Cigarette smoking causes 1 in 5 deaths each year in the United States.
Ongoing work in the lab aims to understand why people can’t quit.
Smoking causes 87% of lung cancer deaths, one third of cancer deaths is caused by smoking, and smoking increases the failure rate of treatment for all cancers. However, despite 50 years of trumpeting the consequences of long-term smoking, ~20% of Americans continue to smoke. Furthermore, we now know that while 80% of smokers desire to quit, less than 5% of them are successful. Our research aims to understand the biology underlying the low success rates of quitters.
Our laboratory’s goal of translational research in substance use disorders is to 1) discover the cellular, molecular, neural, and behavioral basis of early abstinence effects that contribute to relapse, and 2) investigate the relationship of abstinence effects to relapse in clinical studies. To this end, our current research is focused on the intersection of genetic and functional mechanisms driving the behavioral response to chronic drug use and subsequent withdrawal. For example, we utilize next-gen sequencing techniques to identify novel mechanisms engaged during nicotine dependence with the goal of developing new therapeutics and applying personalized approaches to treatment. One such molecule is the CREB target gene Neuregulin 3 (NRG3), which has been implicated in both schizophrenia and ADHD. Identification of this candidate gene in the mouse nominated it for analysis of single nucleotide polymorphisms (SNPs) for association with prospective smoking cessation among two independent cohorts of smokers. Individual SNP and haplotype analysis suggest that a specific SNP in this gene is associated with reduced smoking cessation success, strongly implicating this pathway in the molecular mechanisms underlying nicotine dependence.
We are currently applying these types of experimental approaches to understand how cell-type specific genomic and genetic changes impact therapeutic outcomes. This pharmacogenomic approach will hopefully yield more effective ways of treating nicotine dependence by utilizing an individual’s genetic makeup when prescribing therapeutics.
