MSACL 2018 US Abstract

Topic: Endocrinology

Mass Spectrometric Studies of Apolipoprotein Proteoforms and their Role in Lipid Metabolism and Type 2 Diabetes

Dobrin Nedelkov (Presenter)
Isoformix

Bio: Dr. Nedelkov received his Ph.D. in Biochemistry from Arizona State University in 1997. After a year as a Postdoctoral Associate at Yale University, Dr. Nedelkov joined Intrinsic Bioprobes where over the span of 15 years he progressed through the ranks to ultimately become Scientific Director and CEO of the company, leading the early commercialization efforts in technology development for targeted proteomics and protein biomarkers. In 2013 Dr. Nedelkov joined the Biodesign Institute at Arizona State University as a group leader of the Molecular Biomarkers Unit, focusing on proteoform biomarker discovery, validation, and translation. In 2017 Dr. Nedelkov started Isoformix with the goal of translating MS protein tests into the clinic. Dr. Nedelkov has authored over 100 peer reviewed scientific articles, and presented at more than 60 scientific meetings.

Authorship: Dobrin Nedelkov
Isoformix

Short Abstract

Apolipoproteins function as structural components of lipoprotein particles, cofactors for enzymes, and ligands for cell-surface receptors. Most of the apoliporoteins exhibit proteoforms, arising from PTMs such as glycosylation, oxidation and sequence truncations. Presented will be recent studies correlating apolipoproteins proteoforms with specific clinical measures of lipid metabolism and cardiometabolic risk. Mass spectrometric immunoassays toward apolipoproteins A-I, A-II, C-I, C-II, and C-III were applied on large cross-sectional and longitudinal clinical cohorts. Several correlations were observed, including greater apolipoprotein A-I and A-II oxidation in patients with diabetes and cardiovascular disease, and a divergent apoC-III proteoforms association with plasma triglycerides, indicating significant differences in the metabolism of the individual apoC-III proteoforms.

Long Abstract

Introduction

Apolipoproteins function as structural components of lipoprotein particles, cofactors for enzymes, and ligands for cell-surface receptors. Most of the apoliporoteins exhibit proteoforms, arising from single nucleotide polymorphisms (SNPs) and post-translational modifications such as glycosylation, oxidation and sequence truncations.

Methods

Presented will be recent studies correlating apolipoproteins proteoforms with specific clinical measures of lipid metabolism and cardiometabolic risk. Targeted mass spectrometric immunoassays toward apolipoproteins A-I, A-II, C-I, C-II, and C-III were applied on large cross-sectional and longitudinal clinical cohorts.

Results

Several correlations were observed, including greater apolipoprotein A-I and A-II oxidation in patients with diabetes and cardiovascular disease, and a divergent apoC-III proteoforms association with plasma triglycerides, indicating significant differences in the metabolism of the individual apoC-III proteoforms.

Conclusions & Discussion

These are first studies of their kind, correlating specific proteoforms with clinical measures in order to determine their utility as potential clinical biomarkers for disease diagnosis, risk stratification, and therapy decisions. Such studies provide the impetus for further development and clinical translation of the MS-based protein tests.


References & Acknowledgements:


Financial Disclosure

DescriptionY/NSource
Grantsno
Salaryno
Board Memberno
Stockyes Isoformix
Expensesno

IP Royalty: no

Planning to mention or discuss specific products or technology of the company(ies) listed above:

no