= Emerging. More than 5 years before clinical availability. (16.60%, 2024)
= Expected to be clinically available in 1 to 4 years. (37.02%, 2024)
= Clinically available now. (46.38%, 2024)
MSACL 2024 : Van Eyk

MSACL 2024 Abstract

Self-Classified Topic Area(s): Proteomics > Proteomics > none

Podium Presentation in Steinbeck 3 on Thursday at 16:20 (Chair: Timothy Collier / David Colquhoun)

Finding Solutions for Drug Development: Parkin Activator Mitigates Adverse Left Ventricular Remodeling After Myocardial Infarction

Lizhuo Ai, Juliana de Freitas Germano, Aleksandr Stotland, Roberta A. Gottlieb, Jennifer E. Van Eyk

Jennifer Van Eyk, PhD (Presenter)
Cedars-Sinai Heart Institute

Presenter Bio: Jennifer Van Eyk, PhD, is an international leader in the area of clinical proteomics and her lab has focused on developing technical pipelines for de novo discovery and larger scale quantitative mass spectrometry methods. This includes multiple reaction monitoring (MRM, also known as SRM) and most recently data independent acquisition. Dr. Van Eyk's laboratory is well known for the extreme technical quality of the data generated, rigorous quality control with tight %CV while applying these to key clinical questions. The aim is to maximize throughput and reproducibility in order to move targeted and robust discovery methods into large population healthy continuous assessment and clinical grade assays focusing on brain and cardiovascular diseases.


Almost 30% of survivors of myocardial infarction (MI, heart attack) develop heart failure (HF), in part, due to damage caused by accumulation of dysfunctional mitochondria. Organelle quality control through Parkin-mediated mitochondrial autophagy (mitophagy) is known to play a role in mediating protection against heart failure (HF) damage and the remodeling of the subsequent deteriorated heart tissue. Our group used proteomics, metabolomics, and functional approaches to show a single i.p. dose (2hrs post-MI) of PR-364, a Parkin activator, reduced mortality, preserved cardiac ejection fraction, and mitigated the proteome/metabolomic and functional progression of HF in mice. Our cardiomyocyte-like AC16 cell data indicated PR-364 effects are multifactorial: i) increased mitophagy and mitochondrial biogenesis, ii) enhanced ATP production via improved TCA cycle, iii) altered accumulation of calcium localization to the mitochondria, and iv) initiated translational reprogramming with increased expression of mitochondrial translational proteins. However, it is also clear that the effects involve more than just direct parkin activation. To determine the proteomic drivers of the next generation of PR-364 molecules that will provide broad proteomics coverage representing these diverse functional read out, we developed a full automated cell (AC-16) based 96-well workflow, including sample preparation under ischemia and reperfusion for mass spectrometry. As well, we are adapting this for human iPSC-derived cardiomyocyte to allow for high throughput proteomic screening that can accommodate broad genetic background.

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