Stem Cells at the Montagna Symposium on the Biology of Skin (Part II)

GUEST BLOGGER:  Sancy Leachman, Oregon Health & Science University

Welcome back to Montagna, 2015!  The conference keeps getting better and better!

The morning session, chaired by John McGrath, focused on stem cell-based therapies and innovative reprogramming technologies. In this session, it seemed almost possible to glimpse the future — a future where monogenic disorders of the skin like epidermolysis bullosa might be treatable!  John reported on remarkable responses to cell-based therapies which led to life-changing improvements in the quality of life for his patients. Angela Christiano followed with a story about the next generation of 3-D skin models that she is developing that include not only keratinocytes and fibroblasts, but also melanocytes, nerve cells, and even rudimentary hair follicles. Jakub Tolar, a bone marrow transplant (BMT) expert from the University of Minnesota then showed truly amazing responses in recessive dystrophic epidermolysis bullosa with BMT. He demonstrated that stem cells derived from the BMT donor were able to differentiate and populate the skin and that these cells were able to produce collagen VII and improve clinical results in patients. Finally, Tony Oro presented clinical trial results from the Stanford dystrophic EB trial and showed new advances being made in adenoviral-driven reprogramming of autologous cells for therapeutic benefit. Taken together, these talks demonstrate the progress that is being made on all fronts, through the use of stem cells, for the benefit of these patients. It is one of the most optimistic and hopeful times I have seen for this class of disease.

The meeting ended with a bang – in keeping with tradition. Xiao-Jing Wang, from University of Colorado, revealed her new mouse model for patient-derived xenografting. One of the major limitations of the PDX mouse models is the need to use immunosuppressed mice in order to prevent rejection of the human tumor grafts. The immunocompromise in the traditional model eliminates the possibility of investigating the role of the immune system in the cancer progression and does not permit the investigation of immunotherapies. Xiao-Jing has now not only xenografted immunocompromised mice with human squamous cell carcinomas, but also used stem cells harvested from the same donor to reconstitute (or humanize) the mouse immune system. The same patient’s cancer graft is then removed and re-transplanted into the matched humanized mouse. In short, this is a new personalized model of the patient’s own tumor and immune system and opens up the possibility for testing novel drugs and drug combinations to predict response of the tumor to therapy, even immunotherapy. This is truly a preview of personalized medicine.

The last elements of the meeting included a panel discussion that was very lively. Topics included how to compete more successfully for grants, how to publish successfully, and how to position yourself for getting the job of your dreams after you finish your post-doctoral fellowship. I hope the young students and investigators in the room “felt the love” – those more senior members in the room were clearly committed to helping them become a successful next generation of investigators!

The finale of the meeting was a Potlatch Northwest-Style Salmon Barbeque at the home of Drs. Diane and Jim Baker. Just like the science at the meeting, life doesn’t get much better than this!

 

Stem Cells at the Montagna Symposium on the Biology of Skin

GUEST BLOGGER:  Sancy Leachman, Oregon Health & Science University

I am blogging today from the Montagna Symposium of the Biology of Skin. As most dermatologic scientists know, Montagna is developed each year as a new, independent specialty symposium, led by experts in the field, focusing on cutting-edge science that impacts the field of dermatology. The specialty topic for this year is stem cells – understanding the biology of these cells, and figuring out how to harness them to treat disease. The venue this year is spectacular, sequestered on the Oregon Coast, where we are sharing ideas, learning from each other, developing enduring relationships with collaborators, having a great time! I was incredibly “wowed” by all of the talks this year and can’t do justice to the program in this post, but you can see for yourself what the Symposium Director, Molly Kulesz-Martin and the Program Chairs Xiao-Jing Wang and Valery Horsley were able to accomplish by looking at the program online.  Science in dermatology doesn’t get much better than this!

I wasn’t able to get out to the coast in time for the keynote lecture this year because I just launched a new app (Mole Mapper)

Missing Haifan Lin discuss the story of piRNAs and how they are uniting major constituents of our genome was a major disappointment for me. Fortunately, he was willing to sit with me and Valerie over a glass of Oregon wine the next evening and share his “elevator speech” about piRNAs. Anyone who isn’t familiar with the functional importance of these areas of the genome (that had previously been characterized as “junk DNA”) should get up to speed – it is an important, expanding area of human genetics that is certain to have direct implications on human health. One of my favorite lectures so far was Melissa (Missy) Wong’s talk on cancer stem cell and macrophage fusion. It was impressive because it provided direct evidence for a concept that one of my favorite melanoma biologists, John Pawelek, has been trying to prove, for almost two decades. In fact, David Norris made the point (during a robust question and answer session) that John had proposed this hypothesis at a joint Montagna/Pan American Society of Pigment Cell Research Conference about 17 years ago. This illustrates how difficult these important observations can be to understand and prove, how deeply and passionately our scientists think and feel about their contributions to the field, and how important questions must sometimes wait for technological breakthroughs to be answered. Missy provided us with compelling evidence that melanoma and other human cancer cells fuse with macrophages, potentially explaining how cancer cells gain the ability to metastasize. This discovery will impact the full spectrum of dermatologic science, from the perspective of understanding basic biology, providing possible diagnostic clues, and ultimately, perhaps allowing the development of new targeted agents in the future.

Another provocative talk for me was by Matthew Rodeheffer, an adipocyte stem cell biologist from Yale. His presentation brought an important diversity to the conference, expanding the horizons of cutaneous biologists and opening our eyes to ways that skin interfaces and/or recapitulates virtually every organ system in the body. There are so many areas in which nutrition and obesity affect human health (and disease). The contribution Matthew has made to understanding how specific dietary fats impact the expansion of adipocyte precursors and lead to obesity is relevant not only to medicine in general, but dermatology as well.

Congratulations to all of the speakers and meeting attendees – the conference is fabulous!

Reflectance Confocal Microscopy: An Elegant, Revolutionary Technique with Boundless Possibilities

by guest blogger Joshua Davyd Fox, University of Miami, MD class of 2016

 

At the 2015 American Academy of Dermatology Annual Meeting, I serendipitously discovered Reflectance Confocal Microscopy (RCM). I sat mesmerized, watching the presenters quickly flip through black-and-white mosaic images of in vivo skin at microscopic resolution in what may best be described as a fusion between radiology and dermatology. As a fly in a room filled with experts of a drastically underutilized technology, I felt as though I was witnessing something groundbreaking- the next evolution in dermatologic diagnosis since the revolutionary advent of dermoscopy.

 

Before I knew it, I was meeting a faculty member from my University to learn more about RCM and observe a case. The patient was a fair-skinned middle-aged woman with a dark brown macule on her buttock. The dermoscopic pattern was not diagnostic and would have required a biopsy.

 

RCM uses a laser as a source of monochromatic light. As the wavelength of the light increases in the near-infrared region (700-1400 nm), so does its depth of penetration into the skin; however, longer wavelengths have less lateral resolution.¹ Thus, depending on the RCM application, the wavelength will vary based on the desired depth of penetration.

 

It is common to use an 830 nm diode laser on automatic image control, which adjusts the laser power to provide the best contrast (the range is 1-21mW and causes no tissue damage). A skin contact ring is affixed to the skin along with a drop of ultrasound jelly at the site of the lesion, and a small drop of a water-based gel is placed onto the objective lens that is in the housing of the skin-contact device.

 

The laser beam passes through a beam splitter, scanning and focusing optical lens, through the skin contact device and is focused on a couple of microns of skin. The light rays are refracted by various components of the skin such as membranes, melanosomes and keratohyalin granules based on their respective refractive indices. These refracted and reflected rays return to the direction of the detector (which is connected to the computer), though they are physically filtered by a small aperture that only allows the light rays originating from the focal point to strike the detector — hence, this is confocal microscopy. Similar to the contrast created by differing tissue radio-densities in x-ray imaging, in RCM the image depends upon the contrast that is created by the differing refractive indices of skin components. The water-based gel is used because it has a refractive index of 1.33, which is nearly equivalent to the 1.34 of the epidermis, thus eliminating artificial refraction.

 

One can choose how to display the captured images. For example, we captured 12 rows by 12 rows of 500-micron x 500-micron tiles that were combined to form a mosaic of a 6 mm x 6 mm field with resolution at the cellular level. We scanned multiple mosaic images of the lesion at various depths and magnifications and identified cells out of a tempestuous sea of black and white pixels.

 

Although confocal microscopy was developed in the 1950s it was not applied to skin imaging until the 1990s with Rajadhyaksha’s work.² Today RCM is used clinically mainly in the diagnosis of skin cancer and corneal pathologies and in research in skin cancer, skin aging, laser treatment, pigment pathologies, melasma, UV-induced skin responses, wound healing, and conjunctival and corneal evaluation.^3,4,5 In a recent study in the JAAD, handheld RCM was utilized in the evaluation of 47 eyelid tumors clinically suspicious of malignancy, and RCM had 100% sensitivity and 69.2% specificity in the diagnosis of malignant tumors of the eyelid.⁶ Even more impressive results were seen in a recent study in the American Journal of Ophthalmology, in which 30 patients with conjunctival tumors were correctly spared an excisional biopsy (based on at least 12 months of follow-up), and in all patients who did undergo excision (23), the authors found 100% RCM correlation to the histologic diagnosis.³

 

Our patient’s lesion that warranted a biopsy based on the physical exam and dermoscopy was found to be benign based on the RCM features. Nonetheless, the patient wished for the lesion to be excised, which was done in due time.

 

This leads to the question: should we ask patients prior to performing RCM if they want the lesion to be excised regardless, in which case RCM would not be performed? Perhaps there is a benefit to conducting RCM even in these patients, as the tool is still developing and, with each case, more information is added to fine-tune the technique? Are there applications of RCM which we have not even thought of yet? I’m sure there are.

 

Cost and reimbursement issues will likely play a large role in the utility of RCM outside of the university setting. The average device costs between $70,000-$100,000, and each patient requires approximately 10-20 minutes to image.

 

To me, RCM’s ability to image in vivo skin, real-time, at microscopic resolution makes it a beautifully revolutionary technique. Only time will tell on which applications RCM will be most focused.

 

Anyone who would like to learn the technique of reflectance confocal microscopy may be interested in attending a weekend course in November 2015, at the University of Miami School of Medicine and can email umcme@med.miami.edu, or call 305-243-6716 for more information.

 

Acknowledgments:
Thanks to Robert S. Kirsner MD PhD and Theresa Cao DO of the University of Miami who critically reviewed this work.

 

References:

1. Calzavara-Pinton P, Longo C, Venturini M, Sala R, Pellacani G. Reflectance confocal microscopy for in vivo skin imaging. Photochemistry and photobiology. Nov-Dec 2008;84(6):1421-1430.
2. Rajadhyaksha M, Grossman M, Esterowitz D, Webb RH, Anderson RR. In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast. The Journal of investigative dermatology. Jun 1995;104(6):946-952.
3. Cinotti E, Perrot JL, Labeille B, et al. Handheld reflectance confocal microscopy for the diagnosis of conjunctival tumors. American journal of ophthalmology. Feb 2015;159(2):324-333 e321.
4. Ulrich M, Lange-Asschenfeldt S. In vivo confocal microscopy in dermatology: from research to clinical application. Journal of biomedical optics. Jun 2013;18(6):061212.
5. Marchini G, Mastropasqua L, Pedrotti E, Nubile M, Ciancaglini M, Sbabo A. Deep lamellar keratoplasty by intracorneal dissection: a prospective clinical and confocal microscopic study. Ophthalmology. Aug 2006;113(8):1289-1300.
6. Cinotti E, Perrot JL, Campolmi N, et al. The role of in vivo confocal microscopy in the diagnosis of eyelid margin tumors: 47 cases. Journal of the American Academy of Dermatology. Nov 2014;71(5):912-918 e912.

 

 

Controversy: A Dermatology TED Conference: A Lot in Storrs for You

by guest blogger Sancy Leachman, M.D., Ph.D., Oregon Health & Science University

 

This year’s Storrs Lectureship is undoubtedly one of the most unusual meetings I have ever attended.  I don’t want you to interpret “unusual” as a code word for “bad,” but you can interpret it as “unconventional.” The typical didactic format was abandoned in favor of short, TED-type presentations followed by abundant discussion. The lectureship is designed to reflect “Fran Storrs’ mission” in a “Fran Storrs’ way.” For those of you that know Fran, you’ll know what I mean by that. For those that don’t, suffice it to say that Fran doesn’t back away from controversy and doesn’t hesitate to tackle difficult problems, but she approaches them with humor (and a lot of laughter!). The conference was a spectacular embodiment of all those things – more than anything, we addressed the problem of deep thinking. As practitioners of medicine, we are confronted daily with complex problems that require action on our part, but we don’t have time to contemplate these complexities and consider options as thoroughly as possible, especially with the counsel of experts. At this year’s Storrs Lectureship, we all took the time to think deeply, to question thoroughly, to disagree with experts, and most of all, to seek the best answers for our patients, community, and society.

 

This year’s topic was “Melanoma Screening & Diagnostics: Do They Make a Difference?”  This topic was precipitated by the fact that skin cancer screening is not recommended by the U.S. Preventive Services Task Force, which limits coverage by the Affordable Care Act. Before we demand or mandate new screening and diagnostics technologies, it is CRITICAL that we know: Are they making a difference? But the data and answers are complex and incomplete. Experts were assembled to help tease out the key elements in real time and we were able to ask meaningful questions like:  “Should skin cancer screening be recommended by the USPSTF?”; “What evidence do we need to assure it is beneficial for patients and society?” “What are the legal implications of making this recommendation?” For example, if the USPSTF recommends screening and we fail to screen all patients, are we more vulnerable from a legal perspective?

 

Obviously, I can’t capture the conference in a blog (view it online), but I do have a few thoughts: Dermatologists need to participate as actively as possible in this controversy, because our specialty is going to be driven by it for years to come. We need to be careful what we ask for, because we just might get it. And we should never be distracted from the patients’ best interest by our own fear of litigation (though I will continue to manage my highest risk melanoma patients in collaboration with other providers!). So, signing off on this topic until next year – new topics for next year’s committee are welcome now!

 

 

 

Montagna 2014: An immortal organism?

Contributed by Sancy Leachman, MD, PhD, Oregon Health & Science University

 

At Montagna this year, I experienced an intellectual excitement surrounding the discovery of aging processes and mechanisms, but also appreciated that this field is driven by a particular human urge to understand and attain longevity, and perhaps immortality. Both our minds and hearts were stimulated to support discovery of ways to prevent and treat aging disorders such as Werner and Hutchinson-Guilford Progeria syndromes, as discussed by Ray Monnat and Maria Eriksson. A full program on Sunday explored innovative strategies to prevent and reverse skin aging, including opportunities in epigenetic regulation (Vladimir Botchkarev), targeted telomere-based methods (Calvin Harley), mTOR pathway agents (Silvio Gutkind), and even a clever strategy of DNA “photoprotection” with biomimetic acyclothymidine dinucleosides (Abbas Raza). Rosemarie Osborne also reported on the use of powerful transcriptional profiling tools to understand the expression changes that occur during aging in normal human skin.  And finally, the afternoon session reached a zenith with an industry-led panel discussion on future directions. The panel discussion was so powerful because it was preceded by all of the scientific presentations and discussions. This priming effect led to a productive dialogue to explore opportunities for the development of new skin products through fair and productive collaboration between academia and industry.  It was magnificent!

 

Just as magnificent as the science, however, was the conference itself. At 63 years of age, the conference is entering a more mature era and may be a relevant metaphor for the aging theme. At the conference banquet, Molly Kulesz-Martin and Barbara A. Gilchrest provided some history of the conference, which was begun by Bill Montagna to catalyze scientific progress toward improved skin health. They also thanked all of the attendees for continuing the tradition of Montagna. In its 63 years, Montagna might be considered almost organismic in nature. It is composed of a relatively stable population of participants, some of whom have attended more than 20 of these meetings. We had several senior leaders of dermatologic science who attended this year, including Jon Hanifin, Jerry Krueger, John Voorhees, Sewon Kang — individuals who provide a lifetime of experience, stability, quality and relevance to the meeting. In addition, the conference hosts individuals with a wide variety of expertise, including basic cellular and molecular biologists, physical and medicinal chemists, bioengineers, photobiologists, physicians, industrial scientists, businessmen and more. Finally, attendees also vary in age (senescence?) and level of experience, including undergraduate, medical and graduate trainees, young investigators, and senior physicians and scientists. After the banquet, I roasted marshmallows around a firepit with residents, faculty, and a faculty recruit. It occurred to me that we have a solution to the mortality problem at the group level. By bringing in young, enthusiastic, and diverse expertise, we not only maximize the impact of the science, but our work can become in some ways immortal. What an appropriate holy grail!

 

Disclaimer: I can’t deny this blog entry is a bit “corney-fied,” but what do you expect from a dermatologist who’s been at a brain-intense conference all weekend!

Montagna 2014: The quest for the fountain of youth

Contributed by Sancy Leachman, MD, PhD, Oregon Health & Science University

 

The Friday and Saturday Montagna sessions were spectacular – both because of the quality of the presentations and because of the audience engagement! The speakers could barely get off the stage because of all the questions. It’s impossible for me to capture the enthusiastic tone of the meeting.

 

It’s also remarkable that the meeting, though centered on aging, is proving to be a study in the nature of scientific discovery and the relationship between discovery and scientific tools. I suppose it has always been this way; the wheel had to be discovered before a larger world could be explored. In the case of this year’s Montagna, although the specific topic of aging is finite, the principles of discovery that are being applied are enduring.

 

For example, Howard Chang began the meeting with a stated goal of understanding how the activities of thousands of genes are coordinated to create the process and variability of aging. As part of his investigations, he has developed tools to use chromatin itself as a “GPS device” to show which genomic areas comprise an individual’s personal “regulome.” This personalized regulome approach has identified active regulatory areas that are not translated into protein, including long non-coding RNAs. Not long ago, there existed a dogma that these non-coding areas of the genome, including pseudogenes, were functionally “dead” pieces of redundant DNA. Howard’s studies show that these genes are very much alive and functioning, and have also helped to “bring to life” this new field of investigation. A similar theme of life and death of a dogma was articulated by Judith Campisi, who reported her latest thinking on the process and role of cellular senescence. She showed compelling data, proving that senescent cells are not just passive, past-their-prime bystanders, merely sitting quietly in place (as was once believed). She showed that these senescent cells produce a host of SASP (senescent-associated secretory protein) molecules that dramatically impact the tissue microenvironment. Ultimately, she asked a provocative question: if these senescent cells could be selectively removed, would the tissue environment remain younger and healthier?

 

Additional “dogma-bashing” was enabled by the development and utilization of powerful investigational tools and approaches. Valentina Greco showed amazing video coverage of hair follicle regression via consumption of apoptotic cells – not by phagocytic hematopoietic cells as previously believed – but by their neighboring keratinocytes. Gary Fisher showed amazing (3-D, rotating, second harmonic generation) images that revealed physical changes in aging dermis as well as responses of the skin to an injectable cosmetic filler. And Vera Gorbunova showed how the naked mole rat (a remarkable creature that manages to lives longer without cancer than other vertebrates on the planet), has been used to identify high-molecular weight hyaluronan as a potential anti-aging agent. Clearly, these tools are enhancing our ability to test critical hypotheses, but just as the wheel (and boat) permitted discovery that the world was round, the tools presented at Montagna expand our ability to challenge dogma, see new horizons, and construct better hypotheses. Remarkably, as we study the process of aging, death, and immortality, we see the timeless principles of discovery as well.

Montagna 2014: Live and let die – are mutations a key to aging skin?

Contributed by Sancy Leachman, MD, PhD, Oregon Health & Science University

 

Welcome to Montagna 2014! It is hard to believe that this is the 63^rd annual Montagna Symposium on the Biology of the Skin. For any of you unfamiliar with Montagna, it is the only NIH-supported annual scientific meeting in Dermatology that focuses intensely on a rotating special topic of interest to dermatologists. And, it is held in a sequestered resort location where physicians and scientists with like minds and common interests can start and strengthen meaningful working relationships. Because the topic changes each year, new expert program directors are selected each year to develop the program. The concept is to identify a hot topic in dermatology and bring together cross-disciplinary physician, scientific, and industrial leaders in the topic area so that scientific knowledge relevant to patient care can be advanced into clinical care as quickly as possible.

 

This year’s Montagna is on the topic of Skin Aging: Molecular Mechanisms and Tissue Consequences and is being held at the beautiful Salishan beach resort on the coast of Oregon. In true Montagna tradition, the welcome and cocktail reception transitioned into the keynote address. This year’s Program Chair, Barbara A. Gilchrest, introduced the three session chairs Howard Chang, Judith Campisi, and Gary Fisher as well as the Keynote speaker, Jan Vijg, who spoke on “Genome Mosaicism, Aging, and Disease.” Dr. Vijg’s address set the stage for the conference, juxtaposing a testable hypothesis for the molecular cause of aging with epidemiologic trends of aging in our society and philosophical questions surrounding the process of aging and the maximal lifespan of man. He proposed and presented data suggesting that aging may depend on an accumulation of somatic mutations. He also made the point that mutations, in association with natural selection, provide the means for evolution of life on earth. It is fascinating to think that mutations may share the function of creating life, yet predisposing to death – and what a particularly poignant and a perfect opening thought for this conference.

Montagna Symposium on Light and Skin – Day 3

Montagna Symposium on the Biology of the Skin
Skamania Lodge
Sunday October 13, 2013

 

By Guest Bloggger Sancy Leachman, MD, PhD

 

Welcome to the final day of the Montagna Symposium on the Biology of the Skin 2013. The dinner speaker last night was John Parrish (in absentia via video), complemented by symposium co-leaders Barbara Gilchrest, Rox Anderson, and Steve Jacques. It was powerful. John took us through a tour of his adventures in the development of photo-related innovations, from the development of effective sunscreens to therapeutic lasers, and he shared social context along the way. The sustained level of energy and impact he has brought to our field is remarkable. What was clear is that he has been simultaneously driven and humbled by his role as an innovator in dermatology; and the level of intensity he communicated seemed to be fueled by the success he had in making a meaningful contribution for patients. It was also clear that he actively selected important and interesting problems to solve. The video resonated with so many in the audience because we glimpsed the opportunity to apply similar principles to our own work with the possibility of making a difference in the pain and suffering of patients. Our challenge, and one that was tackled in the final session of the meeting (Provocative Problems and Questions), is to harness the energy of the best and brightest minds in our field toward a unified vision to benefit our patients.

Of the provocative presentations, one that struck a chord with me was by Richard Weller, who suggested that despite our understanding that UV radiation causes skin cancer, there is no definitive data to prove that it shortens lifespan. In fact, exposure to UVA may lead to NO2 and NO3 release by the skin that could lower blood pressure and extend life. The presentation of his data and the lively discussion surrounding the pros and cons of sun exposure that ensued was invigorating. It was a fabulous example of the power of academic discourse, where opposing points of view can be clearly articulated and critiqued. Dr. Parrish’s presentation on the previous evening emphasized skepticism by the dermatology community when he first presented data demonstrating the beneficial effects of UV radiation on psoriatic skin. I can imagine this being similar to the skepticism that Dr. Weller experienced today.

Additional lively discourse occurred around the role of business in dermatology and the development of partnerships between industry and academia during the last session in the conference. At the time when Dr. Parrish completed his studies, there was little funding available for clinical trials from the NIH, but there was more support available from the hospital and discretionary clinical income. Now, both NIH funding and clinical revenue are diminishing, and to continue to support innovation and clinical trials for the benefit of our patients, it is going to be necessary to identify additional support, perhaps through industrial partnerships and patient-based philanthropy. Future dermatologic advances must be driven by innovation and the development of devices and treatments that create value, that help make our patients better.

These and other topics will be continued and extended at next year’s Montagna Symposium on the Biology of the Skin on Aging of the Skin to be held at the Salishan Resort on the Oregon Coast, Oct. 9-13, 2014.  Don’t miss it!

Montagna Symposium on Light and Skin – Day 2

Montagna Symposium Blog
Skamania Lodge, Stevenson, WA
Saturday, October 12, 2013

 

By Guest Blogger Sancy Leachman, MD, PhD

 

Good morning from Skamania Lodge as we start day two of the Montagna Symposium on the Biology of the Skin 2013. I want to share a “quintessential Montagna” experience I had last night at the faculty dinner at Nora’s in Hood River (where only local food and wine are served!). I sat directly across from Rox Anderson and we returned to a conversation we had started about 4 years ago. I had explained my frustration with performing autologous pigment cell transfers for vitiligo and the need for a device to simply and easily transfer non-scarring epidermal grafts to a prepped affected surface. Last night, I found out that he (and his wonderful team) created such a device and that it became commercially available about 6 months ago!! Not only that, the story behind it is inspiring. Rox gave this project to an engineering student that came to him through a program for developing countries. Once the device was created (Momelan, derived from “more melanin”), it was licensed to KCI with the stipulation that a portion of the product be supplied to developing countries at a substantially discounted rate. Wow – from a problem, to an idea, to a mentorship, to a product, to a venture-based solution – this is the way it is supposed to work! I will be purchasing one of these devices next week.

The hike on Eagle Creek Trail was strategically scheduled after a very exciting, but sophisticated session on imaging and microscopy led by Steve Jacques.  Again, this session was “quintessential Montagna,” but in a completely different way. Biomedical optics, photonics, and technical details of non-invasive imaging devices are “over my head” scientifically, but I have always loved science fiction. When I was a kid, I read every Jules Verne book I could find – I loved the idea that dreaming about using a technology that didn’t exist could inspire someone to create that technology (think “Nautilus” in 20,000 Leagues Under the Sea). For me, that’s the way this Montagna session felt, like I was living in the development phase of a science fiction novel. The technology presented in this session will undoubtedly revolutionize the way that we practice dermatology, and I feel lucky to be here to learn about it at the ground-level, directly from the inventors and developers. In today’s world of super-sub-specialization and information overload, cross-fertilization between diverse specialties is priceless because it is the foundation of team science. Team science will be mandatory as we choose to solve increasingly difficult problems requiring diverse expertise. This session is a jump-start to that process. As a concluding thought for the day, I would also add that this marriage between medicine and technology is likely our best strategy for reducing health care costs in the long-term. Only by doing it “better, cheaper and faster” can we hope to simultaneously improve health care and reduce costs.

 

Quintessential Montagna.

Montagna Symposium on Light and the Skin – Day 1

Montagna Symposium on the Biology of the Skin
Skamania Lodge, Stevenson, WA
October 10-14

 

By Guest Blogger Sancy Leachman, MD, PhD

 

Greetings from the Montagna Symposium! As many of the “old-timers” in dermatology know, this topic-directed symposium on the biology of the skin has a tradition of identifying the most important scientific breakthroughs in dermatology and of recruiting leadership to develop a cutting-edge program around that topic. All of this intellectual excitement occurs in relative seclusion (this year in the Columbia River Gorge) to foster an atmosphere of reflective collegiality and collaborative problem solving.

This year’s selected topic is “Light and the Skin: How Light Sustains, Damages, Treats, Images, and Modifies Skin Biology” and the program has been developed by four world-renowned leaders in the field of photobiology and pigmentation: Rox Anderson (Program Chair), and David Fisher, Barbara Gilchrest, and Steven Jacques (Session Chairs). Together, they have worked with Molly Kulesz-Martin (Symposium Director) to create a thought-provoking program exploring the biological effects of light and how light can be used to image and treat the skin.  My motivation to blog throughout this meeting is to transmit some of the energy and excitement we are experiencing to dermatologic scientists that are unable to be present this year, including our friends from the NIH who are unable to attend secondary to the government shutdown.

One of the topics that struck me as being particularly intriguing or paradigm challenging was that of pigmentation diversity. Why is there so much diversity of human pigmentation and how does that impact the risk for skin cancer including melanoma? I found it quite thought-provoking to consider the multiple functions of MC1R, not just in pigmentation, but also in the oxidative stress/DNA damage responses, apoptosis, and curiously, in the role it appears to play in addiction and pain sensation. These multiple cellular and molecular roles suggest that melanocytes play roles in the skin beyond production of pigment and may be important mediators of other neurological (e.g. pain) or light sensing processes. There is clearly a complex interaction between pigmentation genes, skin phenotypes, and environmental exposures to UV that, as Dr. Gilchrest mentioned, “are likely to be coordinately regulated toward a common purpose and selected by nature to safeguard and protect the genome, which in skin translates into cancer prevention. Unfortunately one of these safeguards is phtoaging.”  Some of the most interesting conversation I heard on this topic was “off-line.” Nina Jablonski’s work was discussed from the perspective of a strong evolutionary pressure for lightening of the skin (via MC1R heterogeneity) as human migration extended into Northern, light-poor regions. It was suggested that part of this evolutionary pressure might be related to decreased maternal/fetal survival in individuals with rickets. It struck me that MC1R polymorphism effects on both pigmentation and pain might represent a remarkably efficient biological use of a single molecule, simultaneously reducing vitamin D deficiency and pain associated with sunburn. Finally, concern was expressed that investigation of pigmentation diversity has been hampered by a fear that such research may be interpreted as racial or discriminatory in nature. Spanning the fields of genetics, biochemistry, medicine and evolution highlights the purpose and strength of the Montagna.