Q&A: PhD student Joseph Criscione receives American Heart Association Fellowship

Biomedical engineering PhD student Joseph Criscione was recently awarded a competitive predoctoral fellowship from the American Heart Association (AHA).  Criscione’s research focuses on developing cardiovascular models to study new treatments for heart disease.

The two-year, $65,000 fellowship enhances the research and clinical training of promising students seeking careers as scientists, physician-scientists, or clinician scientists interested in improving global cardiovascular, cerebrovascular, and brain health.

In this following Q&A, Criscione, who is advised by Deok-Ho Kim, shares his path to working on cardiac disease modeling, why he chose to come to Johns Hopkins, and how he hopes his research will eventually improve patient outcomes.

Can you tell us about your research?

My research is focused on engineering new models of heart disease and testing new therapies to treat it. More specifically, I work with in vitro engineered heart tissues to model and test gene therapies for Duchenne muscular dystrophy (DMD), a genetic disease that causes progressive muscle weakening in both skeletal and cardiac muscle. Patients are typically unable to walk by the time they are a teenager and pass away around the age of thirty; treatments can help manage the symptoms, but none reverse or cure it.

Animal models have long been the go-to preclinical models for testing new gene therapies, but they are poor predictors of which therapies will be effective in patients. To circumvent this issue, my research uses a technology referred to as engineered heart tissues (EHTs).

EHTs are strips of cardiac tissue just a few millimeters long that we fabricate in vitro using stem cell-derived heart cells. In our case, the stem cells we use were created using non-stem cells donated by DMD patients, so the tissues we create recapitulate many of the disease phenotypes DMD patients experience.The advantage is that EHTs are fabricated using human cells, allowing for faster and more efficient screening of new therapies.

What’s the high-level goal for your work?

One of the broader impacts of my work will be to demonstrate the feasibility of integrating organ-on-a-chip platforms into preclinical therapy testing pipelines. The goal is to use these platforms for higher throughput testing of novel therapies in a more efficient and predictive way of clinical trial outcomes. My research is part of one of the first projects aiming to determine whether these new platforms can deliver on these promises by testing new DMD gene therapies that are currently in clinical trials.

Once both our research and the clinical trials are complete, we will see how our results compare to those from clinical trials and those obtained from previous testing in mouse models. The goal is for our models to be better predictors of clinical trial results than the animal models, so that our models can be used to test future generations of therapies more effectively.

In addition to testing DMD gene therapies that are already in clinical trials, we are testing novel variations of these gene therapies, as well. We hope that the use of our models will allow us to more quickly and efficiently determine which variations will be most effective, so that patients ultimately have access to the best treatments possible.

What led you to focus on this problem?

I was interested in working on this project because I felt it would be a great balance between engineering and translational science. Much of my time has been dedicated to developing and characterizing our new model of DMD — and there were a lot of challenges and failures along the way, but it has been very satisfying to solve those problems as they arise. But now that the model has been developed, I get to put it to use testing new therapies and investigating the mechanisms by which those therapies help treat the disease. Working on a project where I use my engineering skills as well as make new discoveries that will help treat patients has been incredibly rewarding.

Why did you want to pursue your PhD at Johns Hopkins?

The main factor that led me to Johns Hopkins was a genuine excitement for the research I would get to do. As an undergraduate, the research I contributed to was more basic science oriented. While I enjoyed and valued that experience, I knew that for my PhD I wanted to pursue projects that were more focused on translational efforts. Johns Hopkins stood out as the best university to engage in such research given that there was a clear culture of close collaborations between scientists, engineers, and clinicians.

What has been your most memorable experience as a PhD student so far?

The most memorable experience so far was the first time I successfully fabricated EHTs. Quite a few different techniques and methods need to be mastered just to generate all the cells and materials required,before even getting to the point of fabricating the EHTs. There is always a lot of trial, error, and failure for new lab members working with this technology.

However, one of the few benefits of working with EHTs is that they naturally contract and beat on spontaneously. This means that after months of working through problem after problem, I got to come in and look under the microscope to see the tissues moving around and contracting on their own. It was very much an “It’s alive!” type moment that reminded me of why I find working on biological systems so exciting, making all the hard work up until that point worth it.

What do you see yourself doing next?  

While I am not yet certain of how my career will evolve, I am interested in exploring how I can translate my expertise into a career on the business side of science. Whether it be through a career working in biotech/biopharma startups, venture capital, or more entrepreneurial endeavors, I want to be able to help push the adoption of new technologies — such as organ-on-a-chip platforms — to make sure they reach their full potential outside of academia.