Please describe the research questions of your lab.
One of the primary goals of our group is to better understand the genetic susceptibility to pediatric pulmonary disorders, in particular childhood asthma, as well as the underlying genomic mechanisms and regulatory pathways. We are also interested in how different risk factors –such as obesity, dietary patterns, stress/violence, air pollution, and other environmental exposures– interact with and influence epigenetic and transcriptomic pathways to increase asthma risk and severity.
What genetics/genomics techniques do you utilize in your lab?
The majority of our work comes from genome-wide genotype data, as well as genome-wide epigenetic (DNA methylation) and transcriptomic (RNA-Seq) data. We also have started projects working with and integrating miRNA, proteomics, and metabolomic data.
Describe a key technique/assay/instrument utilized in your lab, and what novel insights does it bring to your research question?
More than one single technique or instrument, I think one of the key aspects in our work is the ability to work with data from multiple “omics” sources. This gives us the flexibility to query different aspects of the disease process and the relationships between genetics, the environment, and the resulting phenotypes. We are working to integrate all these multi-dimensional data to help us improve our understanding and better help our patients.
At what point in your life did you decide you wanted to be a scientist/physician?
When I was in seventh grade a group of local medical students came to our school once a month and we got to see and dissect different organs and perform different experiments. That’s when I wanted to be both a physician and a scientist. Early in medical school I realized I wanted to be a pediatrician, with the hopes of making a difference early on in the lives of children and adolescents. Why pediatric pulmonology? Well, respiratory physiology was just the most interesting to me, and the one I understood the most intuitively. In addition, asthma always seemed an extremely interesting disease; despite its high prevalence, we don’t fully understand it, and we don’t have a way to predict it, prevent it, or cure it –yet!
In your opinion, what is one of the most important discoveries in the field of respiratory illness/disease/function that was dependent on genomics or similar techniques?
I think the history of cystic fibrosis certainly represents one of the biggest achievements in respiratory medicine. Since the identification and cloning of the CFTR gene in 1989, a lot of steady progress has been made. Nowadays we have mutation-specific therapies that don’t just treat symptoms but that can partially reverse, overcome, or at least diminish the effects of the basic genetic defect that causes the disease. These therapies are already making a huge difference for thousands of patients. Going forward, I think the field should continue to work on personalized medicine, and hopefully gene therapy one day not too far down the road.
Briefly describe your favorite publication involving genomics/omics that you were involved with.
One of our most exciting recent projects was an epigenome-wide analysis in nasal epithelium and atopic asthma that we recently published (PMID 30584054). In that study we evaluated nasal DNA methylation levels in Puerto Rican children with and without atopy or atopic asthma, and found >7,000 CpG markers associated with each phenotype. I don’t think we were expecting that number of positive results. More importantly, >90% of our top results replicated in two independent cohorts, a case-control study in African-American children (Yang et al., J Allergy Clin Immunol 2017), and a European birth cohort (PIAMA, Xu et al., Lancet Respir Med 2018). Beyond helping improve our understanding of asthma, we wanted to test the clinical utility of this approach, so we designed a 30-CpG “predictive” panel, which accurately classified 88% of children in our cohort, as well as 82%-86% of children in the two replication cohorts. I think this study was particularly interesting because the results replicated extremely well in all three cohorts, despite their very different racial/ethnic backgrounds and environmental exposures. Other studies will have to replicate our findings in different settings, and prospective longitudinal studies will be necessary to validate their predictive utility, but these results constitute a very exciting first step. Finally, this project was a great example of how solid and continued collaboration with different groups can make a huge difference.
What is your favorite aspect of ATS?
There are many aspects of ATS that I really enjoy, including learning about new research, making new connections, and developing new collaborations. I believe the best research happens when people exchange ideas and work together. Especially in genomics, it is important to replicate findings in diverse populations, and this drive has also helped us develop very interesting partnerships beyond ‘simple’ replication attempts. It is always extremely inspiring when you see all the interesting research people are doing, both in asthma and in other fields.
How could your research assist scientists and clinicians in other assemblies at ATS?
I hope that our research will allow clinicians and other investigators better understand the mechanisms behind pediatric lung disease and, ideally, how to better treat their patients. I also hope that our results will be a starting point for other researchers, or perhaps a link that contributes to what they are working on. As I mentioned above, we are always seeking to collaborate with others; I think the best science (ideas and approaches) comes from sitting down and having conversations with other people that are passionate about what they do.
Would you be open to collaborations with GG and/or non-GG scientists and clinicians? Do you have any potential lab openings currently or in the near future?
We are definitely open to partnerships with scientists and clinicians that are interested in the genetics and genomics of pediatric respiratory diseases, in particular asthma! We are also looking for interested, hard-working trainees and faculty to join our team.
