Bio


Dr. Steffes, a Wisconsin native, completed medical school and pediatric residency at the Medical College of Wisconsin. She then moved to the Bay Area and completed her clinical fellowship in pediatric pulmonary medicine at Stanford University in 2020. Additionally, Dr. Steffes received further post-doctoral training in the laboratories of Dr. Maya Kumar and Dr. David Cornfield, studying the cellular and molecular mechanism driving pulmonary vascular disease. In addition to her role as an Instructor in Pediatrics in the division of Pulmonary Medicine, Dr. Steffes is also completing an advanced clinical fellowship in Pulmonary Hypertension at Lucile Packard Children’s Hospital Stanford. Her clinical work consists of caring for patients with pediatric pulmonary and pulmonary vascular diseases such as pulmonary hypertension, bronchopulmonary dysplasia, interstitial lung disease, respiratory failure, chronic cough and asthma. Her research is focused on the vascular changes seen in pulmonary hypertension, more specifically understanding the cellular characteristics of occlusive neointimal lesions, the abnormal cells that block pulmonary blood flow in pulmonary hypertension. In her most recent work, Dr. Steffes identified a subset of healthy vascular smooth muscle cells that are the cell of origin for the pathologic neointimal cells and a specific signaling pathway, that when blocked, inhibits the formation of neointimal lesions.

Dr. Steffes is currently employing advanced single cell sequencing technologies to further understand neointimal cells with the ultimate goal identifying new therapies for pulmonary hypertension, a fatal disease with no known cure.

Clinical Focus


  • Pediatric Pulmonary

Academic Appointments


Professional Education


  • Residency: Medical College of Wisconsin Dept of Pediatrics (2017) WI
  • Fellowship: Stanford University Pediatric Pulmonary Fellowship (2020) CA
  • Board Certification: American Board of Pediatrics, Pediatrics (2017)
  • Medical Education: Medical College of Wisconsin Registrar (2014) WI

All Publications


  • A Notch3-Marked Subpopulation of Vascular Smooth Muscle Cells is the Cell of Origin for Occlusive Pulmonary Vascular Lesions. Circulation Steffes, L. C., Froistad, A. A., Andruska, A., Boehm, M., McGlynn, M., Zhang, F., Zhang, W., Hou, D., Tian, X., Miquerol, L., Nadeau, K., Metzger, R. J., Spiekerkoetter, E., Kumar, M. E. 2020

    Abstract

    Background: Pulmonary arterial hypertension (PAH) is a fatal disease characterized by profound vascular remodeling in which pulmonary arteries narrow due to medial thickening and occlusion by neointimal lesions, resulting in elevated pulmonary vascular resistance and right heart failure. Therapies targeting the neointima would represent a significant advance in PAH treatment, however our understanding of the cellular events driving neointima formation, and the molecular pathways that control them, remains limited. Methods: We comprehensively map the stepwise remodeling of pulmonary arteries in a robust, chronic inflammatory mouse model of pulmonary hypertension. This model demonstrates pathologic features of the human disease, including increased right ventricular pressures, medial thickening, neointimal lesion formation, elastin breakdown, increased anastomosis within the bronchial circulation, and perivascular inflammation. Using genetic lineage tracing, clonal analysis, multiplexed in situ hybridization, immunostaining, deep confocal imaging and staged pharmacologic inhibition we define the cell behaviors underlying each stage of vascular remodeling and identify a pathway required for neointima formation. Results: Neointima arises from smooth muscle cells (SMCs) and not endothelium. Medial SMCs proliferate broadly to thicken the media, after which a small number of SMCs are selected to establish the neointima. These neointimal founder cells subsequently undergoing massive clonal expansion to form occlusive neointimal lesions. The normal pulmonary artery SMC population is heterogeneous and we identify a Notch3-marked minority subset of SMCs as the major neointimal cell of origin. Notch signaling is specifically required for the selection of neointimal founder cells, and Notch inhibition significantly improves pulmonary artery pressure in animals with pulmonary hypertension. Conclusions: This work describes the first nongenetically driven murine model of PH that generates robust and diffuse occlusive neointimal lesions across the pulmonary vascular bed and does so in a stereotyped timeframe. We uncover distinct cellular and molecular mechanisms underlying medial thickening and neointima formation and highlight novel transcriptional, behavioral and pathogenic heterogeneity within pulmonary artery SMCs. In this model, inflammation is sufficient to generate characteristic vascular pathologies and physiologic measures of human PAH. We hope that identifying the molecular cues regulating each stage of vascular remodeling will open new avenues for therapeutic advancements in the treatment of PAH.

    View details for DOI 10.1161/CIRCULATIONAHA.120.045750

    View details for PubMedID 32794408