Blockers of Wnt3a, Wnt10a, or β-Catenin Prevent Chemotherapy-Induced Neuropathic Pain in Vivo Neurotherapeutics

Kim H.K.; Bae J.; Lee S.H.; Hwang S.-H.; Kim M.-S; Kim M.J.; Jun S.; Cervantes C.L.; Jung Y.-S.; Back S.; Lee H.; Lee S.-E.; Dougherty P.; Lee S.-W.; Park J.-I.; Abdi S.; Neurotherapeutics 2020, in press

Although chemotherapy is a key cancer treatment, many chemotherapeutic drugs produce chronic neuropathic pain, called chemotherapy-induced neuropathic pain (CINP), which is a dose-limiting adverse effect. To date, there is no medicine that prevents CINP in cancer patients and survivors. We determined whether blockers of the canonical Wnt signaling pathway prevent CINP. Neuropathic pain was induced by intraperitoneal injection of paclitaxel (PAC) on four alternate days in male Sprague-Dawley rats or male Axin2-LacZ knock-in mice. XAV-939, LGK-974, and iCRT14, Wnt/β-catenin blockers, were administered intraperitoneally as a single or multiple doses before or after injury. ...

PASS-DIA: A data-independent acquisition approach for discovery studies

Mun D.-G.; Renuse S.; Saraswat M.; Madugund A.; Udainiya S.; Kim H.; Park S.-K.R.; Zhao H.; Nirujogi R.S.; Na C.H.; Kannan N.; Yates J.R.III.; Lee S.-W.; Pandey A.; Analytical Chemistry 2020, 92, 21, 14466–14475

Data- independent acquisition (DIA) approach is being increasingly adopted as a promising strategy for identification and quantitation of proteomes. As most DIA datasets are acquired with wide isolation windows, highly complex MS/MS spectra are generated, which negatively impacts obtaining peptide information through classical protein database searches. Therefore, analysis of DIA data mainly relies on evidence of the existence of peptides from pre-built spectral libraries. Consequently, one major weakness of this method is that it does not account for peptides which are not included in spectral library, precluding the use of DIA for discovery studies. ...

Prognostic plasma protein panel for Aβ deposition in the brain in Alzheimer’s disease

Park, J.-C.; Han, S.-H.; Lee. H.; Jeong, H.; Byun, M. S.; Bae, J.; Kim, H.; Lee, D. Y.; Yi, D.; Shin, S. A.; Kim, Y. K.; Hwang, D.; Lee, S.-W.; Mook-Jung, I. Progress in Neurobiology 2019, 183, 1-13

Alzheimer’s disease (AD) is the most common age-associated dementia. Many studies have sought to predict cerebral amyloid deposition, the major pathological hallmark of AD, using body fluids such as blood or cerebral spinal fluid (CSF). The use of blood in diagnostic procedures is widespread in medicine; however, existing blood biomarkers for AD remain unreliable. We sought to discover blood biomarkers that discriminate Aβ deposition status in the brain. This study used 107 individuals who were cognitively normal (CN), ...

Accurate Precursor Mass Assignment Improves Peptide Identification in Data-Independent Acquisition Mass Spectrometry

Mun, D.-G.; Nam, D.; Kim, H.; Pandey, A.; Lee, S.-W. Analytical Chemistry 2019, 91, 8453-8460

Proteomics research today no longer simply seeks exhaustive protein identification; increasingly, it is also desirable to obtain robust, large-scale quantitative information. To accomplish this, data-independent acquisition (DIA) has emerged as a promising strategy largely owing to developments in advanced mass spectrometers and sophisticated data analysis methods. Nevertheless, the highly complex multiplexed MS/MS spectra produced by DIA remain challenging to interpret. Here, we present a novel strategy to analyze DIA data, based on unambiguous precursor mass assignment through the mPE-MMR (multiplexed post-experimental monoisotopic mass refinement) ...

Comprehensive proteome and phosphoproteome profiling shows negligible influence of RNAlater on protein abundance and phosphorylation

Bae, J.; Kim, S.-J.; Lee, S.-E.; Kwon, W.; Kim, H.; Han, Y.; Jang, J.-Y.; Kim, M.-S.; Lee, S.-W. Clinical Proteomics 2019, 16, 18.

Certain tumors such as pancreatic ductal adenocarcinoma (PDAC) are known to contain a variety of hydrolytic enzymes including RNases and proteases that may lead to degradation of RNA and proteins during sample processing. For such tumor tissues with RNA instability, RNAlater containing a high concentration of quaternary ammonium sulfates that denature RNA-hydrolyzing enzymes is often used to protect RNAs from hydrolysis. Although a few studies have been carried out to determine the effect of RNAlater on DNA and RNA, whether RNAlater influences the proteome and phosphoproteome is largely unknown. In this study we carried out a systematic and comprehensive analysis of the effect of RNAlater on the proteome and phosphoproteome using high-resolution mass spectrometry. ...

Proteogenomic Characterization of Human Early-Onset Gastric Cancer

Mun, D.-G.; Bhin, J.; Kim, S.; Kim, H.; Jung, J. H.; Jung, Y.; Jang, Y. E.; Park, J. M.; Kim, H.; Jung, Y.; Lee, H.; Bae, J.; Back, S.; Kim, S.-J.; Kim, J.; Park, H.; Li, H.; Hwang, K.-B.; Park, Y. S.; Yook, J. H.; Kim, B. S.; Kwon, S. Y.; Ryu, S. W.; Park, D. Y.; Jeon, T. Y.; Kim, D. H.; Lee, J.-H.; Han, S.-U.; Song, K. S.; Park, D.; Park, J. W.; Rodriguez, H.; Kim, J. Lee, H.; Kim, K. P.; Yang, E. G.; Kim, H. K.; Paek, E.; Lee, S.; Lee, S.-W.; Hwang, D. Cancer Cell 2019, 35, 111-124.

We report proteogenomic analysis of diffuse gastric cancers (GCs) in young populations. Phosphoproteome data elucidated signaling pathways associated with somatic mutations based on mutation-phosphorylation correlations. Moreover, correlations between mRNA and protein abundances provided potential oncogenes and tumor suppressors associated with patient survival. Furthermore, integrated clustering of mRNA, protein, phosphorylation, and N-glycosylation data identified four subtypes of diffuse GCs. Distinguishing these subtypes was possible by proteomic data. Four subtypes were associated with proliferation, immune response, metabolism, and invasion, respectively; and. ...

A mitochondrial proteome profile indicative of type 2 diabetes mellitus in skeletal muscles

Chae S.; Kim, S.-J.; Koo, Y. D.; Lee, J. H.; Kim, H.; Ahn, B. Y.; Ha, Y.-C.; Kim, Y.-H.; Jang, M. G.; Koo, K.-H.; Choi, S. H.; Lim, S.; Park, Y. J.; Jang, H .C.; Hwang, D.; Lee, S.-W.; Park, K. S. Experimental & Molecular Medicine 2018, 50:129.

The pathogenesis of type 2 diabetes mellitus (T2DM) is closely associated with mitochondrial functions in insulin-responsive tissues. The mitochondrial proteome, compared with the mitochondrial genome, which only contains 37 genes in humans, can provide more comprehensive information for thousands of mitochondrial proteins regarding T2DM-associated mitochondrial functions. However, T2DM-associated protein signatures in insulin-responsive tissues are still unclear. Here, we performed extensive proteome profiling of mitochondria from skeletal muscles in nine T2DM patients and nine nondiabetic controls. A comparison of the mitochondrial proteomes identified 335 differentially expressed proteins (DEPs) between T2DM and nondiabetic...