Review : Application of MALDI Tissue Imaging of Drugs and Metabolites: A New Frontier for Molecular Histology

( Selina Rahman Shanta ),( Young Jun Kim ),( Young Hwan Kim ),( Kwang Pyo Kim ) 한국응용약물학회 2011 Biomolecules & Therapeutics(구 응용약물학회지) Vol.19 No.2

Matrix assisted laser desorption ionization (MALDI) mass spectrometry is commonly used to analyze biological molecules such as proteins, peptides and lipids from cells or tissue. Recently MALDI Imaging mass spectrometry (IMS) has been widely applied for the identification of different drugs and their metabolites in tissue. This special feature has made MALDI-MS a common choice for investigation of the molecular histology of pathological samples as well as an important alternative to other conventional imaging methods. The basic advantages of MALDI-IMS are its simple technique, rapid acquisition, increased sensitivity and most prominently, its capacity for direct tissue analysis without prior sample preparation. Moreover, with ms/ms analysis, it is possible to acquire structural information of known or unknown analytes directly from tissue sections. In recent years, MALDI-IMS has made enormous advances in the pathological field. Indeed, it is now possible to identify various changes in biological components due to disease states directly on tissue as well as to analyze the effect of treated drugs. In this review, we focus on the advantages of MALDI tissue imaging over traditional methods and highlight some motivating findings that are significant in pathological studies.

Mass spectrometry based cellular phosphoinositides profiling and phospholipid analysis: A brief review

김영준,Li-Hua Zhou,Selina Rahman Shanta,김광표 생화학분자생물학회 2010 Experimental and molecular medicine Vol.42 No.1

Phospholipids are key components of cellular membrane and signaling. Among cellular phospholipids,phosphoinositides, phosphorylated derivatives of phosphatidylinositol are important as a participant in essential metabolic processes in animals. However,due to its low abundance in cells and tissues, it is difficult to identify the composition of phosphoinositides. Recent advances in mass spectrometric techniques,combined with established separation methods, have allowed the rapid and sensitive detection and quantification of a variety of lipid species including phosphoinositides. In this mini review, we briefly introduce progress in profiling of cellular phosphoinositides using mass spectrometry. We also summarize current progress of matrices development for the analysis of cellular phospholipids using matrix-assisted laser desorption/ionization mass spectrometry. The phosphoinositides profiling and phospholipids imaging will help us to understand how they function in a biological system and will provide a powerful tool for elucidating the mechanism of diseases such as diabetes, cancer and neurodegenerative diseases. The investigation of cellular phospholipids including phosphoinositides using electrospray ionization mass spectrometry and matrix-assisted laser desorption/ionization mass spectrometry will suggest new insights on human diseases,and on clinical application through drug development of lipid related diseases.

Identification of Protein Markers Specific for Papillary Renal Cell Carcinoma Using Imaging Mass Spectrometry

나찬현,홍지혜,김완섭,Selina Rahman Shanta,방주용,박동민,김학균,김광표 한국분자세포생물학회 2015 Molecules and cells Vol.38 No.7

Since the emergence of proteomics methods, many proteins specific for renal cell carcinoma (RCC) have been identified. Despite their usefulness for the specific diagnosis of RCC, such proteins do not provide spatial information on the diseased tissue. Therefore, the identification of cancerspecific proteins that include information on their specific location is needed. Recently, matrix-assisted laser desorption ionization (MALDI) mass spectrometry (MS) based imaging mass spectrometry (IMS) has emerged as a new tool for the analysis of spatial distribution as well as identification of either proteins or small molecules in tissues. In this report, surgical tissue sections of papillary RCC were analyzed using MALDI-IMS. Statistical analysis revealed several discriminative cancer-specific m/z-species between normal and diseased tissues. Among these m/z-species, two particular proteins, S100A11 and ferritin light chain, which are specific for papillary RCC cancer regions, were successfully identified using LC-MS/MS following protein extraction from independent RCC samples. The expressions of S100A11 and ferritin light chain were further validated by immunohistochemistry of human tissues and tissue microarrays (TMAs) of RCC. In conclusion, MALDI-IMS followed by LCMS/ MS analysis in human tissue identified that S100A11 and ferritin light chain are differentially expressed proteins in papillary RCC cancer regions.

Imaging Mass Spectrometry in Papillary Thyroid Carcinoma for the Identification and Validation of Biomarker Proteins

민경환,방주용,김광표,김완섭,이상화,Selina Rahman Shanta,이정화,홍지혜,임소덕,유영범,Chan-Hyun Na 대한의학회 2014 Journal of Korean medical science Vol.29 No.7

Direct tissue imaging mass spectrometry (IMS) by matrix-assisted laser desorptionionization and time-of-flight (MALDI-TOF) mass spectrometry has become increasinglyimportant in biology and medicine, because this technology can detect the relativeabundance and spatial distribution of interesting proteins in tissues. Five thyroid cancersamples, along with normal tissue, were sliced and transferred onto conductive glass slides. After laser scanning by MALDI-TOF equipped with a smart beam laser, images were createdfor individual masses and proteins were classified at 200-μm spatial resolution. Based onthe spatial distribution, region-specific proteins on a tumor lesion could be identified byprotein extraction from tumor tissue and analysis using liquid chromatography withtandem mass spectrometry (LC-MS/MS). Using all the spectral data at each spot, variousintensities of a specific peak were detected in the tumor and normal regions of the thyroid. Differences in the molecular weights of expressed proteins between tumor and normalregions were analyzed using unsupervised and supervised clustering. To verify the presenceof discovered proteins through IMS, we identified ribosomal protein P2, which is specificfor cancer. We have demonstrated the feasibility of IMS as a useful tool for the analysis oftissue sections, and identified the tumor-specific protein ribosomal protein P2.

Identification of Protein Markers Specific for Papillary Renal Cell Carcinoma Using Imaging Mass Spectrometry

Na, Chan Hyun,Hong, Ji Hye,Kim, Wan Sup,Shanta, Selina Rahman,Bang, Joo Yong,Park, Dongmin,Kim, Hark Kyun,Kim, Kwang Pyo Korean Society for Molecular and Cellular Biology 2015 Molecules and cells Vol.38 No.7

Since the emergence of proteomics methods, many proteins specific for renal cell carcinoma (RCC) have been identified. Despite their usefulness for the specific diagnosis of RCC, such proteins do not provide spatial information on the diseased tissue. Therefore, the identification of cancer-specific proteins that include information on their specific location is needed. Recently, matrix-assisted laser desorption ionization (MALDI) mass spectrometry (MS) based imaging mass spectrometry (IMS) has emerged as a new tool for the analysis of spatial distribution as well as identification of either proteins or small molecules in tissues. In this report, surgical tissue sections of papillary RCC were analyzed using MALDI-IMS. Statistical analysis revealed several discriminative cancer-specific m/z-species between normal and diseased tissues. Among these m/z-species, two particular proteins, S100A11 and ferritin light chain, which are specific for papillary RCC cancer regions, were successfully identified using LC-MS/MS following protein extraction from independent RCC samples. The expressions of S100A11 and ferritin light chain were further validated by immunohistochemistry of human tissues and tissue microarrays (TMAs) of RCC. In conclusion, MALDI-IMS followed by LC-MS/MS analysis in human tissue identified that S100A11 and ferritin light chain are differentially expressed proteins in papillary RCC cancer regions.

Global changes of phospholipids identified by MALDI imaging mass spectrometry in a mouse model of Alzheimer’s disease

Hong, Ji Hye,Kang, Jeong Won,Kim, Dong Kyu,Baik, Sung Hoon,Kim, Kyung Ho,Shanta, Selina Rahman,Jung, Jae Hun,Mook-Jung, Inhee,Kim, Kwang Pyo American Society for Biochemistry and Molecular Bi 2016 Journal of lipid research Vol.57 No.1

<P>Alzheimer's disease (AD) is the most common form of dementia; however, at the present time there is no disease-modifying drug for AD. There is increasing evidence supporting the role of lipid changes in the process of normal cognitive aging and in the etiology of age-related neurodegenerative diseases. AD is characterized by the presence of intraneuronal protein clusters and extracellular aggregates of beta-amyloid (A beta). Disrupted A beta kinetics may activate intracellular signaling pathways, including tau hyperphosphorylation and proinflammatory pathways. We analyzed and visualized the lipid profiles of mouse brains using MALDI-TOF MS. Direct tissue analysis by MALDI-TOF imaging MS (IMS) can determine the relative abundance and spatial distribution of specific lipids in different tissues. We used 5XFAD mice that almost exclusively generate and rapidly accumulate massive cerebral levels of A beta-42 (1). Our data showed changes in lipid distribution in the mouse frontal cortex, hippocampus, and subiculum, where A beta plaques are first generated in AD. Our results suggest that MALDI-IMS is a powerful tool for analyzing the distribution of various phospholipids and that this application might provide novel insight into the prediction of disease.</P>