Dr. Jaime Emmetsberger, PhD

There were some 30,000 experts in Chicago for Neuroscience 2024—the world’s largest gathering of scientists and physicians dedicated to advancing the understanding of the brain and nervous system. Among the crowd was a presenter whose badge turned a few heads: Dr. Jaime Emmetsberger, PhD, La Mer’s lead scientist and neuroscientist at The Estée Lauder Companies (ELC).

But Emmetsberger was in her comfort zone. She has a PhD in Molecular and Cellular Pharmacology from Stony Brook University. There, she investigated the immunological and proteolytic events triggered by central nervous system trauma. After that, she researched the effects of schizophrenia risk genes on neuronal signaling and brain development as a postdoctoral fellow.

Her unique background and training in molecular biology and neuroscience provides La Mer Research Labs with a point of differentiation.

“I can add a very unique perspective with the neuroscience angle when we discuss skin biology,” Emmetsberger told Happi.

Sensory Neurons’ Impact on Cutaneous Inflammation

In Chicago, Emmetsberger presented her latest findings on the complex relationship between the skin’s sensory neurons and the regulation of neurocutaneous inflammatory signals through endocannabinoid pathways. Her research highlights the crucial role sensory neurons play in cutaneous inflammation by releasing neuropeptides and cytokines, which can influence the skin’s stress response. The study explores the bidirectional communication between skin cells and sensory neurons, uncovering feedback mechanisms that may intensify inflammation. This intricate crosstalk is partly regulated by the endocannabinoid system, which plays a key role in maintaining skin homeostasis. The crosstalk offers new insights into skin inflammation.

Findings offer new insights into how neurocutaneous communication influences skin inflammation and opens doors for future innovations in skincare, according to ELC.

Emmetsberger’s research primarily centers on neurocutaneous biology such as skin sensation, neurocutaneous signaling, cutaneous neuromodulation and the impact of cellular senescence on skin aging.

According to The Estée Lauder Companies, her work represents a significant advancement in understanding the interaction between the skin and the nervous system. By unraveling the mechanisms that govern neurocutaneous communication to balance skin, this research lays the groundwork for inspiring the development of precise and effective skincare innovation.

“Having a better understanding of how the nervous system interacts with the skin and particularly one field that is of interest is neuro-inflammation, and these neurons are actually contributing to the inflammatory events in skin,” Emmetsberger told Happi.

“Sensory neurons not only perform a role in carrying information from the environment to the central nervous system, but what’s unique is that they can also promote a very localized inflammatory response by releasing what we term neuropeptides and other type of inflammatory proteins. And it’s this crosstalk between these non-neuronal skin cells and these sensory neurons that can generate these what we term feedback loops. And this can amplify that inflammatory response.”

The La Mer team investigated both natural and fermented ingredients to determine if they can modulate inflammatory signaling in sensory neurons and skin cells—most importantly by affecting the endocannabinoid system, which is a system that’s known to have profound anti-inflammatory effects all throughout the body as well as skin, said Emmetsberger.

The team performed multiple assays, including gene expression analysis where the team looked at human ex vivo skin explants.

“We found that certain ingredients have the capacity to reduce the level of a variety of inflammatory mediators and also enzymes that degrade the extracellular matrix, like collagen and elastin, for example,” said Emmetsberger.

But there’s a limitation there, she insisted.

“Even though we saw a very robust response in reducing these inflammatory mediators, a lot of these models don’t contain functional nerve endings. So, to do this, we must approach it in a different way to investigate the effects of these ingredients on sensory neurons,” Emmetsberger said.

The team used in vitro cell culture models and reprogrammed human skin cells to become human sensory neurons.

“Utilizing these reprogrammed cells allows us to look at the connectivity between keratinocytes, which are the predominant cells of the skin, and their interactions with these sensory neurons,” she said.

The keratinocytes and reprogrammed sensory neurons were mixed together, and then scientists stressed them and applied ingredients.

“What we found is that when we apply certain ingredients, we are able to reduce the release of neuropeptides from those sensory neurons as well as other inflammatory molecules,” she said. “But interestingly, to determine what type of pathway they’re working through we also wanted to analyze the endocannabinoid system.”

According to Emmetsberger, when we blocked endocannabinoid receptors, that reduction was lost.

“What that told us is that these certain ingredients are somehow working through that endocannabinoid pathway,” she said.

The team performed other studies where they found that these ingredients can also block or inhibit the enzymes that degrade these endocannabinoids, “which suggests that we can potentially increase the duration or the existence of these endocannabinoids in the skin. This will basically promote a more amplified anti-inflammatory type of effect,” Emmetsberger added.

According to Emmetsberger, researchers have determined that certain ingredients can reduce inflammatory mediators and   decrease the release of neuropeptides. This is achieved through modulation of this endocannabinoid system.

Passion for Neuroscience

While neuroscience will always be her passion, Emmetsberger is relishing her role at La Mer.

“I think what is the most exciting is that I’m able to bring my passion into skin care. We already know the nervous system can regulate many aspects on how our body functions holistically, even beyond skin. It regulates so many different things, even beyond, let’s say neural inflammation. So, it’s not just about other ways that we can learn to regulate irritation, but also understanding how the nervous system is important in everyday skin quality. How the nervous system is interacting with different cells beyond just keratinocytes. How it is necessary to provide signals and cues to those cells to allow them to divide, for example, or to mature, or to enhance barrier integrity. There’s so much that we’re learning right now with these model systems that opens once again, new doors, new avenues of what we can research and what we can understand. And if we get a better understanding of how these cells are communicating with one another, we know what to target in terms of supporting skin, supporting skin health.”