Modeling the interactions of LAT1

We have once again gained one critical milestone. The second publication for Jussi's Ph.D. thesis was published yesterday. This is actually really interesting study, as here, we were able to combine for the first time our biological data with molecular modeling, in that sense that Tuomo, our modeler or TV-chemist as we call him, was able to explain the interactions of different compounds with our target transporter LAT1 (L-type amino acid transporter 1). So we were able to understand not only binding process of the compounds to LAT1, but also to predict what kind of structural requirements are essential for the compounds, so that they don't only bind to LAT1 but also is transported across the plasma membrane through LAT1's cavity. And this is not a simple process, since the translocation is a multi-step process that involve a conformational changes of the transproter, from the outward-open position of LAT1 (to which the compounds bind) to inward-open position (from which the compound is released to cytosolic side of the cells). However, also in this study, like almost in all cases, you realize that this is only a start and more experiments with more sophisticated methods are needed to understand more. Luckily, in this case, we already have a second Ph.D. student, Kati who is working hard to find more details out of this fascinating field. So I look forward to see what else we can dig out of LAT1!

Anyway, thank you for all the co-authors and congratulation Jussi, one step closer of your graduation!

Link to the publication.

Metformin Research Group

I have had such a great collaboration with Pharos University of Alexndria (PUA, Egypt), which has yielded so far 2+2 publications. Our latest establishment is a "Metformin Research Group" founded by Dr. Ibrahim Komeil and we have such a great variety of experts from PUA from medicinal chemistry to pharmacology and immunology. It will be such a great honor to me to be part of this consortium. Originally, we have now plans to build up 3 independent studies hopefully resulting in 3 publications, but we will see how it goes, good luck, team!

Academy Research Fellow Report

I can't believe but my 5-years' long Academy Research Fellow Project that started in 2015 ended at the end of March. It was already extended by my maternity leave and due to the COVID-19 pandemic. And as expected, at the end I needed to compile a relatively profound report to Academy of Finland. First I thought that I really didn't achieve anything special, but then I read the original plan and started to fill the form and to my surprise, I realized that wow, this project was very successful! I guess the downgrading feeling came from the fact that I needed to do a lot of adjustments by the wishes of the hired Ph.D. students. And I kept having this positive problem that  my Ph.D. student got a lot of personal grants, which meant that I needed to hire new ones to keep the budget in the balance! 

During the 5 years, I was able to pay a salary to 8 persons working at some point in the project, in addition to my own salary.

we had 1 Ph.D. graduation and 3 more to come in the next 1-2 years. 7 graduated M.Sc. students and 7 ERASMUS student were working in the project. 4 Predoctoral and 2 postdoctoral visiting researchers were also working in the project.

We achieved 20 fabulous publications! 

A great amount of external funding was also received, not only granted to me, but also to my Ph.D. students.

In the summary of the report I wrote:

In this project, it was studied if LAT1-utilizing prodrugs can improve the drug delivery into the brain and inside the brain. It was found out that LAT1 is expressed both in neurons as well as in glial cells in addition to the BBB. Therefore, the prepared LAT1-prodrugs were delivered effectively across the BBB into their target brain cells, where they released their active parent drugs. It was also demonstrated that the pharmacological effects of the LAT1-prodrugs were improved due to the increased drug delivery and brain-targeting in vitro and in vivo. Thus, the outcome of the drug therapies of many different brain diseases can be improved with LAT1-prodrug approach in the future, which can have a great impact on the healthcare costs of the aging population.

Let's just hope that I can take this project to the next level on continue to explore the fascinating field of transporters.

Make it double!

A weird thing happened a week ago. And I bet it would never happen again. On the same day, I have got 2 acceptance letters of the submitted articles, in a row! Well, the easy explanation for this is that 2 manuscripts were submitted to the same journal, although at different times, but the reviewing process varied so much that they were accepted finally at the same time, and most likely will be published in the same issue of Journal of Pharmaceutical Sciences. 

The first one, for which I was the corresponding author is:

Improved L-Type Amino Acid Transporter 1 (LAT1)-Mediated Delivery of Anti-Inflammatory Drugs into Astrocytes and Microglia with Reduced Prostaglandin Production (link for the publication)

Here we synthesized 4 LAT1-utilizing ester prodrugs of non-steroidal anti-inflammatories (NSAIDs) and studied the relatioships between the structure and the release of the parent drug, to improve the pharmacokinetic profile and the delivery of NSAIDs into the brain via LAT1 and finally the pharmacological profile (inhibition of prostaglandins). Many of my visiting ERASMUS students were participating to this project, so thank you all for your great contribution!

The other publication is something that I was honored to be co-authoring, as my contribution was really minor in this one:

Oral Genistein-loaded Phytosomes with Enhanced Hepatic Uptake, Residence and Improved Therapeutic Efficacy against Hepatocellular Carcinoma (link for the publication)

I have not much to say about this marvelous publication, as phytosomes are not my core experties, but I must admit that it was a great to learn about them and be part of this project that have potential to improve cancer chemotherapy with these nanoparticles! So thank you for all the co-author of this publication!