TGen-NAU study generates Soviet anthrax pathogen genome from autopsy specimens

Next generation genomic analysis used to probe the former USSR’s biological weapons program

FLAGSTAFF, Ariz. — Sept. 7, 2016 — A new study by the Translational Genomics Research Institute (TGen) and Northern Arizona University (NAU) used deep DNA sequencing methods to generate the anthrax genome sequence from the victims of the 1979 anthrax outbreak in Sverdlovsk, Russia, when it was part of the USSR.

The Soviet Union produced anthrax spores on an industrial scale but repeatedly denied the existence of their biological weapons program. This study, to be published in the September issue of the journal mBio, represents a precise and detailed examination of the anthrax strain used in their weapons development, and includes an anthrax genetic database that puts the weapons strain into a global context.

“I have been studying this anthrax outbreak and these specimens for more than 20 years. Finally, using genomic technology, we could comprehensively characterize this pathogen genome,” said Dr. Paul Keim, a Regents Professor of Biology and the Cowden Endowed Chair of Microbiology at NAU, Director of TGen’s Pathogen Genomics Division, and the study’s lead author.

“This is the signature agent of the world’s largest biological weapons program and now we have it in our genetic databases. Anywhere this strain shows up again, we will be able to identify it and track it back to its source. This is now an essential part of our forensic arsenal,” said Dr. Keim, who also is Director of NAU’s Microbial Genetics & Genomics Center (MGGen).

The anthrax bacterium produces small capsules, or spores, that can lie dormant for decades. After settling inside the human lung, for example, it can cause a severe disease that, if not treated with antibiotics, kills 90 percent of those it infects.

Anthrax is found in many parts of the globe and dispersed through the human movement of animal parts contaminated with spores. Wool and hair from goats and sheep are moved globally as textiles or their precursors. When these originate in anthrax endemic regions, they can carry the spores, which are long-lived. While this bacterium has little variation from strain to strain, whole genome sequencing has identified DNA fingerprints that enable molecular epidemiology, tracing it to its source. When anthrax outbreaks occur, their whole genome profile are now routinely compared to the genetic database to identify possible sources and exclude others. This type of analysis was used by the FBI to track the spores in the 2001 anthrax letter attacks, which infected 22 people and killed five.

The Soviet Union had signed the Biological Weapons convention that prohibited the use of biological agents, including anthrax, as weapons. The United States’ biological weapons program was eliminated in a decree by President Richard Nixon in 1969, but the Soviet program was maintained and expanded in a covert fashion for decades.

In 1992, an investigative team from the United States led by noted Harvard biologist Dr. Matt Meselson characterized the 1979 Sverdlovsk outbreak by interviewing local physicians, visiting cemeteries and examining autopsy specimens. This investigation, along with accounts by Ken Alibek, a former Soviet scientist, revealed that the Sverdlovsk anthrax outbreak was due to an industrial accident.  A faulty filter at a Soviet spore production facility allowed anthrax spores, in a silent plume, to drift with the wind over the city and into the nearby countryside. Nearly 70 Sverdlovsk inhabitants died as far as three miles downwind from the facility, but more anthrax-susceptible farm animals died over 25 miles away. It remains the world’s deadliest human outbreak of inhalation anthrax.

The bacterial genomes were generated from autopsy tissue specimens of two Sverdlovsk anthrax victims. These tissues were moved to the United States with permission of Sverdlovsk pathologists to continue the investigation into the disease outbreak. From these, it was established that the anthrax pathogen was detected within their tissues and the victims died from inhaling the spores.

The Sverdlovsk anthrax genome was compared to the global genome database maintained by NAU to identify its close relatives and to look for evidence of genetic engineering. The Flagstaff research team found that this strain was closely related to other Asian isolates with very few differences to naturally occurring anthrax. There were no signs of genetic engineering.

Dr. Keim notes that the Soviets had to be very meticulous to avoid mutant variants from dominating their production stock. Invariably when wild anthrax strains are grown extensively in the laboratory, they adapt to those conditions and lose the killing power.

“The Sverdlovsk strain’s genome looked very much like those of wild strains we see across Asia,” Dr. Keim said.

Dr. Meselson, who was not part of the current paper, notes: “If this strain had been grown repeated in the laboratory, it would have mutated to a form that had less virulence and less capacity to cause anthrax. The Soviet scientists must been very meticulous in their maintenance of the natural form.”

Dr. Meselson, who is the Thomas Dudley Cabot Professor of the Natural Sciences at Harvard, is known for his 1961 discovery of messenger RNA.

This study was supported by a grant from the U.S. Department of Homeland Security.

Study validates TGen developed test for healthcare-acquired infections

Molecular-based KlebSeq assay could save lives and lower healthcare costs

FLAGSTAFF, Ariz. — Sept. 2, 2016 — A new study by the Translational Genomics Research Institute (TGen) details the design and validation of a low-cost, rapid and highly accurate screening tool — known as KlebSeq  — for potentially deadly healthcare-acquired infections (HAIs), such as Klebsiella pneumoniae. HAIs affect hundreds of thousands of patients annually and add nearly $10 billion in associated healthcare costs.

The findings, to be published in the October issue of the Journal of Clinical Microbiology, detail the workings of the KlebSeq test at detecting HAIs earlier, in particular Klebsiella, which has multiple strains, such as ST258, which are increasingly resistant to treatment by antibiotics.

Unlike traditional assays that require growing a live culture in a laboratory setting, which adds days to the testing process and layers on cost, KlebSeq employs a technique called amplicon sequencing that identifies the presence of Klebsiella and stratifies its characteristics, such as strain type and whether it may be antibiotic resistant.

“KlebSeq is able to accurately and consistently identify and characterize Klebsiella from many different types of specimen samples, including blood, urine, nasal swabs, and respiratory fluids,” said Dr. Jolene Bowers, a Post-Doctoral fellow in TGen’s Pathogen Genomics Division, TGen North, and the paper’s first author.

In 2015, Bowers co-led a study published in PLOS One, in collaboration with the U.S. Centers for Disease Control and Prevention, which documented the rapid global spread of ST258.

According to the CDC, nearly 2 million Americans annually contract bacterial infections that are resistant to at least one antibiotic, and 23,000 die each year from such infections, nearly twice as many who die of AIDS.

“Improved testing technology holds great potential for the rapid detection of HAIs and more quickly identifying antibiotic-resistant infections, such as K. pneumoniae, which have become an urgent public health crisis,” said Bowers. “KlebSeq is a perfect example of the power of genomic-based analytical tools that deliver results faster, more accurately and at a lower cost.”

According to Dr. David Engelthaler, Director of Programs and Operations for TGen North, and one of the authors of the study, transmission of multidrug-resistant strains of K. pneumoniae is rapid and without initial symptoms, leading to outbreaks in the healthcare system and the community that often go undetected.

“Early detection of K. pneumoniae in healthcare patients, especially those with multidrug-resistant strains, is critical to infection control,” said Dr. Engelthaler, who also is a former epidemiologist for the state of Arizona. “Perhaps most concerning is that Kleb acts like a shuttle for critical resistance genes, often transmitting them to other HAI species. It is important for us to detect both the bacteria and these critical genes.”

KlebSeq can be used for routine screening and surveillance, enabling healthcare staff to make more informed patient decisions, and curb outbreak situations by rapidly identifying transmissions prior patients showing signs of infection. Classifying the type of infection in each patient would help enable an institution to decide when and which intervention procedures to enact.

Study results suggest that KlebSeq would be especially helpful for high-risk patients — those in intensive-care units, centers specializing in bone marrow transplantation or chronically immunosuppressed patients, long-term care facilities, and travelers returning from endemic regions.

“The sensitivity of KlebSeq is superior to culture-based methods,” said Dr. Paul Keim, Director of TGen North and the senior author of the study.

“KlebSeq is an important step toward a comprehensive, yet accessible, tool for all pathogen identification and characterization,” said Dr. Keim, who also is the Cowden Endowed Chair of Microbiology at Northern Arizona University, and Director of NAU’s Center for Microbial Genetics and Genomics (MGGen).

The results also suggest that KlebSeq could be easily modified to detect other healthcare-acquired infectious agents, and identify those with antimicrobial resistance. It could also be used for outbreak detection, transmission mapping and tracing the source of infections by being able to screen hundreds of patient samples simultaneously, at a cost of tens of dollars per patient.

KlebSeq: A Diagnostic Tool for Surveillance, Detection, and Monitoring of Klebsiella pneumoniae, will be published in the October 2016 issue of the Journal of Clinical Microbiology.

Nov. 6 stepNout 5K aims for another $1 million for TGen cancer research

11th annual stepNout Run/Walk/Dash seeks end to pancreatic cancer, soon the nation’s 3rd leading cause of cancer death

SCOTTSDALE, Ariz. — Aug. 25, 2016 — This year, pancreatic cancer is projected to eclipse breast cancer as the third leading cause of cancer-related death in the U.S.

The Translational Genomics Research Institute (TGen) is determined to reverse this trend in pancreatic cancer by enlisting the help of more than 1,000 participants at the 11th annual stepNout Run/Walk/Dash for pancreatic cancer research, Nov. 6 in Scottsdale.

“We are incredibly grateful to the hundreds of volunteers who have truly accelerated the development of new treatments for pancreatic cancer,” said Michael Bassoff, President of the TGen Foundation. “These generous runners and community leaders have brought hope and answers to pancreatic cancer patients around the world.”

Be sure to put on your running shoes for stepNout, a family-friendly morning of races, music, games, and activities — including a photo booth and face painting — all celebrating TGen’s efforts to stomp out pancreatic cancer.

Dr. Daniel Von Hoff, TGen Distinguished Professor and Physician-In-Chief, said more effective treatments for pancreatic cancer are needed. Pancreatic cancer this year will take the lives of nearly 42,000 Americans, a more than 10 percent increase in the past 5 years.

“The death rate for other leading cancers have been flat in recent years because of more effective treatments,” said Dr. Von Hoff. “We are making progress in treating patients with improvement in average survival and for the first time having some very long term survivors. We need continued, dedicated funding to improve on these promising results to our studies and benefit pancreatic patients who need our help now.”

Median survival for patients with advanced disease was less than 6 months, and the 5-year survival rate was less than 10 percent. But thanks to fundraising efforts like stepNout, these statistics are improving.

Under Dr. Von Hoff’s leadership, and in collaboration with HonorHealth, TGen pioneered a major international clinical trial that led the FDA in 2013 approved the use of Abraxane in combination with gemcitabine, which now is the nation’s standard of care for this disease. Two ongoing TGen-led studies are showing even greater promise, with tumor reductions of at least 30 percent in 3 in 4 patients, and the elimination of tumors in 1 in 5 patients.

Competitive and fun races at stepNout are geared for all ages and abilities, including the event’s signature 5K run. Online registration ends Nov. 1, though participants can register at the event. This is the third year stepNout will be at the Scottsdale Sports Complex, northeast of Bell and Hayden roads.

The annual event has raised more than $1 million since it started in 2006. Nearly $135,000 was raised last year, and organizers are aiming for $150,000 this year on their way towards an overall goal of $2 million.

And you don’t have to be at stepNout to help. You can donate at www.tgenfoundation.org/step.

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If you go to stepNout:

What: TGen’s 11th annual stepNout Run/Walk/Dash for pancreatic cancer research.
Where: Scottsdale Sports Complex, 8081 E. Princess Drive, northeast of Hayden and Bell roads, between Loop 101 and Frank Lloyd Wright Boulevard.
When: 7:30-11 a.m. Sunday, Nov. 6.  Registration starts at 7:30 a.m.; a competitive 5K run begins at 9 a.m.; a fun 1-mile run/walk starts at 9:15 a.m.; a free 50-yard kids’ dash is planned for 10:30 a.m.
Cost: Registration fees range from $10 to $30, depending on age. Costs increase by $5 after Oct. 21. Children ages 5 and under are free.
Parking: Free.
More information and registration: www.tgenfoundation.org/step and click on events. Contact Andrea Daly at (602) 343-8572 or by email at adaly@tgen.org.

U.S. issues patent for Valley Fever detection technology developed by TGen and NAU

Test for dust-borne fungal infection created by TGen and NAU is licensed to DxNA 

PHOENIX, Ariz. — Aug. 2, 2016 — Valley Fever, a potentially deadly dust-borne fungal disease, should be easier to diagnose and treat thanks to a testing technology developed by the Translational Genomics Research Institute (TGen) and Northern Arizona University (NAU), and now protected by a patent issued today by the U.S. Patent and Trademark Office.

TGen and NAU have exclusively licensed this technology to DxNA LLC, a company based in St. George, Utah, which plans to make this Valley Fever Test commercially available to hospitals and clinics upon completion of FDA clinical trials and a subsequent FDA 510(k) submission for review and clearance later this year.

Valley Fever is endemic to Phoenix and Tucson, but also is spreading throughout the arid regions of North and South America. It is an infection caused by the microscopic fungus Coccidioides, a pathogen that lives in desert soils and typically enters the body through the lungs. An estimated 150,000 Americans are infected annually by Valley Fever, and as many as 500 die each year.

“Currently, there is no definitive test for Valley Fever. Our new rapid, 1-hour, genetic-based test will provide physicians and patients with a precise diagnosis, enabling prompt treatment and preventing this disease from becoming more serious,” said Dr. Paul Keim, Director of TGen’s Pathogen Genomics Division, or TGen North, based in Flagstaff.

“For the past decade, TGen has worked to develop better tools and technology to address Valley Fever, and we think it is critical to be able to apply our cutting-edge science to problems in our own backyard,” said Dr. Keim, who also is the Cowden Endowed Chair of Microbiology at NAU, and Director of NAU’s Center for Microbial Genetics and Genomics (MGGen).

Valley Fever most commonly causes a progressive lung infection, but can also spread to other parts of the body, including the skin, bone, brain and the rest of the nervous system.

Nearly 60 percent of those infected by Valley Fever — including other vertebrates, and especially dogs — develop no significant symptoms. However, some patients develop highly debilitating symptoms, such as cough, fever and fatigue. These symptoms are similar to other respiratory diseases caused by bacteria or virus, and often lead to delayed diagnoses and inappropriate treatment. Very severe Valley Fever can require lifelong treatment with antifungal drugs, and even result in death.

This new genetic-based test can precisely identify both strains of Valley Fever: Coccidioides posadasii, found in Arizona, New Mexico, Texas and much of Latin America, and Coccidioides immitus, which is found in California, Washington and Baja Mexico.

Most infections occur in central and southern Arizona. Each year on average, there are an estimated 150,000 cases in Arizona, resulting in more than 1,700 hospitalizations at a cost of more than $86 million.

“These high costs are driven to a significant degree by the high level of misdiagnosis, resulting in an average time to diagnosis of 5 months from when a patient first seeks care,” said David Taus, CEO of DxNA LLC. “Our test provides definitive results in 60 minutes, dramatically improving the diagnosis of the disease over current methodologies, both in terms of time and accuracy.”

The intellectual property used in DxNA’s Valley Fever Test is exclusive to DxNA LLC, and covers both human and veterinary applications, Taus said.

Ben and Catherine Ivy Foundation funds new ARCS Scholar

 

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The Ben & Catherine Ivy Foundation (Ivy Foundation) is providing a scholarship for John Heffernan, an Achievement Rewards for College Scientists (ARCS) scholar. Heffernan is currently pursuing a Ph.D in bioengineering at Arizona State University and plans to focus on glioblastoma multiforme (GBM) brain cancer research.

The Ivy Foundation is the largest privately funded brain cancer research foundation in North America and has been dedicated to furthering brain cancer research since 2005.

“We are pleased to be able to help John further his studies in such a critical area,” said Catherine Ivy, founder and president of the Ivy Foundation. “With support from Ivy Foundation and ARCS, we hope John can take the steps necessary to grow in this crucial phase of his scientific career.”

The ARCS Foundation advances science and technology in the United States by providing financial awards to academically outstanding U. S. citizens studying to complete degrees in science, engineering and medical research. ARCS Scholars are selected annually by a number of qualifying departments within the ARCS Foundation’s 54 academic partner universities.

The ARCS Foundation Phoenix recently held their 41st Annual Scholar Awards Dinner at the Phoenix Country Club. The proceeds provide financial awards to outstanding graduate Ph.D. science students attending Arizona State University (ASU), Northern Arizona University (NAU) and University of Arizona (UA).

The Phoenix Chapter currently has 39 scholars and has awarded over $5,692,900 to 935 scholars at the three Arizona state universities since 1975.

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SmartPractice Donates $50,000 to TGen Cancer Research

Healthcare consulting firm SmartPractice donates to TGen towards early breast cancer detection

PHOENIX, Ariz. — SmartPractice today donated $50,000 to the Translational Genomics Research Institute (TGen) to support research for the early detection and more precise treatment of breast cancer.

This year’s gift is double what SmartPractice donated to TGen last year in support of research that could help prevent breast cancer from spreading to other parts of the body.

“After discovering TGen for the first time last year, and seeing the how our donation made a difference in the ability of TGen researchers to further the science of cancer treatment, we decided this year to increase our gift,” said Dr. Charlotte Thrall, Healthcare Director of SmartPractice Wellness Clinic. “We at SmartPractice believe we can help make a difference in the lives of breast cancer patients by supporting the leading-edge research happening at TGen.”

Specifically, today’s SmartPractice donation will go toward TGen’s development of what are known as “liquid biopsies:” simple, non-invasive blood tests that could help detect cancer earlier. They seek to identify “at risk” genetic biomarkers in a patient’s blood circulatory system.

Liquid biopsies are less invasive, less costly and less risky than conventional tissue biopsies, which essentially are minor surgeries.

“We are proud to have merited the support of a health industry leader like SmartPractice,” said TGen Foundation President Michael Bassoff. “Through their very generous contribution, Dr. Curtis Hamann (President and CEO of SmartPractice) and his team will help advance TGen research in the early detection of breast cancer.”

SmartPractice® is a family-owned, Phoenix-based firm that has partnered with dental and healthcare professionals nationwide for more than 45 years to improve the health of both practices and patients. A portion of the proceeds of their innovative line of Pink Ribbon exam gloves and supplies generates a donation to fund breast cancer research and awareness programs. To learn more, please visit smartpractice.com/pinkribbon.

Golf Classic will Help TGen Cancer Research

14th annual Seena Magowitz Golf Classic, raising research funds for TGen, is planned Aug. 27-29 in Boston

Baseball, gala dinner and golf will accelerate battle against nation’s 3rdleading cause of cancer death

BOSTON — The 14th annual Seena Magowitz Golf Classic — a multi-million-dollar fundraising spectacular supporting pancreatic cancer research at the Translational Genomics Research Institute (TGen) — is set for Aug. 27-29.

More than 250 golfers and guests are expected at this three-day event, which features a Saturday night baseball game at historic Fenway Park, a Sunday gala dinner at the Boston Harbor Hotel, and Monday morning golf at the Tedesco Country Club in Marblehead, Mass., northeast of Boston.

This is the Golf Classic’s first year in Boston. It previously has been held in Phoenix and Orlando. The event has helped raise more than $7 million over the years.

“Having the Golf Classic based in Boston will provide a new opportunity to raise awareness surrounding this disease throughout New England and across the upper Atlantic seaboard,” said Roger E. Magowitz, founder of the Seena Magowitz Foundation, named for his mother, who passed away from pancreatic cancer.

This year’s Honorary Chairman of the Magowitz Golf Classic is David Dombrowski, Boston Red Sox President of Baseball Operations. The baseball game during this year’s Classic features the Red Sox vs. the reigning World Series Champion Kansas City Royals. The game’s ceremonial first pitch will be auctioned online in July to raise additional research funds.

Dombrowski is a long-standing member of TGen’s Pancreatic Cancer National Advisory Council, a group of business leaders who assist the TGen Foundation in raising funds to support research and clinical trials for pancreatic cancer. In recent years, their efforts have led to a new treatment regimen that holds the promise of improved patient survival.

“We are extremely pleased to have David Dombrowski as the honorary chair and about moving the Seena Magowitz Golf Classic to Boston,” said Michael Bassoff, President of the TGen Foundation. “We hope to attract a whole new region of participants, as well as showcase a beautiful part of the country and all that the Boston region has to offer.”

Funding raised by the Golf Classic has been directed to research and clinical trials led by Dr. Daniel Von Hoff, TGen’s Distinguished Professor and Physician-in-Chief, who will deliver the gala’s keynote address about the progress being made and his vision for the future — to detect pancreatic cancer early and ultimately find a cure.

This year, pancreatic cancer will claim the lives of nearly 42,000 Americans, surpassing breast cancer as the nation’s third-leading cause of cancer-related death.

The Seena Magowitz Foundation, previous Golf Classic Honorary Chairman Gary Fazio, Mattress Firm executives and employees, and Leggett & Platt President Karl Glassman, have provided the foundational support for an ongoing series of revolutionary clinical trials that build on TGen’s previous success in setting the nation’s standard for treating this formidable disease.

One of these, called the TGen Triple, has showed amazing progress. More than half of the patients in this clinical trial saw their pancreas tumors shrink by more than 30 percent. An additional 20 percent – 1 in 5 patients – saw their tumors dissolve completely; complete remission of an advanced cancer.

A new clinical trial, called the Grand Slam, which began in April, takes the treatments successful in the TGen Triple, and adds two key therapeutic agents that will push towards the goal of attaining remission in 100 percent of patients.

Pancreatic cancer’s lethal nature stems from its propensity to rapidly spread to other organs, especially the liver and lungs. Because no early screening test exists, the disease often goes undiagnosed until its late stages, when surgery is often no longer an option, making it difficult to treat.

Importantly, as a result of TGen clinical research, the U.S. Food and Drug Administration (FDA) in 2013 approved the use of albumin-bound paclitaxel in combination with gemcitabine as a front-line therapy for patients with advanced pancreatic cancer. The Seena Magowitz Foundation helped fund the Abraxane clinical trials.

In addition to engaging New England area supporters, event organizers expect to continue attracting major support from the home furnishings and bedding industries.

For more information about the Golf Classic, visit www.seenamagowitzfoundation.org. Prospective sponsors, participants and dinner attendees may contact: Roger Magowitz at 602-524-7636 or roger@seenamagowitzfoundation.org; or Liz McBeth, event director, at 757-773-3622 or liz@seenamagowitzfoundation.org.

Lizard Tails Point Way to Human Regeneration

TGen-ASU researchers find tiny genetic switches in lizard tail regeneration

Findings from lizards may impact future therapies to regrow organs in humans

PHOENIX, Ariz. —Any kid who pulls on a lizard tail knows it can drop off to avoid capture, but how they regrow a new tail remains a mystery.  Now, researchers at the Translational Genomics Research Institute (TGen) and Arizona State University (ASU) have identified tiny RNA switches, known as microRNAs, which may hold the keys to regenerating muscles, cartilage and spinal columns.

In a study published today in the scientific journal BMC Genomics, ASU and TGen scientists for the first time identified three microRNA’s — a which turn genes on and off — that are associated with the regeneration of tails in the green anole lizard, Anolis carolinensis.

Using next-generation genomic and computer analysis, this interdisciplinary team of scientists hope their findings, following nearly 6 years of research, will help lead to discoveries of new therapeutic approaches to switch on regeneration genes in humans.

“Since microRNAs are able to control a large number of genes at the same time, like an orchestra conductor leading the musicians, we hypothesized that they had to play a role in regeneration,” said senior author Dr. Kenro Kusumi, a Professor in ASU’s School of Life Sciences and Associate Dean in the College of Liberal Arts and Sciences, and an adjunct faculty member at TGen. “Our earlier work found that hundreds of genes are involved in regeneration, and we are very excited to study these three new microRNAs.”

Dr. Elizabeth Hutchins, a Post-Doctoral Fellow in TGen’s Neurogenomics Division, and co-lead author of the study, said she hopes this investigation eventually enables such things as regenerating cartilage in knees, repairing spinal cords in accident victims, and reproducing the muscles of injured war veterans.

“It is the translational nature of this work — how it could eventually be applied to people — that led to my interest in this study,” said Dr. Hutchins, who graduated from ASU’s Molecular and Cellular Biology Program. “For example, we currently don’t have the ability to regrow knee cartilage, which would really help someone like my grandmother.”

“This work highlights the importance of tiny RNA molecules in the tissue regeneration process, and showed for the first time an asymmetric microRNA distribution in different portions of the regenerating lizard tails,” said Dr. Marco Mangone, a co-author and Assistant Professor with ASU’s School of Life Sciences and Biodesign Institute. “It seems like microRNAs may play an active role in this process, and are potentially able to shape the regenerating lizard tail like playdough.”

The research team also included: Dr. Justin Wolter of ASU’s Biodesign Institute and School of Life Sciences; and Dr. Walter Eckalbar at the University of California, San Francisco.

This research was funded by grants from the National Institutes of Health and the Arizona Biomedical Research Commission.

SU2C Awards $200,000 to TGen Cancer Research

TGen SU2C Melanoma Dream Team member receives $200,000 Sharp Award

Sharp Innovation in Collaboration Award recognizes teamwork and development of new ideas among SU2C researchers

PHOENIX, Ariz. — Stand Up To Cancer (SU2C) has selected Dr. Muhammed Murtaza of the Translational Genomics Research Institute (TGen), paired with Dr. Antoni Ribas of UCLA, as recipients of a $200,000 SU2C Phillip A. Sharp Innovation in Collaboration Award, named for the Nobel Laureate and Chair of SU2C’s Scientific Advisory Committee.

The award, first established in 2014, supports opportunities for SU2C scientists from different teams to explore innovative collaborations to accelerate the development of new cancer treatments.

One of five awards totaling $1 million, the award to Dr. Murtaza, an Assistant Professor at TGen, and Dr. Ribas, supports a collaboration to investigate whether it’s possible to predict patient response to immunotherapy by studying the makeup of their microbiomes in blood samples.

Dr. Murtaza is a member of the SU2C-Melanoma Research Alliance (MRA) Melanoma Dream Team. Dr. Ribas is a leader of the SU2C-Cancer Research Institute (CRI) Immunology Dream Team. The selections were made Jan. 29 at the SU2C Scientific Summit in Santa Moncia, Calif.

“The selection of Dr. Murtaza for a Sharp award recognizes his knowledge in the field of liquid biopsies and the potential benefits this technique may offer cancer patients, particularly those with metastatic melanoma, as our Dream Team works to accelerate treatment breakthroughs to improve the survival outcomes against this deadly cancer,” said Dr. Jeffrey Trent, TGen President and Research Director, and leader of the SU2C-MRA Melanoma Dream Team.

While immunotherapy has improved outcomes in metastatic melanoma for a number of patients, for some it remains ineffective and carries toxic side effects. The study by Drs. Murtaza and Ribas is titled: “Fingerprinting the systemic microbiome in plasma to predict immunotherapy outcomes in melanoma.” It will analyze an extensive set of clinically annotated longitudinal blood samples available from the SU2C-CRI Immunology Dream Team to predict immunotherapy response and adverse effects. Recent results show that the gut’s microbial composition may, in part, affect response to immunotherapy. If successful, Drs. Murtaza and Ribas will pursue additional funding to validate their findings.

There also is a prospective study of circulating tumor DNA planned with colleagues at Mayo Clinic in Arizona, where Dr. Murtaza holds a joint appointment an Assistant Professor of Medicine.

Dr. Murtaza joined the Melanoma Dream Team upon his arrival at TGen in 2014 from the Cancer Research UK Cambridge Institute, where he began his work on circulating tumor DNA analysis.

“It’s an honor to receive this award, but more importantly the recognition brings further attention to the work of the entire Melanoma Dream Team and the collective efforts of all SU2C Dream Teams to defeat cancer,” said Dr. Murtaza. “Our goal is to investigate if we can predict how patients with melanoma respond to immunotherapy by looking at evidence of the makeup of their microbiomes in blood samples.”

SU2C and MRA established the Melanoma Dream Team — led by Drs. Trent and Patricia M. LoRusso, D.O., of Yale University — to explore the use of genomic sequencing to examine both the normal and cancer genomes of patients with metastatic melanoma. The study leverages advances in genomics, informatics, and health information technology with hopes of yielding more precise medical treatments for patients with this devastating disease.

In June 2015, clinical trials based on the Dream Team’s research findings began enrolling patients lacking a particular genetic mutation in the BRAF gene, and whose treatment for cancer with immune therapy had failed. Trial results will evaluate if using this precision therapy approach improves outcomes over current treatments.

Patients whose melanoma tumors do not have BRAF alterations will have other specific genetic alterations identified, and investigators will match these changes to an appropriate therapy that directly targets those alterations. The hope is that this “precision medicine” approach will lead to more effective and lasting treatments and potentially spare patients from unnecessary treatments that all too often offer little or no benefit.

In addition to Mayo Clinic in Arizona, the initial clinical trial site in Arizona, other locations include Yale Cancer Center, New Haven, Conn.; the Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit; Biometrics Research Branch, National Cancer Institute, National Institutes of Health, Rockville, Md.; University of Michigan Comprehensive Cancer Center (UMCCC), Ann Arbor, Mich.; Baylor Charles A. Sammons Cancer Center/Baylor University Medical Center, Dallas; Indiana University, Indianapolis, Ind.; Vanderbilt University, Nashville, Tenn.

“From the beginning, Stand Up To Cancer has striven to break down silos, encourage collaboration, and bring together the best research that will benefit cancer patients,” said Phillip A. Sharp, PhD, Chair of SU2C’s Scientific Advisory Committee and a Nobel Prize winner for his research in genetics. “These awards will help bring us closer to the day we defeat cancer.”

Gateway for Cancer Research Foundation provided additional support for the SU2C-MRA Melanoma Dream Team. AACR, SU2C’s Scientific Partner, provides expert peer review and grants administration, as well as ongoing scientific oversight.

For more information about this clinical trial, please call the Mayo Clinic Cancer Center Clinical Trials Referral Office at (855) 776-0015.