Andreas Beyer Laboratory

Andreas Beyer Lab

Andreas Beyer, PhD

Andreas M. Beyer, PhD
Associate Professor, Department of Medicine and Physiology
Curriculum Vitae (PDF)
Twitter: @BeyerLab

Andreas M. Beyer is an Associate Professor in the Departments of Medicine and Physiology at the Medical College of Wisconsin and the co-director of the Basic and translational research program in Cardio-Oncology. During his training in Genetics and Physiology, he has gained detailed expertise in generating and evaluating novel approaches in genetics, molecular biology and physiology. In his time spent in the lab he performs experimental troubleshooting involving video microscopy, fluorescent microvascular imaging, generation of genetic rodent models, physiological evaluation of in vivo vascular function and blood pressure. With the support of this research group and important local and national collaborators, The Beyer lab is using live human tissues to address important questions in vascular biology that will lead to clinically relevant findings and drive further exploration of mechanism in rodent models. His lab hopes that clinically relevant data from human tissues will enable a detailed mechanistic understanding of disease that can then be used to develop novel therapeutics and translate both diagnostics and therapies themselves to the clinic.
Mitochondrial Redox Homeostasis in Regulation of Vascular Tone

Our collaborative team has established that the mechanisms of flow-mediated dilation (FMD) changes over the lifespan and shift with the onset of CAD. In healthy patients, FMD is regulated by the vasoprotective dilator nitric oxide (NO). In contrast, in CAD patients or in vessels exposed to acute stressors, NO bioavailability is reduced, and FMD is attributed to a compensatory rise in hydrogen peroxide (H2O2), a pro-inflammatory reactive oxygen species (ROS). These findings expanded our understanding of CAD, which was previously viewed as a disease limited to large conduit arteries, to reflect microvascular pathology to with significant prognostic implications. Our studies pioneered genetic manipulation techniques (siRNA, viral overexpression) in the human coronary circulation to answer mechanistic questions.

Work in my lab has long integrated animal studies with mechanistic evaluation of isolated human microvessels. Recent collaborative projects led us to expand our repertoire to study vascular function in vivo (e.g., brachial artery FMD, arterial tonometry, echocardiography, skin microdialysis/laser Doppler flowmetry). Our work fulfills a critical need to translate preclinical findings into human studies and thus serves as a bridge to clinical investigations. Understanding the molecular and physiological changes that contribute to CVD has clinical implications that, may lead to novel means to predict pathological changes and intervene before irreversible damage occurs.

Current work in understanding the pathological changes that occur with onset of CAD focuses on the role of TERT, the catalytic subunit of telomerase, in maintaining vasodilator function in the human microcirculation. Specifically, we study a noncanonical role of TERT in preserving mitochondrial homeostasis. We discovered previously unrecognized signaling between TERT and well-known regulators of vascular health, such as the renin angiotensin system and autophagy. Data from my lab and that of others implicate decreased levels of TERT with elevated mitochondrial DNA (mtDNA) damage as important regulators of mitochondrial integrity. This evidence led to a new collaborative work designed to understand the contribution of mitochondrial networks and their regulation to pathological changes in the human microcirculation. In specific, we aim to define how mitochondrial fission and fusion and its regulation, a fundamental process to maintain mitochondrial and cellular health, is critically linked as a regulator of FMD in the human microcirculation.

Andreas Beyer Lab Mitochondrial Integrity

Fig. 1. Mitochondrial integrity and microvascular function.

Cardio-Oncology: Effect of Anti Cancer therapy on the human microcirculation

Cardiovascular disease (CVD) and cancer are the number one and two causes of mortality and morbidity, and it is increasingly recognized that cancer and CVD share overlapping risk profiles. Long-term cancer survival is closely tied to CVD, while CVD conditions contribute to the progression of cancer and influence relevant treatment choices. With the use of systemic and targeted anti-cancer therapies (CTx), the number of annual deaths from cancer has been significantly reduced; however, most CTx agents have severe adverse consequences for the cardiovascular system. In fact, CVD related to CTx has emerged as the leading cause of non-cancer related deaths among breast cancer (BC) survivors. Given the magnitude of the clinical problem of cardiovascular-related mortality in cancer survivors, the novel clinical field of cardio-oncology has emerged with the aim of improving long-term, disease-free survival in cancer patients while addressing the underlying mechanism of cardiovascular comorbidity. While injury to the heart resulting from exposure to CTx is well established, little data exist on the contribution of CTx to endothelial cell dysfunction and the direct effect on mitochondria in the microcirculation. Microvascular endothelial dysfunction is the best predictor of future cardiovascular events, superior even to the degree of large vessel disease (i.e., CAD (coronary artery disease)) or ejection fraction in patients with or without coronary stenoses. This suggests that understanding the long-term consequences of CTx on microvascular function represents a novel, to date mostly unexplored, avenue to understanding and predicting the risk of cardiovascular complications in cancer patients.

We are using lessons learned from our ongoing investigations in understanding the changes in microvascular function in patients with CAD and expand them to investigate the vascular and mitochondrial changes and systemic consequences in cancer patients undergoing clinical necessary anti-cancer therapy. The objectives of this proposal are to 1) establish the contribution of microvascular dysfunction to CVD progression with an emphasis on cardio-oncology; 2) Establish the relevance of mitochondrial damage and secondary signaling in development and progression of CV events in cancer survivors; 3) define and predict risk for adverse CV events in cancer patients building on concepts of systems biology.

CTx-induced mitochondrial damage and secondary signaling

Fig. 3. CTx-induced mitochondrial damage and secondary signaling.

Current Members

Laura Norwood Toro

Laura Norwood Toro
Research Scientist I

Laura Norwood Toro is a Research Scientist I in the Andreas Beyer Lab. Her primary responsibility is to explore the effect of chemotherapy on cardiovascular outcomes in coronary circulation and vascular endothelium. One focus of her studies is to investigate the functions of telomerase in the nucleus versus the mitochondria. Her background is in cell biology and molecular biology.

Bill Hughes, PhD

Bill Hughes, PhD
Postdoctoral Fellow

Bill Hughes is a postdoctoral fellow in the Beyer/Gutterman Lab. Prior to starting at MCW he received his PhD from the University of Iowa. His research interests are human integrative cardiovascular physiology and vascular biology in health, aging, and chronic disease. In collaboration with Dr. Beyer and Dr. Gutterman, he is studying the cross-talk between autophagy, a basic cellular recycling process, and telomerase within the context of microvascular function in coronary artery disease (CAD). Flow-mediated dilation is predominately mediated by nitric oxide (NO) in healthy populations, but this mediator switches to hydrogen peroxide (H2O2) with CAD. Autophagy has recently been demonstrated to be sensitive to shear stress, and preliminary data from our lab indicates that inhibition of autophagy switches the mediator of FMD from NO to H2O2 in non-CAD vessels, while activation of autophagy in CAD vessels recapitulates a healthy phenotype (NO-mediated). Additionally, our lab has also demonstrated that upregulation of telomerase reduces mitochondrial release of H2O2 in vessels with CAD, restoring NO-mediated FMD. In this context, it is possible that there is significant crosstalk between pathways, with telomerase upstream of autophagy. Collectively, as numerous chronic diseases modulate both telomerase activity and autophagy it remains unknown how these two processes are inherently linked in the context of CAD.

Shelby Hader

Shelby Hader
Research Technologist II

Shelby Hader is a Research Technologist II in the Beyer/Gutterman Lab. Prior to starting at MCW she received her BA from the Lawrence University. Her primary goal is to analyze the vascular reactivity of human coronary arterioles and adipose micro vessels within different healthy and diseased patients. Some of her projects include: the cardiotoxicity of chemotherapy upon the microvasculature along with measuring the differences between fission and fusion of mitochondria in human arterioles. Additionally, Shelby provides research support for multiple projects in the lab via imaging, dissection of discarded tissue, and rat/mice colony maintenance.

Jane Terwoord Academic Profile

Janée Terwoord
Postdoctoral fellow

Janée Terwoord is a postdoctoral fellow working with Drs Beyer and Gutterman to investigate human microvascular physiology. Prior to joining the team at MCW, Janée earned her PhD in a clinical laboratory focused on the integrative control of blood flow distribution in humans. Her research interests include the signaling mechanisms that regulate vascular tone. Currently, Janée is working to characterize the cellular mechanisms by which cancer therapeutic drugs damage the microvasculature. She is studying how mitochondrial damage induced by these drugs contributes to endothelial dysfunction, which will inform new approaches to mitigate the detrimental cardiovascular effects of anti-cancer therapy.

Erin Birch

Erin Birch
Research Technologist I

Erin Birch is a research technologist in Dr. Beyer and Dr. Zhang’s labs. Erin has experience researching autoimmune diseases, chronic kidney disease, and cardiovascular disease. She is working with Dr. Beyer’s lab to provide support with several projects. Erin also contributes to the analysis of microvascular function in patients with coronary artery disease, COVID-19, and healthy patients. In her free time, Erin enjoys traveling and adventuring in the Rocky Mountains.

Lukas Brandt

Lukas Brandt
Research Assistant

Lukas Brandt is a graduate student in Dr. Beyer's lab. Prior to starting at MCW's physiology program, he received his bachelor's degree from the University of Applied Science Bingen, Germany with a major in biotechnology. He received additional training in a Molecular Biology master program at the Goethe University Frankfurt, Germany before pursuing his education in physiology at MCW. His research interests are whole organ physiology with a focus on cardiovascular pathology in response to clinical used anti-cancer therapy. Lukas aims to utilize rodent models to investigate physiological and molecular changes that lead to cardiovascular disease.

Cristhian Gutierrez Huerta

Cristhian Gutierrez Huerta
Research Assistant

Cristhian Gutierrez Huerta is a graduate MSTP student in the Beyer/Gutterman Lab. He graduated with a BS in Applied Mathematics and Biological Sciences from the University of California, Merced in 2018. He then completed a 2-yr post-baccalaureate research fellowship at the National Heart, Lung, and Blood Institute. In the Beyer/Gutterman group, he will begin work on identifying the role of mitochondrial fission/fusion on microvascular endothelial function and its relationship to coronary artery disease progression.

Alumni/Former Trainees

  • Karima Ait-Aissa
  • Daniela Didier
  • Johnathan Ebben
  • Alena Hanson
  • Joe Hockenberry
  • Andrew D. Kadlec, PhD
  • Minhi Kang
  • Todd Le
  • Jasmine Linn
  • Micaela Young

Recent Publications