Healthy individuals have a remarkable inherent ability to heal after injury. Wound healing involves complex and coordinated actions of dozens of cell populations and hundreds of their molecular products. They collectively act across three distinct and partially overlapping healing phases: inflammation, proliferation and resolution. Critical spatial and temporal processes occur during in each phase of repair, and they result in the restoration of tissue homeostasis. These same healing processes become optimized in oral tissues and dysregulated in chronic diseases, especially in chronic wounds and tumors. In fact, cancer encapsulates the entire wound healing process run amok, and it has been described as a “wound that fails to heal”.
In healthy tissues like skin and oral mucosa, epithelial cells maintain a barrier against the outside world. In the underlying stromal layer, resident cells like fibroblasts maintain a stable microenvironment composed of extra-cellular matrix (ECM) components, including collagen and elastin, that collectively imbue tissues with their unique mechanical properties. Blood vessels help to maintain the environment by supplying the tissue with stable supplies of oxygen. This stable state that defines tissue health is therefore actively maintained by cells in a fine-tuned balancing act called homeostasis.
When the tissue barrier is broken during injury, epithelial cells become activated and release signals into the immediate microenvironment in the form of cytokines and growth factors. These signals in turn recruit and activate immune cells to initiate inflammation, a critical yet self-limiting first phase of healing. The signals stimulate nearby blood vessels to sprout in a process called angiogenesis. Fibroblasts also become activated to produce ECM components in order to recapitulate the damaged connective tissue. These processes naturally resolve as the tissue is repaired and eventually returns to homeostasis.
When epithelial cells mutate into cancer cells, they become chronically activated, proliferate uncontrollably and release excessive amounts of cytokines and growth factors into their immediate tumor microenvironment. These signals in turn hyper-activate immune cells and cause long lasting, chronic inflammation. The signals stimulate blood vessels to continually sprout into an aberrant and leaky vasculature that feeds the growing tumor. Fibroblasts also hyper-activate into cancer-associated fibroblasts, producing excessive amounts of ECM components that lead to localized fibrosis and tissue stiffness.
We leverage powerful new technologies, such as single-cell and spatial transcriptomics, with high-content microscopy and comparative bioinformatics approaches to study complex systems such as wounds and tumors at multiple levels: from cell to tissue. Such tools allow us to more fully appreciate the symphony of coordination between hundreds of cells and thousands molecules in healing tissues. Comparative bioinformatics allow us to learn from the optimized healing response and identify healing pathways that become dysregulated in diabetes and cancer, to more effectively diagnose dysregulated wounds, to better predict disease severity, and even to combat cancer with novel drugs that target these dysregulated healing pathways. Finally, we use cell and animal models of normal, optimized and dysregulated healing and traditional molecular biology methods to validate our discoveries in vitro and in vivo, pushing our findings forward in the translational pathway from bench to clinic.
Science is a team sport, and it only works as intended when scientists from across disciplines work together and support one another.
Our growing list of international collaborators include:
Dr. Olga Baker (Department of Otolaryngology, School of Medicine, University of Missouri)
Dr. Swathi Balaji (Division of Pediatric Surgery, Baylor College of Medicine, USA)
Dr. Lin Chen (Department of Periodontics, UIC College of Dentistry, USA)
Dr. Luisa DiPietro (Department of Periodontics, UIC College of Dentistry, USA)
Dr. Maxim Frolov (Department of Biochemistry and Molecular Genetics, UIC College of Medicine, USA)
Dr. Paul Hiebert (Faculty of Health Sciences, Hull York Medical School, University of Hull, UK)
Dr. Timothy Koh (Department of Kinesiology, UIC College of Applied Health Sciences, USA)
Dr. Mark Lingen (Department of Pathology, The University of Chicago, USA)
Dr. Christina Nicholas (Department of Orthodontics, UIC College of Dentistry, USA)
Dr. David Reed (Department of Oral Biology, UIC College of Dentistry, USA)
Dr. Mariana Reis-Havlat (Department of Periodontics, UIC College of Dentistry, USA)
Dr. Ameen Salahudeen (Department of Internal Medicine, UIC College of Medicine, USA)
Dr. Sabine Werner (Department of Biology, ETH Zurich, Switzerland)
The research being performed at the Wietecha Lab is funded by: