A photo of Cat Makarewich.

Cat A. Makarewich, PhD


  • Assistant Professor, UC Department of Pediatrics

About

Biography

My research lab focuses on understanding the molecular mechanisms that underlie the pathophysiology of cardiovascular disease and skeletal muscle disorders. We use a combination of in vitro and in vivo methods to study the regulatory proteins that control the development, growth and function of cardiac and skeletal muscle in both health and disease. Our long-term objective is to use the information we gain to generate new targeted therapies to prevent and treat heart disease and skeletal muscle disorders.

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 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.

My research has been at the forefront of this evolving field of microprotein discovery and characterization. Our team has found that these microproteins play crucial roles in many essential biological processes including muscle contraction, metabolism and the maintenance of cellular calcium homeostasis.

I have always had a passion for biology and science and have found myself drawn to the intricacies of heart and skeletal muscle from the time I first studied it in-depth as a graduate student. Muscle is a very complex and robust tissue and is absolutely essential for life. Heart disease and skeletal muscle disorders are very prevalent in our population. We desperately need to better understand the causes and effects of these diseases in order to design new therapeutic approaches for their treatment.

I received an NIH K99/R00 Pathway to Independence Award in 2018 to fund my research and support my transition to Cincinnati Children’s Hospital Medical Center, where I started as an Assistant Professor in November of 2019.

Publications

Selected

The cardiac-enriched microprotein mitolamban regulates mitochondrial respiratory complex assembly and function in mice. Makarewich, CA; Munir, AZ; Bezprozvannaya, S; Gibson, AM; Kim, SY; Martin-Sandoval, MS; Mathews, TP; Szweda, LI; Bassel-Duby, R; Olson, EN. Proceedings of the National Academy of Sciences of the United States of America. 2022; 119.

Selected

Gene Therapy With the DWORF Micropeptide Attenuates Cardiomyopathy in Mice. Makarewich, CA; Bezprozvannaya, S; Gibson, AM; Bassel-Duby, R; Olson, EN. Circulation Research. 2020; 127:1340-1342.

Selected

The hidden world of membrane microproteins. Makarewich, CA. Experimental Cell Research. 2020; 388.

Selected

Newly Discovered Micropeptide Regulators of SERCA Form Oligomers but Bind to the Pump as Monomers. Singh, DR; Dalton, MP; Cho, EE; Pribadi, MP; Zak, TJ; Seflova, J; Makarewich, CA; Olson, EN; Robia, SL. Journal of Molecular Biology. 2019; 431:4429-4443.

Selected

The DWORF micropeptide enhances contractility and prevents heart failure in a mouse model of dilated cardiomyopathy. Makarewich, CA; Munir, AZ; Schiattarella, GG; Bezprozvannaya, S; Raguimova, ON; Cho, EE; Vidal, AH; Robia, SL; Bassel-Duby, R; Olson, EN. eLife. 2018; 7.

Selected

MOXI Is a Mitochondrial Micropeptide That Enhances Fatty Acid β-Oxidation. Makarewich, CA; Baskin, KK; Munir, AZ; Bezprozvannaya, S; Sharma, G; Khemtong, C; Shah, AM; McAnally, JR; Malloy, CR; Szweda, LI; et al. Cell Reports. 2018; 23:3701-3709.

Selected

Mining for Micropeptides. Makarewich, CA; Olson, EN. Trends in Cell Biology. 2017; 27:685-696.

Selected

Widespread control of calcium signaling by a family of SERCA-inhibiting micropeptides. Anderson, DM; Makarewich, CA; Anderson, KM; Shelton, JM; Bezprozvannaya, S; Bassel-Duby, R; Olson, EN. Science Signaling. 2016; 9.

Selected

A peptide encoded by a transcript annotated as long noncoding RNA enhances SERCA activity in muscle. Nelson, BR; Makarewich, CA; Anderson, DM; Winders, BR; Troupes, CD; Wu, F; Reese, AL; McAnally, JR; Chen, X; Kavalali, ET; et al. Science. 2016; 351:271-275.

An Integrated Approach for Microprotein Identification and Sequence Analysis. Brito-Estrada, O; Hassel, KR; Makarewich, CA. Journal of Visualized Experiments. 2022.