Dermatology

Really. Come on. Who isn’t interested in hair? Hair growth, hair loss, hair thickness, hair shape, hair location. I’d bet that everyone of us spends at least a minute or two each day thinking about (or, if you’re like me, futilely plucking and prodding at) the state of our locks.

Now Stanford researchers have delved deep into the cells surrounding our hair follicles to better understand what makes them grow and maintain hair. Perhaps not surprisingly, the answer lies in the stem cells (here, called ‘bulge cells’) within the follicle.

Specifically, research associate Yiqin Xiong, PhD, and associate professor of medicine Ching-Pin Chang, MD, PhD, have identified a signaling circuit that controls the cells’ activity. The research was published yesterday in Developmental Cell (subscription required). As Chang explained in an e-mail to me:

By promoting self-renewal of stem cells, this circuit maintains a healthy pool of bulge cells for repeated cycles of hair growth and regeneration. Each cycle of hair regeneration is initiated by the activation of this circuit in those bulge cells, and subsequent growth of the hair is sustained by the circuit in hair matrix cells. Besides hair regeneration, the circuit is triggered by skin injury to stimulate migration of the bulge cells to the wounded area to differentiate into epidermal cells, thereby regenerating epidermis over the wounded skin.

In the past, news about hair growth (and how to stimulate it) has been a trigger for a deluge of interest from media and individuals struggling with… (how shall we say it?) ‘hair problems.’ But the research has many implications beyond hair, or the lack thereof. For example, the presence or absence of hair follicles on the skin affect how the skin heals after a wound, and whether a scar remains. According to Chang:

This molecular circuit in the hair follicle can be targeted for therapeutic purposes. Because of its activity in hair regeneration, inhibition of this circuit can reduce hair growth in patients with excessive hairiness (hirsutism), whereas activation of this pathway can promote hair growth for people with baldness (alopecia). Also, for its activity during epidermal regeneration, activation of the circuit can facilitate wound healing for patients receiving surgery and for diabetic patients who have wounds that are difficult to treat. The activity of the circuit in both hair follicle and epidermal regeneration may have additional therapeutic benefit. Lack of hair follicles in a wounded area is a hallmark of scar formation. Targeting this pathway has the advantage of promoting both hair follicle formation and wound repair, thus reducing scar formation in the wound.

Interestingly, one of the key molecules, called Brg1, involved in this regulatory circuit has also been implicated in previous work from Chang’s lab in the enlargement of the heart and in fetal heart development. It’s apparent this story has many layers, some more than skin deep.

Previously: Examining the role of genetics in hair loss and Epigenetics: the hoops genes jump through,
Photo by Furryscaly

There has been a lot of interest in the Stanford study suggesting that aspirin reduces the risk of melanoma in women; dermatologist Jean Tang, MD, PhD, spent much of her day today discussing the findings with reporters from NPR and the three networks’ evening news programs. Earlier, in a 1:2:1 podcast, Tang talked about her work and described the importance of the Women’s Health Initiative (WHI), from which she and her co-investigators pulled their data:

The Women’s Health Initiative was funded by the National Institutes of Health and American taxpayers’ dollars… This was a huge investment of taxpayers’ dollars, and it has incredibly paid off, [producing] many published papers and, more importantly, many important messages and conclusions about the health of American women.

…

Women were enrolled [in the WHI] to reflect the multi-ethnic population of the U.S. So American Indians are represented, Mexican-American women are represented, black women are represented. You are never going to get the richness and diversity of the women represented in this database anywhere else in the world.

Previously: New research shows aspirin may cut melanoma risk

Researchers at Stanford have conducted the largest study ever examining new methods for preventing melanoma and found that women who took aspirin on a regular basis decreased their risk of developing the dangerous form of skin cancer.

The findings are significant because they have the potential to reduce the number of people diagnosed with melanoma, an estimated 76,600 for 2013, and to save lives. The skin cancer is projected to cause nearly 9,500 this year alone.

In the study, which was published today in the journal Cancer, researchers drew on data from the Women’s Health Initiative (WHI), which collected health information (including information on such things as aspirin and non-aspirin NSAIDs use) from postmenopausal U.S. women for an average of 12 years. As my colleague explains in a release:

The Stanford study focused on the data of roughly 60,000 Caucasian women who were selected because less skin pigment is a risk factor for melanoma. The Stanford researchers found that those who took aspirin decreased their risk of developing melanoma by an average of 21 percent. Moreover, the protective effect increased over time: There was an 11 percent risk reduction at one year, a 22 percent risk reduction between one and four years, and as much as a 30 percent risk reduction at five years and beyond.

…

One way aspirin may prevent melanomas is through its anti-inflammatory effects, [Jean Tang, MD, PhD, senior author of the study] said. Even though non-aspirin NSAIDs also reduce inflammation, they don’t use the same pathways that aspirin uses to become activated in the body. That difference may be the key to aspirin’s effectiveness.

The results are promising, but researchers caution that more studies need to be completed before they can definitively say “an aspirin a day will keep melanoma away.” Tang commented, “We don’t know how much aspirin should be taken, or for how long, to be most effective.”

Previously: New skin cancer target identified by Stanford researchers, How ultraviolet radiation changes the protective functions of human skin and Working to prevent melanoma
Photo by Andrew Ranta

Targeted cancer therapies block specific molecules involved in cancer-causing pathways. Some, such as the recently approved skin cancer drug vismodegib (marketed as Erivedge), have had remarkable results - for a while. Vismodegib works by blocking the activity of a biological signaling cascade called the Hedgehog pathway. But eventually tumors become resistant.

Now, Stanford dermatologist Anthony Oro, MD, PhD, and his colleagues have published a study (subscription required) in Nature describing how targeting another, previously unknown component of the pathway can kill even vismodegib-resistant cancer cells. From our release:

“These new, highly targeted therapies work really well,” said dermatology professor Anthony Oro, MD, PhD, who was one of several Stanford researchers involved in the multiyear effort that brought vismodegib to market in 2012. “But this type of treatment is a race against evolution. Within a year, many of the tumors recur when the cancers become resistant to the inhibitor.” [...]

“Although these tumors evolve in response to targeted drug treatment, we believe there’s a limited number of ways they can escape these therapies,” said Oro. “If we were able to hit them at the time of diagnosis with drugs that target more than one step in the pathway, they may be less able to evade treatment. We’ve identified a new target in the Hedgehog pathway and we’ve developed an inhibitor of this target that we hope will work in human cancers.”

The researchers, including postdoctoral scholar Scott Atwood, PhD, hope that the finding can one day help patients by providing another way to tackle skin cancers called basal cell carcinomas - either sequentially or in tandem at the time of diagnosis. As explained in our release:

Taken together, the recent studies illustrate the nature of the constant battle among physicians and the rapidly growing and changing cancer cells they strive to eradicate. Targeted treatments that focus on unique vulnerabilities exhibited by specific types of cancers can be highly effective. They can also minimize the unpleasant side effects of less-specific treatments that kill many other non-cancerous cells. But their very specificity encourages and drives the tumor cells to evolve resistance in a way that might not be possible against a more broad-based therapeutic approach. Many researchers believe that a multipronged attack targeted at more than one point in critical cancer-causing pathways could be an effective way to combat resistance.

Previously: Studies show new drug may treat and prevent basal cell carcinoma, Hope for basal cell carcinoma prevention? and Common drug might help prevent skin cancers

When I first interviewed Brian Kobilka, MD, winner of the 2012 Nobel Prize for Chemistry in October, I was struck by an off-hand comment about his motivation for his near-obsessive two-decades long research quest to uncover the workings of GPCRs, or G-protein-coupled receptors, which serve as one of the main methods of molecular communication within the body.

The research, which it’s believed will lead to the creation of new drugs for clinical care, was not originally done for this purpose. It was motivated by simple scientific curiosity - the kind that often leads to amazing discoveries that help cure suffering or save lives. Initially, Kobilka just really wanted to know how it worked.

In a story published in today’s Inside Stanford Medicine, I describe the success of research based on scientific curiosity in leading to clinical care breakthroughs. The story describes the 30-year history of scientific breakthroughs that led to the approval of a new drug called vismodegib that is used to treat inoperable basal cell carcinomas, and how the drug helped save the eyesight of 101-year-old Winnie Bazurto of San Mateo, Calif. It’s a story that begins with a similar motivation - basic scientific interest - and ends with discoveries that help patients in a very practical way. As Jean Tang, MD, PhD, Bazurto’s dermatologist and vismodegib researcher, says in the article:

If a patient only knew the whole story — how the happenstance of science led to their treatment… If they could go back to when this molecular pathway was first discovered in fruit flies, they’d be amazed. It’s not until the dots are connected 30 years later that it begins to make sense.

Stanford’s Matthew Scott, PhD, one of the key players in this basic-science success story, commented to me in an e-mail just how essential it is for future clinical discoveries that basic science continues to be funded. He expressed concern about a current trend toward conservatism in funding that requires much quicker results that lead to treatment options for patients saying, “Current conservatism in funding asks for translational work that gives cures in a few years (which never happens). Far-sighted funding of basic science … pays off big time.”

The vismodegib story illustrates just how essential basic science is to the future of clinical discoveries:

For many of the basic scientists involved in this research, the clinical use of hedgehog-inhibiting drugs to treat patients like Bazurto — while not the original goal of their research — is the ultimate success.

Previously: Why basic research is the venture capital of the biomedical world, Future of medical research is at risk, says Stanford medical school dean and The economic benefits of publicly funded medical research
Photo by Norbert von der Groeben

Past research from the Pew Internet & American Life Project showed that online resources, including advice from peers, are a significant source of health information for patients in the United States. Now Inspire, a company that builds and manages online support communities for patients and caregivers, has teamed up with Manhattan Research and the National Psoriasis Foundation to better understand the role of social media in the lives of chronic-disease patients.

The study was conducted online among 317 psoriasis patients from the Inspire and National Psoriasis Foundation’s TalkPsoriasis community during the second quarter of 2012. Findings from the study were recently posted online and show:

• Psoriasis patients are avid users of both general and psoriasis-relates social media, with 70 percent of this audience using any type of online community, social network, message board or blog at least several times a week, and 44 percent using psoriasis-specific social media multiple times per week.
• Surveyed psoriasis patients say they tend to rely on communities more for practical advice related to their disease than emotional support. About 8 in 10 say they used psoriasis social media because they wanted to learn how others managed the disease as well as get tips and ideas that they couldn’t find anywhere else.
• Among surveyed psoriasis patients who disagree that they have lots of support from family and friend when it comes to dealing with and managing psoriasis half say they use online communities regularly on a long-term basis, compared with just under one-third surveyed psoriasis patients who agree they have this type of support.
• Moderate to severe psoriasis patients are more apt to rely on psoriasis user-generated content for emotional support than their counterparts suffering from mild forms of psoriasis. Half of the moderate to severe psoriasis patients say they use social media for connecting with others for emotional support, compared to one-third of surveyed mild psoriasis patients.

Previously: Patient online peer group offers community, drives research, A detailed look at how Americans search for health information online and Survey shows patients with rare diseases and their caregivers are avid Internet users

About one in four breast-cancer survivors eventually develops lymphedema, a painful inflammatory condition resulting from the blockage of lymphatic vessels that ordinarily drain fluid from the tissues throughout the body. While in the developed world lymphedema most often arises as an unintended consequence of radiation therapy for cancer, there are numerous other causes as well. An estimated 10 million people in the U.S. alone suffer from it.

But by the time the main symptom of lymphedema — swelling of one or more limbs — is detectable, the condition may have gotten such a foothold that it becomes difficult or impossible to reverse, at least given the treatment choices now available.

In a study just published in PLoS ONE, veteran vascular expert Stan Rockson, PhD, and his Stanford colleagues have identified a set of proteins circulating in blood whose levels accurately flag lymphedema’s presence. This could make a difference. As I wrote in my release about this study:

The only known way to diagnose lymphedema now is via physical inspection, and all too often it is misdiagnosed or overlooked altogether. But the biological events underpinning this condition may be present five years or more before symptoms become evident, said Rockson. Moreover, there are no effective drugs for combating lymphedema, just costly, time-consuming and annoying physical therapy, which virtually never completely eliminates the symptoms. While physical therapy can arrest progression and reduce swelling by as much as half, the condition typically remains a long-term problem. “Lymphedema virtually never just goes away on its own,” said Rockson. Indeed, it tends to progress in severity over time, whether it is treated or not.

When I asked Rockson about the findings’ significance, he told me, “A standardized, accurate bioassay for lymphedema could help to pave the road for future human clinical trials of drugs to treat it.” Monitoring trial subjects at the molecular level with a lymphedema-detecting blood test could provide early evidence regarding whether an experimental treatment was working. Rockson is conducting clinical trials of pharmaceutical agents for lymphedema, and expects to incorporate the new test into those trials.

The upshot: some reason for optimism that a common but relatively neglected condition finally will be amenable to detection and, eventually, treatment with 21^st-century techniques.

Previously: New Stanford registry to track lymphedema in breast cancer patients and New breast cancer finding suggests limiting surgery
Photo by Kalyber

This young football fan is rockin’ a SUNSPORT tattoo (the temporary kind) during a sun-drenched November afternoon at Stanford Stadium. The 27-23 victory over Oregon State was one of seven straight wins on the Cardinal’s dramatic run to the Rose Bowl.

SUNSPORT is a new education and research program to improve sun-protection knowledge and habits among Stanford student-athletes - as well as outdoor athletes and fans of all ages. The SUNSPORT logo tattoo delivers a message: “I’ve got my sunscreen on. Do you?”

A partnership among the Stanford Cancer Institute, the medical school’s Department of Dermatology, Stanford Athletics, and Stanford Hospital & Clinics, SUNSPORT is establishing the most comprehensive sun protection outreach and research program of any university in the country. SUNSPORT research focuses on surveying Stanford’s outdoor athletes to identify attitudes and sun-protection practices in this high-risk population, and program dermatologists also work closely with athletes, coaches and athletic trainers to improve sun safety behaviors.

Going to the Rose Bowl? Post your photos wearing the SUNSPORT logo on the Stanford SUNSPORT Facebook page. Tattoos are available by e-mailing a request with your mailing address to [email protected].

Photo by Kristin Nord/Stanford Department of Dermatology

You may be lucky enough to have perfect skin. But no matter how smooth and clear its surface (known as the epidermis) appears (or doesn’t!), it’s a complex mixture of many different cell types - each with a very specific job. The production, or differentiation, of such a sophisticated tissue requires an immense amount of coordination at the cellular level.

Now Stanford dermatologist Paul Khavari, MD, PhD, has cracked part of the code governing the development of the epidermis. The research, which was published yesterday in Nature (subscription required), could lead to a better understanding of many skin disorders, from eczema to skin cancer. As explained in our release:

Khavari and his colleagues have found that, like a traffic cop motioning cars to specific parking spaces in a large, busy lot, a newly identified molecule called TINCR is required to direct precursor cells down pathways toward particular developmental fates. It does so by binding to and stabilizing differentiation-specific genetic messages called messenger RNAs. Blocking TINCR activity, the researchers found, stopped the differentiation of all epidermal cells.

“This is an entirely unique mechanism, which sheds light on a previously invisible portion of the regulation of this process,” said Khavari.

TINCR is particularly interesting because it’s not a protein, but is instead what’s known as a long, non-coding RNA. These lncRNAs play an important role in regulating the expression of other genes - in this case, by binding to and stabilizing other RNAs. Khavari’s research marks the first time that an lncRNA has been shown to play a role in epidermal differentiation. According to dermatologist and co-author Howard Chang, MD, PhD:

This work revealed a new role for regulatory RNAs in gene activation - by stabilizing select messenger RNA transcripts. This finding highlights the ability of regulatory RNAs to fine-tune gene expression.

Unfortunately, the finding won’t lead immediately to flawless skin for all. It might, however, help scientists figure out how to stop the unwanted division of epidermal cells (in the case of some skin cancers, for example) or to stimulate new skin growth in the case of burns or trauma.

Previously: My pet tumor-Stanford researchers grow 3D tumor in lab from normal cells
Photo by Flickr user dermatology.com

Beyond the well-documented DNA damage and cancer risk, ultraviolet rays can also change the way the cells in our outermost layer of skin hold together and respond to strain, according to new research from Stanford engineers.

In the study (subscription required), a team of researchers led by Reinhold Dauskardt, PhD, a professor in the Materials Science and Engineering Department at Stanford, subjected samples of human tissue to varying doses of UVB radiation, the range of ultraviolet wavelengths that are largely absorbed by the epidermis and don’t penetrate deeper layers. The samples were later put under varying kinds of stress until they tore to test their mechanical limits. Study results showed that the sun takes a dramatic toll on our mechanical barrier function, makes it more prone to cracking and chapping and leaves deeper layers vulnerable to infection.

A Stanford release explains the findings and the study’s importance from a global-climate and public-health perspective:

“UV exposure doesn’t just make the stratum corneum weaker,” said Dauskardt, “It also increases the actual stresses that cause the stratum corneum to fail. So it’s sort of a double-whammy, which we didn’t expect.” In other words, UV radiation introduces more force driving skin cells apart while making the cells more helpless to resist.

This double threat is especially relevant to public health as global climate change will gradually change the way people interact with the sun. The spectrum of sunlight that penetrates to earth’s surface is increasing, while warmer temperatures cause people to wear less clothing, making them more vulnerable.

Mechanical testing is also confirming the vital importance of wearing sunscreen to protect the skin’s integrity. “It’s totally cool,” said Dauskardt, “You put a sunscreen on the sample and it causes a huge change in the way the skin is affected.” This line of research offers a straightforward strategy for finding the best protection. Instead of trying to establish risk of carcinoma or gene damage, these methods can quickly and accurately model how different sun protection products affect the skin’s mechanics. Dauskardt has already started comparative testing of sunscreens and thinks the work could be relevant in settling a currently raging debate about which types are most effective.

Previously: More evidence on the link between indoor tanning and cancers, Working to prevent melanoma, Intense, rapid sun tanning may increase skin cancer risk and California cities score below 50th percentile on ‘sun-smart’ survey
Photo by Ed Yourdon