Inside HGG Advances: A Chat with Maria Gutierrez-Arcelus

Posted By: HGG Advances

Each month, the editors of Human Genetics and Genomics Advances interview an early-career researcher who has published work in the journal. This month we check in with Maria Gutierrez-Arcelus (@mariaGTAC) to discuss her paper “Functional genomics implicates natural killer cells in the pathogenesis of ankylosing spondylitis.”

Maria Gutierrez-Arecelus, PhD
Maria Gutierrez-Arecelus, PhD

HGGA: What motivated you to start working on this project?

MG: The pathogenesis of ankylosing spondylitis (AS) remains poorly understood. In other immune-mediated diseases, integrating genome-wide association studies with epigenomics and transcriptomics has successfully identified key pathogenic cell types, such as T cells in rheumatoid arthritis and B cells in systemic lupus erythematosus. Inspired by these successes, we aimed to apply similar methodologies to AS to uncover the candidate cell types mediating the genetic susceptibility of this highly heritable disease.

HGGA: What about this paper/project most excites you?

MG: What excites me most is how our unbiased approach consistently identified natural killer (NK) cells as key mediators of AS genetic risk. These findings align with existing studies that implicate NK cells in AS and underscore the biological plausibility of their involvement—particularly through their interaction with HLA-B, encoded by the primary risk gene for AS. I am excited to see how future studies build on this work to confirm our findings and uncover new insights into the role of NK cells in AS pathogenesis.

HGGA: What do you hope will be the impact of this work for the human genetics community?

MG: This study points to NK cells as a key cell type for an immune-mediated disease. Using public eQTL datasets available for NK cells, we found four candidate target genes of AS risk variants. As has occurred for other complex diseases, there remain a lot of risk loci for which we haven’t found their regulatory effects. Ours and others’ previous work suggests that many “missing regulatory effects” may only become apparent under specific activation states of relevant cell types. While most eQTL studies of activated cell types have focused on T cells and myeloid cells, I hope this work underscores the importance of conducting eQTL studies for NK cells under various activation states to capture their full regulatory potential.

HGGA: What are some of the biggest challenges you’ve faced as a young scientist?

MG: I am passionate about discovery-based science, particularly in the genomics era, which has enabled us to investigate molecular features at an unprecedented scale. However, one of the biggest challenges I am facing is that most funding mechanisms tend to favor hypothesis-driven research over discovery-driven studies. While I recognize the critical importance of hypothesis-driven projects in dissecting specific mechanisms involving particular genes or proteins, I believe discovery-based projects play an equally vital role in advancing biomedical science. By leveraging genomic technologies, we can uncover new biology that leads to novel hypotheses, providing a deeper understanding of life and its dysregulation in disease.

HGGA: And for fun, what is one of the most fascinating things in genetics you’ve learned about in the past year or so?

MG: One of the most fascinating things I’ve learned recently is the significant presence of human endogenous retroviruses (HERVs) in our genome, comprising around 8% of it. While these ancient viral remnants were once thought to be “junk” DNA, emerging evidence shows that some HERVs play important roles in immune regulation. I’m particularly intrigued by how these elements may influence transcriptional programs and immune responses, potentially shaping our susceptibility to diseases. I look forward to upcoming studies that delve deeper into the functional roles of HERVs and their contributions to disease pathogenesis.

Maria Gutierrez-Arecelus, PhD is an Assistant Professor in the Division of Immunology, Department of Pediatrics, at Boston Children’s Hospital and Harvard Medical School, and an affiliate member of the Broad Institute.

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