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The Key to Locks: Columbia Team’s Breakthrough Led to Hair Loss Treatment

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For over a decade, Columbia geneticist Angela Christiano , PhD, has attended the annual meeting of the National Alopecia Areata Foundation, where hundreds of individuals affected by the hair loss disorder gather to support one another and learn about the latest scientific research. The meeting is a safe space where patients with alopecia, many of whom have lost all their hair, joyfully remove their wigs and head coverings for the three-day celebration, without fear of shame or judgment.

But this year’s meeting was a bit different. Christiano had trouble recognizing conference attendees she’s known and worked with for years, because many of them now have full heads of hair.

For people with alopecia areata, an autoimmune disease that can cause hair loss so complete that people even lose their eyebrows, the change in appearance was dramatic.

drug_restores_hair_growth_in_patients_with_alopecia_areata

It was also a direct result of Christiano’s groundbreaking research on the condition, which led the FDA in June to approve the first systemic treatment specifically developed for severe alopecia areata.

“It’s a strange feeling. It’s what every geneticist dreams of, to find the genes for a condition and develop a treatment that can directly benefit patients. But it’s extremely rare that it actually works out that way,” says Christiano, who has studied alopecia areata for more than 20 years, motivated by her own bout with the disease.

Mysterious origins

Unlike hormone-driven male pattern baldness, alopecia areata is an autoimmune disease in which the body’s own immune system mistakenly attacks the hair follicle and shuts down hair production.

When Christiano began working on it, though, nobody knew exactly what caused the problem.

Starting with a series of basic research studies on the genetics and cell biology of hair growth, Christiano and a multidisciplinary team of collaborators produced a steady stream of advances, first in the lab and then in the clinic.

The first major clue came in 2010, from a study led by Christiano’s team that looked through the genomes of a thousand patients. The study, published in Nature, uncovered a gene that, when abnormally expressed, produces a known "danger signal" that causes the body to recognize the hair follicle as foreign.

The genome study was also crucial since the findings also explained why previous efforts to treat the condition hadn’t worked.

“Drugs for other autoimmune skin diseases had been tested in alopecia, but they had largely failed,” Christiano says.

“At that point, we realized that was because alopecia doesn’t share genetic pathways with other autoimmune skin diseases.”

Taming killer T cells

The genome study led the team to focus on investigating a particular kind of "killer" T cell recruited by the danger signal, which became central to understanding the mechanism of hair follicle destruction.

Christiano is not an immunologist, so she needed to enlist an expert to help make inroads into understanding the behavior of these cells. She approached Raphael Clynes, MD, PhD, at that time a faculty member in the Department of Medicine, who was an expert in studying the same kinds of killer T cells in type 1 diabetes and in cancer.

Clynes looked at the list of genes from the genome study and images of the "swarm" of killer T cells surrounding the hair follicle and suggested that inhibiting enzymes known as JAK kinases might be one way to treat the disease.

The team showed that small molecule drugs called JAK inhibitors could shut down signaling inside the killer T cells. Amazingly, by inhibiting the JAK pathway, the team found they could reverse alopecia areata in a mouse model of the disease.

Dramatic regrowth of hair

Armed with photos of mice with alopecia that had regrown all their hair, Christiano next approached her colleague Julian Mackay-Wiggan, MD, a Columbia dermatologist who specialized in hair disorders and had an interest in early-stage clinical research.

Excited by the early results in the mice, Mackay-Wiggan began treating a few patients with alopecia areata using JAK inhibitors that were already FDA-approved for other disorders. The first few patients experienced dramatic regrowth of their hair, just as the researchers had observed in the mice. Christiano’s team reported these groundbreaking studies in 2014.

Building on these early results, Mackay-Wiggan conducted additional Columbia clinical studies that showed that 75% of patients experienced significant hair regrowth after treatment with two different JAK inhibitors.

Pharma attention

Soon after the Columbia team reported its findings, additional case reports began appearing in the published literature that replicated the results in alopecia patients from around the world.

Because there were no FDA-approved drugs for alopecia when their work began, it didn’t take long for pharmaceutical companies to turn their attention to developing JAK inhibitors specifically for alopecia treatment. These efforts led to newly approved Olumiant from Eli Lilly, Incyte (previously approved for rheumatoid arthritis and hospitalized patients with COVID-19), and two additional JAK inhibitors being developed by Pfizer and Concert Pharmaceuticals and now in late-stage clinical trials.

Christiano welcomes the pharmaceutical companies’ new attention to alopecia areata after the condition had long been neglected and was frequently dismissed as a cosmetic problem.

For patients with complete hair loss, the barrage of stares and intrusive questions can be demoralizing and psychologically devastating. “It’s the stigma of unwanted attention; how do you quantify that?” says Christiano. “The impact of this treatment on patients has been truly transformative.”

Male pattern baldness next?

While Olumiant and other new JAK inhibitors are often life-changing for patients who respond well to them, the treatments are still far from perfect.

“These are potent immunosuppressive drugs, so there are safety considerations to be taken into account when assessing the risk/benefit ratio for individual patients,” says Christiano. After the treatment ends, some patients’ alopecia relapses for reasons the researchers don’t fully understand. In addition, about a third of patients don’t respond to the drugs.

Fortunately, Christiano has no intention of resting on her laurels. Her lab is hoping to understand what causes the condition to relapse after JAK inhibitor treatment.

And by continuing to investigate alopecia areata with new tools and techniques, her team is developing both new biological insights and more potential ways to attack the disease process. “We’re now looking upstream of the JAK signaling pathway to see if other mechanisms can lead to the common endpoint of alopecia areata,” she says.

Christiano’s team also hopes to extend these insights and apply the same approaches to treat other types of hair loss.

In one recent study, for example, Christiano’s team found that JAK inhibitors also reawaken dormant hair follicles , a problem common to male and female pattern baldness.

They also discovered a previously unknown type of immune cell that puts hair follicles into a dormant state by secreting a substance called oncostatin M and that the hair cycle can be reactivated by blocking this pathway.

While translating these results into effective treatments for hair loss will likely take years, it’s a process Christiano now knows well.

More information

Angela M. Christiano, PhD, is the Richard and Mildred Rhodebeck Professor of Dermatology, vice chair of research in the Department of Dermatology, and professor of genetics & development at Columbia University Vagelos College of Physicians and Surgeons. She also serves as an Advisory Dean for Basic Science Faculty. In 2020, Christiano was elected to the National Academy of Sciences.

Raphael Clynes, MD, PhD is currently vice president of translational biology at Xencor Inc.

Julian Mackay-Wiggan, MD, MPH, is currently in practice in the Siperstein Dermatology Group.

Angela Christiano and Raphael Clynes are co-inventors on several patents filed by Columbia University on the use of JAK inhibitors in treating hair loss disorders, which have been licensed to Aclaris Therapeutics, Inc. Angela Christiano is a shareholder of Aclaris Therapeutics, Inc. and has served as a consultant/scientific advisor for Arcutis Biotherapeutics, Inc., Almirall, S.A., Aclaris Therapeutics, Inc., Bioniz Therapeutics, Inc., Dermira, Inc., Intrinsic Medicine, Inc., Janssen Pharmaceuticals, Inc., and Pfizer, Inc. She is a shareholder of Intrinsic Medicine, Inc., has received research grant support from Bristol-Myers Squibb, Inc., Pfizer, Inc., and Sanofi Genzyme S.A. and serves on/chairs the scientific advisory boards for the Dystrophic EB Research Association of America and the National Alopecia Areata Foundation. She previously served as president of the Society for Investigative Dermatology and currently serves as president of the American Hair Research Society. She is a scientific co-founder of Rapunzel Bioscience.

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4 effective hair-loss treatments we discovered in 2022

Losing your hair can be frustrating because there aren't a ton of great options for treatment.

For decades, doctors have essentially relied on two proven medications : Rogaine, a topical liquid or foam that must be applied to the scalp routinely, or Propecia, an oral tablet and prostate medication that sometimes works to control and prevent male pattern baldness.

But this year, multiple new options have emerged to treat hair loss in people of every gender, each with promising years of research behind it.

"I realize I'm biased as somebody who studies hair, but I think 2022 was actually a very big year for lots of things hair-related," Dr. Arash Mostaghimi, a dermatologist and hair researcher at Harvard and Brigham and Women's Hospital, told Insider.

Here's what's new:

Dermatologists discovered a much cheaper way to use the active ingredient in Rogaine

new research about hair regrowth

Rogaine is a brand name for the drug minoxidil, which has been FDA-approved as a topical treatment for baldness since 1988.

But the drug was never originally designed to put on your head. It was actually developed to treat high blood pressure. In 1979, the FDA approved a minoxidil-based drug by Pfizer, called Loniten, to treat blood pressure.

It was only later discovered how well minoxidil could grow hair. That's when the topical solution called Rogaine — from The Upjohn Company , but now owned by Johnson & Johnson — became available as a foam or lotion.

This year, more than four decades later, dermatologists are still using minoxidil to treat hair-loss, but differently. It's now something of an open secret in the field that a tiny dose of oral minoxidil — the same pill that doctors prescribe at a higher concentration to treat hypertension — can work just as well as the head rub Rogaine. And it's dirt cheap, too.

Like Rogaine, oral minoxidil doesn't work for everybody who's balding, but it's a nice alternative to the sticky topical formulation of the medicine, which can be a hassle to apply.

In 2022, the FDA finally approved a treatment for alopecia areata, the balding condition Jada Pinkett Smith has

new research about hair regrowth

Alopecia areata is different from hormonal or genetic hair loss.

It's an autoimmune condition that triggers inflammation inside your skull, around the root of the hair shaft.

"Once that inflammation occurs, the hair becomes thinner and falls out, and then it gets stuck in a part of the hair cycle where it doesn't grow," Mostaghimi explained.

This can result in round, smooth bald patches, or even complete hair loss all over the body.

The new drug is called Olumiant, and it's a once-a-day pill for adults with severe alopecia areata

new research about hair regrowth

Mostaghimi said the genetic research to make this new drug possible started in the late 1990s, when a patient advocacy group (The National Alopecia Areata Foundation) partnered with Columbia University to do genetic sequencing on alopecia areata patients.

Over the years, they've discovered how people with alopecia areata have more mutations in their JAK-STAT pathway, a critical component of the immune system that is also targeted to treat other diseases like rheumatoid arthritis and psoriasis.

In June, the FDA approved rheumatoid arthritis drug Olumiant (baricitinib) to treat alopecia areata, after successful late-stage trials. Scientists found that a four-milligram dose of the drug led to "significant scalp hair regrowth" within a year for 40% of patients. That meant around 80% or more scalp coverage.

2 more alopecia areata treatments reached late-stage trials this year, and could hit the market soon

new research about hair regrowth

Ritlecitinib, a once daily pill from Pfizer, is under FDA review . If approved, it would be available to alopecia areata patients 12 and up.

Another pharmaceutical maker, Concert, is also trialing a twice daily pill for alopecia areata (CTP‑543). Its results look promising too: some patients trialing the drug were able to regrow a near-full head of hair.

Mostaghimi, whose daughter has alopecia areata , said it would be great to "go from having no FDA-approved options" to treat the condition earlier this year "to, hopefully, up to three, by 2024."

This year, we also got the first ever comprehensive study of supplements for hair loss

new research about hair regrowth

Mostaghimi says he was "inspired by my patients" to research supplements for hair loss.

He knows his patients are "bombarded by ads for all of these supplements" to regrow hair.

"I interpret this as, mostly, the fact that we haven't done our job as the medical field to appropriately develop enough interventions that work," he added.

Because supplement brands can sell and market products without undergoing research or FDA approval, "it's difficult to know what is working and why and how."

So the doctor and his colleagues authored a first of its kind systematic review on the safety and effectiveness of supplements for treating hair loss in November.

The data he collected on supplements, he cautioned, is still "of limited value," because most of the research done on supplements is conducted in-house, by supplement companies themselves.

Add to that the fact that "any negative studies were just likely never published," and it's very hard to tell how well supplements can actually work to grow hair.

But using supplements for hair loss might just be a waste of money

new research about hair regrowth

The reality is that "for the vast majority of types of hair loss, we have better pharmaceutical interventions" that "provide more consistent and reliable impact" than supplements, Mostaghimi said.

Drugs like minoxidil (Rogaine) and finasteride (Propecia) are typically cheaper than pricey supplements.

Mostaghimi says he doesn't bother with supplements to treat his own androgenetic alopecia .

"For me, it's not the right treatment, and I don't actually encourage my patients to take these medications," he said.

But, for patients who are "dead set" on supplements, he does recognize that there are some which "take advantage of pathways that we already target in dermatology with medication." For example, the plant called saw palmetto, which can be bought as a supplement, targets the 5-alpha reductase pathway, important in the development of male pattern baldness.

Studies have suggested saw palmetto supplements may help treat some baldness, but finasteride does the job better, and more cheaply, Mostaghimi said.

What's next? Training skin to regrow hair, without the need for transplants

new research about hair regrowth

"Eventually things like that will happen , and when they occur, they'll look like they're an overnight success, whereas in fact, you've been working on this since 1970, " Mostaghimi said.

There isn't yet any one-size-fits-all hair loss treatment, in part because "the biology is just very complex."

Some hair loss is genetic, some hair loss is autoimmune, some hair loss comes as a side effect of cancer treatment, or it can be the result of tight hairstyles .

"Hopefully, we'll continue to make breakthroughs," Mostaghimi said, "but, for now, these are the main treatments we have."

New Molecule Discovered That Strongly Stimulates Hair Growth

A team at the University of California, Irvine, has identified a signaling molecule that potently stimulates hair growth.

SCUBE3 has been found to be a potential therapeutic option for treating androgenetic alopecia.

The research, which was recently published in the journal Developmental Cell, uncovered the precise mechanism by which the dermal papilla cells, specialized signal-producing fibroblasts found at the bottom of each hair follicle, encourage new development. Although the critical role dermal papilla cells play in regulating hair growth is widely established, the genetic basis of the activating chemicals involved is little understood.

“There is a strong need for new, effective hair loss medicines, and naturally occurring compounds that are normally used by the dermal papilla cells present ideal next-generation candidates for treatment,” says Maksim Plikus, Ph.D., UCI professor of developmental and cell biology and the study’s corresponding author. Credit: Julie Kennedy / UCI

“At different times during the hair follicle life cycle, the very same dermal papilla cells can send signals that either keep follicles dormant or trigger new hair growth,” said Maksim Plikus, Ph.D., UCI professor of developmental & cell biology and the study’s corresponding author. “We revealed that the SCUBE3 signaling molecule, which dermal papilla cells produce naturally, is the messenger used to ‘tell’ the neighboring hair stem cells to start dividing, which heralds the onset of new hair growth.”

For mice and humans to effectively develop hair, the dermal papilla cells must produce activating chemicals. Dermal papilla cells malfunction in people with androgenetic alopecia, drastically lowering the typically plentiful activating chemicals. For this study, a mouse model with excessive hair and hyperactivated dermal papilla cells was created. This model will help researchers learn more about the regulation of hair growth.

“Studying this mouse model permitted us to identify SCUBE3 as the previously unknown signaling molecule that can drive excessive hair growth,” said co-first author Yingzi Liu, a UCI postdoctoral researcher in developmental & cell biology.

Several large human hair follicles and numerous small mouse hair follicles are shown growing in response to treatment with SCUBE3 protein. Credit: Nitish Shettigar, Plikus lab

“These experiments provide proof-of-principle data that SCUBE3 or derived molecules can be a promising therapeutic for hair loss,” said co-first author Christian Guerrero-Juarez, a UCI postdoctoral researcher in mathematics.

Reference: “Hedgehog signaling reprograms hair follicle niche fibroblasts to a hyper-activated state” by Yingzi Liu, Christian F. Guerrero-Juarez, Fei Xiao, Nitish Udupi Shettigar, Raul Ramos, Chen-Hsiang Kuan, Yuh-Charn Lin, Luis de Jesus Martinez Lomeli, Jung Min Park, Ji Won Oh, Ruiqi Liu, Sung-Jan Lin, Marco Tartaglia, Ruey-Bing Yang, Zhengquan Yu, Qing Nie, Ji Li and Maksim V. Plikus, 30 June 2022, Developmental Cell. DOI: 10.1016/j.devcel.2022.06.005

UCI has filed a provisional patent application for the use of SCUBE3 and its related molecular compounds for hair growth stimulation. Further research will be conducted in the Plikus lab and at Amplifica Holdings Group Inc., a biotechnology company co-founded by Plikus.

More on SciTechDaily

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Diseases & Conditions

It’s not too late to save thinning hair

By Heidi Godman , Executive Editor, Harvard Health Letter

It’s possible to keep hair loss from progressing, thanks to a number of noninvasive treatments.

Hair loss doesn’t typically cause pain, but it can be emotionally distressing when you realize that your hair is thinning, especially if you can see space in between hairs and your scalp peeking out in places. Fortunately, there are a number of ways to treat thinning hair and keep the problem from advancing.

Why is your hair thinning?

Two common conditions account for most age-related hair loss.

The most common is androgenetic alopecia, also called male- or female-pattern hair loss. Thinning hair is the first sign. "Hair follicles become smaller, which makes the hair strands finer. Some hair follicles stop producing hair altogether," says Dr. Kathie Huang, co-director of the Hair Loss Clinic at Harvard-affiliated Brigham and Women’s Hospital and assistant professor of dermatology at Harvard Medical School.

This type of hair loss can result from genetics or age-related hormone changes. It occurs gradually, in patterns specific to men and women. "In men, the front hairline tends to recede, or they might have thinning at the temples or the crown on top of the head. In women, it can involve most of the scalp, or affect certain areas such as the middle part, the temples, and the frontal scalp area," Dr. Huang says. "But in androgenetic alopecia, women do not develop balding the way men can."

Another common type of hair loss is called telogen effluvium. This type of thinning occurs suddenly, often as a reaction to emotional or physical stress. "It might happen after you’ve had a high fever, a urinary tract infection, or surgery. Shedding can also occur as a reaction to an underlying medical condition or from taking a new medication," Dr. Huang says.

Protecting your hair

The type of treatment your doctor prescribes will depend on the cause of hair loss. Telogen effluvium corrects on its own or once the underlying cause is treated. "Telogen effluvium usually gets better in three to six months," Dr. Huang says.

For people with androgenetic alopecia, treatment aims to enhance the hair follicles, so the hair strands become thicker and your hair appears to be denser over all. The following treatments may help.

Topical drugs. The FDA has approved minoxidil (Rogaine), available over the counter, as a hair loss treatment for both men and women. It helps thicken hair follicles and promotes hair lengthening. It comes in a liquid or foam that’s applied to the scalp. "If you have a lot of hair, it may be easier to apply the liquid form. But more people experience irritation with the liquid, compared with the foam," Dr. Huang says. "And you have to use it on a daily basis for at least nine months to see improvement."

Oral medications. Recent studies suggest that taking minoxidil as a pill, which has been used for decades to treat high blood pressure, is safe and effective for treating hair loss. "We’ve seen an increase in the use of oral minoxidil for hair loss in the past year," Dr. Huang says. "It’s helpful for people who aren’t getting enough benefit from topical minoxidil, or those who have scalp irritation from the topical form."

Other oral medications to treat hair loss include finasteride (Propecia, Proscar) and spironolactone (Aldactone). "Oral medications can have side effects. For example, oral minoxidil can cause low blood pressure or heart palpitations. Therefore, we carefully tailor the treatment regimen for individual patients," Dr. Huang says.

Platelet-rich plasma injections. In this procedure, high concentrations of components of your own blood are injected into your scalp to stimulate hair growth. Dr. Huang says each treatment can cost from $500 to $1,500. You typically repeat the process monthly, for three months, and require follow-up treatments every year. The effectiveness of platelet-rich plasma for hair regrowth is not yet proven.

Laser light treatments. Devices that emit low-level LED laser light might promote hair growth. They’re available (without a prescription) in combs and helmets that you use regularly in your own home. Prices range from a few hundred to a few thousand dollars.

Supplements. Supplements are sometimes expensive, and there isn’t solid evidence that they make hair grow. "But if they won’t interfere with your medications, it’s probably okay to try them," Dr. Huang says.

And for any of these treatments, the key is starting them as soon as you detect hair loss. Once the follicles stop working, the only option to restore your locks is hair transplant surgery.

Image: © Peter Cade/Getty Images

About the Author

Heidi Godman , Executive Editor, Harvard Health Letter

Disclaimer:

As a service to our readers, Harvard Health Publishing provides access to our library of archived content. Please note the date of last review or update on all articles.

No content on this site, regardless of date, should ever be used as a substitute for direct medical advice from your doctor or other qualified clinician.

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About half of all Americans routinely take dietary supplements. The most common ones are multivitamin and multimineral supplements. Making Sense of Vitamins and Minerals: Choosing the foods and nutrients you need to stay healthy explains the evidence behind the benefits and safety profiles of various vitamins and minerals. It also includes the recommended minimum and maximum amounts you should consume, as well as good food sources of each.

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Skin Problems and Treatments

Is Balding Unavoidable? New Research Suggests Not

new research about hair regrowth

July 29, 2022 – While upwards of 80% of men and nearly half of women have substantial hair loss in their lifetime, there are two FDA-approved medications for male-pattern hair loss and one for women.

But as millions worldwide search for a way to slow or stop balding, a single chemical has stepped up to the plate.

New research from the University of California, Riverside suggests the cure for baldness resides in understanding just one thing: transforming growth factor beta (TGF-β). The study, published in the Biophysical Journal , identifies TGF-β – one of many small proteins called cytokines that help control other immune system cells and blood cells – as the moderator of the hair follicle growth cycle, determining when hair follicle cells grow and when they die.

By studying hair follicles – a source of stem cells – the research also dips into regenerative medicine and proposes a model to speed wound healing.

“In science fiction, when characters heal quickly from injuries, the idea is that stem cells allowed it,” UC Riverside mathematical biologist and study co-author Qixuan Wang, PhD, said in a news release . “In real life, our new research gets us closer to understanding stem cell behavior, so that we can control it and promote wound healing.”

TGF-β to the Rescue

The power of TGF-β depends on its intensity, and the researchers describe the chemical’s mechanism as a “threshold-like switch”: Too much of the chemical causes the cell to die, causing hair to fall out. At the same time, lesser doses allow the cell to grow and divide.

Being able to precisely control TGF-β levels and understand how the chemical interacts with specific genes could allow future scientists to stimulate hair growth, according to researchers .

Your Shape-Shifting Cells

Stem cells are like blank canvases – the body can program them to turn into other types of cells. Within hair follicles, stem cells play a unique role that captured the researchers’ attention: Hair follicles are the only organ in the human body that constantly regenerates, even without injury, according to researchers.

“Even when a hair follicle kills itself, it never kills its stem cell reservoir. When the surviving stem cells receive the signal to regenerate, they divide, make new cells, and develop into a new follicle,” Wang said.

The bald truth is that by focusing on these unique regenerative cells, researchers hope to promote complete wound healing, which requires hair regeneration.

“Potentially, our work could offer something to help people suffering from a variety of problems,” said Wang.

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Press Release

Mount Sinai Researchers Identify Details of Muscle’s Role in Regulating Hair Growth Cycle

Discovery could improve development of future hair loss treatments.

Paper Title : Progenitor-derived endothelin controls dermal sheath contraction for hair follicle regression

Journal : Nature Cell Biology (January 30, 2023)

Authors : Michael Rendl, MD, Professor of Cell, Developmental and Regenerative Biology, and Dermatology, and Associate Director, Black Family Stem Cell Institute, at the Icahn School of Medicine at Mount Sinai; and other coauthors.

Bottom Line : Hair growth occurs in a cycle starting with growth of the hair from a follicle, followed by a regression phase in which the follicle recedes and an inactive resting phase, then the regrowth of the follicle from stem cells. The newly formed follicle produces new hair after which the old hair is shed. Drastic hair follicle changes during the regression phase are coordinated by contraction of the dermal sheath smooth muscle. But how the contraction of the sheath muscle is regulated is largely unknown. This new study identifies space- and time-controlled endothelin signaling, a well-known pathway that otherwise regulates the narrowing of blood vessels to help control blood pressure, as the key activating mechanism of sheath contraction. Medications that block both endothelin receptors ETA and ETB, or removal of gene expression with genetically modified DNA in mice, impede dermal sheath contraction and halt follicle regression. Cells known as progenitors, which originated from stem cells and are located at the bottleneck structures of regressing hair follicles in the outer layer of the skin surface, produce endothelin-1, a small protein that constricts blood vessels and is required for follicle regression. Endothelin-1 signaling in dermal sheath cells and downstream contraction are regulated by calcium levels in the cytoplasm, a fluid that protects and holds the components of cells, through channels in the cell membrane.

How : The researchers first obtained pure dermal sheath cells during the transition from tissue growth to regression using fluorescence-activated cell sorting of cells from the back skins of mice and performed transcriptomic analyses discovering endothelin receptor expression.

Results : Using their analysis, the researchers identified endothelin signaling as a potential dermal sheath contraction-activating pathway. Functional and genetic manipulations of the endothelin receptors established the need for endothelin signaling in dermal sheath contraction and hair follicle regression. Furthermore, spatiotemporal examination of protein expression for endothelin-1 uncovered signaling from nearby progenitors. Examining the molecular mechanisms of endothelin signaling in cultured dermal sheath cells confirmed that this small protein triggers contraction in the dermal sheath through cytoplasmic calcium channels in the plasma membrane and skeletal muscle cells.

Why the Research Is Interesting : A potent muscle-contraction signaling pathway activated by progenitor cells controls the contraction of the cells surrounding hair follicles, which is essential for regression during the normal hair growth cycle. These findings reveal an interaction between mesenchymal and epithelial cells in which progenitors, which ultimately undergo cell death, control the contraction of the surrounding sheath smooth muscle to manage tissue regression and reorganization for the next stem cell activation and regeneration cycle. This discovery has implications for development of treatment for hair loss.

Said Dr. Rendl of the research : “Our study highlights that progenitors orchestrate remodeling of their microenvironment during tissue regression, in addition to their well-known role as the main architects of the stem cell niche during homeostasis and regeneration. It will be interesting to determine whether endothelin-induced contraction can also regulate other hair cycle phases. From a translational point of view, it may be beneficial to explore contraction-blocking strategies to ameliorate hair loss conditions. Further studies will be important to determine the upstream transcriptional regulation of endothelin expression in progenitors in the bottleneck region of the follicle.”

Researchers from the University of Utah Health in Salt Lake City, Utah, and the University of Tsukuba in Tsukuba, Japan, contributed to this study.

View the full paper here . To schedule an interview with Dr. Rendl, contact the Mount Sinai Press Office at [email protected] or 347-346-3390.

About the Mount Sinai Health System

Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with more than 43,000 employees working across eight hospitals, over 400 outpatient practices, nearly 300 labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time — discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it.

Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients’ medical and emotional needs at the center of all treatment. The Health System includes approximately 7,300 primary and specialty care physicians; 13 joint-venture outpatient surgery centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and more than 30 affiliated community health centers. We are consistently ranked by U.S. News & World Report 's Best Hospitals, receiving high "Honor Roll" status, and are highly ranked: No. 1 in Geriatrics and top 20 in Cardiology/Heart Surgery, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Neurology/Neurosurgery, Orthopedics, Pulmonology/Lung Surgery, Rehabilitation, and Urology. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 12 in Ophthalmology. U.S. News & World Report ’s “Best Children’s Hospitals” ranks Mount Sinai Kravis Children's Hospital among the country’s best in several pediatric specialties. The Icahn School of Medicine at Mount Sinai is one of three medical schools that have earned distinction by multiple indicators: It is consistently ranked in the top 20 by U.S. News & World Report 's "Best Medical Schools," aligned with a U.S. News & World Report "Honor Roll" Hospital, and top 20 in the nation for National Institutes of Health funding and top 5 in the nation for numerous basic and clinical research areas. Newsweek ’s “The World’s Best Smart Hospitals” ranks The Mount Sinai Hospital as No. 1 in New York and in the top five globally, and Mount Sinai Morningside in the top 20 globally.

For more information, visit https://www.mountsinai.org or find Mount Sinai on Facebook , Twitter and YouTube .

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