Overview of Research in the Sharma Lab at Ball State:
Research in the Sharma Lab at Ball State University delves into the intricate cellular and molecular processes governing coronary angiogenesis during both cardiac development and regeneration. Central to our investigations is the pivotal role of Aplnr, a G-protein coupled receptor, alongside the influence of hypoxia and the transcription factor Sox17 in orchestrating the regulation of coronary angiogenesis. Our research endeavors encompass a comprehensive array of methodologies spanning both in vivo and in vitro domains, allowing for a holistic understanding of this complex phenomenon. Leveraging a mouse model system in conjunction with endothelial and cardiomyocyte cell cultures, as well as 3D whole organ and explant cultures, we aim to elucidate the intricate interplay between these molecular players in driving coronary angiogenesis. Employing cutting-edge molecular biology techniques including quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and RNA sequencing, we delve deep into the genetic and molecular underpinnings of angiogenic processes. Furthermore, histological and microscopy approaches are employed to visualize and characterize the structural and cellular dynamics involved in coronary angiogenesis. By integrating these multidisciplinary approaches, our research seeks to unravel the fundamental mechanisms underpinning coronary angiogenesis, offering insights that may ultimately inform novel therapeutic strategies for cardiac regeneration and disease intervention.
Overall, our laboratory is interested in understanding the basic biology of cardiovascular development and its function at the cellular and molecular level. We want to understand how embryonic progenitor stem cells give rise to tissues of cardiovascular system. We use developing mouse heart as a model system to study these questions. Our study focuses on two aspects of heart development: development of coronary vessels and great arteries (Aorta and Pulmonary trunk) of the heart.
Ongoing Research Projects in the Sharma Lab:
Development of coronary vessels. One of our main focus in the Sharma lab is to study embryonic progenitor stem cells that give rise to coronary vessels. We are particularly interested in understanding the cellular and molecular mechanisms that guide coronary endothelial cells arising from sinus venosus and endocardium progenitor stem cells during coronary angiogenesis. Currently, we are looking into the roles of APJ signaling (SV-derived pathway) and hypoxia inducible signaling (Endocardium-derived pathway) as potential regulators of coronary vessel development. We are using a combination of in-vitro and in-vivo systems, mouse genetics, modern cell and molecular techniques, and advance imaging technology to understand these questions. There is a huge need for our understanding of endothelial cell biology to cope with diseases due to defective vascular tissues.
Project #1: To determine Differential signaling mechanism from ELABELA/APJ vs. APELIN/ APJ mediated signaling in cardiovascular development and function.
Project #2: To determine whether APJ signaling interacts with ECM within the subepicardium to mediate SV-derived coronary angiogenesis.
Project #3: To characterize the role of DHX36, a helicase enzyme, in coronary vessel development.
Project #4: To determine whether DHX36 modulate hypoxia, SOX17, VEGFR2, and APJ-mediated signaling in coronary ECs.
Project #5: To determine the role of Acetylcholine/Nicotinic Receptor signaling during cardiovascular organogenesis.
Project #6: To test whether reinforcement of these developmental signals (APJ, hypoxia, and DHX36) repair and regenerate injured heart models.
Development of great arteries (Aorta and Pulmonary Trunk) of the heart. In addition to coronary vessel formation, we are also interested in understanding how the second heart field (SHF) progenitor stem cells differentiate into the great vessels of the heart, the aorta and pulmonary trunk. We want to unravel the cellular and molecular mechanisms of aorta and pulmonary differentiation and morphogenesis from common SHF progenitor stem cells.
Project #1: To determine whether APJ and TBX-mediated signaling interact within the second heart field domain to regulate Aorta and Pulmonary Trunk development.
Project #2: To perform transcriptomic analysis of APJ+ vs. APJ- progenitor population in the second heart field to establish a broader APJ-mediated signaling network within the SHF.
Research in the Sharma Lab at Ball State University delves into the intricate cellular and molecular processes governing coronary angiogenesis during both cardiac development and regeneration. Central to our investigations is the pivotal role of Aplnr, a G-protein coupled receptor, alongside the influence of hypoxia and the transcription factor Sox17 in orchestrating the regulation of coronary angiogenesis. Our research endeavors encompass a comprehensive array of methodologies spanning both in vivo and in vitro domains, allowing for a holistic understanding of this complex phenomenon. Leveraging a mouse model system in conjunction with endothelial and cardiomyocyte cell cultures, as well as 3D whole organ and explant cultures, we aim to elucidate the intricate interplay between these molecular players in driving coronary angiogenesis. Employing cutting-edge molecular biology techniques including quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and RNA sequencing, we delve deep into the genetic and molecular underpinnings of angiogenic processes. Furthermore, histological and microscopy approaches are employed to visualize and characterize the structural and cellular dynamics involved in coronary angiogenesis. By integrating these multidisciplinary approaches, our research seeks to unravel the fundamental mechanisms underpinning coronary angiogenesis, offering insights that may ultimately inform novel therapeutic strategies for cardiac regeneration and disease intervention.
Overall, our laboratory is interested in understanding the basic biology of cardiovascular development and its function at the cellular and molecular level. We want to understand how embryonic progenitor stem cells give rise to tissues of cardiovascular system. We use developing mouse heart as a model system to study these questions. Our study focuses on two aspects of heart development: development of coronary vessels and great arteries (Aorta and Pulmonary trunk) of the heart.
Ongoing Research Projects in the Sharma Lab:
Development of coronary vessels. One of our main focus in the Sharma lab is to study embryonic progenitor stem cells that give rise to coronary vessels. We are particularly interested in understanding the cellular and molecular mechanisms that guide coronary endothelial cells arising from sinus venosus and endocardium progenitor stem cells during coronary angiogenesis. Currently, we are looking into the roles of APJ signaling (SV-derived pathway) and hypoxia inducible signaling (Endocardium-derived pathway) as potential regulators of coronary vessel development. We are using a combination of in-vitro and in-vivo systems, mouse genetics, modern cell and molecular techniques, and advance imaging technology to understand these questions. There is a huge need for our understanding of endothelial cell biology to cope with diseases due to defective vascular tissues.
Project #1: To determine Differential signaling mechanism from ELABELA/APJ vs. APELIN/ APJ mediated signaling in cardiovascular development and function.
Project #2: To determine whether APJ signaling interacts with ECM within the subepicardium to mediate SV-derived coronary angiogenesis.
Project #3: To characterize the role of DHX36, a helicase enzyme, in coronary vessel development.
Project #4: To determine whether DHX36 modulate hypoxia, SOX17, VEGFR2, and APJ-mediated signaling in coronary ECs.
Project #5: To determine the role of Acetylcholine/Nicotinic Receptor signaling during cardiovascular organogenesis.
Project #6: To test whether reinforcement of these developmental signals (APJ, hypoxia, and DHX36) repair and regenerate injured heart models.
Development of great arteries (Aorta and Pulmonary Trunk) of the heart. In addition to coronary vessel formation, we are also interested in understanding how the second heart field (SHF) progenitor stem cells differentiate into the great vessels of the heart, the aorta and pulmonary trunk. We want to unravel the cellular and molecular mechanisms of aorta and pulmonary differentiation and morphogenesis from common SHF progenitor stem cells.
Project #1: To determine whether APJ and TBX-mediated signaling interact within the second heart field domain to regulate Aorta and Pulmonary Trunk development.
Project #2: To perform transcriptomic analysis of APJ+ vs. APJ- progenitor population in the second heart field to establish a broader APJ-mediated signaling network within the SHF.
