Ksenija Bernau
Credentials: PhD
Position title: Assistant Professor
Email: kbernau@medicine.wisc.edu
Phone: 608-262-3518
Address:
H4/616 Clinical Science Center, 600 Highland Ave., Madison, WI 53792
Education
PhD: Biomedical Engineering (Major), Neuroscience (Minor), University of Wisconsin-Madison
Research Summary
Our lab is dedicated to developing novel, clinically-translatable molecular imaging methods to non-invasively characterize biological and pathological events in vivo. We are particularly interested in developing positron emission tomography (PET) probes for real-time assessment of pulmonary disease status and progression. These probes would enable physicians to tailor therapeutic course toward the individual patient’s disease progression, something that is critically needed in the clinic.
Research Detail
Our laboratory is dedicated to developing novel, clinically-translatable imaging methods to characterize biological and pathological events, with particular emphasis on pulmonary fibrosis. Idiopathic pulmonary fibrosis (IPF) is a devastating disease that causes relentless scar formation, lung stiffening, and respiratory failure, leading to over 40,000 deaths annually in the U.S. The average survival following diagnosis is 3-5 years, but disease progression varies drastically and unpredictably from patient to patient. Beyond IPF, other forms of progressive lung fibrosis have similarly bleak prognoses and unpredictable progression. Current methods that enable characterization of pulmonary fibrosis disease activity, high resolution computed tomography (HRCT) and pulmonary function tests, only detect disease progression retroactively, as there is a 6-12 month delay between clinical assessments. Development of novel tools for real-time assessment of clinical disease activity would have a major, positive impact on patient care, allowing for more efficient therapeutic decision-making, potentially enabling targeted disease management and improved clinical outcomes.
The presence of exuberant extracellular matrix is one of the key elements of fibrosing disorders. Given its importance in the fibrotic elaboration, our group is targeting extracellular matrix proteins to develop novel positron emission tomography (PET) imaging probes that would enable sensitive detection of new fibrotic activity. Fibronectin is an ECM glycoprotein that is: 1. highly upregulated in the fibrotic lung, 2. associated with clinical metrics of pulmonary fibrosis disease progression, 3. preferentially localized to fibroblastic foci, the leading edge of active fibrosis, and 4. serves as a scaffold required for deposition of other ECM proteins, including fibrillar collagens. In addition to its regulatory roles, fibronectin serves as a target for bacterial attachment, with many bacteria expressing fibronectin-binding peptides. These peptides bind the 70kDa N-terminal domain of fibronectin via low nanomolar affinity interactions. Our team is leveraging these peptides to develop novel probes for fibronectin in the fibrotic lung. In addition, we are assessing small molecules directed against activated fibroblasts through the fibroblast activation protein (FAP), a serine protease specifically expressed on activated fibroblasts during tissue remodeling, including in pulmonary fibrosis. For our pre-clinical/translational studies, we utilize ex vivo human lung tissue samples, subjected to molecular characterization with respect to peptide binding. We also use in vivo mouse models of lung fibrosis, administering fluorescently labeled or radiolabeled peptides for small animal imaging-based assessments, as well as downstream tissue analysis. Importantly, we are dedicated to translating these methods for clinical studies to expedite the process of bringing these tools into the clinic. For this, we are characterizing the probe biodistribution and uptake in larger animal models.
Beyond PET imaging, we are also interested in the development of novel imaging approaches, such as advancements in HRCT technology for detection of early interstitial lung abnormalities which may be precursors to fibrotic changes. For this, we are collaborating with other scientists at UW-Madison and beyond to develop novel image analysis tools that would enable rapid, non-invasive characterization of these interstitial lung abnormalities, leading to early treatment of patients with particularly progressive profile.
Publications