$13.5 million NIH grant awarded to MSU College of Osteopathic Medicine researcher


Prestigious grant funds four ground-breaking PVAT research projects

“This was on my bucket list as a professional. It’s really magic,” shares Stephanie Watts, Ph.D., a leading researcher at the College of Osteopathic Medicine in the field of vascular research.

Watts led an interdisciplinary team of researchers and professionals at MSU to pull together a successful NIH application in 2021—a feat that required over four years of intensive work. In December 2021, the team received the exciting notification of a five-year, $13.5 million program project grant award from the National Heart, Lung, and Blood Institute of the National Institutes of Health to study Perivascular Adipose Tissue (PVAT) as a central integrator of vascular health.

This grant will greatly expand the capacity of Watts’ team to build on work already underway.

The Program Project Grant (PPG) involves four projects that will explore different mechanisms of PVAT, a tissue essential to normal functioning of blood vessels. Each project will be led by a different Principal Investigator.

“The PPG centers different brains with different perspectives and techniques around the same work/question,” explains Watts.

Each of the following four projects will add to the growing body of knowledge around PVAT, potentially leading to therapeutic interventions and overall improvement of health:

Project 1: Mechanotransduction and stiffness

Led by Watts (COM) and Dr. Sara Roccabianca in mechanical engineering, this team will assess whether PVAT adds mechanical strength to the artery by helping to reduce stiffness. This could inform whether arteries get stiffer with disease because of or in spite of PVAT, and could lead to treatments to prevent stiffening.

Project 2: Nervous innervation and/or neurohumoral control

Led by Dr. Brian Gulbransen in the department of physiology and Bill Jackson in the department of pharmacology and toxicology (COM), this team will study whether PVAT is innervated by any branch of the nervous system.  This is disputed, and thus important to validate. The team will use cutting edge microscopic techniques to test this hypothesis.

Project 3: Microenvironmental influence on immune cell function

Led by Dr. Cheryl Rockwell along with Dr. Andres Contreras and Dr. Jamie Bernard (from the departments of pharmacology and toxicology as well as veterinary medicine), this team will study the collaborative community of immune cells in the PVAT. This special community of immune cells—including microphages, P-cells, T-cells, and others—changes prior to animals becoming hypertensive. If the team is able to identify the dysfunction before the disease sets in, they could create a therapeutic intervention.

Project 4: Adipogenic progenitor cell fate

Led by Dr. Andres Contreras, this team will study whether PVAT has a different stem cell progenitor cell—meaning that it can determine what cell it becomes based on what it’s exposed to. Exposed to pressure, PVAT may develop a more bone-like (less adipocyte-like), stiff substance, rather than a fat. The study will also look at differences in men and women, which can inform different hypertensive treatments and therapies.  The team also hopes to compare PVAT with non-PVAT fat experimentally to identify a PVAT-specific gene or cell that would allow for tissue-specific interventions.

Together, these four projects seek to understand the underappreciated functions of PVAT as an integrator of vascular health, to determine whether PVAT ameliorates or contributes to disease, to discover distinct PVAT elements, and to begin to design an integrative view of PVAT function in computer simulation.

Four cores will support the quality management of data as well, and include cores to support administrative work, animals, bioinformatics, and equipment (including specialized microscopes and the creation of new equipment if needed).  These are led by Dr. Adam Lauver (department of pharmacology and toxicology) and Dr. Gregory Fink (department of pharmacology and toxicology); Dr. Sudin Bhattacharya (BME, department of pharmacology and toxicology) and Dr. Rance Nault (department of biochemistry); and Dr. William Jackson (department of pharmacology and toxicology) and Nathan Tykocki (department of pharmacology and toxicology).  The whole PPG is supported by the In Vivo Facility headed by Teresa Krieger-Burke (department of pharmacology and toxicology) and the Transgenic and Genome Editing Facility led by Elena Demireva.  

“The synergy of these experts and their teams will push each other in exciting ways, and they’ll be able to accomplish more together. This project reflects the goal of the college to foster the linking of some of the best minds on campus,” says Dr. Andrea Amalfitano, dean of the College of Osteopathic Medicine. “I am extremely proud of all the researchers and staffers who poured their time, energy, and talents into this project, and look forward to seeing the results of their work.”

He continues, “Our recent initiation of the Dell Fellowship program—including Dr. Watts and her colleagues, who were inaugural awardees—will further expedite these types of research collaborations. Together, these efforts add to our college’s ranking as a top college of osteopathic medicine in terms of NIH funding, and is a testament to the collaborative approach of our faculty and their innovative thinking.”

“The science grows better when you have other people to help you think of new things in new ways,” observes Watts.

It’s also a huge opportunity for scientists and researchers in the early stages of their careers—the PPG brings together the lead researchers, as well as their teams of assistant and associate professors, post docs, graduate students, and undergraduate students. “We’ll have science meetings with 35 people to brainstorm ideas about therapies, data interpretations, and ways to do things differently,” she shares excitedly.

“Increasing program project grants and other significant center grants is a key metric outlined in the university’s strategic plan. To reach our aggressive goals, it will take the sustained drive of our outstanding faculty and leaders like Dr. Watts to collaborate and take advantage of these opportunities,” stated Doug Gage, vice president for research and innovation. Targeted collaborative research, bringing together the expertise of multiple investigators around a focused problem, is an important pathway to innovation in human health and well-being.”

Watts is confident that work from this collaborative research project will advance the field of medicine, and hopes the team will renew for an additional five-year grant down the road.