Davis Lab

The Davis Lab, led by Dr. Frank M. Davis, works to improve the diagnosis and treatment of patients with abdominal aortic aneurysms through rigorous scientific research and compassionate clinical care.

Current Research in the Davis Lab

Led by Dr. Frank M. Davis, the Davis Laboratory studies the pathological mechanisms that drive aortic aneurysm development. We are interested to better understand the role of immune cell infiltration and vascular smooth muscle cell dysfunction within the arterial wall during pathological aortic dilation. Our team of scientists explores this using a complement of biochemical assays, in vivo animal models, and biobank of vascular tissue specimens. Our vascular clinical team translates its findings from bench-to-bedside through ongoing clinical research trials. Ultimately, our aim is to develop effective new therapeutic modalities for the treatment of patients with aortic aneurysmal disease.

Background

Abdominal aortic aneurysm (AAA) represent the abnormal dilation of the aorta present in approximately 6% of men over 65 years old and usually remain asymptomatic until they progress to aortic rupture. Rupture of an AAA, and its associated catastrophic physiological insult carries a mortality in excess of 80%. Recent studies suggest there may be greater than 1 million people living today in the United States with an AAA. Equally alarming, current therapeutic options to prevent AAA rupture are restricted to surgical repair, as there remains a lack of pharmaceutical approaches to limit AAA growth. The absence of proven medical therapies is a direct consequence of the paucity of knowledge on mechanisms of aneurysmal initiation, progression and rupture.

Our Approach

Within the Davis Laboratory, we employ a wide range of standard and advanced techniques, including tissue analysis, cell-based experiments, mouse models of aortic disease, and single-cell transcriptome/multiomics analysis. Additionally, we also pursue translational studies investigating the clinical relevance of the mechanisms we uncover in the laboratory through surgical samples and clinical diagnostic imaging.

Contributions to Science

Our laboratory is making discoveries that have the potential to change how we approach the treatment of AAAs so that they are safer for our patients. We are making important contributions to understanding how different types of immune cells interact with the environment around the aortic wall and how those interactions can lead to changes in the expression of the cells' genetic code, a process known as epigenetic regulation.

Using our murine models and surgical samples, we were the first research team to identify a how during aortic aneurysm development, monocytes/macrophages are “programmed” toward a proinflammatory state through the epigenetic enzyme JMDJ3. These inflammatory monocytes/macrophages are detrimental to the aortic wall as they result in the breakdown of the aorta. Pharmacological inhibition of JMJD3 was able to prevent aortic dilation and rupture. Additionally, we were the first to perform single-cell RNA sequencing analysis of the human abdominal aorta to gain an improved understanding of the cell populations and cell-cell communications that occur during aortic aneurysm disease.

We have also made advances in the understanding of what happens to the aortic wall during aneurysm development, clarifying the interactions among vascular smooth muscle and immune cells in the affected area. Better understanding these relationships and processes will help us identify and translate new immune-focused therapeutics from the lab into human trials.