Biotechnology
Finding What You Weren’t Looking For
- March 7, 2025
MDI Biological Laboratory’s faculty study the complex biological underpinnings of human health and disease, in what is often termed “basic research” or “discovery science”. Yet they keep a sharp eye out for insights that can be directly applied to human therapies – what is sometimes called “translational” research.
Over its long history, the deep expertise developed by researchers at MDI Bio Lab has sparked valuable clinical applications: Homer Smith’s mid-20th century discoveries in kidney physiology provide a classic example: often using fish from Frenchman Bay for comparative studies, his insights led to the development of a measure of healthy human kidney function that’s still widely used today.
“That’s one of the great benefits of doing basic research in comparative biology – when you explore the fundamental processes of life, you sometimes make unexpected discoveries that can lead to important medical therapies,” says Romain Madelaine, Ph.D., an Assistant Professor at MDI Bio Lab.
Madelaine has experienced the phenomenon himself: he recently patented his unexpected discovery that a certain compound that holds promise for treating skin pigmentation disorders and even reducing the proliferation of some cancerous melanomas.
The story begins with Madelaine’s work to engineer the “sarcofish”, a transgenic zebrafish whose muscle fibers atrophy much more quickly than in normal fish. His lab uses it as a platform for aging studies, and for testing therapeutic drugs aimed at treating symptoms of sarcopenia – a debilitating decline in muscle mass, strength and coordination as we age.
During experiments on those issues, Madelaine and his team treated the transgenic fish with a specific compound, called ML233, they believed could affect muscle degeneration and regeneration.
They noticed something odd: the treated fish turned a lighter color.
With some experimentation, they revealed that the compound inhibits the production of melanin — the pigment responsible for skin coloration in fish (and in humans).
“We noticed that in some of our studies, the zebrafish were producing melanin at a slower rate, which led us to take a closer look at the effect of ML233 on skin pigmentation,” Madelaine says.
Melanin production involves intricate processes inside specialized cells called melanocytes. Defects in the process can cause various skin conditions, from pigmentation disorders like, hyperpigmentation, albinism and vitiligo to blotchy or over-pigmented skin, as well as the transformation of melanocytes into malignant melanomas.
After observing the change in zebrafish melanin production, Madelaine focused on an enzyme called tyrosinase.
“Tyrosinase is an enzyme that’s essential to the production of melanin, and tremendous efforts have been made to identify potent and safe inhibitors of tyrosinase function,” he explains. “This one appears to have no observable side effects.”
Madelaine’s team found that ML233 inhibits tyrosinase’s ability to catalyze melanin production. In experiments with zebrafish larvae and mammalian cells, they observed reduced pigmentation without toxicity and found that the effects were reversible.
Using lab-grown human tumors (called “organoids”), they also documented reduced proliferation of certain types of melanoma cells. “We believe that using ML233 is also a potentially effective approach to reduce skin cancer progression, and overall, to alleviate the symptoms of melanocyte-associated diseases, and thereby substantially improve human health,” he says.
Madelaine adds that in these early stages of discovery, the compound’s most immediate application would be to address cosmetic pigmentation issues that accompany some skin disorders. Its potential use for fighting cancers will require significantly more research.
Last year, the U.S. patent office approved a joint patent for ML233 held by Madelaine and MDI Biological Laboratory. Madelaine and the Laboratory’s entrepreneurial initiative, MDI Bioscience, are working to develop strategies for potential commercial uses of ML233.
A scientific article on the discovery by Madelaine and MDI Bio Lab colleagues was accepted this month for publication in a peer-reviewed journal. A pre-print version of the work can be found here.