The ASEMV2020 organizing committee would like to congratulate the winners of this year’s Young Investigator Awards. There were three speaker awards, for talks by a Young Investigator, a postdoctoral scholar, and a Ph.D. candidate. There are also two poster winners.
Moran Amit Assistant Professor Department of Head and Neck Surgery – Research Division of Surgery University of Texas MD Anderson Cancer Center
for work on the role of p53 and axonogenesis in cancer
Frederik Verweij Post-Doctoral Fellow Team van Niel Institute of Psychiatry and Neuroscience of Paris
for research on EV biology in a zebrafish model system
See Dr. Verweij’s recent #WebEVTalk outlining the zebrafish model system for tracking EVs.
Hannah McMillan Ph.D. Candidate Kuehn Lab Department of Molecular Genetics and Microbiology Duke University
for studies on the protective immune pathways in plants elicited by bacterial OMVs
Killian O’Brien Post-Doctoral Fellow Breakefield Lab Harvard Medical School & Massachusetts General Hospital
for research on understanding the intracellular fate of EV-delivered content
Kathleen Lennon Ph.D. Candidate Talisman Lab Irell and Manella Graduate School of Biological Sciences City of Hope
for work on EV characterization using quantitative Single Molecule Localization Microscopy (qSMLM)
This blog originated as a press release from The Ohio State University. Thanks to them for allowing us to repost it here.
Dr. Raphael Pollock has earned the reputation as one of the world’s best surgical oncologists for patients facing one of the toughest cancers to treat, sarcoma. Frequently these tumors start out in the very deepest recesses of the retroperitoneum, the part of the abdomen where the kidneys, pancreas and inferior vena cava are located.
Dr. Raphael Pollock
Director of The Ohio State University Comprehensive Cancer Center, Pollock’s 30 years of experience in the operating room naturally led him to ponder the steps before surgery, specifically if there were better ways to diagnose or detect sarcomas. In early 2019, he tapped into Ohio State’s scientific breadth and depth to investigate a new diagnostic method based upon research he conducted while at MD Anderson Cancer Center in Houston. He reached out to Shaurya Prakash, associate professor of mechanical and aerospace engineering and an expert in microfluidics.
Currently, there are two predominant options to acquire a diagnostic biopsy of a tumor deep in the abdomen: invasive surgery under general anesthesia; or a method utilizing computed tomography (CT) scans to guide a long needle through the skin to acquire tissue from the mass. Both are expensive and take time to schedule.
“I’ve been interested for a while in the role of exosomes in the spread of cancers,” Pollock said. Exosomes are extracellular vesicles containing constituents—protein, DNA, and RNA—of the cells that secrete them. They can affect function and behavior of other cells with which they interact. Until recently, they were regarded as merely cell waste products without much clinical research relevance.
Dr. Shaurya Prakash
“We learned that there are a number of things inside the exosomes that interact potentially with cells in the tumor microenvironment,” he added. “Then they circulate in the bloodstream and land in other parts of the body.”
So Pollock asked Prakash if there could be an efficient way of extracting these exosomes from a peripheral blood sample to obtain the contents that might be used to diagnose a tumor deep within the body. The microfluidics expert was intrigued.
“I learned that often by the time sarcomas are diagnosed, the disease state is very advanced,” Prakash said. “The value of isolating these circulating biomarkers is earlier detection. Prognosis is better with earlier detection and diagnosis.”
In the past, Pollock had employed ultracentrifugation to isolate exosomes from blood, but it was arduous and expensive. He and Prakash reviewed the literature and realized there might be several different engineering concepts that could be leveraged to improve the process.
Size-based filtration was first, since exosome size is quite specific. Prakash’s previous water treatment research was useful in developing a microfluidic filtration system. Their second area of focus was targeting a surface marker or protein with monoclonal antibodies to attach, secure and extract the exosomes.
Microfluidic device prototype
The duo’s prototype microfluidic device integrates size-based separation followed by immunoaffinity-based capture of extracellular vesicles in one process. They also are exploring the use of electrical charge to enhance the exosome filtering.
Prakash and Pollock have submitted two manuscripts—one of which was published recently in the Journal of Microelectromechanical Systems—demonstrating their device is more effective than ultracentrifugation in terms of time, yield, and purity.
The collaboration is just the latest example of an emerging partnership between the College of Engineering and The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute.
“These circulating biomarkers are a very small fraction of the overall constituency of blood,” explained Prakash. “The real engineering challenge is extracting that proverbial needle from a haystack. And how do you sort that out and get the right needle.”
Exploded view of microfluidic channels separated by a nanocapillary array membrane. The dotted line represents the cross-section that was utilized for SEM characterization of the device, as seen inset. Only a portion of captured exosomes may have been connected to the tumor, so capturing as many as possible within a blood sample is critical.
Beyond the manuscripts, the research team is gearing up to submit a proposal. Coincidentally, the National Cancer Institute is now seeking proposals that focus on developing new methodologies to extract exosomes to investigate whether the cargo inside may be applicable as biomarkers for cancer.
“We’re now in a position to really drill down into the engineering concepts of the device,” Pollock said.
He added that while this type of device could be applied to many types of cancers, it is especially advantageous for sarcoma diagnosis.
“After a long operation to remove a confirmed tumor, it is very difficult in scans to differentiate tumor recurrence from post-surgical scarring,” he explained. “But if you can detect something a tumor releases in the bloodstream, that provides you with a higher index of suspicion of what you may be seeing on a scan.
“Instead of relying on repeat scans over months to determine size increase or decrease, we can potentially identify recurrence at a very early point when the total volume of recurrence is small and more amenable to treatment. We’re very excited about the potential.”
Looking ahead, Prakash and Pollock want to build toward a systematic clinical trial. While there is nothing in the prototype device that cannot be used in a clinical trial, Prakash said some optimization would be required.
“It’s been a total partnership,” Pollock said. “None of this would have happened without the mutual interest and opportunities to communicate about possibilities.”
The research team included mechanical and aerospace engineering PhD student Prashanth Mohana Sundaram, and Lucia Casadei, Gonzalo Lopez, Danielle Braggio and Gita Balakirsky from the Comprehensive Cancer Center.
This blog originated as a press release from Duke Health. Thanks to them for allowing us to repost it here.
DURHAM, N.C. – A team of Duke Health scientists have identified biomarkers that accurately identify numerous viral infections across the clinical stages of disease, advancing a potential new way to guide treatment, quarantine decisions, and other clinical and public health interventions in the setting of endemic and pandemic infectious diseases.
The blood-based test uses a gene expression assay to correctly predict nine different respiratory viral infections including influenza, enterovirus, adenovirus, and coronaviruses known to cause common colds. It shows the body’s genes responding to a pathogen before symptoms are present.
This blog originated as a press release from Cedars-Sinai. Thanks to them for allowing us to repost it here.
Analysis of particles shed by tumors points to new, less invasive way to diagnose malignancies
A recent study sheds light on proteins in particles called extracellular vesicles, which are released by tumor cells into the bloodstream and promote the spread of cancer. The findings suggest how a blood test involving these vesicles might be used to diagnose cancer in the future, avoiding the need for invasive surgical biopsies.
This blog originated as a press release from the University of Sussex. Thanks to them for allowing us to repost it here.
Scientists at the University of Sussex have identified a potential pattern within blood which signals the presence of motor neuron disease; a discovery which could significantly improve diagnosis.
Currently, it can take up to a year for a patient to be diagnosed with amyotrophic lateral sclerosis (ALS), more commonly known as motor neuron disease (MND).
But after comparing blood samples from patients with ALS, those with other motor-related neurological diseases, and healthy patients, researchers were able to identify specific biomarkers which act as a diagnostic signature for the disease.
This blog originated as a press release from ISGlobal, the Barcelona Institute for Global Health. Thanks to ISGlobal for permission to post it here.
A new study shows that extracellular vesicles from the malaria parasite Plasmodium vivax promote parasite adhesion to spleen cells
Extracellular vesicles (EVs) play a role in the pathogenesis of malaria vivax, according to a study led by researchers from the Barcelona Institute for Global Health (ISGlobal), an institution supported by the ”la Caixa” Foundation, and the Germans Trias i Pujol Research Institute (IGTP). The findings, published in Nature Communications, indicate that EVs from P. vivax patients communicate with spleen fibroblasts promoting the adhesion of parasite-infected red blood cells. These data provide important insights into the pathology of vivax malaria. The study was carried out at the Can Ruti Campus, with the participation of the IGTP Genomics platform, the Nephrology service of the Germans Trias i Pujos Hospital, and researchers from the Irsicaixa AIDS Research Institute.
With a focus on screening local healthcare workers and first responders, the epidemiological study seeks to understand the prevalence of coronavirus infections in the community. The lab of ERCC2’s Louise Laurent is part of the core research team.
LA JOLLA, CA—A consortium that includes many of San Diego’s top medical and scientific research institutes has launched a large-scale COVID-19 screening effort to better understand the spread and prevalence of the virus in the local community, with an initial focus on evaluating healthcare workers and first responders.
As testing for the coronavirus continues throughout the United States, researchers have been closely watching results, particularly reported rates of false negatives.
According to the Radiological Society of North America, a reported 40 to 70 percent of coronavirus tests from throat swab samples returned false negatives at the onset of the epidemic. Given the highly infectious nature of this particular coronavirus, individuals receiving false negative results — told they do not carry the virus when in fact they do — could continue to infect others.
“It is very concerning,” said Hsueh-Chia Chang, the Bayer Professor of Chemical and Biomolecular Engineering at the University of Notre Dame. “In an overcrowded hospital, where there is only room to quarantine the COVID-19 carriers, false negatives would mean some carriers can continue to infect other patients and healthcare workers. This, unfortunately, is also true for other infectious viral diseases such as dengue and malaria, when there is an epidemic. False negatives are usually not an urgent problem, when every symptomatic patient can be quarantined and there are fewer people to infect — until an epidemic overcrowds our hospitals and we have only enough space to sequester the carriers.”
At Notre Dame, Chang’s research lab focuses on the development of new diagnostic and micro/nanofluidic devices that are portable, sensitive and fast. His work includes diagnostics with applications to DNA/RNA sensing. Current coronavirus tests are RNA-based.
Chang said technology his lab developed for other uses could easily be extended to apply to testing for the coronavirus.
Researchers at the University of California San Diego discovered that high blood levels of RNA produced by the PHGDH gene could serve as a biomarker for early detection of Alzheimer’s disease. The work could lead to the development of a blood test to identify individuals who will develop the disease years before they show symptoms.
The PHGDH gene produces RNA and proteins that are critical for brain development and function in infants, children, and adolescents. As people get older, the gene typically ramps down its production of these RNAs and proteins. The new study, led by Sheng Zhong, a professor of bioengineering at the UC San Diego Jacobs School of Engineering in collaboration with Dr. Edward Koo, a professor of neuroscience at the UC San Diego School of Medicine, suggests that overproduction of extracellular RNA (exRNA) by the PHGDH gene in the elderly could provide an early warning sign of Alzheimer’s disease.
“Several known changes associated with Alzheimer’s disease usually show up around the time of clinical diagnosis, which is a little too late. We had a hunch that there is a molecular predictor that would show up years before, and that’s what motivated this study,” Zhong said.
Extracellular vesicles (EVs) regulate many processes in the healthy body. They also play a role in cancer, sending signals between cells in the tumor microenvironment. EVs can stimulate tumor cell migration, invasion, blood vessel growth, immune response, and cell survival, as well as metastasis. However, we know little about the cargo of these EVs that play such diverse roles. Analysis of vesicle cargo can shed light on the molecular mechanisms of vesicle biology and be helpful in disease diagnosis and prognosis.
I am lucky to be a member in Jan Lötvall’s lab in Gothenburg, Sweden, which pioneered the field of extracellular vesicles with the early discovery of exosomes shuttling RNA between cells. An exciting collaboration with Yong Song Gho from POSTECH in South Korea led us to develop a new approach to isolate vesicles from human tumor tissues. Using this technology, we were able to isolate and characterize subpopulations of extracellular vesicles from melanoma metastatic tissue. We just published our findings in the Journal of Extracellular Vesicles. Jan Lötvall also discussed them in a recent ERCC webinar.