Yes chef! These researchers are cooking up something extraordinary. 🧑🍳

To better understand this week’s paper funded by The V Foundation, I’d like for you to think of your skin cells like a kitchen that’s constantly cooking up melanin, the pigment that gives us our skin, hair, and eye color. 

The head chef in this kitchen is an enzyme called tyrosinase. When tyrosinase works normally, we get the right balance of color. But when it goes into overdrive, or slows down too much, it can cause big problems: dark spots, pigment disorders like vitiligo or albinism, and can fuel the growth of deadly skin cancers like melanoma. 

To understand, and control, this enzyme, Dr. Quanyin Hu at the University of Wisconsin, Madison asked a bold question: what if we could hijack this “head chef” and make it cook up therapies inside cells?

And, that’s exactly what they did: they discovered a way to turn tyrosinase into a drug factory, making treatments right where they’re needed:

• For dark spots and pigment disorders: the team built tiny “self-destruct recipes” that tyrosinase triggers against itself. They used tyrosinase to help make a drug that turns down its own activity, and thus cooling off excess pigment production. In mouse models, this cleared up darkened skin patches in just two days.

• For drug-resistant melanoma: Melanoma cells often learn to block drugs inside them, like a bouncer at a club. Here, Dr. Hu and team tricked tyrosinase into activating hidden “prodrugs” in cancer cells, sneaking drugs past the bouncer. Once inside, the drug was unleashed, resensitizing tumors that had stopped responding to chemotherapy. 

The approach the Hu lab used could be transformative - instead of delivering massive amounts of a therapy, (which can cause side effects and stop working over time), the treatment is made in tiny, targeted batches inside the cells themselves.

That means a recipe for success:

1 Cup of Faster and more effective treatment of pigment problems. 

2 Tablespoons of A new way to crack open resistant melanoma, one of the hardest cancers to treat.

1 pinch of Lower toxicity, since the drug only activates where it’s needed.

I am not a great cook, but I love great food and always appreciate help in the kitchen… I think of this discovery like finding out that the biggest troublemaker in the kitchen, someone who’s been oversalting the soup, is also the only one who can ‘fix’ the recipe. If the strategy Dr. Hu developed holds up in human studies, it could rewrite the 'recipe' for how we treat skin diseases and give melanoma patients new hope when other therapies stop working. 

Read this incredible paper at Endogenous tyrosinase-catalyzed therapeutics | Nature Communications and find the Hu lab at CIPT lab-Hu group at UW-Madison.