Protein biosynthesis determines how genetic information is converted into cellular function. Despite decades of research, many fundamental questions about translation regulation remain unanswered. Our laboratory combines molecular biology, biochemistry, cell biology, and genome engineering to investigate how the translational machinery adapts to changing physiological conditions and how these adaptations influence human health and disease.
Oxygen deprivation is a hallmark of many physiological and pathological conditions, including development, ischemia, cancer, and inflammation. Although global protein synthesis is strongly suppressed during hypoxia, cells continue to produce specific proteins required for survival and adaptation. The molecular mechanisms that enable this selective translation remain poorly understood.
Our laboratory investigates how hypoxia remodels the translational machinery and determines which mRNAs continue to be translated under oxygen limitation. We are particularly interested in understanding how changes in translation initiation, elongation, and RNA regulatory elements contribute to this process.
By combining genome editing, biochemical approaches, ribosome profiling, and cell biology, we aim to define the molecular principles that allow cells to maintain protein synthesis under hypoxic stress and identify mechanisms that may become therapeutic targets in cancer and cardiovascular disease.
PROJECT 2. MECHANISMS OF VIRAL TRANSLATION
Viruses rely entirely on the host translational machinery to produce their proteins, yet many viral RNAs have evolved remarkable mechanisms to bypass normal cellular regulation. Understanding these mechanisms provides unique insights into both viral biology and the fundamental principles of translation.
Our laboratory studies non-canonical mechanisms of viral protein synthesis, including programmed ribosomal frameshifting, stop codon readthrough, internal ribosome entry sites (IRESs), and other specialized translation strategies. We seek to understand how viral RNAs manipulate the ribosome, how host factors regulate these processes, and how translation can be selectively inhibited without disrupting normal cellular protein synthesis. These studies not only improve our understanding of virus–host interactions but also reveal fundamental mechanisms of translational regulation that extend beyond virology.
EXPERIMENTAL APPROACHES
Human Cardiomyocytes Culture
Human iPSCs-derived neurons
Scheme of Prime Editing experiment
Representative polysome profile from human cell extract
A scheme of construct for the transposon-mediated stable integration of a transgene into the human genome
(A) Purification of human adenine desaminase (ADAT2/3), (B) Scheme of reaction and (C) detection of modified in vitro tRNA
Green Fluorescent Protein
Cell-free expression of nanoLuc luciferase