Above: Horizontal 3D section of the limbic system overlaid with NRG3 and ErbB4 expression (ABA)
Last year marked the 50th Anniversary of the Surgeon General Report on Smoking and Health.
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.
To do this, our lab investigates the genomic alterations resulting from chronic nicotine administration and withdrawal using ChIP-Seq and RNA-Seq technologies and how these changes impact both behavior as well as the concordant transcriptionally-driven circuitry adaptations. These altered preclinical genomic targets observed following chronic treatment and withdrawal are then candidates for SNP analysis in the smoking population.
In addition to understanding the key genomic mechanisms of nicotine dependence and withdrawal phenotypes, we are interested in how we might apply this knowledge to further personalized medicine. For example, we observe that nicotine withdrawal symptoms are altered in mice harboring a mutation in the Nrg3 gene, the endogenous ligand to HER4 (ErbB4). Additionally, we have seen that SNPs in the Nrg3 gene of smokers associate with reduced smoking cessation success. Therefore, we are now examining HER4 antagonists as possible smoking cessation therapies for specific application in smokers undergoing cancer treatment, especially if they possess target SNPs in the Nrg3 gene. This pharmacogenomic approach will hopefully yield more effective ways of treating nicotine dependence by utilizing an individual’s genetic makeup when prescribing therapeutics.
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.
To do this, our lab investigates the genomic alterations resulting from chronic nicotine administration and withdrawal using ChIP-Seq and RNA-Seq technologies and how these changes impact both behavior as well as the concordant transcriptionally-driven circuitry adaptations. These altered preclinical genomic targets observed following chronic treatment and withdrawal are then candidates for SNP analysis in the smoking population.
In addition to understanding the key genomic mechanisms of nicotine dependence and withdrawal phenotypes, we are interested in how we might apply this knowledge to further personalized medicine. For example, we observe that nicotine withdrawal symptoms are altered in mice harboring a mutation in the Nrg3 gene, the endogenous ligand to HER4 (ErbB4). Additionally, we have seen that SNPs in the Nrg3 gene of smokers associate with reduced smoking cessation success. Therefore, we are now examining HER4 antagonists as possible smoking cessation therapies for specific application in smokers undergoing cancer treatment, especially if they possess target SNPs in the Nrg3 gene. This pharmacogenomic approach will hopefully yield more effective ways of treating nicotine dependence by utilizing an individual’s genetic makeup when prescribing therapeutics.
