Dr. Jordi Tauler arrived to the US in 2001, from Spain, after graduating in Molecular Biology from University of Navarra (Spain) and obtaining his PhD in Genetics and Molecular Biology from University of Barcelona (Spain). As a post-doctoral fellow, he joined Dr. James Mulshine’s lab at the National Cancer Institute, National Institutes of Health where he was introduced to lung cancer research.
In 2005, Dr. Mulshine and Dr. Tauler moved to Rush University, Chicago. Dr. Tauler lead the Lung Cancer Biology Lab at Rush University along with Dr. Mulshine. After very intense years of research, where several ideas were developed and explored, the lab could no longer be sustained. Dr. Tauler joined then Dr. Skip Garcia’s lab at University of Illinois at Chicago (UIC) in 2011. Dr. Garcia’s research was focused on lung pathology. Dr. Tauler participated in the development of a lung cancer group in Dr. Garcia’s lab. Unfortunately, budget cuts also affected Dr. Garcia’s lab and in 2013 Dr. Tauler joined the new lab of Dr. Winn, recently hired by UIC as Associate Vice President for Health Affairs and Director of the Lung Cancer Program. Dr. Tauler is conducting now the project that was developed along with Dr. Mulshine over several years.
What is the context of this research?
Lung cancer is the leading cause of cancer death in the United States. Despite extensive research efforts, the five-year survival rate remains around 15%. It has been described that in 25% of the cases of lung cancer adenocarcinoma, activating mutations in EGFR protein are the driving cause of lung cancer. Targeted therapy against these mutations is available and has shown significant clinical activity. These drugs, called tyrosine kinase inhibitors (TKIs), block the effect of the activating mutation. However, inevitably, resistance to these drugs develops during the course of therapy. Some mechanisms of resistance have been described. But in 30% of the patients treated with TKIs, mechanism of resistance remains unknown.
What is the significance of this project?
We are studying a protein (hnRNP A2/B1) that is involved in the processing of genetic information, at different levels. hnRNP A2/B1 protein is more abundant in lung cancer than in normal cells. We hypothesize that, this change in abundance along with the pressure of the targeted therapy, could be affecting the outcomes of mechanisms of processing of genetic information, regulated by hnRNP A2/B1 and resulting in generation of forms of proteins that change cell resistance to a specific treatment and modify tumor growth. Results from this project will open up new avenues for therapeutic intervention. New therapeutic agents could be designed targeting hnRNP A2/B1 or the new forms of proteins generated and they could be delivered in combination with TKIs or upon disease progression.
What are the goals of the project?
1) Generate lung cancer cells resistant to TKI, starting from sensitive cells, by small increases of doses of TKI.
2) Modify levels of activity of hnRNP A2/B1 in lung cancer cells using stable constructs that either will down-regulate or overexpression of hnRNP A2/B1
3) Measure levels of specific mRNAs from candidate genes that could be affected by hnRNP A2/B1, in all different conditions
4) Repeat measurements, at protein level, under the same conditions of the candidate genes.
This will get a basic picture of how hnRNP A2/B1 can affect resistance to targeted therapy and offer information about mechanism involved in this process and how genes are alternative spliced by hnRNP A2/B1.
Processing this information, publishing it and developing novel questions will allow us to apply for funding.
"Actually our lab works on a very tight budget however we are working on generating preliminary data in different approaches. We are a young lab and we have not been able to get funding from major agencies. It is very important that we generate this preliminary data to be able to apply for major agencies such as NIH. This budget will allow to generate this data since if funded at 100% we will have enough resources for at least a year. Without this budget, this research will be conducted on the side and it will take a long time to be completed. Unfortunately, there is a chance that we will have to abandon it for lack of funding." Says Dr. Tauler.
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