Located in Milwaukee, Wisconsin, the Versiti Blood Research Institute (VBRI) is the largest blood-focused research institute in the United States. With over 30 basic, translational, and clinical researchers, the institute is dedicated to advancing scientific knowledge and developing innovative therapies related to blood and blood disorders. The institute's research interests encompass a wide range of topics, including transfusion medicine, cellular therapy, thrombosis/hemostasis, immunology, and hematologic malignancies. As a vital part of Versiti, a non-profit organization with a blood bank at its core, the VBRI strives to improve lives through innovative research and the development of novel diagnostics and treatments.
VBRI is part of the Milwaukee Regional Medical Campus, a rapidly growing clinical-translational research hub. VBRI’s proximity to the Medical College of Wisconsin, Childrens’ Hospital of Wisconsin, and Froedtert Hospital facilitates seamless interdisciplinary collaborations. A range of exemplary core facilities support highly competitive research. In the summer of 2024, construction of a new research building will start, doubling existing VBRI research space to enable the recruitment of 10-15 new faculty. With its renowned researchers, strategic expansion plans and location in a highly collaborative environment, the VBRI is poised to maintain and expand its position as one of the leading hematology institutes in the world.
Under the direction of a Principal Investigator, further develops and expands understanding of scientific theory in his/her area of interest. Incumbent also learns and applies scientific laboratory techniques and gains experience in other areas of research that will lead to increased probability of success as an independent scientist. This is a training position with an expected duration of 1 – 3 years.
The Zhu Lab is primarily focused on unraveling the mechanisms of receptor transmembrane signaling. Specifically, our attention is directed towards cell surface receptors featuring single transmembrane domains, such as integrins, receptor tyrosine kinases, and receptor-like tyrosine phosphatases. Through a multidisciplinary approach encompassing structural biology, protein engineering, biochemistry, and cell biology techniques, we aim to elucidate how these receptors transmit signals across the cell membrane. Our investigations center on understanding the conformational regulation triggered by ligand binding at the extracellular domain or cytoplasmic domain stimulations. Our goal is to illustrate the intricate mechanisms governing receptor-ligand interactions and the conformational changes necessary for transmembrane signaling, spanning the extracellular, transmembrane, and cytoplasmic domains.
We are currently engaged in several projects, delving into the conformational requirements for bi-directional transmembrane signaling in integrins, elucidating the structural and functional basis of integrins as pathogen receptors, exploring integrin ligand interactions, and developing antibodies and small molecules that target or stabilize specific integrin conformations. Integrins, crucial cell surface receptors, play a pivotal role in regulating cell-cell and cell-matrix interactions across various biological processes, including development, hemostasis, antigen recognition, homing, and inflammation. Dysregulation of integrin activation is observed in pathological conditions such as autoimmune diseases and thrombosis. Our overarching goal is to uncover the intricate correlation between receptor conformational regulation and signal transduction, aiming to contribute to the design of more efficient and safer therapeutic agents.
A new focus of our lab entails unraveling the mechanism behind coronavirus spike protein-mediated cell fusion and viral infection. We aim to apply the gained knowledge to develop inhibitors for antiviral treatment and diverse virus-based applications, including cell-specific gene delivery and oncolysis.
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