Featured Researchers

Craig Hersh, MD


Please describe the research questions of your lab.

My research integrates the tools of genetics, genomics and epidemiology to improve precision in the diagnosis and treatment of chronic obstructive pulmonary disease (COPD.)  I am a co-investigator in the COPDGene Study, an NIH-funded observational study of smokers with and without COPD at 21 clinical centers across the U.S.  Two of the current projects in the lab are COPDGene ancillary studies. One ancillary study is using RNA-sequencing and microRNA profiling to study clinically relevant subtypes, including emphysema-predominant COPD and frequent exacerbators. Another ancillary utilizes serum biomarkers, RNA sequencing, and network methods to refine the definition of another important COPD subtype, the asthma-COPD overlap syndrome. Integration of multiple ‘omic data types is an important direction in precision medicine, and I am project leader in a program project in which we have performed gene expression profiling and genome-wide genotyping in human lung tissue and expression profiling in mouse models of COPD.

What genetics/genomics techniques do you utilize in your lab?

Prior and ongoing work has included GWAS genotyping and gene expression arrays. For expression analysis, we have now moved to RNA sequencing. Small RNA (e.g. miRNA) sequencing is our newest area.

Describe a key technique/assay/instrument utilized in your lab, and what novel insights does it bring to your research question?

Network methods are a recent area of interest, such as weighted gene co-expression network analysis and cluster analysis. These methods highlight that the interactions between genes influence phenotypes. We also leverage the integration between datasets, such as integrating genotyping and gene expression (eQTL analysis) and combining mouse and human expression data.

At what point in your life did you decide you wanted to be a scientist/physician?

In college, I decided to become a physician, but it was not until fellowship that I decided on a career in research. I had worked in basic science labs in college and medical school, but was more drawn to patient care.  After my clinical fellowship in Pulmonary and Critical Care Medicine at Harvard Medical School, I had the opportunity to pursue a research fellowship in Genetic Epidemiology at Brigham and Women’s Hospital, where I learned the tools needed to combine human studies with genetics.

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?

The rapid expansion of genetics in oncology, with lung cancer as the most relevant to respiratory disease, is quite amazing, as it applies both to disease subtyping and precision treatment. I think we have a long road ahead to make similar gains in benign respiratory diseases, due to such factors as disease heterogeneity and limited tissue availability, but we have a model to follow and revise.

Please describe your favorite publication involving genomics/omics that you were involved with.

I am proud of the work we have done on the asthma-COPD overlap syndrome (ACOS), including both epidemiology and genetics, much of which was done by Megan Hardin (Hardin M, Eur Respir J. 2014;44(2):341-50. PMID: 24876173). Despite the high prevalence of ACOS among COPD patients and the clinical significance including increased hospitalization, this group has not been well-studied. In the COPDGene Study, we used a clinical definition of ACOS relying on a doctor’s diagnosis of asthma before the age of 40 and fixed airflow obstruction to define COPD. We found that ACOS was more common in women and African Americans. These subjects more commonly had hay fever and a family history of asthma, pointing to the validity of our definition. They had the same reduction in FEV1 despite being younger and have similar smoking histories, implying that the asthma and COPD toghether were leading to lung function impairment. Interestingly, bronchodilator response on spirometry could not accurately distinguish asthma-COPD subjects from COPD alone.  Examining chest CT scans, subjects with asthma-COPD overlap had less emphysema, but more airway disease. GWAS in these subjects did not show genomewide significant associations, but there were several interesting associations including genes involved in eosinophil activation and steroid metabolism, and genes previously associated with COPD and lung development. We are exciting to continue working in this area, by adding serum IgE levels to try to refine the diagnosis and RNA sequencing to uncover biologic pathways in ACOS.

What is your favorite aspect of ATS?

Despite all of the great lectures at the annual meeting, my favorite part of the ATS meeting is the more personal interactions, including conversations with collaborators about new or ongoing projects as well as learning about new research from fellows and trainees as they present their posters. Walking through the poster sessions is a great way to meet new people and see old friends, since people tend to congregate in the areas of their interest. We hope that the Genetics and Genomics Section can serve a similar role to bring together trainees and established researchers with a common interest, whether to learn about new techniques, to form new collaborations or just to say hello.

How could your research assist scientists and clinicians in other assemblies at ATS?

More and more scientists are utilizing next-generation sequencing in their projects, and sequencing is growing in the clinic as well. Through ongoing work, we have learned a lot about RNA sequencing methodologies and data analysis. Personally, I would be interested in a forum to discuss best practices in sequencing as they apply to respiratory, critical care, and sleep research (and eventually clinical care).

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?

I am always open to new collaborations, for example using our genomic data to translate laboratory findings into human populations or to examine other COPD phenotypes or subtypes identified by clinicians and scientists. I would be especially interested in talk to trainees or junior investigators working in this area. Between my group and others in my department, we are always looking for talented postdocs from various backgrounds (e.g. medicine, genetics, bioinformatics, statistics, etc.) who are interested in ‘omics of respiratory disease. Please feel free to contact me at craig.hersh@channing.harvard.edu.