Kishore Kumar Jella, PhD
Winship Cancer Institute postdoc Kishore Kumar Jella has been invited to speak at the NATO advanced research workshop “BRITE (Biomarkers of Radiation In the Environment): Robust tools for Risk Assessment” in Yerevan, Armenia, on 28-30 November, 2017. The workshop brings together leading international experts to evaluate currently and developing radiation biomarkers for environmental applications.
Jella works in the Departments of Biochemistry and Radiation Oncology under the direction of Professors William S. Dynan and Mohammad K. Khan. He will speak on “Exosomes as Radiation Biomarkers”. He will describe how radiation influences exosome production and how these exosomes influence the immune system. The work has applications both to radiation carcinogenesis and combination radio-immunotherapy.
Jella is supported in part by a grant from the National Aeronautics and Space Administration to Dynan.
Exosomes are nano-sized membrane-clothed capsules containing proteins and RNA that are thought to facilitate cell-cell communcation. They were previously implicated in the ability of cancer cells to influence healthy neighbor cells, and have also been proposed as anti-cancer therapeutic vehicles. Jella’s previous research on exosomes and radiation-induced bystander signaling was published in Radiation Research in 2014.
Thanks to biomedical engineer Mike Davis for writing an explanation of “Exosomes: what do we love so much about them?” for Circulation Research, a companion to his lab’s November 2016 publication analyzing exosomes secreted by human cardiac progenitor cells.
We can think of exosomes as tiny packages that cells send each other. They’re secreted bubbles containing proteins and regulatory RNAs. Thus, they may be a way to harvest the regenerative capacity of pediatric heart tissue without delivering the cells themselves.
Davis’ lab studied cardiac tissue derived from children of different ages undergoing surgery for congenital heart defects. The scientists isolated exosomes from the cardiac progenitor cells, and tested their regenerative activity in rats with injured hearts.
They found that exosomes derived from older children’s cells were only reparative if they were subjected to hypoxic conditions (lack of oxygen), while exosomes from newborns’ cells improved rats’ cardiac function with or without hypoxia. Read more
More than 9 million people donate blood in the United States every year, according to the American Red Cross. Current guidelinesÂ say that blood can be stored for up to six weeks before use.
What happens to red blood cells while they are in storage, which transfusion experts call the â€œstorage lesionâ€? Multiple studies have shown that older blood may have sub-optimal benefits for patients receiving a transfusion. The reasons include: depletion of the messenger molecule nitric oxide, lysis of red blood cells and alterations in the remaining cellsâ€™ stiffness.
To that list, we could add the accumulation of microparticles, tiny membrane-clothed bags that contain proteins and RNA, which have effects on blood vessels and the immune system upon transfusion. Note: microparticles are similar to exosomes but larger â€“ the dividing line for size is about 100 nanometers. Both are much smaller than red blood cells.
EUH blood bank director John Roback recently gave a talk on the blood storage issue, and afterwards, cardiologist Charles Searles and research fellow Adam Mitchell were discussing their work on microparticles that come from red blood cells (RBCs). They have been examining the effects RBC-derived microparticles have on endothelial cells, which line blood vessels, and on immune cellsâ€™ stickiness.
Mitchell mentioned that he had some striking electron microscope images of microparticles and some of the particles looked like worms. With the aim of maintaining Lab Landâ€™s â€œCool Imageâ€ feature, I resolved to obtain a few of his photos, and Mitchell generously provided several.
â€œThose worms definitely had me mesmerized for a while,â€ he says.
In his talk, Roback described some of the metabolomics research he has been pursuing with Dean Jones. Instead of focusing only on how long blood should be stored, Robackâ€™s team is examining how much differences between donors may affect donated bloodâ€™s capacity to retain its freshness. Read more
Biomedical engineer Mike Davis reports he has obtained NHLBI funding to look into therapeutic applications of exosomes in cardiology. But wait. What are exosomes? Time for an explainer!
Exosomes are tiny membrane-wrapped bags, which form inside cells and are then spat out. Theyâ€™re about 100 or 150 nanometers in diameter. Thatâ€™s smaller than the smallest bacteria, and about as large as a single influenza or HIV virion. Theyâ€™re not visible under a light microscope, but are detectable with an electron microscope.
Scientific interestÂ in exosomes shot up after it was discovered that they can contain RNA, specifically microRNAs, which inhibit the activity of other genes. This could be another way in which cells talk to each other long-distance, besides secreting proteins or hormones. Exosomes are thus something like viruses, without the infectivity.
Since researchers are finding that microRNAs have potential as therapeutic agents, why not harness the vehicles that cells use to send microRNAs to each other? Similarly, if so much evidence points toward the main effect of cell therapy coming from what the cells make rather than the cells themselves, why not simply harvest what the cells make? Read more