Daniel Isom, Ph.D., researcher with Sylvester Comprehensive Cancer Center and assistant professor in the Department of Molecular and Cellular Pharmacology at the University of Miami Miller School of Medicine, is living like he just drove a brand-new Corvette off the lot and all the lights are green. He and his team are conducting groundbreaking research, publishing in prestigious journals, and creating patented technologies, and have recently renewed an R35 Maximizing Investigator Research Award, a unique five-year grant from the National Institutes of Health that gives them incredible opportunities to answer difficult scientific questions.
“The R35 funding mechanism supports unrestricted creativity and the potential to make unanticipated discoveries and advances,” said Dr. Isom. “It gives us a lot of freedom to pursue scientific leads and develop technologies we believe could have a profound impact in several areas of science, medicine, and biotechnology.”
The World of Synthetic Biology and GPCRs
Though he’s experiencing tremendous success now, Dr. Isom had to work hard and be patient to get here. He was a postdoctoral researcher for nine years. In some ways, being a postdoc is a lot like being a minor league baseball player: It’s a nice place to be, but the show — in this case, a faculty position — is tantalizingly close.
“Being a postdoc with a family, especially through a recession, was extremely challenging emotionally and financially, but we finally made it and our risk has been rewarded,” said Dr. Isom. “This perspective is timely, as many postdocs are currently in crisis as they navigate the headwinds of the pandemic and inflation in pursuit of their academic dreams.”
In 2016, Dr. Isom made the leap to Miller School tenure-track faculty, in part due to his creative blend of computational and experimental lab work on a class of molecules called G protein-coupled receptors (GPCRs), which play an essential role in cellular communications and are targeted by more than a third of FDA-approved drugs.
“There are 800 GPCRs in the human genome, half of which are found in the nose and eyes and tongue,” said Dr. Isom. “The other half are distributed throughout the body in pretty much every tissue, including tumor microenvironments. They are the largest and most therapeutically targeted class of cell surface receptors for cardiovascular drugs, psychiatric drugs, diabetes drugs, you name it.”
However, GPCRs are not major cancer drug targets — something Dr. Isom’s team is trying to change. They have developed high-throughput CRISPR gene editing and drug discovery technologies to study hundreds of human GPCRs in Saccharomyces cerevisiae (yeast).
Yeast offers many advantages over human cell models, particularly for translational studies in cancer. It’s relatively easy to edit human genes into the yeast genome; yeast has only one GPCR pathway; and the model organism tolerates external pH changes.
These traits have helped the Isom lab explore pH-intelligent GPCR ligands (molecules that bind to these receptors), illuminate GPCR activation mechanisms, and regulate GPCR signaling.
“With synthetic biology and the power of CRISPR, simpler model systems, such as yeast, have incredible potential to advance therapeutics for cancer and other human diseases,” said Dr. Isom.
“Dr. Isom takes an interdisciplinary approach that integrates protein structure, computational analyses, innovative synthetic biology, ligand/drug discovery platforms, and fundamental cell signaling. This research is essential for understanding cell behavior in normal and disease states to include inflammation and cancer,” said Kerry Burnstein, Ph.D., associate director of education and training for Sylvester and professor and chair of the Department of Molecular and Cellular Pharmacology at the Miller School. “Given that GPCRs constitute such a large proportion of current drug targets, Dr. Isom’s work has broad impact.”
Dr. Isom’s team is continuing to tap this potential by developing GPCR nanobodies and biosensors, viral surveillance platforms to anticipate future pandemics, and pH-driven adaptations for cancer cell models.
An Advocate for Coding Literacy
Since 2016, Dr. Isom has also been teaching data science and coding to graduate and medical students. So far, nearly 150 students have gone through his program, which is being expanded to accommodate demand.
“Graduate students are busy and need a programming course that fits into their demanding schedules,” said Dr. Isom. “They need the skill, but also need to be at the bench.”
Dr. Isom wants to help his students think about data in ways that help them build bigger, more impactful experiments.
“Coding is an enabling skill,” said Dr. Isom. “I love Excel, but if your data only fits into Excel, you design your experiments to that scale. But if you could look at larger datasets and process more data, your science is going to scale up. Programming helps people ask questions differently, ask more questions, and answer them effectively because they can generate and process larger volumes of information.”
Outside of coding, Dr. Isom was tapped to develop and teach the pharmacology and pharmacokinetics unit for UM’s NextGenMD curriculum.
“Working with first-year medical students to develop their understanding of how drugs function in the body has been gratifying,” said Dr. Isom. “At times, it feels as though I learn as much from them as they learn from me. They are so eager, driven, and bright, and are just a pleasure to work with.”