Dr. Maggie Freeberg received a B.S degree in Biomedical Engineering from the University of Minnesota in 2011. In 2018, she obtained her PhD in Biomedical Engineering from the University of Rochester, working under the mentorship of Dr. Hani Awad. She completed her post-doctoral research training with Dr. Patricia Sime in the Department of Internal Medicine at Virginia Commonwealth University.
She is a recipient of both the Parker B. Francis fellow and a NIH K99/R00 Pathway to Independence Award. Dr. Freeberg recently joined the faculty at VCU as an Assistant Professor in the Departments of Internal Medicine and Biomedical Engineering. Her research centers on development of novel anti-fibrotic therapies with a particular focus on the mechanobiology and metabolic reprogramming present in lung fibrosis.
Education
University of Rochester
PhD
Biomedical Engineering
2018
NIH T32 Pre-doctoral fellowship training in orthopaedic research
University of Rochester
MS
Biomedical Engineering
2014
University of Minnesota
BS
Biomedical Engineering
2011
Affiliations
American Thoracic Society
Media Appearances
PFF Celebrating 25 years of progress
Pulmonary Fibrosis Foundation online
For 25 years, the Pulmonary Fibrosis Foundation has led the way in support, research, and education for those living with pulmonary fibrosis and interstitial lung disease. Thanks to dedicated patients, caregivers, researchers, and supporters, we've seen incredible advances in science, increased awareness, and a growing number of clinical trials bringing us closer to new treatments - and ultimately, a cure. But this milestone is about more than research. It's about connection, hope, and a shared commitment to improving lives. As we look to the future, our determination has never been stronger. We won't stop until we find a cure.
Press Release - Study Identifies Novel Pathway with Potential to Slow the Progression of Pulmonary Fibrosis
Elsevier print
2025-03-25
Researchers have found a potential new way to slow the progression of lung fibrosis and other fibrotic diseases by inhibiting the expression or function of Piezo2, a receptor that senses mechanical forces in tissues including stress, strain, and stiffness. The new study in The American Journal of Pathology, published by Elsevier, sheds light on the underlying mechanisms of pulmonary fibrotic diseases and identifies potential new targets and options for therapy to improve patients’ outcomes.
Through a multidisciplinary approach involving the VCU School of Pharmacy, Dr. Freeberg is working to create a therapy that targets Piezo2 by blocking its ability to worsen the fibrosis. “We have limited therapeutic options, and they’re not great for patients,” Dr. Freeberg said, adding that those with the most severe fibrosis cases often have no alternative but transplants. “Where my project threads the needle is by taking what we already know about the disease and what the drugs currently do, then taking a little bit out of the cancer playbook by testing combinatorial therapies,” Dr. Freeberg said. “These are complex conditions where multiple things are going wrong, so a target drug is probably not going to be sufficient.” “We’re working hard to think deeply about these problems, and part of that is thinking about them from the whole perspective of the patient,” she said. “We have a really strong team — I’m just one piece of the puzzle.”
Targeting Mechano-sensors and altered metabolism in lung fibrosis
PFF Scholars Program
2021 - 2023
Piezo2 as a novel mechanosensor in the pathogenesis of fibrosis
Parker B Francis Fellowship
2024 - 2027
Mechanotransduction regulation of cellular metabolism in pulmonary fibrosis
(PI) NIH NHLBI R00HL169903
2025 - 2028
Selected Articles
Transglutaminase 2 knockout mice are protected from bleomycin-induced lung fibrosis with preserved lung function and reduced metabolic derangements
Physiological Reports
Margaret AT Freeberg, Thomas H Thatcher, Sarah V Camus, Linghong Huang, John Atkinson, Wade Narrow, Jeannie Haak, Andrew M Dylag, L Ashley Cowart, Timothy S Johnson, Patricia J Sime
2024-06-03
Pulmonary fibrosis is an interstitial scarring disease of the lung characterized by poor prognosis and limited treatment options. Tissue transglutaminase 2 (TG2) is believed to promote lung fibrosis by crosslinking extracellular matrix components and activating latent TGFβ. This study assessed physiologic pulmonary function and metabolic alterations in the mouse bleomycin model with TG2 genetic deletion.
Mechanical Feed-Forward Loops Contribute to Idiopathic Pulmonary Fibrosis
The American Journal of Pathology
Margaret AT Freeberg, Apostolos Perelas, Jane K Rebman, Richard P Phipps, Thomas H Thatcher, Patricia J Sime
2021-01-01
Idiopathic pulmonary fibrosis is a progressive scarring disease characterized by extracellular matrix accumulation and altered mechanical properties of lung tissue. Recent studies support the hypothesis that these compositional and mechanical changes create a progressive feed-forward loop in which enhanced matrix deposition and tissue stiffening contribute to fibroblast and myofibroblast differentiation and activation, which further perpetuates matrix production and stiffening. The biomechanical properties of tissues are sensed and responded to by mechanotransduction pathways that facilitate sensing of changes in mechanical cues by tissue resident cells and convert the mechanical signals into downstream biochemical signals.
Piezo2 is a key mechanoreceptor in lung fibrosis that drives myofibroblast differentiation
The American Journal of Pathology
Margaret AT Freeberg, Sarah V Camus, Valentina Robila, Apostolos Perelas, Thomas H Thatcher, Patricia J Sime
2025-04-01
Idiopathic pulmonary fibrosis (IPF) and other progressive fibrotic interstitial lung diseases have limited treatment options. Fibroblasts are key effector cells that sense matrix stiffness through conformation changes in mechanically sensitive receptors, leading to activation of downstream profibrotic pathways. Here, the role of Piezo2, a mechanosensitive ion channel, in human and mouse lung fibrosis, and its function in myofibroblast differentiation in primary human lung fibroblasts (HLFs) was investigated. Human samples from patients with IPF and mouse tissue from bleomycin-induced pulmonary fibrosis were assessed. Primary HLFs from nonfibrotic donors were grown on substrates of different stiffness to induce myofibroblast differentiation and treated with a Piezo2 inhibitor. Piezo2 expression was up-regulated in tissue from patients with IPF and in fibrotic mouse lung tissue. Additionally, analysis of published single-cell RNA-sequencing data showed that Piezo2 was expressed in the profibrotic collagen triple helix repeat containing 1 (Cthrc1)+ fibroblast subpopulation. Myofibroblast differentiation was increased in HLFs grown on substrates with fibrotic levels of stiffness compared with that seen in softer substrates. Piezo2 inhibition reduced stiffness-induced expression α-smooth muscle actin and fibronectin in HLFs. Piezo2 expression was elevated in fibrotic lung disease in both patients and rodents, and its presence was key in the differentiation of fibroblasts to the profibrotic myofibroblasts. Blocking Piezo2 may play a key role in fibrosis and, thus, be a novel therapeutic approach to treat pulmonary fibrosis.
