A research first for OUWB

Oakland University William Beaumont School of Medicine’s first wet lab has opened — a big step in furthering the school’s commitment to increasing its research endeavors.

Located in Oakland University’s Dodge Hall, the lab — valued at more than $450,000 — is led by Luca Cucullo, Ph.D., an OUWB professor primarily serving on a research track.

Cucullo joined OUWB in September, 2020. Along with 20-plus years of research experience, Cucullo brought a number of significant projects for which he serves as principal investigator.

The projects have been funded by the National Institutes of Health (NIH), and specifically by the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute of Drug Abuse, and the Food and Drug Administration.

With the exception of the basic infrastructure, the new lab has been set up with pieces of equipment Cucullo bought with NIH funding, and those acquired through startup funding.

It all serves as a big step in the evolution of OUWB.

“Once a medical school establishes itself with scholarly activity, wet labs are basically the next step,” says Cucullo. “You cannot move forward without that.”

Cucullo leads a of team of researchers already working on the funded projects with plans to take on even more new research.

“Having the lab is really good because we will be able to pursue so many different kinds of research questions that we have,” says Aditya Bhalerao, one of three graduate research assistants working in the lab.

“We are excited to use all of this technology that is available to us, and hopefully have some good scientific data that could help patients.”

Pushing boundaries

Ramin Homayouni, Ph.D., was hired as founding director of Population Health Informatics on Dec. 1, 2018. He was the school’s first faculty to primarily serve on a research track.

Cucullo was the second. When hired, Cucullo said he wanted OUWB “to be a medical school that pushes boundaries beyond what we currently know.” His background indicates he is well-suited to help lead those efforts.

Originally from Italy, he earned his doctoral degree in chemistry and pharmaceutical technology (biotechnology) from the University of Pisa, School of Pharmacy, in 2000.

He continued his education via post-doctoral training at the Cleveland Clinic Lerner College of Medicine in the Department of Neurosurgery/Cerebrovascular Research Center, where his specialty was in vitro cerebrovascular modeling with emphasis on CNS vascular pathophysiology.

After rising in the ranks at the Cleveland Clinic — and prior to OUWB — Cucullo spent nearly a decade at Texas Tech University. During his tenure as a faculty member at Texas Tech, he held the positions of associate professor and vice chair for Research in the Department of Pharmaceutical Sciences.

Concurrently, he built a strong research portfolio with a large portion focused on investigating the pathophysiology of tobacco smoke and e-cigarette toxicity at the neurovascular unit.

Among other things, Cucullo has led research efforts that have uncovered and exploited side mechanisms of action of well-established antidiabetic drugs (such as Metformin and Rosiglitazone) to promote nuclear erythroid-related factor 2 (Nrf2) activity to counteract oxidative stress-related cerebrovascular pathologies inherent to chronic smoking/vaping. Those research endeavors are supported by two of the NIH-funded projects where Cucullo is principal investigator (see infographic for more on the NIH-funded projects).

Along with new projects, Cucullo says his team will continue working on smoking-related research — including one study funded for about $2.9 million that extends to 2025.

The new lab

In addition to Bhalerao, Cucullo’s team of researchers consists of Salvatore Mancuso, Aditya Bhalerao, Farzane Sivandzade, and Snehal Raut, Ph.D.

Bhalerao, Raut, and Sivandzade followed Cucullo to OUWB from Texas Tech.

With the exception of Raut, the research assistants are graduate students from OU’s Department of Biological Sciences.

Cucullo says OUWB’s medical students are focused on learning the practice of medicine, which is the primary reason graduate students from other programs are recruited.

“Even if (medical students) wanted to they wouldn’t have enough time to spend in a lab,” says Cucullo.

For the last year, the team has been planning the logistics of the lab. For numerous reasons, including the impact of COVID-19, it wasn’t until this past summer that they were able to finally install equipment and begin working in their new space.

The lab consists of about 1,200 square feet split between two rooms that are now full of equipment that will allow the research team to further its work.

The equipment includes, among other things, a microfluidic system that allows the researchers to mimic blood vessels in the brain, as well as a cell imaging machine, a super high-powered fluorescent microscope, a 3D printer, a protein analysis machine, incubators, and a freezer. There also is a machine that allows for the researchers to study the effects of cigarette smoke and e-cigarette vapor in vivo using mice models.

To put the value of the advanced equipment in perspective, the cell imaging machine alone cost about $127,000.

More equipment is on the way, too, including a bioprinting platform enabling the design and creation of 3D cell multi-culture microfluidic constructs or organs-on-a chip for in-depth mechanistic study and drug discovery/testing applications.

“There are a lot of hypotheses that requires us to do trial-and-error,” says Raut. “These technologies…can save time and allow us to focus on the topics and problems that we are working on.”

The protein analysis machine, for example, allows the team to analyze proteins in about three hours compared with the Western Blot method that takes three days and can be more susceptible to human error.

Having these research tools at their disposal allows for the researchers to get involved in projects requiring fast and accurate analysis.

One example of how such computing power can be useful is a collaboration with Beaumont Hospital. Cucullo’s team of researchers is comparing proteins of patients who had COVID-19 and were or were not smokers.

“Before, this would have taken months to complete,” says Cucullo. “Now, it takes a few weeks. It speeds up the process a lot…and basically, there is no manual error involved.”

It’s those kinds of capabilities in his lab that have Cucullo often smiling these days.

“My job as a (principal investigator) is to make sure (the researchers) have everything they need,” says Cucullo. “I’m happy that I’ve been able to make that happen. Now, the real fun begins.”