Miami CTSI

CTSI Spotlight: Lina Shehadeh, Ph.D.

12.20.2017

Lina Shehadeh, Ph.D., Assistant Professor of Medicine in the Division of Cardiology and an investigator in the Miller School’s Interdisciplinary Stem Cell Institute (ISCI) was recently awarded a four-year, $2 million RO1 grant from the National Heart, Lung and Blood Institute to study the role of Osteopontin in mitochondrial function in Heart Failure with Preserved Ejection Fraction (HFpEF) in cardiorenal syndrome.

Ten years ago, Lina was studying Complex Systems at Florida Atlantic University, using computational analysis to study biological data. Wanting to investigate problems outside of the digital space, Lina moved to the University of Miami Miller School of Medicine to do cardiovascular research on an

NIH post-doctoral grant applying mathematics to a wet lab environment.

She found her passion was in the lab where she felt her work had the most potential to impact the lives of patients.

In 2016, the Miami CTSI sponsored Lina and three other faculty to attend the Eureka Institute for Translational Medicine – a weeklong, intensive course that trains and mentors early-career investigators in translational medicine. The experience inspired and invigorated her as well as opened her eyes to understanding the true translational potential of her work.

Lina sat down with CTSI Communications Manager, Raquel Perez, to talk about her translational “aha” moment that set her on a path of success.

How has the CTSI support helped you in what you’re trying to accomplish?

The biggest advantage for me was getting support to attend the Eureka Certificate Program. I had been working on genes and RNAs, and I had filed for some patents. I always thought that I was doing translational research. In the course, I learned that most studies fail in clinical trials because investigators don’t validate their studies early on in human cell lines or large animal models. And it hit me, I am studying, for example, cholesterol reduction in mouse cells but never thought to validate this in a human liver cell line. It’s very easy to do such validation, but I never thought about it before because I was focused on the wrong things.

Everything clicked for me at Eureka. Their message made it through me very convincingly. I came away with an enthusiasm to spread the word because at the end of the day you want young investigators who are growing out of academia to start off on the right path. The more you expose the younger generation to this translational mission, the change will become easier and easier.

It sounds like you were able to come back and refocus. Then once you knew the right questions to ask others, it opened many doors.

I came back and I met with my lab members and I told them that we are going to make some major changes. We’re going to try and validate in human cell lines as much as possible; we’re going to try to do pig studies. Being at ISCI, am I lucky because I have so many resources. Dr. Joshua Hare, ISCI’s Director, and Dr. Ivonne Schulman, who works in the pig model, were happy to collaborate and help.

And not only at UM, but I also reached out to Dr. David Alan Kass at Johns Hopkins, who is an expert in clinical heart failure with preserved ejection fraction (HFpEF) – that’s the model I am studying. He’s been funded and has been collecting samples from human patients for years. When I told him that I was trying to validate my findings, he asked what genes I wanted to look for and his team screened their human samples for my genes. That gave me a good push. My grant became stronger because of all this.

Talk about the importance of finding good mentors.

It’s crucial. Mentors can really facilitate the process for you. Everyone is busy at the end of the day, and so you really have to be self-driven and pick your mentors. By that I mean, find the senior person who can help you even a tiny bit in his/her own way.

For example, I am in a very rich environment here at UM Miller School of Medicine. Both Dr. Hare and Dr. Keith Webster, Director of the Vascular Biology Institute, have been mentors on two main transition grants that I had (KO1 from the NIH and the Florida Biomedical Grant). Both of them have different expertise. Dr. Webster would give me advice on my science and the mechanics of my writing. Dr. Hare helps me with the big picture, making sure I always maintain my translational focus. It is also important to look for mentors outside of your institution. That is why I went and met with Dr. Kass at Johns Hopkins.

You mentioned you have a bioinformatics background – how does this inform your research?

It has been advantageous. It has helped me pick the molecules that I wanted to invest in. Whether it is a micro RNA or gene, it all started from masses of data sets – comparing different diseases or the same disease in the mice versus humans. For example, I have mouse and human data sets on heart failure and cellular data set on stressed cardiac cells, and I can see what’s common, and I focus on those genes.

It can be very hard to pick your target. There are tens of thousands of genes that you can pick from and each gene you alter changes the phenotype. But you want to know which one is the right one to manipulate, meaning which one is druggable, and develop further.

What is the future? Where do you see your research going?

So we now developed a potential therapeutic – a monoclonal antibody that can block Osteopontin in the blood. What is interesting about this molecule/Osteopontin is that it’s been proven in many studies to be pro-disease and therefore when you block it, you can reduce the severity of cardiovascular disease (like we’ve shown), kidney disease, cardiorenal disease, cancer and neurological diseases. So there’s a lot of evidence in mouse models that blocking Osteopontin is therapeutic, but there has been very little attempt to make this work in humans.

I formed a start-up company, filed a patent to treat cardio renal syndrome by blocking this molecule (Osteopontin) and am applying for an STTR (Small Business Technology Transfer) grant. This is where we are at now. We are trying to get the funding to do those experiments. It’s only the beginning, but it is super exciting, and it is what gets me out of bed early in the morning!

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