Sex Differences in Cardiometabolism in Health and Disease

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Heart disease remains the leading cause of death worldwide, yet it affects women and men differently - in how frequently it occurs, how effectively treatments work, and how quickly patients recover. In Lukas Chmatal lab, we aim to uncover the molecular mechanisms underlying these sex differences. Specifically, we want to understand what provides cardioprotection in women and why men are at higher risk of developing cardiovascular disease. Our research focuses on biological sex - the unique combination of sex chromosomes and sex hormones - and how it shapes heart metabolism in both health and disease.

To address this complex question, we study the body at multiple biological scales, from the whole organism to heart tissue, cardiomyocytes, and cardiomyocyte-specific mitochondria. We combine cutting-edge omics technologies with cellular and molecular approaches and computational analyses, using both genetically engineered mouse models and human samples.

Illustration of human bodies with highlighted hearts and a detailed artistic depiction of a human heart, featuring various colorful circles and abstract designs on a red background.

Image © Lukas Chmatal

Research Topics in Lukas Chmatal lab

Heart metabolic regulation in health and disease

Our recent study (Talukdar & Chmatal, Circulation, 2025) demonstrated a key role of biological sex in shaping mitochondrial function in non-failing human heart. Specifically, we found that genes involved in mitochondrial fatty acid oxidation - a central pathway in cardiac energy production - are expressed at higher levels in female cardiomyocytes than in males.

What remains an unresolved question is what the underlying molecular mechanisms of these sex differences are and to what extend are they driven by sex chromosomes, gonadal hormones, or a combination of both.

Short Documentary: Science still doesn’t understand how our sex affects our health

This 15-minute video offers a glimpse into the exciting opportunities in the field of Sex Differences research, which aims to uncover the molecular mechanisms underlying sex-specific aspects of human physiology.

Scientific American, a leading popular science magazine known for making complex research accessible to the general public, produced this documentary about sex differences research at leading scientific institutions in the USA. Lukas Chmatal contributed to this work as a postdoctoral researcher in David Page’s laboratory at the Whitehead Institute at MIT, alongside many talented colleagues whose efforts are also featured. Participating in the filming was a unique opportunity to share research findings with a wider audience.

Advancing the filed of Sex Differences will be instrumental in explaining why many human diseases, including cardiovascular diseases, manifest differently in men and women, and will help develop future therapies that benefit all patients.

Sex differential mitochondrial biology

Given that cardiac mitochondria are highly responsive to cell-specific nutritional and physiological cues, we investigate biological sex as a multidimensional variable that modulates their function to meet the distinct metabolic demands of males and females. Using genetically engineered mouse models, we can isolate the contributions of sex hormones and sex chromosomes and assess their effects on mitochondrial physiology and function. Our goal is to define the molecular mechanisms that underpin these sex differences in mitochondrial biology and to explore pathological contexts in which these mechanisms are relevant and potentially amenable to intervention.

Meet Our Team

  • A man running on a trail beside a lake with mountains in the background, participating in a race on a sunny day.

    Lukas Chmatal, PhD

    Principal Investigator

    Dr. Lukas Chmatal earned his Ph.D. from the University of Pennsylvania, where he investigated the mechanisms of chromosome segregation during both meiotic and mitotic cell division. As a postdoctoral associate in David Page’s laboratory at the Whitehead Institute at MIT, he received comprehensive training in sex chromosome biology, mouse genetics, and cardiac metabolism. In 2025, he established his independent research group at the Institute of Physiology in Prague, Czechia, to investigate how sex chromosomes regulate metabolism in cardiac health and disease. Dr. Chmatal has received several honors, including the Praemium Bohemiae Award for outstanding representation of the Czech Republic at the International Biology Olympiad, the Kaluza Prize from the American Society for Cell Biology for excellence in graduate research, and the Whitehead Spirit Award for exceptional contributions to the institute's community. He is passionate about mitochondria, heart biology, and sex chromosomes - three themes he also channels into his longtime hobby: long-distance running.

  • Alena Schützmeister

    Lab manager / Lab technician

    Alena Schützmeister comes to us from Prague, Czechia, but she earned her first bachelor’s degree in Animal Welfare and Protection from the Veterinary Faculty in Brno. After that, she came back to Prague to complete a second Bachelor’s degree in Conservation and Taxidermy – the art and science of preserving an animal’s body.


    Alena is skilled in caring for a wide range of animals, including mice, rats, and rabbits, and is trained in collecting mouse blood, tissues, and other biological samples. These talents make her the perfect caretaker for the lab’s mouse colonies. Combined with her sharp organizational skills, proactive mindset, and unwavering reliability, she is also the ideal person to serve as lab manager.

    As the lab’s very first hire, Alena is a safe bet for keeping everything running smoothly from day one. She enjoys the company of people as much as chilling alone in nature, and dreams of one day stuffing a mammoth – ideally a prehistoric one.

  • A young woman with blonde hair wearing a black turtleneck.

    Roxana Ehsani

    PhD student (Faculty of Science, Charles University)

    Roxana’s passion for genetics and cellular biology was sparked in her early childhood through science fiction movies, and she is now excited to apply that enthusiasm to studying sex differences in mitochondrial biology.

    Roxana received her Master’s degree in Molecular Genetics from the University of Guilan, Iran, where she studied genes involved in the late-onset progression of Alzheimer’s disease - a condition that disproportionately affects women compared to men. During this time, she developed a strong interest in sex differences in health and disease, as well as in the molecular mechanisms underlying these differences.

    Before joining our lab, Roxana worked as a research assistant at the Avicenna Research Institute, where she gained hands-on experience in in vitro embryo production and cell culture. In addition, her training at the National Institute of Genetic Engineering and Biotechnology equipped her with bioinformatics skills that will be highly valuable for the multi-omics approaches employed in our lab.

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Our Philosophy

A black-and-white cartoon image of a mitochondrion holding a stick and wearing a laurel wreath, representing a philosopher.

Laboratory:

In the Chmatal lab, we work as a team of highly motivated individuals driven to solve exciting and relevant biological questions. We believe that the best science arises from a collaborative, supportive, and diverse environment - one that respects all ideas and all people. We fully embrace the value and importance of the “night science” philosophy - a concept that emphasizes the context and process of creating scientific ideas - and we aim to foster a culture of open dialogue, creativity, and critical thinking to support such an environment https://night-science.org/.

Leadership:

In our lab, we believe that leadership is fundamentally about recognizing and nurturing the unique gifts and potentials of each individual, and inspiring them to work together towards a shared vision. The cornerstone of my leadership philosophy is rooted in five core values: listening, trust, excellence, integrity, and vision.

In Chmatal lab, we believe that…

Six icons representing the ethical values of our laboratory: Science is real, Love is love, Mitochondria are cool, Immigrants are welcome, Feminism is for everybody, and a raised fist symbolizing that all lives matter.

Selected Publications

lab members in bold

Genes of the Fatty Acid Oxidation Pathway are Upregulated in Female as Compared to Male Cardiomyocytes

Maya Talukdar*, Lukas Chmatal*, Linyong Mao, Daniel Reichart, Danielle S Murashige, Helen Skaletsky, Daniel M DeLaughter, Zoltan Arany, Jonathan G Seidman, Christine E Seidman, David C Page. (2025) Circulation, 151(7):511-514

* equal contribution

https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.124.071973

Efficient in vivo genome editing prevents hypertrophic cardiomyopathy in mice

Daniel Reichart*, Gregory A Newby*, Hiroko Wakimoto*, Mingyue Lun, Joshua M Gorham, Justin J Curran, Aditya Raguram, Daniel M DeLaughter, David A Conner, Júlia D C Marsiglia, Sajeev Kohli, Lukas Chmatal, David C Page, Nerea Zabaleta, Luk Vandenberghe, David R Liu, Jonathan G Seidman, Christine Seidman. (2022) Nature Medicine, 29(2):412-421

* equal contribution

https://www.nature.com/articles/s41591-022-02190-7

Spindle asymmetry drives non-Mendelian chromosome segregation

Takashi Akera, Lukas Chmatal, Emily Trimm, Karren Yang, Chanat Aonbangkhen, David M Chenoweth, Carsten Janke, Richard M Schultz, Michael A Lampson. (2017) Science, 358(6363):668-672

https://pubmed.ncbi.nlm.nih.gov/29097549/

Centromere strength provides the cell biological basis for meiotic drive and karyotype evolution in mice

Lukas Chmatal, Sofia I Gabriel, George P Mitsainas, Jessica Martínez-Vargas, Jacint Ventura, Jeremy B Searle, Richard M Schultz, Michael A Lampson. (2014) Current Biology, 24(19):2295-300

https://www.sciencedirect.com/science/article/pii/S0960982214009956?via%3Dihub

Join Our Team – Opened Positions for a Ph.D. Candidate & Research Data Scientist

About Us
We are a young and dynamic research group exploring the molecular mechanisms underlying sex differences in metabolism, with a particular focus on medically relevant questions such as cardiovascular health and disease. Our lab values inclusivity, collaboration, and open scientific exchange, and we are committed to providing personalized mentoring to support your long-term career goals. Located in one of Europe’s most beautiful cities, we offer a stimulating environment with competitive compensation, opportunities for international collaborations (including research exchange with our collaborators abroad), and support for attending international conferences to present your work and expand your professional network.

Ph.D. Candidate (Charles University, Fall application deadline: mid-December 2025; anticipated start: April 2026)

Requirements

  • Master’s degree (completed or near completion) in biological, medical, chemical, or biochemical sciences.

  • Strong self-motivation, attention to detail, and hands-on experience in cell biology, molecular biology, metabolomics, or computational biology.

  • Comfort working with mouse and human samples.

  • Fluency in English and excellent communication skills.

  • Enthusiasm for working in an inclusive, collaborative, and supportive team.

What We Offer

  • Personalized mentoring to develop your scientific skills and research independence.

  • Competitive stipend up to $1,600 / €1,400 / 36,000 CZK per month for four years.

  • Opportunity to participate in research exchange programs abroad.

  • Funding to present your work at international conferences and participating in EMBO workshops focused on relevant scientific methods and skills

Research Data Scientist (Application deadline: November 1st 2025; anticipated start: January 2026)

Requirements

  • Ph.D. degree (completed or near completion) in bioinformatics or computational data sciences.

  • Ability to lead research projects focused on large-scale dataset analyses (metabolomics, transcriptomics, proteomics, single-cell data).

  • Interest in learning basic wet lab experiments

  • Proactive and creative approach to addressing biological research questions.

  • Strong collaboration skills with both local team members and international partners.

  • Fluency in English and excellent communication skills.

What We Offer

  • Supportive environment aligned with your career development.

  • Participation international conferences and EMBO workshops focused on relevant scientific methods and skills

  • Salary up to $3,000 / €2,600 / 65,000 CZK per month + annual bonuses

  • Up to 6 weeks of vacation per year.

  • Initial two-year contract with a six-month probation period and the possibility of a long term contract

How to Apply
Please send your CV, a brief statement of your research interests in your motivation letter, and contact information for three references to lukas.chmatal@fgu.cas.cz

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