THE
BIO ISSUE
05 Prescription: Precision 014 Measuring Up 018 Medical Mending
FALL 2019
PUBLISHERS Sandra Watson Steven G. Zylstra
EDITOR
Don Rodriguez
EXECUTIVE EDITORIAL DIRECTOR Susan E. Marie
ART DIRECTOR Erin Loukili Lucky You! Creative
www.luckyyoucreative.com
DESIGNER
Jaclyn Threadgill
CONTRIBUTING WRITERS
05 PRESCRIPTION: PRECISION
+ TGen
Kerry Bennett Joe Caspermeyer Monique Clement Paul Tumarkin Steve Yozwiak
E-MAIL techconnect@aztechcouncil.org For queries or customer service call 602-343-8324
Translational Genomics Research Institute offers a glimpse of how it’s changing lives. 014
ASU team takes charge of characterizing body’s electrical properties.
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TechConnect is published by the Arizona Technology Council, 2800 N. Central Ave. #1530, Phoenix, AZ 85004.
Entire contents copyright 2019, Arizona Technology Council. Reproduction in whole or in part without permission is prohibited. Products named in these page pages are trade names or trademarks of their respective companies. Publication of TechConnect is supported by the Arizona Commerce Authority.
NAU researchers’ technology speeds process of wound healing.
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Radioisotope detection at UA leads to rewarding results.
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Publisher’s Letter
Living the Good Life hether you first heard the term used in school or traced its origin to the ancient Greeks, “bio” is the root word meaning “life.” Who would have thought it also would represent a sector that has breathed life into the Arizona economy? Whether you use the word biotechnology, bioscience or one of a number of related words— the lines are quickly blurring—“bio” in Arizona has made a major impact as it has taken root in our state. In this issue of TechConnect, we turn the spotlight on regular editorial contributors to our magazine and the bio industry here: the Translational Genomics Research Institute (TGen), Arizona State University, Northern Arizona University and The University of Arizona. It was hard to decide what news to feature from each since they all are making their marks. So, consider this just a sample. By no means are they the only names you’ll find on the bio landscape. According to the report “2017 Progress of the Biosciences in Arizona” published by the Flinn Foundation, the state in 2016 had 1,446 bioscience firms, including hundreds of small businesses. Also, the number of Arizona bioscience grew by 58% from 2002 to 2016. Add to that, bioscience workers’ annual wages were on average 33% higher than those in the private sector here. Apparently, we’re just getting started. The collective efforts of the bio community laid the foundation for new developments that made headlines recently. Over the next two years in Phoenix, it’s estimated that more than $3 billion in private, institutional and university capital investment in bio will be made
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STEVEN G. ZYLSTRA
throughout the city. When the last construction worker leaves the final worksite, the city will have more than 4 million square feet of new bioscience and healthcare facilities. The buildings are expected to be filled with more than 7,000 new jobs projected to have an annual payroll of nearly $500 million. The catalyst that ultimately led to this point was TGen, which launched its operations in downtown Phoenix in 2002. The late Sen. John McCain and then-Gov. Jane Dee Hull convinced Dr. Jeffrey Trent to leave his post as scientific director of the National Genome Research Institute at the National Institutes of Health and return to his home state to lead operations at TGen. The universities also took on bigger roles in the arena over the years. Expect more to come as the Arizona Legislature recently authorized the three universities to use $1 billion in bonding for construction and expansion of bioscience research facilities, increasing opportunities for stronger research performance and economic impact. So, if the term “bio” stirs memories of that high school science class that made you wonder if it would ever be useful to you, the answer is “yes.” Because no matter what you call it, bio has found its home in Arizona and we’re all the better for it. STEVEN G. ZYLSTRA is president and CEO of the Arizona Technology Council and Arizona Technology Council Foundation.
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BUILDING A BRIDGE Study reveals tie in human and canine cancer treatment Dr. Will Hendricks
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espite those velvet paintings of poker-playing dogs smoking pipes, cigars and cigarettes, our canine friends really don’t use tobacco. But like many humans who have never smoked, dogs still get lung cancer. And, like many women who develop a particular type of breast cancer, the same gene — HER2 — also appears to be the cause of lung cancer in many dogs, according to a promising new study of pet dogs led by the Translational Genomics Research Institute (TGen), an affiliate of the City of Hope, and The Ohio State University. Published Aug. 20 in the journal Clinical Cancer Research, the study “Identification of recurrent activating HER2 mutations in primary canine pulmonary adenocarcinoma” could have significant implications for people who have never smoked. Lung cancer is the leading cause of cancer death in the U.S., annually taking the lives of more than 154,000 Americans. TGen and Ohio State found that neratinib—a drug that has successfully been used to battle human breast cancer—might also work for many of the nearly 40,000 dogs in the U.S. that annually develop the most common type of canine lung cancer known as canine pulmonary adenocarcinoma (CPAC). Neratinib inhibits a mutant cancer-causing form of the gene HER2, which is common to both CPAC and HER2-positive human breast cancer patients. “With colleagues at Ohio State, we found a novel HER2 mutation in nearly half of dogs with CPAC. We now have a candidate
therapeutic opportunity for a large proportion of dogs with lung cancer,” says Dr. Will Hendricks, the study’s senior author who is an assistant professor in TGen’s Integrated Cancer Genomics Division and director of Institutional Research Initiatives. Based on the results from this study, a clinical trial using neratinib is planned for dogs with naturally occurring lung cancer that have the HER2 mutation. No dogs were harmed in the study, which lays the foundation for potential rapid translational development. Only pet dogs with naturally occurring cancer were examined. CPAC is an aggressive disease that clinically resembles human lung cancer among never-smokers. There is no standard-of-care treatment and little was known of the disease’s genetic underpinnings prior to the work performed by the TGen-Ohio State team. While the sequencing of hundreds of thousands of human cancer genomes has driven the transformational development of precise targeted cancer treatments for humans over the past decade, relatively few canine cancer genomes have undergone similar profiling. The canine cancer genomic discovery and drug development efforts of the TGen-Ohio State team are pieces of a larger puzzle that could similarly transform veterinary oncology, while creating bridges between canine and human cancer drug development. “This study is groundbreaking because it not only identified a recurring mutation in a
All stories written by Steve Yozwiak, senior science writer for the Translational Genomics Research Institute (TGen).
CONNECT AT WWW.TGEN.ORG FALL 2019 TECH CONNECT
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canine cancer that had never been found before but it actually led directly to a clinical trial,” says Dr. Jeff Trent, TGen president and research director, and one of the study’s contributing authors. “This clinical translation from dog to human and back is the holy grail of comparative cancer research.” Hendricks adds, “This study is really
A DIFFERENT PATH FORWARD Sen Peng
Team finds unique way to battle children’s brain cancer
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n international team of researchers led by Yale University, University of Iowa and the Translational Genomics Research Institute (TGen), an affiliate of City of Hope, has discovered a new pathway that may improve success against an incurable type of children’s brain cancer. The study results published Aug. 22 in the scientific journal Nature Communications suggest scientists have identified a unique way to disrupt the cellular process that contributes to diffuse intrinsic pontine gliomas (DIPG), a highly aggressive and inoperable type of tumor that grows in the brain stem. While the number of patients affected in the U.S. is small—about 300 annually—DIPG is recognized as a profoundly tragic illness. This cancer usually strikes children younger than 10, with most patients not surviving more than a year after diagnosis. Earlier studies identified a genetic mutation called PPM1D—critical for cell growth and cell stress response—as a contributor to DIPG. Previous efforts to directly attack the PPM1D mutation, however, proved futile in controlling DIPG. The TGen-Yale-Iowa led team discovered a vulnerability in the metabolic process for creating NAD, a metabolite that is necessary for all cell life.
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exciting to us because, not only have we found a recurrent hot-spot mutation in a canine cancer that had never been found before but it actually has direct clinical translational relevance. For humans, we already have drugs that can inhibit many dysregulated proteins. We hope to show that we can provide the same benefit for dogs with canine cancers.”
“This is really an amazing new way to attack this cancer. We found that the mutated gene PPM1D essentially sets the stage for its own demise,” says Michael Berens, one of the study’s senior authors who is a TGen deputy director and head of TGen’s DIPG research. Researchers found that mutated PPM1D silences a gene called NAPRT, which is key to the production of the NAD metabolite. With NAPRT unavailable, the cell switches to another protein needed to create NAD called NAMPT. By using a drug that inhibits the production of NAMPT, researchers found they could essentially starve to death those cancer cells with the PPM1D mutation. Researchers had long thought DIPG was a childhood version of adult brain tumors, so similar treatments for adult gliomas were tested extensively in children—and failed. Frustration over the lack of an effective therapy for DIPG led the researchers to take a different approach in the search for new drugs to treat this disease. They chose to look at the tumor in terms of its potential vulnerabilities, thus beginning a year-long molecular journey to understand what role the PPM1D mutation played in altering cancer metabolism. “When epigenetic silencing results were analyzed, we were gratified to discover that DIPG cells with the PPM1D mutation had created a vulnerability to a key enzyme for which small molecule inhibitors were already available,” says Sen Peng, a bioinformatician in TGen’s Cancer & Cell Biology Division and one of the study’s contributing authors.
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CLUES TO THE FUTURE Alzheimer’s memory changes may appear decades before onset
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esults from a study of nearly 60,000 individuals suggest those at higher risk of developing Alzheimer’s disease due to family history may demonstrate changes in memory performance as early as their 20s. Researchers from the Translational Genomics Research Institute (TGen), an affiliate of City of Hope, and The University of Arizona gathered the data through an online word-pair memory test called MindCrowd, one of the world’s largest scientific assessments of how healthy brains function. Published June 18 in the scientific journal eLife, study data suggests that those with a family history of Alzheimer’s disease and are younger than 65 on average do not perform as well as their peers who do not have a family history of Alzheimer’s, the most common form of dementia. The study results suggest that the family history effect is particularly pronounced among men, as well as those with lower educational attainment, diabetes and carriers of a common genetic change in APOE, a gene long associated with Alzheimer’s disease risk. While family history has previously been associated with the risk of Alzheimer’s, this is the first study of its kind that in these numbers indicates the risk can be detected up to four decades before the typical age of onset. The study looked at 59,571 MindCrowd participants aged 18-85, and the effect of family history was shown across every age group until age 65. “In this study we show that family history is associated with reduced paired-associate learning performance as many as four decades before the typical onset of Alzheimer’s disease,” says Dr. Matt Huentelman, the study’s senior author who is TGen professor of neurogenomics. Because there is no cure or proven way of slowing progressive memory loss among those with Alzheimer’s, early indicators of the disease can help those at risk to focus on ways to help stave off dementia.
Dr. Matt Huentelman
Alzheimer’s is a progressive neurological disorder that typically presents clinically as deficits in memory and thinking. It is estimated that more than 5 million Americans are living with Alzheimer’s, and that by 2050 that number will nearly triple to almost 14 million. The MindCrowd study (www.mindcrowd. org) began in 2013. By August 2018, it had nearly 60,000 qualified participants whose performance is reflected in the study. Today, more than 125,000 people, aged 18-95—from all 50 states and 150 nations around the world—have completed the MindCrowd assessment. MindCrowd cannot tell you if you have Alzheimer’s. What it does give researchers is a set of data baselines about how people not suffering from the disease perform at different ages; among men and women, among those with quick and slow physical responses, among those who smoke and those who don’t, and among many other demographic, lifestyle and health factors. Establishing these baselines will help researchers to more properly evaluate Alzheimer’s patients and usher in a new era of what the MindCrowd developers describe as Precision Aging. The Arizona Alzheimer’s Consortium, the Norwegian University of Science and Technology, and the University of Miami also contributed to the study. The authors also acknowledge the support of many individual donors, and the social media recruitment efforts of actors Lynda Carter, Valerie Bertinelli and Ashton Kutcher. FALL 2019 TECH CONNECT
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‘LIQUID BIOPSY’ New blood test improves breast cancer diagnostics
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new type of blood test for breast cancer could help avoid thousands of unnecessary surgeries and otherwise precisely monitor disease progression, according to a study led by the Translational Genomics Research Institute (TGen) and Mayo Clinic in Arizona. TGen is an affiliate of City of Hope, which along with The Cancer Research UK Cambridge Institute at Cambridge University and the Biodesign Institute at Arizona State University (ASU) also contributed to this study. Published Aug. 7 in the premier journal Science Translational Medicine, the study “Personalized circulating tumor DNA analysis to detect residual disease after neoadjuvant therapy in breast cancer” suggests that the test called TARDIS—TARgeted DIgital Sequencing— is as much as 100 times more sensitive than other blood-based cancer monitoring tests. TARDIS is a “liquid biopsy” that specifically identifies and quantifies circulating tumor DNA (ctDNA), which are small fragments of cancer DNA circulating in the patient’s bloodstream. According to the study, TARDIS detected ctDNA in as low as 2 parts per 100,000 in patient blood. “By precisely measuring ctDNA, this test can detect the presence of residual cancer and inform physicians if cancer has been successfully eradicated by treatment,” says Muhammed Murtaza, a senior author of the study who is assistant professor and co-director of TGen’s Center for Noninvasive Diagnostics. He also holds a joint appointment on the research faculty at Mayo Clinic in Arizona. For example, Murtaza explained, TARDIS is precise enough to tell if early-stage breast
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Muhammed Murtaza
cancer patients have responded well to pre-operative drug therapy. It is more sensitive than the current method of determining response to drug therapy using imaging. Unlike traditional biopsies, which only produce results from one place at one time, liquid biopsies use a simple blood draw, and so could safely be performed as often as needed to detect a patient’s disease status. Following further clinical testing and trials, TARDIS could someday be routinely used for monitoring patients during cancer treatment, and discovering when patients are essentially cured and cancer free. “The results of these tests could be used to individualize cancer therapy, avoiding overtreatment in some cases and undertreatment in others,” Murtaza says. “The central premise of our research is whether we can develop a blood test that can tell patients who have been completely cured apart from patients who have residual disease. We wondered whether we can see clearance of ctDNA from blood in patients who respond well to pre-surgical treatment.”
UPDATE TGEN
Current tests and imaging lack the sensitivity needed to make this determination. The study results suggest that personalized ctDNA analysis using TARDIS is a promising approach to identifying patients with a curative response following pre-surgical drug therapy. “Together with imaging and tissue-based
predictive biomarkers, ctDNA is rapidly becoming a useful diagnostic test to determine individualized decisions about additional treatment,” Murtaza says. Patient samples for this study were collected at Mayo Clinic, Addenbrookes Hospital at the University of Cambridge, and City of Hope.
LINKS TO LIVER Research reveals connection between gene and severe organ damage
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esearchers have found that a gene known as AEBP1 may play a central role in the development, severity and potential treatment of liver disease, according to a study by Temple University, the Geisinger Obesity Institute and the Translational Genomics Research Institute (TGen), an affiliate of City of Hope. The findings are detailed in the study “AEBP1 expression increases with severity of fibrosis in NASH and is regulated by glucose, palmitate, and miR-372-3p” published July 12 in the scientific journal PLoS One. The study results suggest that increased expression of AEBP1 correlates with the severity of liver fibrosis in patients with NASH (nonalcoholic steatohepatitis), a type of NAFLD (nonalcoholic fatty liver disease) that is the most common cause of liver damage. NASH indicates there is both inflammation and liver cell damage along with fat in the liver. “Given the strong link between fibrosis and risk of liver-related mortality, efforts to identify and characterize the specific mechanisms contributing to NAFLD progression are critical for the development of effective therapeutic and preventative strategies,” says Dr. Johanna DiStefano, head of the Diabetes and Fibrotic Disease Unit at TGen.
Dr. Johanna DiStefano
One of the study’s major findings is that AEBP1 regulates the expression of a network of at least nine genes related to fibrosis: AKR1B10, CCDC80, DPT, EFEMP1, ITGBL1, LAMC3, MOXD1, SPP1, and STMN2. “These findings indicate that AEBP1 may be a central regulator of a complex fibrosis gene expression network in the human liver,” says DiStefano, the study’s senior author. The study suggests that: • AEBP1 contributes to liver fibrosis by modulating a gene network specific to stellate cells, the key fibrogenic cells of the liver. • AEBP1 expression is increased by obesity-related factors linked to NAFLD, including the sugars glucose and fructose, and palmitate, a fatty acid commonly found in processed foods. • Two microRNAs—miR-372-3p and miR373-3p—that otherwise limit the expression of AEBP1 are reduced in NASH patients with advanced fibrosis. MicroRNAs constitute a recently discovered class of non-coding RNAs that play key roles in the regulation of gene expression. FALL 2019 TECH CONNECT
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Associate Professor Rosalind Sadleir’s research focuses on accurately measuring the electrical signals of various tissues in the human body, often for the first time. photo by erika gronek/asu
MEASURING UP
Team works to better gauge electrical properties in the body WRITING BY >< MONIQUE CLEMENT
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our body is bustling with electrical activity. Knowing how cells and tissues conduct electricity is important to understanding readings from medical imaging systems that detect traces of these signals. Distinguishing between normal and unexpected electrical activity in the body is a key part of diagnosing many diseases. However, measuring the electrical properties of different types of tissue is tricky, and common methods of measurement don’t fully capture what’s happening in the body. Rosalind Sadleir, an associate professor of biomedical engineering in the Ira A. Fulton Schools of Engineering at Arizona State University, is working to resolve these shortcomings. She’s exploring how new methods and applications of current technologies can better characterize the body’s electrical properties, especially in the brain. Sadleir’s research is being supported by three National Institutes of Health grants—including one that is part of the Brain Research through Advancing Innovative Neurotechnologies, or the BRAIN
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Initiative—which fund her work to detect neural activity and map current flow. “The focus is to figure out the operation of the normal brain, and to try to give us some information about the connection between where current is flowing and what parts of the brain are active as a result,” Sadleir says. Historically, electrical properties have typically been measured with electrodes placed on dissected or biopsied tissues, often from dissected animal tissues or anesthetized animals—an invasive procedure that yields inaccurate results. “The moment you cut tissue out of somebody, the properties start changing immediately,” says Sadleir, who leads the Neuro-electricity Laboratory where researchers are working to advance the understanding of electrical activity and properties of the brain. The last major publication of this type of data was released in 1996, with relatively few updates since then. However, many models of tissue electrical properties use this outdated, possibly inaccurate data. Sadleir wants to go back to square one, gathering the baseline data in humans in
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noninvasive ways to determine the normal electrical conductance values of living tissues. In particular, she wants to measure the low-frequency range of detection because it is the hardest range to capture and the least measured. Of most interest to researchers are properties in the range of 1 kHz to 20 kHz because those are the frequencies characteristic of the body’s natural processes. For example, the heart beats around 1 Hz, or once per second, and neural activity mostly occurs in the 1 kHz range. Measurement of electrical properties in this low-frequency range therefore aids understanding of the interplay of activity and conduction of signals through the brain. One method her team is using is magnetic resonance electrical impedance tomography, or MREIT. This involves putting electrodes on a person’s body that deliver an electrical current and create a magnetic field. The person then is placed inside an MRI machine that measures the magnetic field. Through this process, Sadleir’s team is able to characterize living tissues’ electrical properties. Because electrical current can also be used as a therapy, the passage of current to different brain tissues can also be measured, potentially allowing mechanisms of action of these methods to be explored. “The image we see from the MRI data is the direct effect of the current flow through the tissue,” Sadleir says. This isn’t a new method but Sadleir’s team is tailoring it to be used with living humans—a key difference from past use that involved simulated tissues or animal tissues. The results will help scientists conducting neuroscience and neuromodulation research (changing the brain’s activity by applying electricity). In these types of research, accurate values are necessary for developing new treatments and new understanding of the brain. Beyond low-frequency measurements, Sadleir’s team is also developing a
spectroscopic technique to help fill this knowledge gap for living human tissue. Knowing the measurements along the range of frequencies helps reveal the biophysics of the tissue, making it possible to get an accurate picture of what’s happening in the body as it interacts with both the body’s own internal signals, and with externally applied therapies. In electroencephalogram, or EEG, for example, tiny signals that originated deep inside the body are measured on the scalp to help scientists “see” what’s happening in the brain. “The way signals travel between the place where they originate and your scalp has all to do with the electrical properties of the tissues in between,” Sadleir says. “In order to figure out where the signals are coming from, people have relied on the old conductivity measurements to make their estimations, which means their estimations are affected.” Going forward, Sadleir is interested in measuring a wider variety of tissues than brain tissues and at a wider range of frequencies. She is particularly interested in skull bone conductivity “because its properties are very difficult to measure using traditional techniques, and they are critical determinants in locating (electrical signal) sources using EEG.” “There’s been some controversy about what the properties of the skull are, and they’re extremely important—perhaps the most important tissue—for all of these transcranially applied techniques,” Sadleir says. This fall, she’s joined by a new cohort of magnetic resonance researchers in the School of Biological and Health Systems Engineering, one of the six Fulton Schools, who will bring a “fantastic breadth of diversity of skills and areas of interest” to the faculty. MONIQUE CLEMENT is a communications specialist for the
Ira A. Fulton Schools of Engineering.
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PLANTING THE SEED High-risk therapeutic program led to discovery of Ebola antidote
Charles Arntzen
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ecently, dramatic news came out of Africa concerning Ebola, one of the world’s deadliest and most feared diseases. New drugs can overcome the virus and save lives. Health officials from the World Health Organization (WHO) and National Institutes of Health (NIH) announced that four antidotes— including one first developed by Arizona State University and its commercial partners—had been tested in the largest Ebola clinical trial to date. The trial proved so successful, it was ended early to make the best performing antidotes widely available for the ongoing Ebola crisis in the Democratic Republic of the Congo (DRC). This is the first time that dramatic evidence has been obtained to show improved survival rates in people who had already been infected by the deadly virus. The trial also showed that the earlier health care workers can administer the antidotes after an Ebola infection, the more potential lives can be saved. This included survival rates as high as 96% for one particular antidote. The WHO trial in the DRC began last November. One of the drugs that served as the “control” was ZMapp, which had its discovery origin in work by ASU scientist Charles Arntzen in a collaboration with San Diego-based Mapp Biopharmaceutical and Kentucky Bioprocessing. The roots of the amazing Ebola cure can be traced back to Arntzen’s groundbreaking research center at ASU’s Biodesign Institute,
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WRITING BY >< JOE CASPERMEYER
where he also served as the founding director. Arntzen, who retired from ASU in 2017, had worked closely for several years with Mapp Biopharmaceutical on the idea of plant-based therapeutics to fight infectious diseases, which are still the world’s No. 1 killer. After 9/11 and the 2001 anthrax attack in the U.S. Senate office building, the government invested heavily in biodefense, including $3.7 million in 2002 to Arntzen and a small San Diego-based startup called Mapp Biopharmaceutical led by Larry Zeitlin and Kevin Whaley. The goal was to develop defenses against pathogens, including Ebola, that could be used to thwart potential bioterrorist attacks using infectious agents. “I think the real gain is from all of the money that was invested early on. It takes a long time to build up that core competency that is necessary for drug development,” Arntzen said. With a dream team of collaborators, Arntzen’s team created a “molecular toolbox” to transform tobacco plants into biological factories. Within three years after proposing this very novel concept to U.S. Army collaborators, the team achieved production of anti-Ebola monoclonal antibodies. Three antibodies with high levels of virus inactivation were included in the Ebola antidote called ZMapp. An outbreak in eastern DRC began in August 2018 and is the second-largest of the 10
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to hit the country since 1976, when Ebola was first discovered. What made the latest outbreak more alarming was news that Ebola for the first time was spreading to big city populations. This time, the world is much better prepared for the virus. There has been remarkable progress made toward developing an Ebola vaccine, which has been shown to be 99% effective. The first vaccine made by the drug company Merck was successfully deployed in Guinea in 2015. More than 160,000 people have received it to date. But for those who haven’t been vaccinated until now, there was little hope and no cure after infection. Not everybody is vaccinated. The vaccine has been reserved for only those who come into direct contact with an Ebola patient and their families. And some people simply refused to take it. Last November, the WHO and NIH began a new clinical trial to test the newest available Ebola antidotes in the DRC. The clinical trial used ZMapp as the control drug, and compared it to three different drugs, including two newer drugs based on the ZMapp concept. ZMapp is a cocktail made up of three monoclonal antibodies, Y-shaped proteins in the body that can recognize the specific spiky shapes on the outer shell of the Ebola virus then recruit immune cells to attack it. The goal of the trial was to compare ZMapp with newer formulations based on the same principle. The drug mAb114 was developed using antibodies harvested from survivors of Ebola while REGN-EB3, like ZMapp, is a cocktail of antibodies which specifically target the
Ebola virus to inactivate it. A broad-spectrum antiviral compound, remdesivir, was the fourth drug tested in the trial. Since the start of the recent clinical trial, the four experimental drugs have been tested on around 700 patients, with the preliminary results from the first 499 now known. There were only limited and preliminary data available at this point but they showed mortality rates of 49% in people treated with ZMapp, 53% in those who received remdesivir, 34% in people treated with mAb114, and 29% for people who received the Regeneron cocktail (compared with two out of three people, or 67%, who die if not treated). The results were most striking for patients who received treatments soon after first becoming sick with Ebola symptoms. In this instance, death rates dropped to 11% with mAb114 and just 6% with Regeneron’s drug, compared with 24% with ZMapp and 33% with remdesivir. As a result of the trial, the WHO and NIH agreed that all Ebola treatment units in the DRC outbreak zone will move forward, administering the two most effective monoclonal antibody drugs, the NIH’s mAB114 and Regeneron. Does the trial spell the end of ZMapp as an Ebola therapeutic? Not necessarily. Clinical trials using naturally infected individuals in settings with minimal health care facilities are complex. U.S. government agencies are continuing their funding support of more extensive ZMapp testing, including studies to find optimal dosages of the drug. JOE CASPERMEYER is manager, media relations & strategic
communications at Arizona State University.
“It takes a long time to build up that core competency that is necessary for drug development.” - FORMER ASU SCIENTIST CHARLES ARNTZEN FALL 2019 TECH CONNECT
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From left: Robert Kellar, Nathan Nieto and Andy Koppisch
MEDICAL MENDING
Patented technology speeds wound healing, prevents infection WRITING BY >< KERRY BENNETT
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he American population is aging, and conditions such as diabetes and cardiovascular disease are on the rise. With those factors in place, the medical community has growing concerns about wound treatment. According to the American Professional Wound Care Association, about 15 percent of Medicare recipients suffer chronic, nonhealing wounds at an annual cost of about $30 billion. One challenge physicians repeatedly face in treating wounds is the threat of bacterial infection. Closing the wound helps reduce the risk but if pathogens infect the compromised tissue, they can readily form biofilms, hardy communities of cells covered by a protective biopolymeric layer. This layer is difficult for conventional antibiotics to penetrate, and, as
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a consequence, biofilm mediated infections require long treatment regimens. Microbial biofilms can result in chronic infection and often cause havoc in hospitals, where they can spread. Recently, scientists have been exploring tissue engineering to treat wounds and promote better healing. One new approach is to use three-dimensional skin substitutes formed from native skin proteins through a process called electrospinning. These electrospun protein â&#x20AC;&#x153;scaffoldsâ&#x20AC;? guide cell adhesion and growth, and can be used to deliver cells, drugs and even genes into the body. Research is shifting from using synthetic materials for scaffolds to degradable, porous materials that can provide a more natural, effective and aesthetic healing environment.
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Three Northern Arizona University researchers—Robert Kellar, associate professor of practice of biology; Nathan Nieto, associate professor of biology; and Andy Koppisch, associate professor of chemistry—along with Rico Del Sesto of Dixie State University in Utah have invented a technology that speeds healing and reduces the risk of infection. The result of their effort recently was awarded a patent. The scientists developed this technology by incorporating antimicrobial materials known as ionic liquids into skin wound-healing scaffolds. Incorporation of the ionic liquid sterilizes the wound healing device and enables the resultant scaffold to resist colonization by a wide variety of microbial pathogens. The researchers envision that these properties of the scaffold will similarly reduce the risk of infection during the process of wound closure. “The unique chemical properties of ionic liquids offer significant biochemical advantages as a therapeutic to combat biofilm development,” Koppisch says. Ionic liquids are formally salts but unlike table salt, they are fluid at room temperature and at a wider range of temperatures relevant to living systems. Consequently, ionic liquids are often described as “molten organic salts.” Because they are temperature-stable and adaptable, ionic liquids can serve a variety of applications. One such application is the disruption of the protective biopolymer covering microbial biofilms and neutralization of the underlying cells, which many ionic liquids have proven uniquely suited to do. The team identified choline geranate, an ionic liquid that not only serves as a vehicle for tissue-generating cells and medications but also has powerful biofilm-killing properties of its own. It can attack established infections as well as prevent new ones from developing. The researchers see a two-fold application for the
solution: adding it to dressings commonly used in treating wounds and incorporating it into wound-healing scaffolds. Through their work, the researchers established a protocol for formation of the ionic liquid-containing scaffolds and demonstrated that choline geranate can prevent the scaffolds themselves from becoming contaminated, even with high concentrations of pathogens. The researchers are hopeful that the scaffolds will ultimately improve outcomes for patients with healing difficulties, such as diabetics with chronic wound-based infections. The technology the team uses to create scaffolds uses native skin proteins that closely align to skin, facilitating the natural healing process. “This novel technology represents a co-development effort from multiple disciplines to create a game-changing therapeutic in the space of combating chronically infected wounds,” Kellar says. The researchers have identified several other potential healing applications for the technology: • surgical incisions • burns • skin conditions such as acne • traumatic injuries from military-grade weaponry • wounds animals may suffer in a variety of contexts “We are encouraged by our early discoveries and the speed at which the university was able to secure patent protection for our ideas,” Kellar says. “Our plans moving forward include seeking additional grant funding to support continued development and investigations into opportunities to spin out the technology for commercialization.” KERRY BENNETT is Northern Arizona University’s Research
Communications Officer. Connect at nau.edu.
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SIMPLY SCINTILLATING Nanomaterials sharpen focus for radioisotope detection WRITING BY >< PAUL TUMARKIN
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o be able to treat disease, researchers must first be able to understand its workings. Given the chemical and biological complexities of disease—and life in general—this is a tall order. The development of personalized medicine will depend heavily on increased, highly detailed levels of understanding of processes that are inherently difficult to measure. For over seven decades, researchers have been using radioisotope labeling as a method for studying biochemistry and cell biology. Through this technique, scientists are able to replace atoms in chemical compounds with radioactive alternatives, allowing them to trace their progress through chemical reactions without affecting the outcome. The technology has found countless applications, from helping to discover the mechanisms of metabolism to radioactive dating to imaging the organs of the body to diagnosing and treating disease. While these detection methods are very sensitive, the results lack the resolution and timing needed to capture the biological complexity necessary for a deep understanding of the processes. To better understand biological processes, new methods for returning high-resolution data from detection of these radioisotopes are critically needed. To address the challenge, researchers at The University of Arizona have developed new materials for detecting radioisotopes that provide faster and higher resolution results than today’s generally accepted methods. These new materials were developed by Craig Aspinwall and Colleen Janczak. Aspinwall is a professor in the Department of Chemistry and Biochemistry and the Department of Biomedical Engineering, and a member of the UA BIO5 Institute and the UA Cancer Center and Sarver Heart Center at the College of Medicine – Tucson. Janczak is a research scientist in the department.
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The new technology provides previously unseen temporal and spatial resolution in radioisotope detection, and offers a more environmentally sound alternative by reducing overall hazardous chemical usage and waste associated with previous radioisotope detection methods. Development of these materials began with research projects in the Aspinwall lab. Upon realizing that these materials could provide several key advantages over the current state-of-the-art in radioisotope detection, Aspinwall and Janczak began to explore commercialization options. Working through Tech Launch Arizona (TLA), the office of the UA that commercializes inventions stemming from research, the two started the company Scintillation Nanotechnologies, LLC and licensed the technology from the UA. The company’s focus is the development and manufacture of composite nanomaterials for detecting radioisotopes in biochemical research and drug discovery applications. Janczak serves as the chief operations officer and Aspinwall as the chief science officer. The team took advantage of two key services TLA offers UA startups. First, they took part in its National Science Foundation I-Corps program, a six-week hands-on course for academic entrepreneurs that teaches lean startup methods and customer discovery. Janczak and Aspinwall also took advantage of TLA’s Asset Development funds, a program that provides funding to UA inventors for development of the technology beyond basic research and move it closer to readiness for licensing either into a startup or an existing company. Today, Scintillation Nanotechnologies has four products available that it formulates for direct sales to customers, and they continue to develop new technologies based on customer demand. PAUL TUMARKIN is senior manager, marketing and communications
at TechLaunch Arizona.
NEW MEMBERS Ambitious Spirit offers engineer design services for new product development. Drafting, design, analysis and sourcing services also are provided. American Association of University Women’s Tucson chapter of the national organization is dedicated to promoting equity for women through research, advocacy and scholarship awards. tucson-az.aauw.net/ Arizona Forward is one of the state’s leading sustainability organizations focused on major initiatives to enhance quality of life and economic growth for Arizona. arizonaforward.org Auer Precision/Auer Medical Tier 1 are contract manufacturers specializing in high- precision die cutting (stamping), close tolerance machining, tooling solutions, assembly and supply chain management. www.auerprecision.com Aviture is a dynamic, innovative software solutions firm that seeks to make a meaningful difference in the lives of its customers. It serves as a technical partner for clients across the USA. www.aviture.us.com Boreale Law brings high-quality legal advice to small and medium-sized companies with the belief that even the smallest of companies deserves access to quality legal counsel. www.borealelaw.com CCG Catalyst Consulting is a global management firm that specializes in financial services: banking, FinTech and payments. www.ccg-catalyst.com Clarkston Consulting partners with businesses in the consumer products and life sciences industries to enhance strategic decision-making, improve operational efficiency, implement new technologies, and promote business growth and market diversification. www.clarkstonconsulting.com. Cognizant innovates to find a better way for the clients who depend on the company and the customers who rely on them by implementing the technologies needed to become future-ready. www.cognizant.com
Columbia West Capital is an investment bank that advises companies on capital raising (debt and equity, and acquisition financing) and M&A (company sales, partial sales, owner exits, add-on acquisitions and valuations). www.columbiawestcap.com Crimson Agility is a services firm with an indepth knowledge of the Adobe and Magento platforms and e-commerce, including design, development, integration and marketing practices. www.crimsonagility.com Cyr3con’s unique combination of machine learning and deep web/dark web mining produces actionable cyber threat intelligence for clients. www.cyr3con.com Cyxtera Technologies combines a worldwide footprint of 50+ best-in-class data centers with a portfolio of modern, cloud-, and hybrid-ready security and analytics offerings. www.cyxtera.com Desert Metal Works fabricates a wide range of products for a large customer base—individuals, small businesses and large corporations—in a wide variety of industries. lasercutting.com First Internet Bank began with a moment of insight: Banking could be more. Do more. Its team saw that an online bank could serve customers across the nation but without the overhead costs of other banks. www.firstib.com Flora Coatings is an innovation-driven company that develops and manufactures high-performance smart sustainable coatings. It is committed to delivering safer alternates to toxic coatings and paints. www.floracoating.com HealthTrio is an SaaS provider for the health care market, providing secure webbased solutions that improve experiences in value-based care, data integration, care coordination, and member and provider engagement. www.healthtrio.com JW Marriott Tucson Starr Pass Resort & Spa is cradled in the mountains, and is rich in comfort, culture and natural beauty. jwstarrpass.com
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NEW MEMBERS Persosa is a personalization solutions company that helps brands better engage and convert customers through personalized on-site experiences. www.persosa.com PioneerB1 is an SAP Business One Gold Partner specializing in enterprise resource planning implementation and service for the SME market. www.pioneerb1.com Pipeline Design & Engineering’s engineering team can develop any tangible product or piece of equipment made from metal or plastic, and is used every day by consumers and industry. www.designtheproduct.com Precision Shooting Equipment is an archery equipment manufacturer and offers CNC machining services/anodizing services. www.psearchery.com PSG Solutions offers a seasoned and flexible team of consultants, contractors and developers who work with clients to deliver exceptional products, services and programs. www.psg-solutions.com Qlik is committed to changing the world by making it easier for people to make more insightful, data-driven decisions and act on them. www.qlik.com Renren US Holdco is the parent of Lucrativ, a sales acceleration platform; Chime, Inc., a real estate IDX platform; Lofty, an app for the real estate industry; and Trucker Path, an app for truckers. www.renren-inc.com Rogers Corporation is the world’s technology leader in innovative solutions for power electronics, advanced foams for cushioning and protective sealing, and high-frequency printed circuit materials. www.rogerscorp.com Ronstadt Insurance helps employers solve their recruitment and retention problems by offering a full suite of human resources services, as well as employee benefits and insurance products. www.ronstadtinsurance.com Rugo Machine Shop Services is a contemporary machine shop that embraces technology and innovation to provide highquality metal and plastic components at a competitive price. www.rugomachineshop.com
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To join the Arizona Technology Council, a member-supported group that represents the interests of the state’s technology community, go the www.aztechcouncil.org.
Saratech is an award-winning provider of engineering and manufacturing solutions, including product lifecycle management software, engineering and consulting services, and manufacturing hardware. www.saratech.com
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Snell & Wilmer has the ability and resources to serve countless diverse clients globally with a unique blend of gifted attorneys, exceptional staff and a commitment to service. www.swlaw.com
TowerHunter is a national retained search firm with a history of successful placement of top executives ranging from director level to CEO positions. www.towerhunter.com
Southern Arizona Arts & Cultural Alliance is a nonprofit organization dedicated to the creation, preservation and advancement of the arts. www.SAACA.org
Triad Wireless is an Internet service provider. www.triadwireless.net
SquadPod brings the people in your life together to get stuff done. Squads are the people in your life who share a common interest, and pods are where the action happens with those people. www.squadpod.com Star2Star Communications’ awardwinning, patent-pending Constellation technology overcomes the reliability and quality limitations of other hosted technologies, guaranteeing 99.999% uptime reliability while saving costs. www.star2star.com/ Structured Communication Systems is an award-winning solution provider delivering secure, cloud-connected digital infrastructure to help clients through all phases of digital transformation. www.structured.com Sunbelt Medical Management is a multi-specialty medical management and billing group focused on bringing greater efficiency to health care revenue cycle management. It also owns several medical clinics in Tucson. sunbelt-medical.com SW Presentation Skills’ services include public speaking coaching. www.swpresentationskills.com TECHSTAFF is a full-service staffing agency that specializes in placing highly skilled and professional candidates in some of today’s hottest engineering, technical and IT areas. www.techstaff.com
UC Cloud Solutions is an independent IT consulting and sales agency representative for select cloud service and IT as a service provider across the United States. www.uccloudsolutions.com University of Arizona Applied Research Corporation is a nonprofit corporation established by the university to expand its research profile by facilitating access to defense, security and intelligence research opportunities. dsri.arizona.edu/about User10 designs and develops web and mobile applications to improve how businesses engage people. It ideates, strategizes, plans, and leads collaborations that solve business problems using technology. www.user10.com Washington Technology Industry Association is a trade association serving technology companies. www.washingtontechnology.org Wexford Science + Technology works exclusively with universities, academic medical centers, and major research institutions to build mixed-use knowledge communities to spur discovery, innovation and entrepreneurs. wexfordscitech.com Yellowshark Group is a strategy consulting and technology managed services company catering to large and small businesses. www.yellowsharkgroup.com
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Marketing strategies to change your business: This intense half-day program features expert keynote speakers, interactive panel discussions, top-tier content and networking with marketing industry leaders. AZTC/ANA Members: $40 Non AZTC/ANA Members: $60
Tania Katan, CEO of Creative Trespassing How to Find Innovation Where Others See Only Limitations Steve Johnson, VP of Products at Pragmatic Marketing When Problems Drive Innovation Sheila Kloefkorn, CEO & President of KEO Marketing Whatâ&#x20AC;&#x2122;s coming in B2B Marketing and Tech Jamie Glass, CMO and Founder of Artful Thinkers How Marketing can Work with the C-Suite Dara Schulenberg, Marketing Strategies Director, Forrester The B2B Buyer has Changed, Have You?
Register now to attend: www.aztechcouncil.org/event/2019martech