7th Annual ABRC-Flinn Research Conference Highlights Groundbreaking Research From Across the Valley

Researchers shared findings that will improve care for diverse patient populations

Translational research on pancreatic and chronic lung disease, opioid receptors, West Nile virus, transmission of Rocky Mountain spotted fever, autism in the elderly, and insulin-dependent diabetes were among the topics discussed at the of the 7and CARL-Flinn Research Conference.

Stewart Goldman, MD, chair of the University of Arizona College of Medicine – Phoenix Department of Child Health, was the keynote speaker. In his talk, “My Career: Clinical Trials, Lessons Learned,” Dr. Goldman recounted his long history of neuro-oncology research in pediatric patients and the informative nature of his clinical work. “Medicine is really just about additive knowledge,” he said. Investigators are building on the findings and work that came before.

Stewart Goldman, MD
Stewart Goldman, MD

Some of these lessons included: no matter how good a trial, outside forces can kill it; sometimes compromising and not running a trial exactly as you designed it can pay off; when the opportunity arises, jump into it; encouraging results and golden opportunities still require funding; research opportunities come in many forms; and it’s fine to try controversial ideas, just do it with integrity and smart design.

Dr. Goldman emphasized the value of mentorship. “There is nothing more important than being a mentor; and there is nothing more important than having a mentor,” he said. The impact his mentors had on him played a huge role in his own career trajectory, and he was happy to pay for it by sharing the wisdom he accumulated over his career.

Dr. Goldman is also Senior Vice President of Research and
Sybil B. Harrington Endowed Chair in Pediatric Oncology at Phoenix Children’s.

The featured speaker for the event was Rachna Shroff, MD, MSDirector of the Office of Clinical Trials at the UArizona Cancer Center and Associate Dean for Clinical and Translational Research at the UArizona College of Medicine – Tucson.

Dr. Shroff’s presentation, “Biliary Cancers – We’re Closing the Gap!” focused on intrahepatic and extrahepatic carcinomas – or advanced versions of bile duct and gallbladder cancers.

Rachna Shroff, MD, MS
Rachna Shroff, MD, MS

“This is a disease that has historically been considered a rare and heterogeneous group of ‘orphan’ malignancies and over the past decade has been, I think, a wonderful example of precision oncology and incredible drug development,” she said. mentioned.

In her presentation, she chronicled the past 10 years of studies and how they have affected outcomes for people with advanced stages of these cancers. Much of this effort has sought to surpass the results of the 2010 UK ABC-02 study.

ABC-02 was a large, randomized phase III trial that set the bar for the treatment of biliary cancers and, “demonstrated a statistically significant improvement in overall survival compared to the standard of care at the time”, a- she declared.

Until the past 18 months, researchers have been unable to match or exceed its results. But recent studies have provided encouraging data, including his own.

His study, sponsored by the National Cancer Institute, is the first randomized phase III trial in biliary cancers to be conducted in North America.. Using a triplet chemotherapy treatment plan, the target increase was 441 patients – a number thought to be unattainable at the start of the study. They reached 441 participants in February 2021.

Even more encouraging is the amount of information he has allowed them to compile. “This is actually the largest repository of prospectively collected biliary cancer biospecimens in the world, so we’re really excited about the kind of questions we can ask and what we can learn from them,” said she declared.

Medical student Dara Farhadi presents her research poster at the conference
Medical student Dara Farhadi presents her research poster at the conference

Hosted at UArizona College of Medicine – Phoenix’s Biomedical Sciences Partnership Building and including an online component through Whova, the day-long conference featured the work of 15 fellows and 90 research posters sponsored by the Arizona Biomedical Research Center (ABRC) , Flinn Foundation and Valley Research Partnership (VRP). Over 300 people registered to attend; and its hybrid setup has allowed it to go global, attracting participants from countries like Australia, India and Poland.

Chris Glembotski, PhD, Associate Dean for Research and Director of the Center for Translational Cardiovascular Research, expressed his enthusiasm for the event and thanked the partners who helped make it happen. “This exciting conference featured presentations of cutting-edge research made possible by a collaboration between CARL, the Flinn Foundation and the VRP,” he said.

Learn about three funded researchers who presented at this year’s conference:

Claire Faulkner

Presentation: Characterization of extracellular vesicles in pancreatic ductal fluids from patients with pancreatic diseases
Founded by: VRP

Claire Faulkner
Claire Faulkner

Claire Faulkner is a member of the college’s Class of 2024. His research focuses on analyzing better methods for detecting pancreatic cancer. The need for detection in the early stages of the disease is vital.

Pancreatic cancer is the third leading cause of cancer-related death in the United States with the lowest five-year survival rate at just 10%; most patients have advanced, unresectable pancreatic cancer at diagnosis.

Using extracellular vesicles (EVs), blood, and root canal fluid, Faulkner’s research aims to isolate EVs from root canal fluid and compare them to EVs separated from plasma and serum. To date, most research has focused on blood-derived EVs. She proposes that EVs in root canal fluids may serve as a stronger biomarker for disease.

“We hypothesize that the proximity of ductal fluids to pancreatic diseases may offer more robust and disease-specific EV cargo than that of blood,” she said.

The research is being conducted in coordination with Faulkner’s mentors at the Institute for Translational Genomics Research, Kuntal Halder, Aiai Price-Smith, Aidan David, John Cunningham, Daniel Von Hoff and Haiyong Han.

John Streicher, Ph.D.

Presentation: Development of a heterodimeric opioid receptor antagonist Mu-Delta to improve opioid therapy and treat withdrawal
Founded by: CARL

John Streicher, Ph.D.
John Streicher, Ph.D.

John Streicher, PhD, is Assistant Professor of Neuroscience – GIDP and Associate Professor of Pharmacology at the College of Medicine – Tucson.

Dr. Streicher’s presentation, as the title suggests, was about opioid receptors. As a rule, when interacting with single receptors, they produce changes in the body – side effects or analgesia (the inability to feel pain).

The mu-delta opioid receptor heterodimer has a higher level of organization, where multiple receptors bound together signal differently. “They can act as a negative feedback loop on the opioid system – to block analgesia and increase side effects; so it’s kind of a natural negative feedback breakdown on the actions of opioids in the body,” he said.

“If this is true, this would imply that if you are able to block or reverse this in some way, you may be able to reverse these effects, improving analgesia and blocking the side effects,” he added.

The challenge was to develop a drug that selectively interacts with the heterodimer. Dr. Streicher’s team was able to do this. As a result, their studies showed significant pain relief and reduced withdrawal, suggesting that their drug could be used to improve opioid therapy.

Ruslan Rafikov, PhD

Presentation: Enabling early diagnosis of chronic lung disease with blood-based metabolomics diagnostics powered by machine learning
Founded by: Flinn Foundation

Ruslan Rafikov, PhD
Ruslan Rafikov, PhD

Almost four years. This is the time it takes for a patient with pulmonary arterial hypertension to receive a proper diagnosis after first treating nonspecific symptoms.

During this journey, a patient may incur costs of more than $12,000, all without ever knowing what is wrong with them. Worse still, such a late diagnosis leaves them with a great chance – 50% of patients with this condition die within five years. So how do we fix this? Metabolites and machine learning.

“When we did the metabolic profile, we saw rapid changes in metabolites – which actually preceded any changes in physiology,” Dr. Rafikov said. The results were encouraging enough to be investigated further.

From there, Dr. Rafikov and his team were able to use artificial intelligence (AI) and machine learning to isolate the metabolites that were the main indicators of the disease. “Not all metabolites tell the story,” he said. The team used AI to identify the metabolites, reducing the number from 175 to 11 and increasing the accuracy of the results.

With this data, they were able to take well-phenotyped samples and run them through mass spectrometric analysis and AI algorithms to create disease-specific metabolic patterns. Essentially, it produced a fingerprint unique to the disease they were trying to identify.

“Using this refined metabolic panel, we achieved 100% accuracy – no negative data or false positives or negatives,” he said.

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