Research

The Boehm Lab’s research interests are to identify and better understand the molecular mechanisms underlying human vascular diseases and to develop new therapeutic approaches.

Studies of patients with rare monogenetic vascular diseases are pivotal for understanding human vascular pathophysiology and have significant implications for comprehending more common complex, polygenetic vascular diseases. The diverse human research programs at the NIH provide a unique opportunity to study patients having monogenetic diseases with vascular implications.

The Boehm lab established the Patient-Centered Vascular Translational Program to conduct research on clinically relevant questions focused on vascular injury, remodeling, and repair, and to translate research findings into developing new therapeutic strategies.

The aims of the Vascular Translational Program align with the principles of Precision Medicine, investigating how individual variations in genes, environment, and lifestyle contribute to vascular disease. This program was designed to link high-throughput sequencing data with molecular disease mechanisms to facilitate the development of targeted therapies for patients with vascular disorders. New clinical protocols developed for this program include comprehensive clinical evaluations, collection of human biospecimens for diagnostic and research purposes, and a first-in-humans treatment study. We also successfully established a patient-specific disease-modeling platform using human induced pluripotent stem cells (hiPSCs) and hiPSCs-derived vascular and inflammatory cell lineages, including endothelial cells (iECs), vascular smooth muscle cells (iVSMCs), mesenchymal stromal cells (iMSCs), hematopoietic stem cells (iHSCs), and myeloid lineage cells (iMLCs). These cells are used for screening approaches, including high throughput sequencing, loss- and gain-of-function studies, and in vitro and in vivo disease modeling to identify disease-causing genetic variants and associated signaling pathways. Patient-specific hiPSCs and their derivatives will be used to test drugs or small molecules for development of new therapeutic strategies.

The Boehm Lab has successfully identified and/or is currently working on the mechanism underlying rare monogenetic diseases with vascular implications, including Arterial Calcification due to Deficiency of CD73 (ACDC), Systemic inflammation and early-onset recurrent stroke in children due to Deficiency of Adenosine Deaminase 2 (DADA2), STING-associated vasculopathy with onset in infancy (SAVI), and Hyper IgE syndrome (AD-HIES), a primary immunodeficiency caused by loss-of-function mutations in Signal Transducer and Activator of Transcription 3 (STAT3).  Research findings from these human rare monogenetic vascular diseases have lead to novel treatment strategies for affected patients.