Makarewich Research Lab

Our lab investigates the molecular mechanisms that underlie the pathophysiology of cardiovascular disease and skeletal muscle disorders. The long-term goal of our research is to use the knowledge we gain to develop new targeted therapies to prevent and treat these devastating diseases. To achieve this, we utilize a combination of in vitro and in vivo approaches to study the regulatory proteins that control the development, growth and function of cardiac and skeletal muscle in both health and disease.

Recently, the cellular proteome has expanded to include a novel class of small proteins called microproteins, or micropeptides. These microproteins are translated from small open reading frames (smORFs) of less than 300 nucleotides in length to generate proteins that are 100 amino acids or smaller. Due to their small size, many microprotein-coding genes have been unintentionally overlooked by standard gene annotation methods and have been incorrectly classified as noncoding RNAs.

In recent years, innovative bioinformatic and technological advances have led to the discovery of hundreds of putative microproteins, but to date, functional roles have only been assigned to a small fraction of these proteins. Our lab has shown that microproteins play important roles in a broad range of essential cellular processes, including development, differentiation, calcium homeostasis, stress signaling and metabolism, which indicates that an enormous amount of interesting biology still remains hidden in this unique class of largely uncharacterized proteins. By elucidating the biological functions of more of these microproteins, we aim to uncover new insights into the regulatory mechanisms that are important for muscle biology and to translate this information into novel therapeutics that can be used to treat cardiovascular and muscle diseases.