Collaboration identifies marine molecules as leads to treat pain

Newly published research by Dominican’s Dr. Tyler Johnson and scientists from the University of California San Francisco (UCSF) and the University of California Santa Cruz (UCSC) identifies molecules derived from marine sponges that have the potential to spearhead an alternative approach to develop opioids with reduced abuse liability.

Dominican students Nicole McIntosh ’17 and Eptisam Lambu ’18 are credited as co-authors of the study, which appears in the peer-reviewed journal ACS Chemical Neuroscience.

The researchers identified molecules derived from marine sponges that demonstrate a proof of concept that there exist, in the marine environment, molecules that could serve as novel opioids for the treatment of pain and depression. The research suggests an avenue for developing a new class of opioids with reduced dependence and abuse liability compared with traditional opioids such as Morphine, OxyContin, and Vicodin.

Working in the Johnson lab has provided both Nicole and Eptisam with experiences and insight that will enhance their preparation for careers in medicine and scientific research. At Dominican, faculty mentored research is central to the undergraduate science program, often giving students an advantage when applying for medical and graduate school.

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A graduate of North Bay Christian Academy, Nicole, a chemistry major, has been accepted into Dominican’s Master’s of Science in Biological Sciences program, a research-intensive program that has partnerships with both BioMarin Pharmaceuticals and the Buck Institute for Research on Aging.

Eptisam, also a chemistry major, has a passion for neuroscience and medicine. She selected Dominican over larger research universities because of Dominican’s focus on undergraduate research. Her work in the Johnson lab is preparing her for medical school, where she plans to study for a career in either ER medicine or neurosurgery.

Both students have gained invaluable insight into medical careers by participating in the two-semester Pre-Med Mentor Program, offered in collaboration with Kaiser Permanente. The program provides students in-depth exposure to the medical field, helping them make a more informed choice when choosing a career in medicine.

Working in collaboration with researchers from UCSF and UCSC, the Johnson lab identified the mechanism of action for one of the first marine natural products (aaptamine) reported to have in vivo anti-depressant like effects. These findings provided a foundation for researchers to investigate other marine-sponge derived compounds with analgesic and anti-depressant effects for their effects on pain and depression.

Very few investigators have explored marine natural products for the treatment of pain and depression in neuroscience research. Marine sponge-derived compounds offered an attractive starting point as most have only been investigated for their biological activity in the areas of oncology, Dr. Johnson said.

“The goal is to identify novel opioids with a signaling profile distinct from traditional opioids that instead mimic the endorphins – the body’s natural pain suppressants and anti-depressants,” he said.

In this paper Dr. Johnson and colleagues went on to identify fascaplysin from the sponge Fascaplysinopsis reticulata, as the first marine-derived opioid with a signaling profile that resembles the endorphins.

In contrast, all the opioids used to treat pain in clinical medicine today have a signaling profile that is similar to that of morphine.
Endorphins provide excellent pain relief and anti-depressant like effects, but with reduced dependence and abuse liability compared to traditional small molecule opioids. This suggests that optimizing an opioid to have the signaling profile of endorphin could provide a novel avenue to develop safer therapeutics for the treatment pain.

Since joining Dominican in 2014, Dr. Johnson has worked with undergraduate students in his laboratory to identify biologically active natural products from marine sources to: a) target cancer, inflammation, and neurobiological orders, and b) to serve as novel molecular probes in chemical biology research.

Dr. Johnson received a PhD in Chemical Oceanography from UC Santa Cruz. He conducted postdoctoral studies at UC Berkeley in collaboration with UC Davis, UC Santa Cruz, and UCSF. His background is in the area of analytical and bioorganic chemistry with an emphasis in biomedical research involving natural products.

Photo credit: Colon Cook

April 24, 2017