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DTSTART;TZID=UTC:20240205T160000
DTEND;TZID=UTC:20240205T170000
DTSTAMP:20260407T183119
CREATED:20240128T235733Z
LAST-MODIFIED:20240128T235733Z
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SUMMARY:BE Seminar: Drug Delivery across Biological Barriers for combatting and preventing infectious diseases
DESCRIPTION:  \nTitle: Drug Delivery across Biological Barriers for combatting and preventing infectious diseases. \nProf. Dr. Claus-Michael Lehr \nHelmholtz Institute for Pharmaceutical Research Saarland (HIPS)\, Helmholtz Center for Infection Research (HZI) Dept of Drug Delivery. and \nSaarland University\, Dept of Pharmacy\, \nSaarbrücken\, Germany. \nAbstract: Urgently needed anti-infective drugs and vaccines must reach their targets safely and efficiently. Not only the body’s outer epithelia\, like e.g.\, gut\, skin and lung\, but also the bacterial cell envelope as well as the polymer matrix of bacterial biofilms represent important biological barriers which may delimit the transport of anti-infectives to their site of action (“bacterial bioavailability”). \nTo model the air-blood barrier of the peripheral human lung\, our group was the first who published a protocol for growing monolayers of human alveolar epithelial cells in primary culture (hAEpC) to develop functional tight junctions and high transepithelial electrical resistance (TEER). Later we introduced a first polyclonal human alveolar epithelial (hAELVi) and just recently a monoclonal cell line (Arlo) with similar properties. These epithelial cells may be implemented in various micro-physiological systems\, also to study the effect of breathing and co-cultivated with other cells types\, like e.g.\, macrophages or endothelial cells. A particular challenge is the mixed culture with bacterial biofilms to model chronic lung infections\, which can meanwhile be realized most elegantly by 3D bioprinting. \nSuch complex in-vitro models aim to reflect the (patho)physiology of specific organs or tissues either in healthy or reduce diseased state and to generate clinically meaningful readouts. They have been used for developing novel anti-infectives\, like e.g.\, quorum sensing inhibitors\, aiming to eradicate pathogens without inducing antimicrobial resistance. Aerosolizable nano-antibiotics are also being investigated to combat intracellular infections\, such as e.g.\, tuberculosis or viral infections by Crispr/CAS-like approaches. \nAbout The Speaker: Claus-Michael Lehr is Professor at Saarland University as well as cofounder and head of the department “Drug Delivery and Biological Barriers” at the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS)\, which was established as a branch of the Helmholtz Centre for Infection Research (HZI) Braunschweig in 2009. Prof. Lehr has also been cofounder of Across Barriers GmbH and of PharmBioTec GmbH\, a non-for-profit contract research organization. \nThe research theme of Professor Lehr’s team is (preferentially: non-invasive) drug delivery across biological barriers\, in particular the epithelia of the gastrointestinal tract\, the skin\, and the lungs. Recently\, this has been expanded to microbial barriers\, such as the bacterial cellular envelope\, biofilms and host cell membranes. A substantial part of the lab’s activities is dedicated to innovative carrier’s systems\, often based on nanotechnology\, capable of safely and efficiently delivering drugs and vaccines across these barriers. In this context\, the lab systematically investigates predictive cells and tissue models\, preferentially human-based\, to evaluate the safety and efficacy of novel therapeutic concepts and to facilitate their translation into the clinic.
URL:https://be.iisc.ac.in/event/be-seminar-drug-delivery-across-biological-barriers-for-combatting-and-preventing-infectious-diseases/
LOCATION:CES Seminar Hall\, CES Seminar Hall\, 3rd Floor\, Biological Science Building
CATEGORIES:Seminar
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DTSTART;TZID=UTC:20240212T160000
DTEND;TZID=UTC:20240212T170000
DTSTAMP:20260407T183119
CREATED:20240205T224249Z
LAST-MODIFIED:20240205T224249Z
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SUMMARY:BE Seminar : Extracellular Matrix- A Transport Barrier for Drug Delivery
DESCRIPTION:Speaker: Dr. Rashmi Mohanty \nTitle: Extracellular Matrix- A Transport Barrier for Drug Delivery \nAbstract: Extracellular Matrix (ECM) determines crucial cellular responses through cell-matrix interactions. Specific qualitative and quantitative changes occur in the ECM during disease and\, in part\, regulate critical events that determine pathological tissue phenotype. For example\, in solid cancers\, the extraordinarily dense fibrotic ECM is primarily responsible for the increased interstitial tissue pressure and stiff mechanical properties. The resulting dense stroma impedes the transport of therapeutic anticancer drugs\, limiting effective drug delivery and\, therefore\, the therapeutic potential of drug candidates. To overcome the tumor ECM drug delivery barrier\, during my PhD\, I leveraged favorable surface physicochemical interactions between the tumor ECM and drug carriers to enhance the delivery and\, hence\, the therapeutic outcomes of antitumor drugs. I used genetically engineered peptide-presenting phage libraries as a high-throughput approach to screen and identify peptide coatings that would facilitate improved transport through the tumor microenvironment. Interestingly\, in contrast to most studies\, I found that a positively charged peptide “surface” enhanced penetration\, uptake\, and retention of particles in tumor tissue when compared to neutrally charged peptides. Next\, I conjugated the peptide to immune checkpoint inhibitor antibodies\, which\, in a murine melanoma tumor environment\, recruited a higher number of activated tumor-infiltrating T-cells\, resulting in delayed tumor growth. \nHaving worked with cell culture\, ex vivo tissue culture\, and animal model development during my Ph.D.\, I realized there is an unmet gap in developing models that can more easily recapitulate the dynamic and transport features of disease. Believing that the emerging\, complex multicellular 3D organoid systems would more accurately reflect the human physiological environment\, I joined the Weiss lab for my postdoctoral study to implement synthetic biology tools for organoid design. Currently\, I am working on recapitulating the native-like organ architecture in liver organoids by mimicking the honeycomb-like patterns in human livers. Combining synthetic biology\, micro-robotics\, and machine learning\, we deliver biological cues at precise locations to control the differentiation of human-induced pluripotent stem cells (hiPSCs) in a spatiotemporal fashion. \nAlthough organoids have emerged as the next-generation tool for disease modeling and drug screening\, the formation of matured organoids remains a challenge\, partly because the current models lack the natural context of endogenous cell-governing ECM secretion and assembly formation. In my future research program\, I will employ synthetic biology principles to genetically engineer hiPSCs to secrete relevant ECM (as occurs in vivo) for designing tailor-made disease-specific organoids to investigate drug transport and drug delivery with an aim to accelerate the drug development pipeline. \nAbout the speaker: Dr. Rashmi Mohanty is am a postdoctoral associate in the Department of Biological Engineering at the Massachusetts Institute of Technology. My current work focuses on employing synthetic biology tools to control cell fate decisions for the formation of programmable organoids. She has completed Ph.D. in the College of Pharmacy at the University of Texas at Austin (UT). During Ph.D.\, she worked on developing therapeutic moieties that can overcome the transport barrier of the tumor microenvironment for improved drug delivery. Prior to matriculating at UT\, she received my Bachelor of Technology in Chemical Engineering from the National Institute of Technology (NIT) Rourkela and my Master of Technology in Chemical Engineering from the Indian Institute of Technology (IIT) Kanpur. Building from my knowledge and gained experiences with the limitations of current models used to recapitulate stroma-rich disease environments\, in the long run\, she is interested in designing 3D models that better reflect various disease environments to accelerate the progress of disease diagnostics and drug discovery.
URL:https://be.iisc.ac.in/event/be-seminar-extracellular-matrix-a-transport-barrier-for-drug-delivery/
LOCATION:CES Seminar Hall\, CES Seminar Hall\, 3rd Floor\, Biological Science Building
CATEGORIES:Seminar
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