Predicting the Future – Hywel Williams, our Yogi Berra, Is at the Plate

Hywel
Hywel Williams

One of Yogi’s famous quotes — or misquotes — is that “it is very tough to make predictions, especially about the future.” Hywel Williams is one of Dermatology’s experts in explaining the present and predicting the future of health related events using quantitative data. He has been given the responsibility for directing the NIHR Health Technology Assessment Program for the UK National Health Service. Essentially all 400+ current major clinical trials within all medical specialties will be under his purview. A wonderful recognition of his analytical skills and his ability to put together large groups of investigators in endeavors such as the International Cochrane Skin Group systematic reviews and various national clinical trials within the UK Dermatology Clinical Trials Network, which he founded. Hywel likes to understand and predict events, so it is important to understand the path that brought Hywel to this next stage of his academic life.

Hywel-Dda-from-Wikipedia-CC-License-public-domain
Hywel Dda (Hywel the Good)

Even more important than Hywel’s horoscope, which is still being crunched by my supercomputer, is the name “Hywel.” “Hywel” is Welsh for ‘eminent’ or ‘remarkable’; thus he was given his life’s direction from the get-go by his family. Hywel comes from the small hillside village of Cymmer Afran in South Wales, and he attended a tiny comprehensive school there. Hywel Dda (meaning “Hywel the Good”) was a ninth century Welsh king whose major accomplishment was codifying Wales’ laws and customs and for ensuring equal rights for women. Yes, our Hywel has followed the direction of his namesake king and has given extraordinary service in codifying clinical trial data and global burden of disease, both in the United Kingdom and internationally.

Just go through Pubmed listings for HC Williams and you cannot help being impressed by the extent and breadth of his interests and accomplishments. In addition to the big picture items, Hywel’s most recent paper in the British Journal of Dermatology (2015) looks at the micro-level on how to improve teleconferencing; for him no issue is too big or too small to be studied and improved. His multiple accomplishments and awards are easily searchable on the University of Nottingham web site. When I was the Editor of the JID, Hywel was clinical trials Editor, and he improved the Journal‘s approach to clinical trial data and publication. His service to our specialty has been extraordinary and exemplary.

We know that the entire British National Health Service and the individuals it serves will benefit from having Hywel in his new position. Although Hywel comes from Nottingham, he is no Robin Hood and will be judicious in supervising the reviewing and awarding grants for clinical research. It is his nature and in his name.

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

Photograph of Sancy LeachmanGUEST 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

Photograph of Sancy Leachman

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!

How Does Science Happen? The Basal Cell Nevus Saga

image of a lightbulb with a brain inside

Was Newton sitting under an apple tree? Was Kekulé dreaming while snakes were forming benzene rings during his rapid eye movements? Hard to say, it was a long time ago. That is why it is especially interesting to have a contemporary scientific narrative told by one of the key movers within the story. The October 2015 issue of JID includes an editorial by Ervin Epstein, Jr., who has been thinking of, dreaming of, and exploring the secrets of the basal cell nevus syndrome in the laboratory. He has been a great networker, even before the notion of networking was named, and he has interacted with clinicians and basic scientists throughout the world, as documented in his editorial. He starts with thoughts induced by sleep — or possibly hypoxia — on a transcontinental flight, reading, and integrating models and information from other diseases. Key steps of interacting with drug companies and convincing the money managers that basal cell nevus syndrome is important and that it could help their bottom line are expounded. The story is still in progress, so it is useful for the historians who will be digging though his emails and laboratory notebooks that Erv has shared his narrative in this issue.

 

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