A Molecule to Block Skin Cancer Growth

The National Institutes of Health (NIH) has awarded a 2022 NIH Director’s New Innovator Award to biomedical engineer Felipe Garcia Quiroz for his innovative molecular approaches to monitoring clumps of proteins associated with neurodegenerative diseases.

The research will advance sensors that could allow scientists to track disordered proteins thought to drive neurodegeneration—while the proteins move inside living brain cells. Many neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, and amyotrophic lateral sclerosis (ALS), are characterized by clumps of sticky disordered proteins, which accumulate in aging brain cells. Quiroz is pioneering new molecular tools for visualizing those proteins’ physical state.

Quiroz is an assistant professor in the Wallace H. Coulter Department of Biomedical Engineering at Emory and Georgia Tech. New Innovator Awards are part of the NIH’s High-Risk, HighReward Research program and recognize exceptionally creative early career investigators. The award to Quiroz will provide $2.4 million in funding over the next five years.

Quiroz and colleagues at Rockefeller University previously engineered similar sensors to show that certain proteins undergo liquid-liquid phase separation in the skin, like the process seen in a shaken jar of salad dressing or the globules in a lava lamp. During the continual maturation and death of skin cells, these phase-separated proteins are critical for skin barrier function.

With the new project, Quiroz will take the lessons he learned from the skin and apply them to disordered proteins that are pathological hallmarks of neurodegenerative diseases, such as tau (Alzheimer’s), TDP-43 (ALS), and alpha-synuclein (Parkinson’s).

—Quinn Eastman

MELANOMA IS THE DEADLIEST TYPE OF SKIN CANCER despite accounting for only a small percentage of all skin cancer diagnoses. Existing therapies can be effective, but in many cases advanced melanomas develop resistance to treatment.

Researchers at Emory University have synthesized a novel molecule that could pave the way for future advancements in melanoma treatment. The molecule, named indolium 1, has demonstrated ability to block the growth of melanoma cells and is well tolerated in animal subjects, according to findings published in the journal Antioxidants

“Only about 15 to 20 percent of melanomas respond to immunotherapy and targeted therapy, so there is an unmet need for new treatments,” says senior author Jack Arbiser, Thomas J. Lawley Professor of Dermatology. “This novel compound works differently than any other therapies on the market and shows promise as a potential treatment for melanomas with poor prognostic features.”

Most melanomas are caused by a mutation in the BRAF molecule that can stimulate cells to grow out of control. Targeted therapies aim to inhibit molecules in the BRAF pathway that regulate cell growth, and immunotherapies help the body mount a stronger response against cancer cells.

While these treatments can shrink and slow the progression of melanomas, cancer cells that have developed resistance to therapies are often left behind. In developing indolium 1, Arbiser and colleagues sought to target alternative pathways that have not yet been the subject of significant study to combat the aggressive cancer cells that remain.—Rosemary Pitrone