March 2019 Meeting – LATE LOCATION CHANGE, SEE BELOW

Speaker: Liangliang Sun, Michigan State University

Topic: Top-down Proteomics Using Capillary Zone Electrophoresis-Tandem Mass Spectrometry

Date: Monday, March 11, 2019

Time: 6:15 pm Dinner, 7:15 pm Presentation

Location: Hampton Inn & Suites Columbia, 7045 Minstrel Way, Columbia, MD 21046 (Directions)

Dinner: Please RSVP to Yan Wang (yanwang@umd.edu) by Friday, March 8th if you will be attending the dinner.

Abstract: Genome-level and transcriptome-level information cannot accurately reflect proteome-level information because post-transcriptional regulations modulate gene expression,because protein post-translational modifications (PTMs) influence protein function, and because most proteins in cells function as complexes with proteins, RNAs, metals or other small molecules. Characterization of the proteome is imperative to understand the roles played by proteins, protein PTMs and even protein complexes in development and diseases.

Top-down proteomics is a well-known strategy for large-scale characterization of proteome at the intact protein level and is very useful for high-resolution characterization of proteoforms that represent all kinds of protein molecules derived from the same gene due to gene-level variations, RNA-level alternative splicing, and protein-level PTMs. The number of proteoforms in the human proteome has been estimated to be over 1 million. High-capacity separation of proteoforms before electrospray ionization-mass spectrometry and tandem mass spectrometry (ESI-MS and MS/MS) is essential for deep and high-resolution top-down proteomics.

The top-down proteomics community has made tremendous efforts in improving liquid chromatography (LC)-MS and MS/MS for top-down proteomics. We argue that capillary zone electrophoresis (CZE)-MS and MS/MS is another powerful tool for top-down proteomics because CZE can approach high-capacity separation of intact proteins and because CZE-MS has shown obviously higher sensitivity than LC-MS for protein detection. In my talk, I will talk about our recent work on boosting CZE-MS and MS/MS for large-scale and highly sensitive top-down proteomics. I will also introduce our work on developing CZE-MS and MS/MS methodologies for native top-down proteomics that aims to characterize the endogenous protein complexes in cells in discovery mode.

February 2019 Meeting (note location change)

Speaker: W. Andy Tao, Purdue University

Topic: Analyses of Protein Phosphorylation and Their Applications in Liquid Biopsy

Date: Monday, February 11, 2019

Time: 6:15 pm Dinner, 7:15 pm Presentation

Location: University of Maryland College Park, room 1208, Biology-Psychology building, 4066 Campus Drive, College Park, MD 20742 (parking: 200 Regents Dr, College Park, MD 20742) (Directions)

Dinner: Please RSVP to Yan Wang (yanwang@umd.edu) by Friday, February 8th if you will be attending dinner.

Abstract: Protein kinases and their substrates comprise extensive signaling networks that regulate many diverse cellular functions. However, methods and techniques to systematically identify kinases directly responsible for specific phosphorylation events have remained elusive. Here we describe integrated proteomic strategies to dissect kinase networks in high throughput and demonstrate their applications in multiple systems. Our group has introduced a set of chemical tools and proteomics strategies to analyze protein phosphorylation, in particular, to identify direct kinase substrates and upstream kinases. Recently, for the first time, we identified thousands of phosphoproteins isolated from small volumes of plasma samples and quantitatively measured phosphoproteins that are significantly higher in patients diagnosed with breast cancer as compared to healthy controls. Our studies demonstrate that the development of phosphoproteins as disease biomarkers is highly feasible and may transform disease early detection and monitoring.

CANCELLED FOR WEATHER (January 2019 Meeting)

Speaker: Asher Newsome, Smithsonian Museum Conservation Institute

Topic: Ambient Sampling and Ionization for Mass Spectrometry of Museum Objects and Materials

Date: Monday, January 14, 2019

Time: 6:15 pm Dinner, 7:15 pm Presentation

Location: Shimadzu Scientific Instruments, Inc. Training Center 7100 Riverwood Drive, Columbia, MD 21046 (Directions)

Dinner: Please RSVP to Yan Wang (yanwang@umd.edu) by Friday, January 11th if you will be attending the dinner.

Abstract: Over thirty years after the creation of an atmospheric pressure ionization source for mass spectrometry, development of ambient sampling and ionization sources for use without chromatography exploded beginning in 2004. Whether a given technique moves from academia to industry or follows some other path, oftentimes a design originally intended to be a general-purpose analytical MS tool – versatile, based on fundamental principles, relatively open-source – becomes increasingly engineered toward niche applications, particularly the biomedical and defense markets. With some 150 million objects (including living specimens) in its collection that have been selected for conservation and are available for study, the interests of the Smithsonian Institution fill every niche. The versatility, modularity, and throughput of our mass spectrometry systems are of the utmost concern. A varied selection of our recent projects using ambient ionization, direct analysis in real time (DART), and solid phase microextraction (SPME) to analyze ancient, historic, and modern objects is presented, as well as some of our instrumental modifications to accommodate the particular concerns of a museum.

December 2018 Meeting

Speaker: Amina Woods, The National Institute on Drug Abuse Intramural Research Program

Topic: Tracking the Progression of Traumatic Brain Injury and the Therapeutic Response to a Peptide Drug Using Innovative Imaging MS

Date: Monday, December 17, 2018

Time: 6:15 pm Dinner, 7:15 pm Presentation

Location: Shimadzu Scientific Instruments, Inc. Training Center 7100 Riverwood Drive, Columbia, MD 21046 (Directions)

Dinner: Please RSVP to Yan Wang (yanwang@umd.edu) by Friday, December 14th if you will be attending the dinner.

Abstract: Traumatic brain injury (TBI) is a serious public health problem and a leading cause of death in children and young adults. It also contributes to a substantial number of cases of permanent disability. As lipids make up over 50% of the brain mass and play a key role in both membrane structure and cell signaling, their profile is of interest. In this study, we show that advanced mass spectrometry imaging (MSI) has sufficient technical accuracy and reproducibility to study the progression of TBI as well as a therapeutic response. The anatomical distribution of 50 μm diameter microdomains demonstrate changes in brain lipid levels in a rat model of controlled cortical impact (CCI) 3 days post injury with and without treatment.

November 2018 Meeting

Speaker: Daniele Fabris, University at Albany

Topic: MS-based approaches for the elucidation of nucleic acid higher-order structure and dynamics

Date: Monday, November 19, 2018

Time: 6:15 pm Dinner, 7:15 pm Presentation

Location: Shimadzu Scientific Instruments, Inc. Training Center 7100 Riverwood Drive, Columbia, MD 21046 (Directions)

Dinner: Please RSVP to Yan Wang (yanwang@umd.edu) by Friday, November 16th if you will be attending the dinner.

Abstract: The discovery of ribozymes and riboswitches has keenly reasserted the critical role played by higher-order structure in determining the function of nucleic acid sequences that do not code for actual proteins. Mass spectrometry-based approaches can provide valuable information about base-pairing and longrange interactions, which define the secondary, tertiary, and quaternary structure of nucleic acids. We have been developing strategies based on high-resolution and ion mobility spectrometry (IMS) mass spectrometry to investigate the structure-function relationships in noncoding viral RNA. We have demonstrated that the concerted application of footprinting and crosslinking methods can provide valid spatial constraints for modeling operations, leading to the solution of actual 3D structures. Top-down strategies can provide direct information on the position and strength of base-pairing interactions that stabilize higher-order structure. Putative structures are corroborated by IMS determinations that reveal the global topology of target RNA. These approaches constitute a valuable alternative for the investigation of systems that, owing to their large size and flexibility, are not directly amenable to classic high-resolution techniques employed in structural biology. Their implementation has been providing new insights into the processes of genome recognition, dimerization, and packaging of HIV-1 and other retroviruses, which have the potential of leading to the development of novel therapeutic strategies.