Dr. Hoyo, an epidemiologist, was recruited to NC State in 2014 as a part of their Environmental Health Science cluster, which brings together faculty from all 10 colleges within the university to collaborate on interdisciplinary projects.

Dr. Hoyo grew up in Zimbabwe and went to college in Sierra Leone, before coming to the U.S. to pursue additional education. She received a master’s degree from UC Berkeley and her Ph.D. from UNC Chapel Hill in 1998. Her postdoctoral work was done in Malawi as part of a collaboration between the UNC Medical School and the Malawi Ministry of Health. She has been on the faculty at North Carolina Central University (2 years) and Duke University (12 years), before moving to NC State.

Mutation to the DNA sequence of a gene is not the only — or, arguably, even the main — source of genetic variation and disease: the degree to which that gene is expressed is also variable. (Expression can be measured in a few ways, including as the number of copies of the mRNA from that gene present at a given time or as the number of copies of the protein product.) Gene expression is controlled by other DNA sequences called gene regulatory elements. The most well-studied gene regulatory element is the promoter, which is a region close to the start of a gene that helps recruit RNA polymerase to that site to start transcribing an RNA. Many promoters contain a stretch (“island”) of repeated pairs of C followed by G (“CpG”). The C in a CpG pair can be modified by the addition of a methyl group (a small carbon chain), which typically has the effect of turning down expression of the gene.

In a recent paper, Dr. Hoyo and collaborators at USC Keck School of Medicine and Duke University examined the relationship between CpG methylation status of a gene called AXL with childhood asthma. Two previous reports had linked variation in CpG methylation status of AXL to prenatal exposure to tobacco smoke, and the same exposure is linked to risk of childhood asthma. So the authors wanted to know if AXL methylation could be a link between prenatal smoke exposure and asthma, particularly since AXL is thought to block overactive immune responses.

They collected DNA from blood samples taken from newborns in the LA area and the Raleigh/Durham area and then followed up with these children (who are now 6-7 years old) to see which ones had developed asthma. Average methylation of AXL was higher in newborns who had developed asthmatic symptoms by age 6 than in those who had not. The CpG region of AXL most strongly associated with asthma is near a region of the gene predicted to increase its expression in lung cells, which suggests that the kids with higher CpG methylation and thus less AXL in their lungs are at higher risk of asthma because they don’t have enough AXL to suppress overactive inflammatory responses.