Beth Kozel, M.D., Ph.D., is known for her work on the molecular mechanisms underlying vascular diseases, especially those that have genetic origins. Below is an overview of the types of research a student might expect to conduct in her lab:1. Study of Genetic Disorders Affecting the Vasculature. One of the primary areas of research in Beth Kozel’s lab revolves around understanding how genetic mutations impact vascular function. Her lab has a particular interest in Williams-Beuren syndrome, a rare genetic condition caused by the deletion of genes on chromosome 7. This syndrome often leads to cardiovascular issues such as supravalvular aortic stenosis (narrowing of the aorta) and other vascular abnormalities. 

Students in the lab would likely be involved in projects aimed at deciphering the molecular and genetic pathways that contribute to these vascular problems. Research in this area may involve genetic sequencing, gene expression analysis, and functional studies in model systems to understand how specific gene deletions affect vascular development and function. Techniques such as PCR, Western blotting, and immunohistochemistry might be utilized to investigate how these genetic changes translate into altered protein function and cellular behavior.2. Elastin Function and Its Role in Vascular Disease. Kozel’s lab has a strong focus on the role of elastin, a key protein that provides elasticity to blood vessels. Elastin mutations are implicated in conditions like supravalvular aortic stenosis and other vascular pathologies. The lab often explores how elastin deficiency or dysfunction affects the structure and function of blood vessels. A student could participate in biomechanical studies aimed at understanding how changes in elastin content or structure impact the mechanical properties of blood vessels. This could involve using animal models or human tissue samples to measure vascular stiffness and elasticity. Techniques such as atomic force microscopy, tensile testing, or pressure-diameter measurements in blood vessels may be employed to assess these properties. Additionally, molecular biology techniques could be used to investigate how elastin gene mutations lead to altered cellular behavior in vascular smooth muscle cells or endothelial cells. For example, students might explore how elastin dysfunction leads to altered signaling pathways that contribute to abnormal blood vessel development or disease progression.3. Preclinical Models and Therapeutic Approaches. 

Another key area of research in the lab is the development and use of preclinical models to study vascular diseases. This could involve working with mouse models that mimic human genetic conditions, such as elastin-deficient mice or models of Williams syndrome. A student might engage in projects that involve observing the development of vascular abnormalities in these models or testing potential therapeutic interventions. This research may include pharmacological studies, where students could help test drugs or compounds that target specific molecular pathways involved in vascular disease. These studies could involve monitoring how these treatments affect vascular structure, function, and gene expression.4. Cellular and Molecular Mechanisms of Vascular Remodeling. A crucial aspect of Beth Kozel’s research involves understanding the cellular and molecular mechanisms of vascular remodeling—the process by which blood vessels change their structure in response to injury, disease, or genetic mutations. Students may explore how specific genetic mutations or deficiencies lead to abnormal vascular remodeling and contribute to diseases such as hypertension, aortic aneurysms, or vascular stiffness. Projects might involve in vitro studies using cultured endothelial or vascular smooth muscle cells. Students could investigate how different genes regulate cellular behavior, such as proliferation, migration, or extracellular matrix production. They might also explore the molecular signaling pathways that are disrupted in vascular disease, such as TGF-beta signaling, which plays a key role in vascular development and pathology.5. Collaborative and Translational Research Kozel’s lab often collaborates with clinicians and other researchers to translate basic science findings into potential clinical applications. Students in the lab may have the opportunity to engage in translational research that bridges the gap between the bench and the bedside. This could include studying patient-derived samples or collaborating with clinical researchers to validate findings in human populations. 

Techniques and Tools a Student Might Use:         

• Molecular biology: PCR, Western blotting, qRT-PCR, immunohistochemistry         

• Genetic studies: Gene sequencing, CRISPR gene editing, gene expression analysis         

• Biomechanical testing: Tensile testing of blood vessels, atomic force microscopy        

• In vitro cell culture: Endothelial and smooth muscle cell assays        

• Animal models: Work with transgenic mice or models of human genetic disorders 

In conclusion, a student rotating in Beth Kozel’s lab would gain a comprehensive experience in vascular biology, genetic research, and translational medicine. They would be involved in studying genetic disorders affecting the vasculature, with a particular focus on understanding how elastin and other key molecules contribute to vascular disease, and exploring potential therapeutic strategies to address these conditions