025
Johns Hopkins Medicine
2019-2024
University of Baltimore
2024
Johns Hopkins Hospital
2021
Institute of Chemistry, Academia Sinica
2017-2018
Institute of Information Science, Academia Sinica
2014-2017
National Yang Ming Chiao Tung University
2015-2016
Academia Sinica
2015-2016
To elucidate the deregulated functional modules that drive clear cell renal carcinoma (ccRCC), we performed comprehensive genomic, epigenomic, transcriptomic, proteomic, and phosphoproteomic characterization of treatment-naive ccRCC paired normal adjacent tissue samples. Genomic analyses identified a distinct molecular subgroup associated with genomic instability. Integration proteogenomic measurements uniquely protein dysregulation cellular mechanisms impacted by alterations, including...
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor patient survival. Toward understanding the underlying molecular alterations that drive PDAC oncogenesis, we conducted comprehensive proteogenomic analysis of 140 pancreatic cancers, 67 normal adjacent tissues, and 9 tissues. Proteomic, phosphoproteomic, glycoproteomic analyses were used to characterize proteins their modifications. In addition, whole-genome sequencing, whole-exome methylation, RNA sequencing...
Clear cell renal carcinomas (ccRCCs) represent ∼75% of RCC cases and account for most RCC-associated deaths. Inter- intratumoral heterogeneity (ITH) results in varying prognosis treatment outcomes. To obtain the comprehensive profile ccRCC, we perform integrative histopathologic, proteogenomic, metabolomic analyses on 305 ccRCC tumor segments 166 paired adjacent normal tissues from 213 cases. Combining histologic molecular profiles reveals ITH 90% ccRCCs, with 50% demonstrating immune...
We characterized a prospective endometrial carcinoma (EC) cohort containing 138 tumors and 20 enriched normal tissues using 10 different omics platforms. Targeted quantitation of two peptides can predict antigen processing presentation machinery activity, may inform patient selection for immunotherapy. Association analysis between MYC activity metformin treatment in both patients cell lines suggests potential role non-diabetic with elevated activity. PIK3R1 in-frame indels are associated AKT...
Although genomic anomalies in glioblastoma (GBM) have been well studied for over a decade, its 5-year survival rate remains lower than 5%. We seek to expand the molecular landscape of high-grade glioma, composed IDH-wildtype GBM and IDH-mutant grade 4 astrocytoma, by integrating proteomic, metabolomic, lipidomic, post-translational modifications (PTMs) with transcriptomic measurements uncover multi-scale regulatory interactions governing tumor development evolution. Applying 14 proteogenomic...
Glycosylation is a highly complex modification influencing the functions and activities of proteins. Interpretation intact glycopeptide spectra crucial but challenging. In this paper, we present mass spectrometry-based automated identification platform (MAGIC) to identify peptide sequences glycan compositions directly from N-linked collision-induced-dissociation spectra. The Y1 (peptideY0 + GlcNAc) ion critical for correct analysis unknown glycoproteins, especially without prior knowledge...
Abstract Core fucosylation of N-linked glycoproteins has been linked to the functions in physiological and pathological processes. However, quantitative characterization core remains challenging due complexity heterogeneity glycosylation. Here we report a mass spectrometry-based method that employs sequential treatment intact glycopeptides with enzymes (STAGE) analyze site-specific glycoproteins. The STAGE utilizes Endo F3 followed by PNGase F generate signatures for glycosites are formerly...
Clear cell renal carcinoma (ccRCC), a common form of RCC, is responsible for the high mortality rate kidney cancer. Dysregulations glycoproteins have been shown to associate with ccRCC. However, molecular mechanism has not well characterized. Here, comprehensive glycoproteomic analysis conducted using 103 tumors and 80 paired normal adjacent tissues. Altered glycosylation enzymes corresponding protein are observed, while two major ccRCC mutations, BAP1 PBRM1, show distinct profiles....
Metabolite identification remains a bottleneck in mass spectrometry (MS)-based metabolomics. Currently, this process relies heavily on tandem (MS/MS) spectra generated separately for peaks of interest identified from previous MS runs. Such delayed and labor-intensive procedure creates barrier to automation. Further, information embedded data has not been used its full extent metabolite identification. Multimers, adducts, multiply charged ions, fragments given metabolites occupy substantial...
Abstract Background Proteomic characterization of cancers is essential for a comprehensive understanding key molecular aberrations. However, proteomic profiling large cohort cancer tissues often limited by the conventional approaches. Methods We present landscape 16 major types human cancer, based on analysis 126 treatment-naïve primary tumor tissues, 94 tumor-matched normal adjacent and 12 using mass spectrometry-based data-independent acquisition approach. Results In our study, total 8527...
Serum PSA, together with digital rectal examination and imaging of the prostate gland, have remained gold standard in urological practices for management intervention cancer. Based on these adopted practices, limitations serum PSA identifying aggressive cancer has led us to evaluate whether urinary levels might any clinical utility diagnosis. Utilizing Access Hybritech assay, we evaluated a total n = 437 urine specimens from post-DRE patients. In our initial cohort, tests one hundred...
Protein–protein interactions (PPIs) are fundamental to understanding biological systems as protein complexes the active molecular modules critical for carrying out cellular functions. Dysfunctional PPIs have been associated with various diseases including cancer. Systems-wide PPI analysis not only sheds light on pathological mechanisms, but also represents a paradigm in identifying potential therapeutic targets. In recent years, cross-linking mass spectrometry (XL-MS) has emerged powerful...
Rapid development and wide adoption of mass spectrometry-based glycoproteomic technologies have empowered scientists to study proteins protein glycosylation in complex samples on a large scale. This progress has also created unprecedented challenges for individual laboratories store, manage, analyze proteomic data, both the cost proprietary software high-performance computing long processing time that discourages on-the-fly changes data settings required explorative discovery analysis. We...
ABSTRACT Liquid chromatography (LC) tandem mass spectrometry (MS/MS) is one of the widely used proteomic techniques to study alterations occurred at protein expression level as well post-translation modifications (PTMs) proteins that are relevant different physiological or pathological statuses. The spectrometric analysis peptides fragmented from (bottom-up proteomics) has emerged major approaches for proteomics. In this approach, first cleaved into and with PTMs further enriched followed by...
Abstract In this study, we generated label-free data-independent acquisition (DIA)-based liquid chromatography (LC)-mass spectrometry (MS) proteomics data from 261 renal cell carcinomas (RCC) and 195 normal adjacent tissues (NAT). The RCC tumors included 48 non-clear (non-ccRCC) 213 ccRCC. A total of 219,740 peptides 11,943 protein groups were identified with 9,787 per sample on average. We adopted a comprehensive approach to select representative samples different mutation sites,...
Background: There is an urgent need for the detection of aggressive prostate cancer. Glycoproteins play essential roles in cancer development, while urine a noninvasive and easily obtainable biological fluid that contains secretory glycoproteins from urogenital system. Therefore, here we aimed to identify urinary are capable differentiating non-aggressive Methods: Quantitative mass spectrometry data glycopeptides discovery cohort comprised 74 (Gleason score ≥8) 68 = 6) specimens were...
Single-cell proteomic analysis provides valuable insights into cellular heterogeneity allowing the characterization of microenvironment which is difficult to accomplish in bulk analysis. Currently, single-cell studies utilize data-dependent acquisition (DDA) mass spectrometry (MS) coupled with a TMT labelled carrier channel. Due extremely imbalanced MS signals among channel and other reporter ions, quantification compromised. Thus, data-independent (DIA)-MS should be considered as an...
Aberrant glycosylation has been shown to associate with disease progression, and glycoproteins representing the major protein component of biological fluids this makes them attractive targets for monitoring. Leveraging glycoproteomic analysis via mass spectrometry (MS) could provide insight into altered patterns that relate progression. However, investigation large sample cohorts requires rapid, efficient, highly reproducible preparation. To address limitation, we developed a high-throughput...
The emergence of castration-resistance is one the major challenges in management patients with advanced prostate cancer. Although spectrum systemic therapies that are available for use alongside androgen deprivation treatment castration-resistant cancer (CRPC) expanding, none these regimens curative. Therefore, it imperative to apply systems approaches identify and understand mechanisms contribute development CRPC. Using comprehensive proteomic approaches, we show a glycosylation-related...
N-linked protein glycosylation is a key regulator in various biological functions. Previous studies have shown that aberrant associated with many diseases. Therefore, it essential to elucidate modifications of by quantitatively profiling intact glycopeptides. Data-independent acquisition (DIA) mass spectrometry (MS) cost-effective, flexible, and high-throughput method for global proteomics. However, substantial challenges are still present the quantitative analysis glycopeptides high...
Recently, the rapid development and application of mass spectrometry (MS)-based technologies have markedly improved comprehensive proteomic characterization global proteome protein post-translational modifications (PTMs). However, current conventional approach for analysis is often carried out separately from PTM analysis. In our study, we developed an integrated workflow multiplex global, glyco-, phospho-proteomics using breast cancer patient-derived xenograft (PDX) tumor samples. Our...
Prostate-specific antigen (PSA) is commonly used as a serum biomarker for the detection of prostate cancer. However, levels PSA in do not reliably distinguish aggressive cancer from non-aggressive disease. Therefore, there an urgent need biomarkers that can differentiate cancers phenotypes. Fucosylation one glycosylation-based protein modifications. Previously we demonstrated increased fucosylated patients with using lectin selection followed by immunoassay.We developed two...