IIT-Affiliated Faculty Part of Research Team Awarded $13.5 Million Program Project Grant from NIH

May 17, 2022

Several IIT-affiliated faculty have joined a team of MSU researchers on a recently awarded $13.5 million program project grant from NIH titled, “Perivascular Adipose Tissue (PVAT) as a Central Integrator of Vascular Health.” The Program Project Grant (PPG) involves four projects that will explore different mechanisms of PVAT, a tissue essential to normal functioning of blood vessels. The grant is led by Dr. Stephanie Watts from the College of Osteopathic Medicine. After four years of intensive work pulling together a successful NIH application, Watts and her interdisciplinary team were awarded the five year, $13.5 million program project grant (PPG) in December 2021 from the National Heart, Lung and Blood Institute of the National Institutes of Health.

“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 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 IIT-affiliated faculty member, Dr. Brian Gulbransen from the department of physiology and Bill Jackson in the department of pharmacology and toxicology, 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 IIT-affiliated faculty member, Dr. Cheryl Rockwell along with Dr. Andres Contreras and IIT-affiliated faculty member, 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); IIT-affiliated faculty members, 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.”

To read more about the PPG and to view the original article on the College of Osteopathic Medicine website, please visit: https://com.msu.edu/news_overview/news/2022/jan/135-million-nih-grant-awarded-msu-college-osteopathic-medicine-researcher