Douglas Sheffler was named as a new associate professor at Sanford Burnham Prebys, effective August 1, while two faculty members garnered promotions as of July 1.
Douglas Sheffler, PhD, was recruited to join the Sanford Burnham Prebys faculty as associate professor in the Center for Therapeutics Discovery. Previously, Sheffler was a research assistant professor working in the lab of Nicholas Cosford, PhD, co-director of, and professor in, the Cancer Molecular Therapeutics Program.
Cosimo Commisso, PhD, was promoted to professor in the Institute’s Cancer Metabolism and Microenvironment Program. He also was appointed deputy director of the Institute’s NCI-designated Cancer Center, effective July 15.
Lukas Chavez, PhD, was promoted to associate professor in the Cancer Genome and Epigenetics Program. He also is scientific director of the Pediatric Neuro-Oncology Molecular Tumor Board at Rady Children’s Hospital in San Diego.
Interrupting the intractable problem of nicotine addiction
In his work in the Cosford lab, Sheffler has studied many facets of addiction, including addiction to the nicotine found in tobacco products. Smoking continues to be the leading cause of preventable deaths in the United States, and the second leading cause of preventable deaths worldwide after hypertension (of which smoking is a risk factor).
Cosford and Sheffler, in collaboration with colleagues at UC San Diego and Camino Pharma LLC, a San Diego-based biotechnology company Cosford co-founded, recently received a $9 million award from the National Institutes of Health (NIH) and National Institute on Drug Abuse (NIDA) to advance an investigational drug called SBP-9330 to Phase 2 clinical trials.
SBP-9330 targets a neuronal signaling pathway that underlies addictive behaviors, including tobacco use. If ultimately approved for market, it would be a first-in-class oral therapeutic to help people quit smoking.
“Our research suggests that SBP-9330’s mechanism of action—how it works—may also be effective for other types of addiction, such as cocaine, opioid and methamphetamine,” says Sheffler.
“In the future, we hope to explore and broaden the drug’s therapeutic uses.”
Investigating one of the deadliest cancers
Commisso focuses on pancreatic cancer, which is projected to become the second most deadly cancer in less than 20 years unless new ways are found to better diagnose and treat the disease. He recently co-hosted the 2024 PancWest Symposium, which brought more than 120 pancreatic cancer researchers from the West Coast to San Diego from as far away as Vancouver. The PancWest Symposium was founded in 2014 to regularly bring the scientific community studying pancreatic cancer together to discuss advances in the field and foster new collaborations.
Within his lab, Commisso investigates pancreatic cancer from many angles, including recent work that suggests an entirely new approach to treat pancreatic cancer. The research shows that feeding tumors a copycat of an important nutrient starves them of the fuel they need to survive and grow. The method, described in the journal Nature Cancer, has been used in early clinical trials for lung cancer. However, the unique properties of pancreatic cancer may make the strategy an even stronger candidate in the pancreas.
One of the metabolic quirks of pancreatic cancer is that it relies heavily on glutamine to produce energy for growth and survival. The new method relies on a molecule called DON that has structural similarities to glutamine but can’t actually be used as a nutrient source. The researchers combined DON with an existing cancer treatment that blocks the metabolism of asparagine, another important nutrient. The combined treatment had a synergistic effect, helping prevent the spread of pancreatic tumors to other distant organs, such as the liver and lungs.
“This is particularly exciting, because exploring it further for pancreatic cancer patients could be relatively simple, since the study designs exist for other solid tumors,” adds Commisso. “This could be a game changer for pancreatic cancer, and a lot of the preclinical work needed to rationalize it is already happening.”
From precision diagnostics to precision treatment for pediatric brain cancer
Chavez and his team have analyzed thousands of whole genome sequencing datasets within international data repositories, identifying numerous structural rearrangements of genes and genetic mutations associated with pediatric brain tumors. Their focus is on a type of structural rearrangement called circular extra-chromosomal DNA elements (ecDNA).
These circular ecDNA are pieces of DNA that have broken off the normal chromosomes and then were stitched together by DNA repair mechanisms. This phenomenon leads to circular DNA elements floating around in a cancer cell.
“We have shown that they are much more abundant in solid pediatric tumors than we previously thought,” says Chavez. “And we have also shown that they are associated with very poor outcomes.”
The Chavez lab is working on ways to use this finding as part of their overall efforts to more precisely diagnose subtypes of pediatric brain tumors.
“I’m optimistic that in the future we will have drugs that target these DNA circles and other genetic variants and mutations to improve the therapeutic outcome of patients,” notes Chavez. “Our vision is to move from precision diagnostics to precision medicine as therapies evolve.”