About the PPG - pvatppgmsu.com

Overview

Vascular health is essential to the normal regulation of cardiovascular function. The fact that dysfunctions of blood pressure regulation, such as hypertension, remain difficult to treat suggests that the scientific community does not fully understand the mechanisms by which normal and pathological changes in blood pressure are achieved, nor how the vasculature can both influence and be impacted by changes in blood pressure.

This new Program Project Grant is based on the overall hypothesis that perivascular adipose tissue (PVAT) has bidirectional interactions with the other layers of a blood vessel and is a critical partner with these layers to form an integrated system that maintains vascular health.

Mission

Our mission is to use the PPG mechanism and take a comprehensive, diverse approach to the questions at hand. We have four projects (figure below), supported by four cores.

Our collective preliminary work has led to the hypothesis that PVAT and its primary components – the adipocyte and progenitor cells, the immune cells, and neuronal innervation/neurohumoral control —are central integrators of overall vascular health/function. Investigators are deeply invested in the planning of, execution of and learning from experiments carried out in projects and cores other than theirs; this work was developed in this way to be purposefully synergistic.

This integrated work advances human health by redefining the functional vessel, a redefinition that could have significant impact on not only hypertension but all physiologies and dysfunctions which involve the vasculature.

Project I) PVAT possesses the ability to mechanotransduce and has significant stiffness that contributes to vascular stiffness.

Project II) PVAT is innervated or under neurohumoral control with functional consequence.

Project III) whether the unique microenvironment of PVAT influences immune cell function;

Project IV) how the fate of adipocyte progenitors is influenced by vascular stretch.

Stephanie Watts

Full Professor, Dept of Pharmacology and Toxicology
Director of the PPG, Project I Leader, Core A Leader

Director of Project I. Stephanie’s contribution is to bring the smaller and seemingly disparate pieces of information into a larger, integrated picture. She also helps us stay connected to the other projects of this PPG effort, helping to feed information to and from such that the science of all projects informs that of the others.

Andres Contreras

Associate Professor, ESI; Dept of Large Animal and Clinical Sciences
Project IV Leader

Director of Project IV that seeks to determine how high blood pressure driven vascular mechanical forces and structural cues alter the capacity of perivascular adipose tissue (PVAT) to exert its vasoactive functions and direct preadipocyte and adipocyte phenotypes. Dr. Contreras is a DVM with background on adipose tissue biology and will supervise the team of research assoaciates and graduate students that will develop project IV. His duties include designing experiments, mentoring students and associates, data analysis, and manuscript drafting.

Sara Roccabianca

Associate Professor, Dept of Mechanical Engineering
Project I Co-Leader, Project IV Collaborator

Sara is the head engineer of this project (!) and provides the knowledge needed to think about PVAT as a tissue that should be considered mechanically. She was and is essential to thinking about PVAT in this novel way.

William F. Jackson

Professor of Pharmacology and Toxicology
Core D Leader, Project II Collaborator

Dr. Jackson is an expert in the optical imaging of cells amd tissues and will assist Project Leaders and other team members in the design and analysis of imaging experiments involving PVAT and blood vessels. He will also collaborate with Dr. Gulbransen and team members in Project II in imaging and quantifying PVAT innervation.

Jamie Bernard

Associate Professor, Dept of Pharmacology and Toxicology
Project III Collaborator, Project IV Collaborator

Jamie is our resident expert in adipose biology. She also has a particular interest in immune cells, which makes her a valuable team member for Project III. She provides consultation on experimental design and approach. She and the members of her laboratory also train students and postdocs on how to make conditioned media from PVAT for in vitro studies.

Cheryl Rockwell

Associate Professor, Dept of Pharmacology & Toxicology.
Acting Director, Applied Immunology Center for Education and Research

Director of Project III. As the leader of Project III, Cheryl is responsible for the overall research direction and progress of the project. She works with the other team members to conceptualize the experiments and interpret the data to try to gain a greater understanding of how immune cells function within the physiology of PVAT. She also assists with writing the manuscripts that result from this research.

Adam Lauver

Assistant Professor, Dept of Pharmacology and Toxicology
Core B Leader

Leader of the Animal Core. Dr. Lauver is responsible for the overall supervision of animal purchase, housing, maintenance and health assessments. He coordinates the multiple uses of individual animals, and tissue derived from individual animals, among Program investigators. He assists other Program investigators with the development of new animal models or in vivo methods to facilitate their research goals.

Gregory Fink

Full Professor, Dept of Pharmacology and Toxicology
Core B Co-Leader

Co-Leader of the Animal Core. Dr. Fink has extensive expertise with animal models of hypertension and related cardiovascular complications. He consults with Dr. Lauver and Core members on a regular basis concerning refinement, characterization and quality control of the animal models used by all investigators in the Program.

Elena Demireva

Director, Transgenic and Genome Editing Facility
Core B Member

Dr. Demireva heads the Molecular Services Program at the MSU Transgenic and Genome Editing Facility. She oversees the creation and procurement of all transgenic animal lines used by the Program and coordinate the use of common genetic models across different projects. Her expertise in genome editing, molecular biology and rodent genetics will be available to Project PIs and she will advise on the selection, validation and design of transgenic animal model experiments.

Sudin Bhattacharya

Assistant Professor, Depts of Biomedical Engineering, Pharmacology and Toxicology
Core C Leader

Dr. Sudin Bhattacharya will lead Core C and coordinate the effort in integrating computational modeling with analysis of high-throughput sequencing experiments and computational training. He has a background in various types of systems biology and bioinformatic modeling, including ordinary differential equation-based kinetic models, mapping transcriptional regulatory networks from functional genomics data, and multiscale “virtual tissue” modeling.

Rance Nault

Assistant Professor, Dept of Biochemistry
Core C Co-Leader

Dr. Rance Nault, co-lead of Core C, has over a decade of experience in carrying out high-throughput functional genomics experiments from study design to data generation including both bulk and single-cell RNA-Seq. He also has a strong background in computational analysis of RNA-Seq data, and will support Dr. Bhattacharya as co-Investigator of Core C. Dr. Nault will also aid in providing computational training to PPG trainees and PIs as part of Core C.

Nathan R. Tykocki

Assistant Professor of Pharmacology and Toxicology
Core D Co-Leader

Dr. Tykocki is an expert in the design and construction of devices to control and measure tissue biomechanics and vascular function. He operates the PPG’s 3-D Printer and Device Fabrication Core, which is part of Core D. He also is experienced in imaging living tissue and will assist Dr. Jackson in managing Core D.

A strength of this PPG team is our ability to investigate hypotheses in a granular way individually, but then integrate our individual/collaborative findings into a whole picture of PVAT function in health and disease.

We test our hypotheses from the single cell level to a collection of cells, to an isolated tissue, to a collection of tissues and to the whole animal, with many complementary approaches used. The investigators and their laboratories exemplify the intention of a Program Project by bringing individuals together with significantly different expertise - both disciplinary and experimental - that improves the work and facileness of their collaborators.

Each individual possesses a knowledge and a skill that can inform and help the science of the others; we can achieve things together that we could not achieve apart. There are particular questions that are best answered by such a joint effort. It is through our discussions of over four years that we arrived at the ideas you see on this website. Each project has explicit, experimental and analytical interactions with other cores and projects. Synergy extends in every direction.