Babenko Lab
Andrey P. Babenko, M.D., Ph.D.
Dr. Babenko studies the molecular physiology, biophysics and pharmacology of metabolism-sensing neuroendocrine and cardiovascular KATP channels
Dr. Babenko’s group was the first to identify ATP-sensitive potassium (KATP) channels in adult human cardiomyocytes, demonstrate activation of these metabolic sensors upon hypoxia, and find KATP-opening peptides. In collaboration with Dr. Joseph Bryan, he pioneered structure-function analyses of neuroendocrine and cardiovascular KATP channels. He revealed the pharmacotopology of their regulatory subunits, uncovered how these ABC ATPases control KATP pore, and made several other key observations in the field of ABCC and KCNJ proteins.
In collaboration with the French Network for the Study of Neonatal Diabetes for Genetic Diagnosis, he discovered that hyperactivating mutations in ABCC8 cause human Neonatal Diabetes (ND). Based on his analysis of the tolbutamide-sensitivity of ND-ABCC8/KCNJ11 recombinants, Dr. Babenko predicted which patients with transient and permanent ND can be successfully switched from daily insulin injections to oral sulfonylureas. Today, this new therapeutic strategy improves lives of ~85% of ND-ABCC8 patients.
After joining PNDRI, Dr. Babenko established a novel mechanism of metabolism-excitation uncoupling, hyperstimulation of the sulfonylurea receptor 1 (SUR1), and the subunit stoichiometry of this common diabetogenic effect, thus clarifying how the majority of heterozygous ND-ABCC8 mutations uncouple the excitability of pancreatic beta-cells from glucose metabolism.
Dr. Babenko focuses on defining the principal biophysical and biochemical mechanisms by which mutations and polymorphisms in the ABCC8/KCNJ11 cluster cause or predispose to diabetes in infants and type 2 diabetes mellitus. Dr. Babenko also develops pharmacological tests on mutant channels identified in patients with diabetes, which could allow personalized treatment of disease. His demonstrated expertise in electrophysiology, structure-function analyses, and pharmacology of key regulators of insulin secretion and glucose homeostasis advance prediction and therapy of disease that is the very mission of PNDRI and many other institutions, associations, and foundations.