Discovery May Help Identify Potential Brain Aneurysms

The discovery, which represents a portion of his doctoral dissertation, is important because when brain aneurysms rupture, the consequences are usually death or severe disability. However, most people with aneurysms show no symptoms until the aneurysm ruptures.

In the study, neutrophils, a form of white blood cell, were collected from patients undergoing brain imaging, and a complete map of all the genes expressed by the neutrophils was made for each patient. The maps from patients who had aneurysms (as indicated by the brain imaging) were compared to maps from patients without aneurysms. 

Among the thousands of genes that were expressed, 258 genes were different in patients with aneurysms versus those without, and from these 258, a subset of 82 of the most different genes could be used to separate the two groups in a new set of blood samples from patients with and without aneurysms.

Tutino’s co-advisers for his graduate study work were Hui Meng, PhD, professor of mechanical and aerospace engineering, and John Kolega, PhD, associate professor of pathology and anatomical sciences. Meng holds secondary appointments in the departments of Biomedical Engineering and Neurosurgery.

In his early graduate work, Tutino started research on the anatomy of the circle of Willis (the primary blood vessels of the brain) and how vascular pathologies/abnormalities such as carotid occlusion/ligation change the distribution of blood flow and the vascular architecture.

At that time, Kolega and Meng were among the investigators on a National Institutes of Health grant for studying how certain forces exerted by blood flowing against artery walls can cause the artery to remodel and form an aneurysm. 

Tutino joined the group to study this process in rabbits and rats in order to understand the fundamental biological mechanisms of aneurysm formation. This work ended up comprising his master’s degree. 

The Department of Pathology and Anatomical Sciences contributed heavily to the cell biology and histology elements of Tutino’s training during this period.

Technical staff in the department’s histopathology lab provided histology services and taught some of the methodology of tissue processing and staining. Faculty advised on interpretation of pathology in the animal tissues. 

Tutino, who is currently a research assistant professor in the departments of Neurosurgery and Biomedical Engineering, published three peer-reviewed papers on the work.

For his doctoral work, Tutino began a new project, which he says was inspired by a neighbor in the Gates Vascular Institute (GVI), James N. Jarvis, MD, clinical professor of pediatrics, whose lab studies circulating signatures of immune diseases in children.

“The hypothesis for my study was that because brain aneurysms involve inflammation-driven degradation of the vessel wall, circulating immune cells (namely neutrophils) may be different in patients with aneurysms,” Tutino says.

“To pursue this, my principal investigators and I wrote an Institutional Review Board protocol to start collecting blood samples from patients receiving imaging at the GVI, and we submitted a grant to the Brain Aneurysm Foundation (BAF),” he adds.

Tutino received a Carol W. Harvey Memorial Chair of Research Grant from the BAF, named for a Buffalo woman who died in 2002 from ruptured aneurysms. That led the researchers toward meeting her husband, Jeff Harvey, a local entrepreneur who has been donating to the BAF for many years.

“As research progressed, we filed provisional patents on our intellectual property. Jeff encouraged us to start a small company so that we could begin working to transform this into a diagnostic to identify individuals with unruptured brain aneurysms,” Tutino says.

Harvey, as chief financial officer, launched Neurovascular Diagnostics in 2016 with Meng as the company’s chief scientific officer and Tutino as company president and CEO. Currently, Neurovascular Diagnostics is based in the UB Biosciences Incubator at the Clinical and Translational Science Institute.

“The test we’re developing is important because the way you determine if you have an unruptured brain aneurysm today is to have an MRA,” Harvey says. “An MRA is expensive, and insurance companies may not pay for it because these patients often do not have any symptoms.”

Neurovascular Diagnostics is partnering with DxTerity, a Los Angeles-based genomics company, to design further studies and develop a from-home blood test that can detect these variations.

A Phase I Small Business Innovation Research award from the National Science Foundation will help advance the research.

Tutino’s work exemplifies interdisciplinary graduate study at UB, as the final product ultimately engaged faculty representing seven departments from the Jacobs School of Medicine and Biomedical Sciences and the School of Engineering and Applied Sciences. 

Along with Kolega and Meng, the following Jacobs School faculty members were co-authors on the paper:

Jarvis and Yijun Sun, PhD, associate professor of microbiology and immunology, were essential advisers on Tutino’s thesis committee.

Adnan Siddiqui, MD, PhD, vice chair and professor of neurosurgery; Kenneth V. Snyder, MD, PhD, assistant professor of neurosurgery, radiology and neurology; and Elad I. Levy, MD, L. Nelson Hopkins III, MD, Professor and Chair of neurosurgery and professor of radiology; provided crucial clinical expertise and resources.

Other co-authors from the Jacobs School were:

• Kerry E. Poppenberg, doctoral student in biomedical engineering
• Kaiyu Jiang, research scientist in Department of Pediatrics 
• Ashish Sonig, MD, neurosurgery medical resident