NIH grant renewal supports Fischbein Lab with research opportunities in aortic aneurysm development

by Roxanna Van Norman
August 4, 2022

Michael Fischbein, MD, PhD, Associate Professor in the Stanford Department of Cardiothoracic Surgery, recently received a four-year grant renewal from NIH National Heart, Lung, and Blood Institute to study aortic aneurysm development in patients with Marfan syndrome and other genetic connective tissue disorders.

"It's a tremendous honor to receive this grant, and it provides our lab the support needed to continue investigating the pathophysiology of aortic aneurysm formation," said Fischbein, Director of the Thoracic Aortic Research Laboratory at the Stanford School of Medicine. “Obtaining an NIH renewal grant is confirmation and recognition by our peers that our work is meaningful and, hopefully, will ultimately benefit patients."

With the grant renewal from NIH, Fischbein's lab will continue to advance their understanding of why aortic aneurysms form in patients with connective tissue disorders. They will also explore novel, high-risk ideas for addressing aortic aneurysm development and therapeutics to improve patient health.

The project will build upon the initial NIH grant work, which looked at how thoracic aortic embryologic origin influences localized aortic root aneurysm development noted in Marfan syndrome. The renewed funding for the current project will span from 2022 to 2026.

Thoracic aortic research

Fischbein is a cardiothoracic surgeon at Stanford Medicine, specializing in aortic diseases, as well as the full spectrum of cardiothoracic conditions and treatment approaches. He is the Director of Thoracic Aortic Surgery and a member of the Stanford Center for Marfan Syndrome and Related Aortic Disorders, a collaborative center for treating aortic diseases at Stanford Health Care. 

Dr. Michael Fischbein

Proto credit: Steve Fisch

"People have tried various medical therapies [for treating aortic diseases], but in general, they have been unsuccessful. Currently, the only treatment option that has prolonged life expectancy in these individuals is an invasive open operation," said Fischbein. In addition, he explained there is no perfect test indicating when to operate on a specific individual (a precision medicine approach). Surgeons are limited to operating on the patient based on the aortic aneurysm size alone noted on imaging.

Fischbein’s lab is looking at the potential for applying a multi-omics approach for a more comprehensive understanding of molecular changes in aortic aneurysm development. For example, his research team collected blood samples from patients with aneurysms and will analyze them for specific biomarkers that may predict aneurysm severity.

"We're shifting from the prior grant to this new one where we're using human induced pluripotent stem cell-derived smooth muscle cells to create a disease in the dish [in vitro model of Marfan Syndrome]," said Alex Dalal, MD, a postdoctoral research fellow in Fischbein's lab. Dalal is excited about future studies that will come along with the grant, including looking at the master regulatory genes to see if they can reduce or inhibit aneurysm development. 

Another component of the project will be using different modalities. The lab utilizes multiple models, including in vivo mouse models, human surgical specimens, and in vitro cell culture.

"Having different ways to study, block, or disrupt the pathways in the disease allows us to try things in multiple ways," said Albert James (AJ) Pedroza, MD, another postdoctoral research fellow in Fischbein's lab. The project provides the opportunity for exploring different models in the lab, with the goal of connecting them back to the animal models and ultimately in human patients.

"This will help us determine the best way to develop novel therapies in the future," said Pedroza.

Michael Fischbein, MD, PhD

Future surgeon scientists

Fischbein is the Residency Program Director of the Traditional and Integrated Cardiothoracic Surgery Program, a program he co-founded in 2008 as the nation's first formal integrated eight-year (six years clinical and two years research) cardiothoracic surgery residency in the United States. Since then, 15 residents have completed the program and pursued various clinical and academic endeavors. 

Dalal is among one of the cohorts in the Integrated Cardiothoracic Surgery Program and has been a member of Fischbein's lab since 2011. He came to Fischbein during his undergraduate study at Stanford looking for lab experience and research opportunities and found a lasting mentorship.

"Dr. Fischbein was unbelievably supportive and has been an amazing mentor to me," said Dalal, who received his medical training at Drexel University College of Medicine.

Pedroza, another resident of the Integrated Cardiothoracic Surgery Program in his sixth year, joined Fischbein's lab in 2012. To him, the experience of working in Fischbein's lab has been meaningful to aspiring academic surgeons like himself.

"We are learning to be good scientists in parallel with our clinical surgical training," said Pedroza, who completed his medical training at Stanford. "We've been fortunate to have Dr. Fischbein as a mentor for a long time." 

Fischbein maintains a full schedule dedicated to clinical care, research activities, and programmatic duties, and is fully committed to mentoring future surgeon scientists and making himself available to residents and students. He was instrumental in helping Dalal and Pedroza each separately get an NIH Postdoctoral Fellowship.

"It feels good to come full circle that we were able to contribute to Dr. Fischbein's R01 grant successfully and sort of pay it forward since he supported us so much," said Pedroza.

Thinking bigger, broader 

While still preliminary, Fischbein looks forward to the potential for personalized medicine that could help detect specific cases of aortic aneurysms and the opportunity to collaborate with other labs across campus.

"The great thing about Stanford is it is an extremely collaborative environment," Fischbein said. "When bringing together PIs and incredibly bright postdocs, innovative ideas are created to make great discoveries."

In the future, the team hopes the foundational work using animal and stem cell models will provide targetable pathways for novel treatments of aortic disease, including the repurposing of currently approved drugs or the application of gene-editing technology.

"Trying to think bigger and broader ideas keeps me inspired, and that's why I like Fischbein's lab," said Dalal.

Alex Dalal, MD

Albert James (AJ) Pedroza, MD