Research

The Griffiths lab focuses on defining and overcoming transplant barriers for people with cardiovascular conditions. Our work includes human-to-human transplantation, known as allogeneic transplantation, and animal-to-human transplantation, known as xenogeneic transplantation.

Grant-funded work has covered the entire spectrum of research projects since our lab was launched in 2009. Our lab has received funding from the California Institute for Regenerative Medicine, Regenerative Medicine Minnesota, American Heart Association, Howard Hughes Medical Institute, Mendez National Institute of Transplantation Foundation and National Institutes of Health.

Approaches to tissue engineering

All tissues and organs are composed of the same basic structures: cells; the supporting substance between cells, which is called the extracellular matrix; and signaling molecules.

We're working to combine these essential components to generate functional replacement tissues and organs. Several tissue engineering approaches are under intense investigation.

Our team has developed novel technologies for high-throughput immunoproteomic identification of HLA, non-HLA and nonprotein (for example, carbohydrate) antigens responsible for recipient graft-specific immune responses. For antigens that are commonly associated with rejection, we conduct epitope mapping studies to define the exact portion of the molecule that the immune system recognizes. Epitope mapping allows us to capture epitope-specific antibodies responsible for rejection and perform mechanistic studies in cultured cells to probe such mechanisms.

This work furthers the basic understanding of the molecular initiators and modulators of transplant rejection by:

  • Facilitating development of biomarker panels to guide individualized medicine in transplant recipients.
  • Informing the design criteria for development of immunologically acceptable xenogeneic extracellular matrix scaffolds for cardiovascular regenerative medicine and tissue engineering applications.

Host immune response challenges

Our work on regenerative medicine and tissue engineering focuses on an animal-derived extracellular matrix (ECM) as a scaffold into which human cells and signaling molecules can be placed to form the desired tissue or organ. Animal tissue is widely available and provides an ECM that is identical to that of the desired tissue type.

However, the critical impediment to use of an animal-derived ECM is that such material contains molecules called antigens that stimulate an aggressive destructive recipient immune response when implanted.

Research objectives

With these challenges in mind, our lab has four main research objectives:

  • Identify and understand the antigenic components of allogeneic and xenogeneic tissues and organs that stimulate a destructive immune rejection response upon implantation.
  • Use principles of protein chemistry and cell biology to achieve removal of these antigenic components while leaving the remaining ECM unchanged.
  • Investigate the interaction between cells and ECM scaffolds to achieve the goal of in vitro generation of tissue-engineered tissues and organs.
  • Form immunologically acceptable ECM scaffold-based tissues and organs for clinical application.

We have pioneered a new paradigm in the production of immunologically acceptable animal-derived ECM scaffolds with preserved ECM structure-function relationships and recellularization capacity.

Through application of our antigen-removal paradigm, we aim to overcome obstacles to using xenogeneic scaffolds in tissue engineering applications. Our research could ultimately help lead to durable, lifelong cures for cardiovascular conditions.

Collaborators

To help advance scientific discovery and improve patient care, our lab collaborates with investigators at Mayo Clinic and other institutions.

Mayo Clinic collaborators

Our current Mayo Clinic collaborating researchers include:

External collaborators

Our current external collaborating researchers include:

Kyriacos Athanasiou, Ph.M., Ph.D.
Samueli School of Engineering
University of California, Irvine
Irvine, California

Ian Dixon, Ph.D.
Max Rady College of Medicine
University of Manitoba
Winnipeg, Manitoba, Canada

Maelene Wong, Ph.D.
ViVita Technologies
Davis, California

Hyunwoo Yuk, Ph.D.
SanaHeal
Somerville, Massachusetts

Xuanhe Zhao, Ph.D.
Department of Mechanical Engineering
Massachusetts Institute of Technology
Cambridge, Massachusetts