Mechanical Regulation of Immune Cells in Myelofibrotic Niches
Speaker:
Kyle Vining, DDS, PhD
Assistant Professor of Preventive and Restorative Sciences
School of Dental Medicine, and Materials Science, and Engineering,
School of Engineering and Applied Science, University of Pennsylvania
Abstract:
Fibrotic diseases such as myelofibrosis fundamentally change the physical environment of tissues, with profound effects on immune function. A central feature of these changes is not only increased stiffness of the extracellular matrix (ECM), but also altered viscoelasticity, which is the way tissues dissipate or retain stress over time. These mechanical cues act as regulators of immune cell behavior. In particular, recent work has identified a “mechanical checkpoint” controlling the fate of monocytes, which can differentiate into either immune-suppressive or antigen-presenting cells. In fibrotic, solid-like environments, monocytes adopt pro-inflammatory fates that exacerbate disease, whereas in more fluid-like environments, they support resolution and regeneration. By modeling these environments with engineered ECMs, it becomes possible to dissect the interplay between mechanics, inflammation, and cell differentiation. This line of research has revealed new therapeutic strategies, such as targeting PI3K-gamma signaling to redirect monocyte fate in fibrotic niches. Beyond hematologic disorders, these concepts extend to solid tumors such as head and neck squamous cell carcinoma, where a rigid stroma contributes to immune evasion. Collectively, these studies demonstrate how engineering approaches to mimic and manipulate tissue mechanics can uncover fundamental disease mechanisms and open new avenues for immunotherapy and regenerative medicine.
Dr. Kyle Vining earned his B.S. in Biomedical Engineering from Northwestern University in 2009 and subsequently completed his Doctor of Dental Surgery (DDS) degree at the University of Minnesota in 2014. During dental school, he was selected for the prestigious NIH Medical Research Scholars Program, where he conducted research at the National Institutes of Health from 2012 to 2013. He then pursued doctoral studies at Harvard University, earning his Ph.D. in Bioengineering in 2020 in the laboratory of David Mooney, where he investigated how the mechanical properties of tissues regulate cell behavior. While at Harvard, he also served as a teaching fellow in biomaterials. Following his PhD, Dr. Vining undertook postdoctoral training in medical oncology at the Dana-Farber Cancer Institute in Boston, supported by a highly competitive NIH K99/R00 Pathway to Independence Award. This work expanded his focus into the role of tissue mechanics in cancer and fibrosis. In 2021, he joined the University of Pennsylvania as an Assistant Professor. His academic career has been recognized through multiple NIH awards, reflecting his dual expertise in engineering and clinical science.
