Proteomics is the study of proteins, which are composed of amino acids and are responsible for various essential functions in living organisms. Some examples of proteins are enzymes, hormones and antibodies. I have been eager to study proteins since the beginning of my graduate studies, and finally, in the Summer of 2019, I got introduced to shotgun proteomics by my coolest mentor, Dr. Matthew Sobansky at Streck Inc. Laboratory. He taught me to develop and optimize untargeted, label-free, bottom-up proteomics workflow using Ion-Mobility enabled Q-ToF. Later, I learned intact protein analysis aka top-down proteomics at Northwestern University Proteomics Center of Excellence using Orbitrap Mass Spectrometers.

Metabolomics is the study of small molecule metabolites of cells. It can be considered the terminal step in the central dogma of life, and can be directly linked to phenotypic reactions. Study of metabolome can help to understand the physiology of the cell at any given time and/or condition and can greatly help to study healthy vs diseased state. Mass spectrometer can greatly aid in the structural analysis of small molecule metabolites. Additionally, untargeted metabolomics can help to explore novel secondary metabolites of a given system, for example fungi, bacteria, plant etc. with the potential of drug discovery. Integrated with other 'omics' layers, multiomics studies have been an ever-growing area in the last decade. I am fascinated by mass spec based multiomics studies. During my graduate research, I studied targeted bacterial metabolomics focusing on cell-wall and DNA biosynthesis using reverse-phase HPLC coupled to Triple Quadrupole Mass Spectrometers. During my postdoctoral research, I worked on untargeted fungal metabolomics integrated with genomics to study this untapped natural source for exploring bioactive natural products. We used Orbitrap Mass Spectrometers and various system biology and informatics tools to explore the bioactive natural products in fungi.

Molecular network analysis of natural products.

(Ref.: Caesar et al. Planta Med 2018)

Bioactive molecular networking in which nodes connected in a network represent structurally related compounds based on MS/MS fragmentation patterns.

(Ref.: Nothias et al. Journal of Nat Prod 2018)

Being fascinated by separation and measurement science, I have worked in several projects to develop targeted MRM LC-MS/MS methods to study different endogenous and exogenous molecules including drug, and drug metabolites, amino acids, peptides, DNA nucleosides and nucleotides, hormones, water contaminants etc. Chromatography when coupled to mass spectrometry can help to resolve complex biological mixtures and can help to study convoluted biological phenomena. With the overwhelming number of software to aid in mass spec data analysis, I am intrigued to learn a few to streamline a workflow with which I can study different biological layers of various organisms in order to both explore new bioactive agents and what they do to various organisms.

Multiple Reaction Monitoring (MRM) chromatogram of 20 common proteinogenic amino acid DL stereoisomers.

(Ref. Ayon et al. JASMS 2018)

Robert Langmuir's 1939 US Patent of Mass Spectrometry.

Drug repurposing is the study of existing drugs for new therapeutic actions. One of the greatest examples of drug repurposing is 'Sildenafil', which was originally developed by Pfizer to treat hypertension, later was discovered to treat erectile dysfunction. We attempted a drug repurposing approach by metabolizing chemical libraries using human liver microsomes and then doing a comparative screening to explore drug metabolites with better antibacterial activities than their parent drug. We also did a simultaneous screening in presence of an antibiotic to which the tested bacteria is resistant, to explore synergy and restore the activity of the former. We used liquid handling robotics and mass spectrometry based analysis in this project.

My research journey started with microparticle based formulation development and characterization. We developed polymeric microspheres using solvent evaporation technique, studied drug release, morphological and rheological characteristics and checked drug-excipient compatibility using FTIR and DSC. Although I do not work on formulation anymore, I collaborated with a few formulation labs during my PhD research and studied various formulation characteristics including the stability, drug release and drug uptake into cells from various novel drug delivery systems (NDDSs) . In future, I wish to continue collaborating with labs to keep doing this.

Different drug delivery systems.

(Image © Navid J. Ayon)

Science is more powerful, when combined! Although, I do not have my own lab, but I would like to believe that in future, I will be in a position to be able to collaborate with scientists all around the world. Let's connect! This can be the start of something big!

We need to be humble to begin education, and on our way, it's supposed to make us more humble. (tweaked from Robert Kiyosaki)