Pei Laboratory

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A central question in physiology is how different organs communicate with each other to maintain whole-organism homeostasis. Research in the past 20 years revealed that non-glandular organs such as adipose tissue, liver and skeletal muscle can secrete hormones that regulate whole-body metabolism. In contrast, little is known regarding heart-derived hormones save for ANP and BNP, each discovered over 30 years ago.

The Pei Lab recently discovered that Growth Differentiation Factor 15 (GDF15) is a new heart-derived hormone. Circulating GDF15 acts on the liver to inhibit growth hormone signaling and body growth. Plasma GDF15 is increased in children with concomitant heart disease and failure to thrive (FTT). The results from the investigators in the lab explained a well-established clinical observation that children with heart diseases often develop FTT. More importantly, these studies reveal a new endocrine mechanism by which the heart coordinates cardiac function and body growth.

Plasma GDF15 was recently shown to be elevated in patients with various heart diseases and is associated with increased morbidity and mortality. However, how GDF15 is increased in heart disease remains unclear. The Pei Lab tackled this clinically important question and identified the whole gene regulatory network that induces GDF15 transcription in heart disease, using massively parallel single-nucleus RNA-Seq (~20,000 nuclei). This study also revealed the organ composition, cell type, and heterogeneity in normal postnatal, developing mouse heart, and the profound changes of transcriptional landscape of every cell type in the disease state. In addition, the team has identified the key enzymes that process GDF15 pro-hormone into its mature form. Together, these studies helped pioneer a new field of cardiac endocrinology.

Project Highlights

  • Single-cell analysis of postnatal mouse hearts to understand how heart disease affects cardiac functions at single cell level;
  • Single-cell analysis to mechanistically understand specific disease conditions that induce GDF15 transcription
  • Investigating how heart disease impacts GDF15 maturation through regulating the activity of GDF15 processing enzymes PCSK3, 5 and 6.
  • Identifying the liver GDF15 receptor and elucidating its signaling pathway in the liver
Leader

Liming Pei, PhD

Investigator
Dr. Pei's research aims to understand the molecular underpinnings of cardiac remodeling associated with cardiomyopathy and heart failure. He is particularly interested in two areas of cardiac remodeling: metabolic reprogramming, and secretion of heart-derived hormones to communicate with other organs.