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How Versiti Researchers are Helping Patients with Atherosclerosis

November 07, 2019

We’re excited to introduce you to Bandana Singh, PhD, a postdoctoral fellow at Versiti Blood Research Institute (BRI). Learn more about what fueled her interest in science, and why she believes the BRI is a leading force in the field of vascular biology.

How did you become interested in working in a research lab?

I have been always fascinated by mysterious stories and loved the way detectives analyze something and find the root cause of the issue. I strongly believe that biomedical researchers are like detectives. Both disciplines involve investigation, require understanding the problem to be solved, collection of facts, developing hypotheses to explain the facts, elimination of the least likely hypothesis, and coming to a conclusion. I also like to understand the concepts and past events and dig into all the possible levels of evidence. Earlier in my career, I was interested in medicine and how it cures disease. But later, I realized that it is more interesting to find the causes of disease and cure them. I ended up earning a PhD in Life Science and continued as a researcher, where I can choose any social phenomenon or problem and gather the knowledge to explain and answer those questions. My scientific training started when I was enrolled in Vidyasagar University, India, for a Master of Science in Human Physiology. This gave me the scope to learn and a curiosity about life’s building blocks, from molecules to cells. During my MSc, I participated in a community health survey in a remote area of West Bengal, India. During this time, I studied the cardiovascular status, nutritional status and anthropometric status of community members. My community survey also focused on the prevalence of different diseases, health awareness levels of the community, and immunization. This community survey led me to think more about the causes of different diseases, especially cardiovascular diseases. Being a researcher, I feel there is nothing cooler than knowing that you are contributing to the discovery of something that has an impact on people’s lives or makes a change in the world.

What do you do at the BRI?

I have been working as a postdoctoral fellow in Dr. Magdalena Chrzanowska’s lab for two years.  This is an excellent opportunity to extend my knowledge, develop new, unique ideas, continue researching, and learn techniques related to cardiovascular biology. I really like the hands-on environment in Dr. Chrzanowska’s lab and the freedom and independence we have to work toward solving scientific problems. Dr. Chrzanowska’s lab focuses on the function of the small GTPase protein Rap1 in the cardiovascular system through using transgenic models and using different biochemical, molecular and microscopic approaches to investigate Rap1 signaling in the cellular systems. Dr. Chrzanowska’s lab aims to elucidate molecular mechanisms, through which Rap1 regulates endothelial homeostasis, endothelial cell responses to angiogenesis, and physiological consequences of Rap1-deficiency on endothelial dysfunction, particularly progression of atherosclerosis. Her lab also focuses on the molecular mechanisms through which Rap1 promotes shear stress signaling under laminar, vaso-protective flow, and disturbed flow of blood, which is associated with development of proiflammatory states and progression of atherosclerosis. My current research seeks to understand the molecular mechanisms through which Rap1 restricts inflammatory signaling and protects from progression of atherosclerosis. In my research work, I have been able to demonstrate that Rap1, a small GTPase, plays a key role in maintaining endothelial homeostasis in a chronic inflammatory state, and its deletion accelerates the progression of atherosclerosis. My findings also demonstrated that Rap1 plays a key role in maintaining endothelial homeostasis via two distinct mechanisms: promoting shear stress-induced nitric oxide release and restricting proiflammatory signaling via NFκB pathway. This postdoctoral training in Dr. Chrzanowska’s lab will help me greatly for my future career as an independent researcher.

Why did you come to the BRI?

I obtained my PhD in 2016 from Defense Institute of Physiology and Allied sciences, India. As a part of my PhD training in the laboratories of Dr. Gausal Azam Khan and Dr. Sarada Surya Kumari, I identified how the von Willebrand Factor (vWF) antagonizes insulin-induced nitric oxide production and promotes insulin resistance during hypoxia. After my PhD thesis submission, I was appointed as senior research fellow at CSIR-Institute of Genomics and Integrative Biology (IGIB), India, under supervision of Dr. Dwaipayan Bhardwaj. In his lab, I learned to use different state-of-the art genomic technologies to identify putative novel biomarkers for predisposition to a diverse range of about 20 clinical phenotypes relevant to diabetes, cardiovascular disease and metabolic disorders in a large-scale, genome-wide association studies (GWAS). After understanding the genetic and epigenetic variations of cardiovascular disease, I wanted to pursue my research training further in understanding vascular signaling consequences of cardiovascular disease in a pioneer institute of the world under the supervision of a pioneer mentor. As I became fond of cardiovascular complication, I decided to do my postdoctoral training in Dr. Chrzanowska’s lab. I feel if you are in vascular biology, you can’t do much better than Versiti Blood Research Institute. This institute has become one of the leading vascular biology research organizations globally. And another reason I came here was Dr. Chrzanowska. She is one of the outstanding scientists in the vascular biology field. It’s also fun to work in her lab group and receive her critique and encouragement toward scientific goals.

What innovation are you excited about?

I identified two distinct mechanisms through which Rap1 protects progression of atherosclerosis: promoting shear stress-induced NO release and restricting pro-inflammatory signaling in endothelial cells. Understanding these mechanisms might open new therapeutic avenues for treatment of atherosclerosis. This is of importance since current preventive therapies are focused on lowering lipid levels while neglecting the endothelial function.

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