Advancement Through Collaboration

Volume 24 | October 2016

In this issue:

• Research Highlight: Conditioning of the Premetastatic Niche by Melanosomal miRNA Trafficking
• Meet the New Investigator: Dr Amaya Viros
• SMR Session Highlight: Women, Men and Science: The Changing Landscape
• Funding Opportunities and Job Postings
• A Guide to Boston: The SMR Congress Concierge

LETTER FROM SMR PRESIDENT

Dear SMR Friends and Colleagues,

This is my last SMR Presidential newsletter as, after serving as SMR President for three years, I am delighted to report that I shall be passing the mantle of responsibility to Dr. Keith Flaherty at the SMR Congress in Boston. As November fast approaches, we are putting the final touches to the scientific and social program. I expect this to be a very dynamic and exciting meeting with excellent scientific sessions, topics and discussions for delegates to participate in. The Congress will kick-off with a keynote lecture from Dr. Leonard I. Zon. Len is the Grousbeck Professor of Pediatric Medicine at Harvard Medical School, an Investigator in the Howard Hughes Medical Institute, and Director of the Stem Cell Program at Children's Hospital, Boston. In addition he serves the scientific community in numerous other ways including as: President of the International Society for Stem Cell Research; President of the American Society for Clinical Investigation; Head of the external investigators of the Zebrafish Genome Institution and Chairman of the Harvard Stem Cell Institutes Executive Committee. He is internationally recognized for his pioneering work in stem cell biology and cancer genetics. Indeed, using zebrafish and pioneered by Liz Patton, Len’s lab was the first to generate an experimental animal model of BRAFV600E-driven melanoma. Len is an outstanding scientist and a gifted and inspiring speaker and so I urge you not to miss his keynote lecture on the evening of Sunday, November 6th.

In this issue of the newsletter you will also find new sections such as profiles on new investigators in the field and our Women in Science section. At the annual meeting, our Women in Science session this year will focus on the positive strides that the field has made, and is titled “Women, Men and Science - The changing landscape”. As is customary, the meeting will close with a session of speakers who were selected from the late-breaking abstract submissions. I hope that you will attend the Congress and stay until the very end.

Finally, it saddens me to report that the melanoma scientific, physician and patient-advocate community lost a great friend and a tireless advocate for melanoma research this year, Mr. Randy Lomax. Randy was a 16 year survivor of metastatic melanoma, but sadly the disease reappeared last year and, despite receiving the very best care that science and medicine could offer, Randy succumbed to the complications of his disease in July. Randy’s dear friend and long-time colleague, Meenhard Herlyn, has written an article in the newsletter that describes Randy’s significant impact on our field and the hard work, optimism and enthusiasm that he brought to melanoma science and medicine in general and to the Melanoma Research Foundation in particular. As a regular participant at SMR Congresses, Randy’s absence will be felt particularly acutely this year in Boston.

As usual I leave you with the exhortation to continue to do great science, be enthusiastic and conscientious mentors and colleagues and continue to work and play hard. I am very much looking forward to seeing you at the SMR meeting in Boston!

Best,

Martin McMahon (President of the SMR)

PS: On a final pragmatic note, since the SMR2016 Congress spans the date of the US Presidential Election, I urge you to make appropriate plans to vote in the general election, such as applying for your absentee ballot (final date Nov 1 in most states) or participating in early voting if you have that available in your state.

Early voting information: https://www.vote.org/early-voting-calendar/

Absentee Ballot Info: https://www.vote.org/absentee-ballot/

Member News

Randy Lomax, In Memoriam

Randy Lomax was known to many in the melanoma research and clinical communities, not just in the US but around the world. The last seventeen years of his life he spent fighting melanoma, first his own Stage 3 disease, then as President of the Melanoma Research Foundation (MRF). When initially treated with GM-CSF, it appeared he had drawn a lucky number. Although this treatment remains controversial, he appeared cured – until sixteen years later the disease came roaring back with all its viciousness. He tolerated the combination of Ipi + Nivo relatively well and the tumor responded but few months after initiation of treatment, the immune response went overboard and attacked his heart, which could not sustain its functions. His death opened a large void in the community because Randy had filled a big space by building bridges between the research communities and advocates, by tireless lobbying Congress for more support of the disease and by bringing the clinical, research and industry communities into the same mold. MRF has a strong base of supporters in each of the US states, it draws its support for research grants from many small donors who want to support the cause. MRF sponsored websites for melanoma patients to consult with each other about the newest treatments and how to deal with the psychological and physical challenges of the disease. Randy could be found at each major melanoma meeting but also in the halls of Congress to lobby for more support. His latest brainchild was the Breakthrough Consortium (BC) that allowed MRF to act as the honest broker between industry and academia in the organization of clinical trials. MRF wants to take the burden off the clinical investigators to initiate drug combination trials involving different companies, a challenge that had impossible hurdles just ten years ago but is now becoming more routine. Randy’s energy and communication skills, which came from his years of teaching psychology to college students and as marriage counselor, had a major role in revitalizing the melanoma field and make it a role model for cutting edge signaling and immune-therapies. We will miss Randy and need to work even harder to fill the void his tragic death left for us.

Meenhard Herlyn, D.V.M., D.Sc., Caspar Wistar Professor in Melanoma Research, Director of the WIstart Institute Melanoma Research Center

Research Highlight

Conditioning of the pre-metastatic niche by melanosomal miRNA Trafficking

Written by Marie R. Webster

Changes in the melanoma tumor microenvironment, caused by aging, drug treatment and stress drive tumor initiation and progression. Cancer associated fibroblasts (CAFs), a component of the tumor microenvironment, are reprogrammed fibroblasts which promote tumor progression through increased inflammation, angiogenesis, and growth. Fibroblasts are reprogrammed to CAFs through secreted factors, including TGF-β, osteopontin and IL1-β, as well as miRNA; however, the mechanism responsible for this reprogramming is largely unknown. Recent work out of Dr. Carmit Levy’s lab describes a mechanism where by melanoma cells release melanosomes, which contain miRNAs, that are capable of reprogramming primary fibroblasts (1). The miRNA, which included miR-211, induced a pro-inflammatory gene signature, and increased cell proliferation and migration.

In their study, the authors found that fibroblasts, which aggregated at the dermis at early stages of melanoma, contained melanoma markers suggesting that melanoma cells communicate directly with fibroblasts before they begin to invade. Directly treating fibroblasts with melanosomes resulted in upregulation of genes associated with proliferation and cell motility, and increased collagen contraction, characteristics of CAFs. Co-injection of melanoma cells and fibroblasts pre-treated with melanosomes, induced melanoma cell proliferation further supporting the hypothesis that melanosomes promote reprogramming of fibroblasts, which contributes to melanoma progression.

Upon examination of the mature melanosome content, five microRNAs were found in mature melanosomes, that are known to be associated with melanoma, miR-149, miR-211, miR-23, miR-let7a, and miR-let7b, with miR-211 increasing most significantly in the fibroblasts following melanosome treatment. Treatment of fibroblasts directly with miR-211also resulted in increased proliferation and cell motility, increased collagen contraction and elevated expression of pro-inflammatory genes, suggesting that miR-211 is necessary for reprograming of fibroblasts.

Comparison of genes downregulated following melanosome treatment and miR-211 treatment revealed four common genes, including IGF2R, a known target of miR-211. The authors propose that decreased expression of IGF2R may allow for increased binding of IGF2 to IGF1R, resulting in increased proliferation. Treatment of fibroblasts with miR-211 decreased IGF2R mRNA, and increased phosphor-IGF1R and phospho-ERK levels indicating MAPK signaling in fibroblast reprogramming. An ERK inhibitor mitigated the effects of miR-211 and melanosomes on fibroblast proliferation, migration, and expression of pro-inflammatory markers. These data provide a new mechanism where by melanoma cells condition the pre-metastatic niche by reprogramming fibroblasts through melanosomal miR-211 and activation of MAPK signaling.

1. Dror S, Sander L, Schwartz H, Dheinboim D, Barzilai A, Dishon Y, Apcher S, Golan T, Greenberger S, Barshack I, Malcov H, Zilberbgerg A, Levin L, Nessling M, Friedmann Y, Igras V, Barzilay O, Vaknine H, Brenner R, Zinger A, Schroeder A, Gonen P, Khaled M, Erez N, Hoheisel JD, Levy C. Melanoma miRNA trafficking controls tumour primary niche formation. Nature Cell Biology. 2016, Sep; 18(9): 1006-17.

Meet the New Investigator

This section is intended to introduce scientists who have recently started their own lab, in order to highlight new research in the field and promote collaborations with young investigators.

Dr. Amaya Viros obtained her degree in Medicine and Surgery at the University of Barcelona, and completed her training as a dermatologist and venereologist at Vall d’Hebrón University Hospital in Barcelona. Following the completion of her specialty training, she received a Fulbright Scholarship to work as a Fellow in the Department of Dermatology and Pathology at the University of California, San Francisco, in the laboratory of Prof Boris Bastian. She then moved to Prof Richard Marais’ lab, first at The Institute of Cancer Research, London and then at CRUK Manchester Institute, completing her Ph.D in 2013. She has combined her research with clinical work at Salford Royal NHS Foundation Trust, Manchester.

Earlier this year Dr. Amaya Viros became a Wellcome Trust Intermediate Clinician Scientist Fellow and started her lab, sponsored by CRUK, at the CRUK Manchester Institute. The focus of her lab is on understanding the influence of age on melanoma initiation and progression. Incidence and mortality in patients over 50 years of age is increasing, and these patients often present with aggressive primary lesions, with additional characteristics of poor prognosis, such as ulceration and elevated mitotic rate. Understanding the biology of this aggressive disease in the elderly is critical in order to generate new strategies for adjuvant therapy to address poor clinical outcome in these patients. Dr Viros will focus her efforts in studying these patients as a distinct subgroup. We recently asked her a couple of questions about her training and transition into her new position.

You recently started your own lab at CRUK Manchester, what has been your biggest challenge or inspiration as you move in to this position?

The biggest challenge is to have to adapt and update your skills every day to create a work environment where science can move forward. It is inspiring to work with the enthusiastic and very talented people who make science so rewarding at CRUK Manchester Institute.

What was your greatest inspiration or challenge during your medical or laboratory training?

My greatest inspiration has been interacting and learning with outstanding clinicians and scientists who invested in my training and supported me. My mentors, in particular Richard Marais, have generously helped me turn every challenge to motivation and I am very lucky to join the melanoma research community.

SMR Session Highlight

Women, Men, and Science: The Changing Landscape

This year at the SMR Congress in Boston, Georgina long and Kim Margolin have organized a plenary session on Tuesday morning to discuss the changing environment of women and men in science. The session will begin with a talk by Dr. Andrei Cimplan, an associate professor from NYU, who specializes in the area of gender gaps in achievement and representation. His talk, entitled “Beliefs about Brilliance Undermine Women’s Careers”, will address biases which affect how women are evaluated in fields whose members believe that raw intellectual “gifts or talent” are required for success. Dr. Cimplan will present research which supports the conclusion that the environment in these fields may be less welcoming to women due to cultural stereotypes that portray women as less likely than men to be brilliant. These messages have an undermining effect on girls as young as 6 years old. He will conclude his talk with an outline of some concrete steps that might be taken to increase gender diversity in light of this research. Dr. Cimplan’s talk will be followed by a panel of women and men in academics to discuss the topics further.

Corrections Corner

MRA Team Science award

A hearty congratulations to the following members who received the following MRA team science award! We apologize for omitting Dr. Rizwan Haq as the young investigator on the award.

Congratulations to Drs. David E. Fisher (Massachusetts General Hospital, Dana-Farber Cancer Institute), Frank Schoenen (University of Kansas) and Rizwan Haq (Dana-Farber Cancer Institute, Young Investigator) for winning the Melanoma Research Alliance Team Science Award for their project entitled “Small-molecule targeting of the lineage-specific melanoma oncogene MITF”.

Funding Opportunities

• MRA Young Investigator Award, Application due October 21, 2016
• MRA Established Investigator Awards, application due October 21, 2016
• MRA Pilot Awards, Application due October 21, 2016
• Established Investigator Academic-Industry Partnership Awards, application due October 21, 2016
• MRF 2017 Medical Student Grant Application Due November 1, 2016

Physicians

Scully-Welsh Cancer Center (Duke Affiliated) in Vero Beach FL is interested in physicians with expertise in melanoma/skin cancer detection, MOHs surgery, and/or Dermatopathology of melanocytic lesions. Contact person:

Postdoctoral position

A Postdoctoral position in cancer biology is immediately available at the Pennsylvania State University. Our research interests focus on the regulation of RNA turnover, its role in the regulation of signal transduction and its outcome for tumor development.

We are looking for ambitious highly motivated candidates with Ph.D. degree and a strong background in biochemistry, molecular biology, signal transduction, cell biology, or related disciplines. Applicants should have demonstrated scientific productivity, good interpersonal and communication skills, and be able to conduct independent research.

Interested parties should upload a copy of your CV, a brief statement of research interests, and contact information for three references to:

Melanoma Meetings

• The Australasian Melanoma Conference October 28-29th, 2016 in Sydney, Australia
• Society for Melanoma Research November 6-9, 2016 in Boston Massachusetts

A Guide to Boston: The SMR Congress Concierge

Written By Ken Dutton-Regester

Heading to the SMR Congress in November and never been to Beantown before? Then don’t worry, we’ve got you covered with our handy guide to explore all the best bits of Boston.

The Fast Track Approach to Seeing Boston: Boston Duck Tours

If you’re limited on time during your stay, a quick way to see the highlights and history behind the landmarks is to go on a Boston Duck Tour. These iconic WWII style amphibious landing vehicles depart regularly from three locations; the nearest to the Congress Hotel being the Prudential Center. Tours last 80 minutes, costs approximately $40 and includes a quick splash into the Charles River. For more information: http://www.bostonducktours.com/

See Some Boston Attractions on Discount: CityPass

If you plan to spend time seeing a variety of Boston’s cultural highlights, it might be worth investing in a CityPass which will save you a chuck of change on admission (http://www.citypass.com/boston). For $55, you can get entrance to the Skywalk at Prudential Center (more on this below), Museum of Fine Arts, Museum of Science and New England Aquarium.

For a Good View: Skywalk Observatory

Head to the Skywalk Observatory at the Prudential Center (‘The Pru’), only a couple blocks away from the Congress. Make sure to head here on a clear day and you will get 360-degree view of the greater Boston area. Cost is $18pp or visit using a CityPass (*see above). Pro tip: If you’re only interested in the view and not keen on paying the admission fee, head up to the Top of the Hub restaurant for a quick cocktail (one floor below the observatory floor).

For Some History and Fresh Air: The Freedom and Black Heritage Trails

Boston prides itself on its heritage and history, and you don’t have to adventure far from the Congress to see it. There two self-walk trails that will direct you through historical sites throughout downtown Boston.

1) The Freedom Trail: http://www.thefreedomtrail.org/freedom-trail/

This will take you through most of the main cultural historic sites of Boston in the inner city. The first half (from the Common to Faneuil Hall) can be done relatively quickly, however be prepared to put more time aside for the second half (ending at the USS Constitution in Charlestown). You can also download an app that will help direct you through the official sites on the trail.

2) The Black Heritage Trail: http://maah.org/trail.htm

This is a shorter tour and covers sites important to American Black history throughout the Beacon Hill area. Tour or self-guided, you’ll find out about how Boston’s free African American community lead the nation in the movement to end slavery and achieve equal rights.

Boston Common and Boston Public Garden

Situated in the heart of Boston downtown, a short walk from the Congress and between the neighbourhoods of Back Bay and Beacon Hill (see below for more info) are the Boston Common and Public Garden. Both are worth exploring and contain some notable Boston landmark features. This includes the “Make Way for Ducklings” and George Washington statues, the Robin Williams park bench (famous for the scene in Good Will Hunting), and the famous Swan Boats (although unfortunately closed for the season),

Neighbourhood: Back Bay

The location where the Congress Hotel is situated and also adjacent to the Boston Common and Public Garden contains a number of interesting sites. Newbury St is an iconic Boston street that is loaded with shopping, cafés and restaurants. Boylston St has the Boston Public Library (which has recently been renovated), outside of which has the Boston Marathon Start Line permanently marked on the road. South-west of the Congress Hotel is the Christian Science Plaza which has a remarkable reflection pool.

Neighbourhood: Beacon Hill

One of the most exclusive, expensive and iconic neighbourhoods in Boston is Beacon Hill. The area is worth having a walk-through to see the historic architecture. Charles St is bustling full of boutique shops and restaurants. A quick detour off Charles St worth exploring is Acorn St and is considered to be the most photogenic and quintessential streets in Boston. If you have a love for animals, there a number of resident cats in shops on Charles St. This includes Totes in Charles Street Supply (you might have to ask the staff to find her) and Bordeaux in Beacon Hill Wine and Spirits Co. Also in the area is the Cheers which was the original restaurant that the 80’s TV series was based on.

Charles River: Nice Walk or Running Track

If you’re looking to clear the mind or are searching for a good running trail that’s close by, head down to the Charles River. You can do a good loop between the Harvard and Longfellow bridges. This will also take you directly adjacent to the MIT campus. If you’re looking for a longer distance, it’s easy to keep running west of the river as there are trails stretching all the way down the river. Along this route and on the south side of the river is the Citigo sign, a key Boston landmark.

For a Taste of Academia: MIT and Harvard University

The MIT campus is based just north of Congress on the north side of the Charles River. Easiest access is via the Harvard Bridge. The main Harvard campus is a little further afield, but pretty easy to get to using the T. Either walk or catch a T to the Park St station and change to the Red Line heading to Alewife. It’s approximately a 20 min T ride to Harvard station. There are usually tours of Harvard campus regularly, otherwise you can explore Harvard Yard and track down the John Harvard Statue. A common tourist tradition is to touch the boot of the statue; although there are some interesting stories about this if you ask the locals. There are also museums in close proximity including the Harvard Art Museums and Harvard Museum of Natural History. Harvard Square also has shopping and local boutique stores and restaurants.

For a Different Kind of Museum: The Isabella Stewart Gardner Museum

Located south-west of the Congress in the Fenway/ Kenmore Area is the Gardner Museum (http://www.gardnermuseum.org/about). Curated by the late Isabella Stewart Gardner, an art collector and philanthropist, the museum contains a wide collection of pieces. One of the most unique aspects of the museum is that it is housed in a building designed to emulate a 15th century Venetian palace. Definitely a unique art museum and worth exploring.

Get Getting your Sports on: Fenway Park and TD Garden

Close to the Congress in Fenway and home to the famous Boston Red-Sox is Fenway Park. One of the oldest baseball parks in the US it is packed full of history. Guided tours are available year-round and worth doing to hear the history while seeing all parts of the park, including sitting in the original stadium seats and exclusive area on the “Green Monstah”. Note that baseball season is finished for the year. The other main sports arena that is close-by and located in North End, is TD Garden. This is where you can see the Boston Celtics (Basketball) and Boston Bruins (Ice-hockey). Both teams will be playing during the Congress. Protip: tickets can get expensive and sell-out quick. Another option which can be cheaper is through StubHub (www.stubhub.com), a safe and official website where fans can resell tickets.

For Getting some Nature: The Arnold Arboretum

If need to get a close-by nature fix during the Congress, the Arnold Arboretum is at the south end of the Orange Line at Forest Hills. Here you will find a large expansive area of plants from around the world. Great for trails, there are also some wildlife and birds you might spot along the way.

For Getting your Brewery On: Sam Adams and Harpoon Brewery

If you’re interested in tasting the local drop, some the local breweries are relatively close by and easy to get to. The Sam Adams Brewery is the most iconic of brews in the area and have an extensive range including a wide variety of seasonal beers. Located near the end of the Orange Line, get off at Stony Brook and go for a short 5 min walk to get there (http://www.samueladams.com/boston-brewery/brewery-tours). In the Seaport area (East of the Congress) is the Harpoon Brewery which is another large local that produces a decent selection of beer (http://www.harpoonbrewery.com/breweries/boston). To get out here you will need to take the Silver Line, but there’s also a number of restaurants and bars within the area to make your visit worthwhile.

For Outlet shopping- Assembly Square

If you’re not exploring any other parts of the US during this trip, but still looking to get some good deals on shopping, then head to Assembly Square. Located North of the Congress, you’ll need to get the Orange Line north and get off at Assembly. Here you’re guaranteed to get a good deal with access to a large variety of outlet shopping including Nike and Adidas. Also located here is the LEGOLAND Discovery Center; out front has a large giraffe made of lego. Note that entrance into the center requires you to be present with a child; however, they do run adult nights on occasion with the next one being on the 16th of November.

For an Escape Outside of Boston- Davis Square, Somerville

If you’re looking for something a little different, situated near the end of the Red Line is Davis Square (about 25mins from Park St). A popular escape for Boston locals, the area has a number of bars, restaurants and performance venues. Some highlights include the Flatbread Company (or Sacco’s Bowl Haven) where you can get amazing flatbread pizza and do candle-pin bowling (Surprisingly challenging. Pro-tip: bowling slower seems to get more results). There’s a speakeasy called Saloon that specialises in whiskey. Keep an eye out as the signage is limited to a single lightbulb. It’s down the stairs at the Rockwell performance centre between Found and the Burren. The Rockwell has some interesting events; if you’re arriving before the Congress, Sh*t Faced Shakespeare is on Saturday 5th (one cast member gets excessively drunk before the show). Other popular venues include The Burren (Irish Pub), The Painted Burro (Mexican) and Foundry on Elm (American)and Spoke (Cocktail).

For Close-by Food, Restaurants and Coffee