Take it from someone who’s earned a Ph.D. and two masters degrees all while conducting cutting-edge drug repurposing research: knowing how to handle your stress is important.
Recent graduate Misagh Naderi is involved in research to combat rare or orphan diseases. By using an online database of rare disease research, he and his team have created a system to repurpose existing FDA-approved drugs to treat orphan diseases.
Since 2011, Misagh has taught the longest running student-lead program at the International Culture Center (ICC): Meditation at LSU. Misagh had been involved with mediation long before he came to LSU, and he also enjoys yoga, running, rock climbing, listening to audiobooks and making visually striking scientifically inspired graphics.
We asked Misagh to tell us about his research and how he was able to keep his stress at bay while earning his two latest degrees.
College of Science: Tell us about how you started Meditation at LSU.
Misagh: In 2011, when I joined LSU, the first building that I saw was the ICC. That was the first building I went into. When I went in, I thought this is perfect for my meditation groups. The building manager kind of laughed at me and said it was wishful thinking. A year or two after that, I started giving talks about meditation and how to be calm and how to use alternative medicine. I’ve been teaching the class since 2011, and it’s been very successful. We have 30 students every Monday doing yoga for an hour and meditation for 20 minutes.
Misagh led the Yoga in the Union event that the College of Science hosted. Click here for a video of the warm up from the session. Credit: Jessica Manafi.
Another way Misagh relieves stress while working on a deadline: hammocking.
College of Science: How does hammocking help you relieve stress?
Misagh: People under stress, like students, should understand that you should take some time off or do your more stressful work somewhere that you are very comfortable, balancing the stress and relaxation at the same time. Sometimes when I need inspiration or I’m too stressed out, I grab my laptop, go into the hammock and just work and enjoy it. When it’s done, not only is the job done, but I’ve also enjoyed the process, which is very important for me.
There are many good places to hammock around Baton Rouge, but Misagh isn’t sharing his favorite hammocking hangout.
“I don’t want to lose my spot!”
It’s a good thing Misagh knows a thing or two about how to handle his stress because one could describe his academic repertoire as...stressful! He earned his bachelor’s degree in Iran, and this past May, he defended two degrees in two separate departments: a Ph.D. in biochemistry and a masters degree in biomedical and veterinary medical sciences. He earned his first masters in chemical engineering from LSU in 2012.
College of Science: What lead you to pursue all three degrees?
Misagh: I joined the chemical engineering Ph.D. program when I got here and ended up working on projects that were mainly on reactors and more chemical engineering, not biochemical engineering. Therefore, I chose to to get a masters in chemical engineering and moved to another lab at the Veterinary School that did virology (the study of viruses). I started working on drug delivery and later got into cancer therapy using viruses, which is an amazing field to study. I decided to get my Ph.D. in computational biology, which is a bridge between my engineering and biology background. Computational biology became my Ph.D. and virology became my second masters.
College of Science: What brought you to LSU? How is this campus different from your school in Iran?
Misagh: There’s a difference in environment for sure. In Iran, my university was top two in the country, but was one of the strongest undergraduate electrical engineering departments in the entire world. We didn’t have any vet schools or sciences, but we had the best technical school. LSU is definitely way more fun; there’s so much to do here. It’s a more holistic campus. There are so many opportunities here, like having biology and veterinary studies. The sports and athletic programs here are amazing. I was an athlete back home, so I really appreciate that. I did sprint kayaking and some sport you may have never heard of: canoe polo. You have a canoe and you play water polo. I played on my city team for more than eight years and was invited to the national team, but I didn’t participate. That was the time I decided to come here. I really appreciate the athletic programs here. Where I went in Iran, it was all about intellectual power; your talent was your intellectual talent.
Misagh has been working on finding ways to repurpose FDA-approved drugs to combat rare or orphan diseases. He says that he and his team have developed a way to computationally find matches between rare disease protein structures and functions and existing drug interactions that can help treat patients with some of these orphan diseases.
College of Science: Can you explain your research for us?
Misagh: We know that drugs have side effects, but where do these side effects come from? The small molecule that is in the drug can bind to different targets in the body, which are usually proteins. These proteins are involved in different processes in the body. One small molecule can meddle with one of those different processes. That’s the problem we call a side effect. On the other hand, it could also be a friend in disguise. It also means that the same small drug that can be used for treating a disease could also be used to treat another disease, if it can bind to a protein involved in that disease. Based on that theory, which is true, on average small molecules or drugs we already have can bind to as many as six different targets. That’s a lot. Even if out of the six, one is involved in a totally different disease than what it’s supposed to treat, it can maybe help with some side effects. Maybe some symptoms of another problem. It might not cure it, but it can help. That’s the basis of repurposing a drug from its actual disease to a new disease.
The most famous example of this theory is sildenafil (aka Viagra), which was originally meant for hypertension. In clinical trials, they realized there was something else happening. Serendipitously, they figured out that it could be used for another problem. Now Viagra is being used for erectile dysfunction as well as hypertension.
The question was can we guide this molecular binding process with a computer? That’s basically what we do. With computers, we bind those models of proteins and how these drugs bind to it and test it and come up with a prediction that this drug can bind to these off targets. These off targets would choose them specifically because they are involved in rare diseases. You have to look at it as not finding a cure or a 100% repurposed drug, but as a prediction of this might be one of the off targets that is worth exploring.
Misagh was a lead author on a recently published paper in the Journal of Molecular Biology discussing how he and his team used eRepo-ORP, a database of rare disease research, to fight against rare or orphan diseases. The “e” stands for everything created in their lab, the “Repo” stands for repositioned or repurposed, and the “ORP” stands for orphan diseases. It’s through this program that he and his team built on current FDA-approved drug information to suggest new implications for existing drugs. This database is open to the public through Open Science Framework at https://osf.io./qdjup/.
Computer generated models of repositioning proteins. Credit: Misagh Naderi.
College of Science: Can you explain how you use the eRepo-ORP database for your research?
Misagh: What we do is leverage large databases that are available online. But the information is not connected in a way that, for example, you have information about the drug. We know what it binds to, and we know the protein it’s supposed to be targeting. On the other hand, we have a large database of proteins that are involved in rare diseases. We build the connection between the two. This information on the drug is one-dimensional. It just tells you that it binds to its target. Where does it bind? If you have a protein that’s a 3-dimensional structure, this small molecule should bind a small cavity some place that prohibits the function of that machinery. We build that model on the computer. Not for one, but for all of the FDA-approved drugs and all of their targets.
College of Science: How many FDA-approved drugs are now in your database?
Misagh: We’re talking about in the couple of thousands, but when you look at a couple of thousand drugs and a couple of different targets for each, and then the comparison between all of the possibilities, then you’re adding up into the tens of thousands and hundreds of thousands of possibilities. When you have a few thousand drugs and a few thousand proteins, that creates a combination problem.
College of Science: Now that you’ve completed the database and the assessments on all of the computations, how many promising combinations did you find?
Misagh: That’s a very good question. Our part in this research is not recognizing which one is promising or not. Our part is to deliver (in this step) a new target for FDA-approved drugs that are involved in rare diseases. It’s a scientific approach to look at an actual protein and say if this is meaningful and if this is relevant biologically.
It’s a matchmaking game. We have 715 drugs that were repositioned on to 922 proteins from orphan diseases. The combination between the drugs and the proteins gave us about 31,000 pairings. In general, we have found a couple of good hits by going through the data. But there are case studies we have published in the latest paper that show some of the cases that we think are promising, so researchers in those fields can take them up and improve or test the drug.
College of Science: Why is this research important?
Misagh: Rare diseases affect a small population and therefore do not provide the financial incentive for the pharmaceutical industry to develop new drugs for these patients. Rational drug repositioning research plays a major role in developing low-cost drugs. I am very happy to say that our research has been successful in developing pipelines and strategies to address these diseases.
College of Science: What’s your advice for current and future LSU students?
Misagh: Find good mentors. Watch good talks. Read good books. In other words, be obsessed with improving yourself. Collaborate with others and give credit to those who work with you. Help others grow. Learn and relearn coding, biology, and biochemistry. Scientific research is 10% doing and 90% debugging, so learn to contemplate on what you have done and to edit continuously.