Scientists uncover molecular switch for heart disease

A healthy human heart is a strong, flexible organ that expands and contracts rapidly, pumping rich, oxygenated blood throughout the body

Understanding how genes are turned on or off in the hearts of heart patients, and how drugs can reverse these changes and improve heart function, is the focus of research by Dr Michael Alexandrian, who joined the Gladstone Institute, as an assistant researcher

"We hope to discover new therapeutic targets to treat and reverse heart failure," Alexanian said

Over the past 5 years, as a postdoctoral scholar, Alexanian, in the labs of former Gladstone researcher Saptarsi Haldar, MD, and Gladstone chair Deepak Srivastava, MD, has discovered a link between cardiac fibers Gene programs associated with inflammation and inflammation

"Michael pioneered our understanding of how heart cells communicate in heart failure, one of the most prevalent diseases today," said Dr.

heart reaching heart cells

Every cell in the human body contains nearly the same set of genes that provide instructions for all the molecular programs the body needs to function

Alexanian's lab will focus on fibrosis and inflammation, two changes that often occur in heart disease

When a person's heart is diseased, the DNA inside the heart cells does not change, but the patterns of genes expressed by the heart cells change

Alexandria thinks that if he can describe the transition in new detail and understand the regulatory molecules that trigger it, he can figure out how to reverse it

"The advent of single-cell technology has given us a way to capture the complexity of the heart," he said

His lab will focus on two specific changes that often occur in heart disease: cardiac fibrosis, the hardening and scarring of the heart caused by stress; and inflammation, the accumulation of immune cells and the factors they secrete in the heart

From epigenomics and stem cells to heart disease

Alexander first became interested in epigenomics as an undergraduate at the University of Florence in Italy

"It struck me that the biological complexity of different organisms is not related to the number of genes they have, but to millions of layers of gene regulation, " he said

A longtime drummer and improv teacher, Alexanian was drawn to the creative and storytelling aspects of biology

After graduation, Alexanian spent several months at the Walter and Eliza Hall Institute in Melbourne, Australia, working with epigenomics pioneer Dr.

"My project was very focused on stem cell epigenomics," he recalls

As a postdoctoral fellow at Gladstone, Alexanian combines epigenomics and cardiovascular disease
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In 2021, he and colleagues at the Gladstone Institute of Cardiovascular Disease report that MEOX1, the master switch in cardiac fibrosis, alters the levels of thousands of other genes
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Now, Alexanian plans to continue this work with animal studies showing how MEOX1 is affected by neighboring immune cells and how the MEOX1 gene can be targeted to prevent or treat fibrosis in the heart and other organs
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Inspired by dinosaurs and improvisation

Over the past decade, Alexanian has let his curiosity guide him from lab to lab
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All the while, he's been trying to do research that will allow him to think creatively
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Biology often has an aspect of storytelling that appeals to him, he says
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In fact, he traces his love of science back to the movie "Jurassic Park," which he watched five times in the first two weeks of its opening in Italian theaters
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He then, along with a group of elementary school classmates, pretended to isolate DNA from mosquitoes trapped in amber
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Of course, he never resurrected any ancient animals, but the joy of experimentation always stayed with him
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"The most effective way to do scientific research is to really take advantage of your surroundings and experts
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Gladstone is an easy place to do that
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For Alexandria, however, creative thinking is not limited to his science
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A long-time drummer and theatre enthusiast, he joined an improv group during his graduate studies in Lausanne
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"I absolutely fell in love with improv," he said
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"There's a lot of unappreciated technical preparation behind the scenes, but obviously there's also a creative side to it on stage
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In San Francisco, Alexandria couldn't find a comparable group, so he started a group of his own, "Improv at UCSF" to train scientists in improv
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The course he teaches is not only a fun outlet for scientists of all levels and disciplines, but a way to help them develop leadership and communication skills
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At Gladstone, Alexandria found an outlet for his scientific creativity
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He said the partnership and deep knowledge in epigenomics and cardiovascular science made him feel like this was the right place to launch his lab
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"The most effective way to do scientific research is to really use the environment and the experts around you to your advantage," he said
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"Greston is an easy place to do that
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"