Dr. Melissa Ilardo lives in Salt Lake City with her husband and their two dogs. Following her PhD in evolutionary genomics at the University of Copenhagen, Melissa completed two postdocs simultaneously: at the University of Utah and UC Berkeley. Melissa then spent 3 years working in industry with large-scale health genomics cohorts at genomics-based drug discovery startups before returning to academia at the University of Utah as an Assistant Professor in Biomedical Informatics.
Her research takes an interdisciplinary approach to the understanding of health phenotypes by exploring human evolution and adaptation in populations that have previously been overlooked or excluded from biological research. Thus far, she has partnered with two populations who engage in the practice of breath-hold diving. Melissa uses computational genomics paired with health data to translate discoveries made in these unique populations into medically relevant insights. When not working, Melissa enjoys trail running, mountain biking, and backcountry skiing in the beautiful Wasatch mountains.
Research Statement
Despite the wide range of human phenotypes that span health and physiological resilience, medical genomics research has focused largely on disease and ‘fixing what is wrong’. My research program instead aims to identify genetic adaptations with the ultimate goal of targeting and replicating these evolutionary changes to improve human health. For thousands of years, populations around the world have lived in extreme environments and engaged in dangerous subsistence practices, enabling natural selection to alter and improve their physiological capabilities. In my lab, we seek to discover these genetic enhancements to contribute fundamentally to our understanding of the genetic regulation of human health. Understanding naturally evolved physiological resilience can provide a blueprint for population-level prevention strategies, risk-stratification, and intervention development in public health.
Lessons from Divers: In my PhD, I worked with the Bajau freedivers of Indonesia, a population of breath-hold divers who regularly experience intermittent hypoxia. I found that the Bajau have significantly larger spleens than a nearby, agricultural population called the Saluan. During breath-hold diving, the spleen acts as an oxygen reservoir, storing red blood cells. It contracts as a component of the dive response, increasing the circulating oxygen available to the diver. By pairing spleen size measurements with whole genome sequencing data, I was able to connect the unique Bajau trait to a genetic variant that has evolved in the Bajau.1 In one of two postdocs that I completed simultaneously, I was able to pharmacologically replicate the adaptive large-spleen trait in animal models.2 Hypoxia tolerance is central to a wide range of public health challenges, including chronic obstructive pulmonary disease, sleep apnea, and critical care management. By identifying and replicating genetic pathways that enhance oxygen mobilization, this work provided a candidate target for improving hypoxia resilience in broader populations.
We recently demonstrated a second genetic adaptation to diving in the Haenyeo of Korea.3 The Haenyeo, which literally translates to “women of the sea,” have been diving off Jeju’s coasts for centuries. We paired natural selection and genetic association analyses to identify adaptive genetic variation that may mitigate the effects of diving on pregnancy through an associated reduction of diastolic blood pressure. Our findings further suggest this genetic variation has protective cardiovascular effects beyond pregnancy. We found that, even when accounting for known cerebrovascular risk factors, being from Jeju Island was associated with a 30% reduction of familial stroke risk.4 Stroke remains a leading cause of death and disability worldwide. Identifying naturally occurring genetic variants that reduce cerebrovascular risk may inform prevention strategies, precision risk prediction, and novel therapeutic development aimed at reducing stroke burden at the population level.
A Panorama of Adaptation: Collectively, my research program seeks to shift medical genomics from a disease-centered framework to one that also identifies and leverages naturally evolved resilience.5 By uncovering protective genetic adaptations and translating them into mechanistic insights, my work aims to inform prevention strategies for cardiovascular disease, hypoxia-related illness, heat stress, and metabolic disorders. As populations around the world face rapid environmental change, understanding the biology of resilience will be critical for designing equitable, population-level interventions that improve health outcomes.
New Methods: To enable these evolutionary insights, we are building an innovative computational tool that improves the detection of large changes in DNA structure. Although these structural variants (SVs) have an outsized effect on physiology, most insights in biomedical genomics to date have been driven by the study of single nucleotide variants, leaving SVs underexplored. Current analytical methods leverage short-read sequencing data, missing approximately a third of structural genetic variation. Modern advances in long-read sequencing technologies present exciting new applications and unique mapping challenges. Achieving accurate alignment, particularly in complex regions, remains a critical limitation and a key opportunity for long-read sequencing, especially in SV detection. As a solution to this challenge, we are building a fundamentally new computational approach to long-read mapping and SV detection that leverages techniques from the well-developed field of numerical signal processing by transforming DNA sequence into numerical signals.
References
1 Ilardo, M. A. et al. Physiological and Genetic Adaptations to Diving in Sea Nomads. Cell 173, 569-580 e515 (2018). https://doi.org/10.1016/j.cell.2018.03.054
2 Ilardo, M. et al. An Erythropoietin-Independent Mechanism of Erythrocytic Precursor Proliferation Underlies Hypoxia Tolerance in Sea Nomads. Front Physiol 12, 760851 (2021). https://doi.org/10.3389/fphys.2021.760851
3 Aguilar-Gomez, D. et al. Adaptation to diving in the Haenyeo breath-hold divers of Korea. Cell Reports 115577 (2025). https://doi.org/ 10.1016/j.celrep.2025.115577
4 Heyborne, G. K., S.; Jeong, C.; Tristani Firouzi, M.; Hernandez, E. J.; Ilardo, M. Regional variation in parental stroke history between Jeju Island and mainland Korea. medRxiv 10.1101 (2025).
5 Collins, N., Heyborne, G., Fuentes, A., Lund, J. & Ilardo, M. Salutogenomics: embracing the full spectrum of human health. Trends in Genetics (2025).
