The Society for Melanoma Research Newsletter Published By: The Society for Melanoma Research

Advancement Through Collaboration

Volume 25 | February 2017

Letter from the SMR President

SMR President | Prof. Keith Flaherty

It's been three months since we convened in Boston for the most recent version of the SMR Congress. This past congress featured the largest number of oral presentations from amongst the submitted abstracts ever presented at the meeting. As a consequence, attendees were kept on their toes to catch new insights emerging from the leading melanoma labs and from the field’s rising stars. We will continue this approach going into the 2017 joint SMR Congress/9th World Congress of Melanoma for the SMR track of this meeting. So, please plan on submitting abstracts as vigorously as this past year so that we can feature your work.

The theme that has developed and was reinforced at the 2016 meeting is that significant advances have been made; a significant minority of patients with the most advanced form of melanoma can now achieve remissions that last for years. And, we are closing in on clinical and molecular features that define who those patients are. But we are left with a very large unmet need. And for that reason, we continue to need innovative, cutting-edge research to identify new vulnerabilities. And, we have sub-populations within the larger melanoma, most notably uveal melanoma, for which we have yet to make significant inroads.

The opportunities to make advances in prevention and early detection have never been greater. As a community, we need to raise awareness that new diagnoses and mortality from melanoma continue to rise. And, prioritizing the science of susceptibility and improved communication tools directed to those population will be key priorities for our community. In early detection, technologies are evolving at an inspiring pace and now need to be vetted for effectiveness.

The frontiers on which advances are being made have increased substantially. Our purpose in the SMR is to leverage the diverse interests of our investigator community to bring the collective expertise to bear on all fronts. We are in a unique position to make impact for the field by maintaining the dialogue between our laboratory-based and clinical investigator members.

In 2017 we will increase our focus on creating platforms for communication amongst our research community. So stay tuned on that front.

Summary of the SMR Congress 2016 - Boston, Massachusetts

Written By: Ken Dutton-Regester

Early in November 2016, it wasn’t another Snowpocalyse that stormed the city of Boston, but rather an international community of melanoma researchers eager to catch-up on the latest news being presented at the SMR Congress. Arguably one of the most balanced meetings in recent years, below is a quick snapshot of what was presented.

The Congress’s scientific content kicked off with an engaging presentation from keynote speaker Leonard Zon (Harvard Medical School, Boston Children’s Hospital and HHMI investigator) on Controlling Cell Fate during Melanoma Initiation and Metastasis. The Zon laboratory have pioneered the use of zebrafish as a model system in melanoma, creating a transgenic BRAF V600E, p53-/- zebrafish to identify a number of key melanoma regulators and melanocyte and neural crest lineage genes including SETDB1 (Ceol et al, 2011, Nature), DHODH (White et al, 2011, Nature) and HEXM1 (Tan et al, 2016, Molecular Cell). The group also received significant media attention last year after identifying and following the development of melanoma from initial first cells expressing Crestin (Kaufman et al, 2016, Science). This keynote presentation set the scene for the meeting, leading to numerous conversations during the subsequent Welcoming Reception.

Discussions around the role of the microenvironment were lively. During the first Plenary Session of the meeting, Gretchen Alicea sparked discussion about the role of metabolism in melanoma, showing results that key nutrients used by tumor cells could be influenced by an aged microenvironment. Continuing with this theme and during a Concurrent Breakout Session later in the meeting, some interesting observations highlighting the role of adipocytes influencing lipid metabolism of melanoma cells were also shown (Richard White). Further evidence of age-related microenvironment conferring differential responses to immune-based therapies (Curtis Kugel) was presented alongside age-related loss of integrity of the collagen matrix and its effect on metastasis (Amanpreet Kaur). The biology of Tumour-Associated Macrophages was targeted with the presentation of a nanoparticle-based compound that could block pro-tumorigenic and pro-lymphangiogenesis signals (Daniela Cerezo Wallis) Finally, the roles of tumor heterogeneity (Claudia Wellbrock) and exosome signaling governing melanocyte/ keratinocyte crosstalk were also discussed (Carmit Levy).

Not surprisingly, Immunology featured heavily during this year’s meeting kicking off with Stephin Baylin discussing the “Epigenetic regulation of tumor immune signaling”. Themes on immunotherapy resistance and response were covered, including the significance and difficulties of using PD-L1 expression to predict patient response to immune based therapies and elevated lactate dehydrogenase levels not precluding durable responses in patients treated with pembrolizumab (Antoni Ribas).

Concepts behind Melanoma Heterogeneity were also discussed; this included the identification of CD73 marking an intermediate cell state found in MITF-high, EMT negative melanoma cell lines (Julia Reinhardt). The ZEB1/ZEB2 axis controlling MITF High/MITF low cell states and its modulation through micro-environmental and epidenetic changes was also presented (Niels Vandamme). Finally, Pere Puigserver delved into "Mitochondrial heterogeneity and Melanoma Metastasis" and the role of PGC1α in invasive and proliferative cell states

In regards to the genetics of melanoma, recurrent L129Q inactivating somatic mutations of CYSLTR2 were identified in uveal melanoma and occurred in 4 of 9 samples that were wildtype for driver mutations in GNAQ, GNA11 and PLCB4 common for this subtype of melanoma (Amanda Moore). Whole genome sequencing in primary mucosal melanomas also identified recurrent somatic DGKZ mutations in 30/145 samples (Yan Kong). In the late-breaking abstract session, data from the Australian Melanoma Genome Project using whole-genome landscapes of major melanoma subtypes revealed acral and mucosal melanomas being dominated by structural variations (Graham Mann). Lastly, a number of functional insights into previously identified mutations in melanoma were presented including a role of SDHD promoter mutations (Mai Xu) and a common intronic germline variant in PARP1 (Kevin Brown) regulating melanoma biology through MITF.

Lastly, a number of clinical updates on the latest treatment regimens were presented; this included the results of Phase 1B Atezolizumab (PD-L1i) and Cobimetenib (MEKi) dual-combination therapy (Jeffrey Infante) and a triple-combo with the addition of the BRAF inhibitor Vemurafenib (Ryan Sullivan). Results from a Phase 1B neoadjuvant ipilimumab (CTLA-4i) and Nivolumab (PD-1i) combination for stage III melanoma patients showed promise and will inform an upcoming Phase 2 trial designed to preserve efficacy while reducing toxicity (Christian Blank). Updates on outcomes and survival were also presented from the Phase 3 CheckMate 037 trial of Nivolumab plus investigator’s choice chemotherapy (Jeffrey Weber) and KEYNOTE-006 trial of ipilimumab and pembrolizumab (Georgina Long)

Rounding out the meeting was an illuminating session on “Women, Men and Science: The Changing Landscape” by Andrei Cimpian from New York University. Discussing findings from his high-profile research (Leslie et al, 2015, Science and Bian et al, 2017, Science), Andrei explained how beliefs surrounding ‘Brilliance’ are typically associated with men and that this is a stereotype that can undermine women’s careers. A heated discussion ensued by a panel consisting of Harriet Kluger, Meenhard Herlyn, James Larkin, Jennifer Wargo and Session Chairs Kim Margolin and Georgina Long. Here, topical experiences of the current state of gender diversity amongst institutions were discussed and why achieving balance is a rewarding outcome, for both men and women, within our research sector.

As always, the Awards Ceremony was a great success (list of awardees below), this year being held at the regally outfitted, roman-esque nightclub venue, Royale Boston. Here, Past-President Martin McMahon officially handed over the reins to incoming President Keith Flaherty and the highly-anticipated announcement of the new President-Elect was revealed as Georgina Long! Of course, the long-held tradition of post-awards bowling was upheld, with a few (not-quite-elegant?) pins being knocked over at Kings Boston in Back Bay.

In summary, the meeting finished with a sense of excitement and renewed vigor in preparation for the upcoming year of groundbreaking discoveries that will surely be a feature of 2017. Looking forward, the Congress this year will be held in sunny Brisbane, Australia in October. Make sure to check out the “What to Expect of Brisbane” article highlighted later in this newsletter.

For a refresher of the meeting and more information on what was presented, abstracts are now published online in the January Issue of Pigment Cell and Melanoma Research.

Congratulations to our 2016 SMR Congress Award Winners

Lifetime Achievement Award - Ze'ev Ronai, PhD

Estela Medrano Memorial Award - Sancy Leachman, MD, PhD

Outstanding Research Award - Marisol Soengas, Phd

Young Investigator Award - Poulikos Poulikakos, PhD

Christopher J. Marshall Award - Maria Romina Girotti, PhD

Selected Abstract and Travel Awardees:

Marco Ranzani, The Wellcome Trust Sanger Institute - England, United Kingdom

Jasper Wouters, KU Leuven (University of Leuven) - Leuven, Belgium

Ismael Vergara, Peter MacCallum Cancer Centre - Melbourne, Australia

Najla El Hachem, C3M - Nice, France

Mitchell Fane, University of Queensland - Brisbane, Australia

Amanpreet Kaur, The Wistar Institute - Philadelphia, Pennsylvania

Michael Vido, Thomas Jefferson University - Philadelphia, Pennsylvania

Curtis Kugel, The Wistar Institute - Philadelphia, Pennsylvania

Vito Rebecca, University of Pennsylvania - Philadelphia, Pennsylvania

Juliano Freitas, Florida International University - Miami, Florida

Bishal Paudel, Vanderbilt University - Nashville, Tennessee

Gretchen Alicea, The Wistar Institute - Philadelphia, Pennsylvania

Amanda Shaub, Stanford Hospital & Clinics - Redwood City, California

2016 SMR Congress Awards Ceremony at The Royale in Boston, MA

Now Accepting Nominations for the Christopher J. Marshall Award For Studies on Signal Transduction and Melanoma

For More Information on The Award Please Click Here

Submissions are due by June 1st, 2017. Please Click Here to Submit your Nominee

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Funding Opportunities

  • NCI F32: April 8th 2017 (Round 1), August 8th 2017 (Round 2), December 8th 2017 (Round 3)
  • NCI K99/ R00: June 2nd 2017 (Round 2), October 12th 2017 (Round 3)
  • NCI K22: June 12th 2017 (Round 2), October 12th 2017 (Round 3)
  • NCI R01: June 5th 2017 (Round 2), October 5th 2017 (Round 3)
  • Melanoma Research Foundation: March 1st 2017 for Established Investigator Awards, Career Development Awards and Medical Student Awards.

Posting 1: Investigating Genetic Variants Underlying Risk of Melanoma and Renal Cell Cancer

A postdoctoral position is available in the Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute within the laboratory of Dr. Kevin Brown.

The main interest of our laboratory focuses on inherited predisposition to melanoma and renal cell cancer, and functional characterization of common and infrequent risk variants identified by genome-wide association studies (GWAS) and sequencing-based approaches. We also work in the area of characterization of non-coding somatic variants on tumor development and progression. We are members of the International Melanoma Genetics Consortium (GenoMEL) and collaborate in the areas of GWAS and family-based studies of melanoma risk, as well as lead ongoing melanoma and renal cell cancer GWAS efforts at the NCI National Cancer Institute, NIH.

Specifically, this opening is for a highly-motivated individual interested in functional and translational laboratory investigations to identify target genes and understand the functional consequences of carrying melanoma and or renal cancer risk variants. We apply both targeted and genome-wide (e.g. RNA sequencing, ChIP sequencing, methylation arrays) genetic and epigenetic methods to evaluate potential functional risk variants within associated chromosomal regions. We also apply cell biological methods to evaluate the phenotypic consequences of altered regulation of susceptibility genes on phenotypes associated with cancer progression.

Qualifications:

Candidates should have a Ph.D. in molecular biology, genetics, cell biology, or biochemistry and no more than five years of post-doctoral experience. We seek self-motivated individuals who have an excellent understanding of molecular and cellular biology and experience in the analysis of gene expression, transcriptional control, gene regulatory elements, protein function, signal transduction and growth control. Aptitude for genomic data analysis and an understanding of genetics and genomics is a plus, as well as a strong publication record and effective written and verbal communication skills.

To Apply:

Interested candidates should send a CV, statement of research background and interest, and names and contact information for three references to:

Email: brownkm2@mail.nih.gov

http://dceg.cancer.gov/about/staff-directory/biographies/K-N/brown-kevin

This position is subject to a background investigation. The NIH is dedicated to building a diverse community in its training and employment programs.

Posting 2: The Rhian and Paul Brazis Translational Melanoma Immunology Fellowship

Full time

Peter MacCallum Cancer Centre, VCCC, Parkville

An opportunity exists immediately for a highly motivated and skilled post-doctoral scientist to be appointed as a Research Fellow in Translational Melanoma Immunology. The candidate will join the Cancer immunotherapy laboratory whilst working closely with the Melanoma and Skin Service and the Division of Cancer Surgery.

The fellow will investigate fundamental questions of melanoma immunology of clinical relevance to patients. Our program encompasses novel predictive biomarkers, mechanisms of response and resistance to immunotherapies, understanding immune-mediated dormancy and adoptively transferred gene-modified T cells.

Suitable candidates will possess a PhD with experience in immunological and molecular techniques. Skills in tissue culture, flow cytometry, immunohistochemistry and mouse experimentation are desirable.

The successful applicant will work closely with A/Prof Michael Kershaw, A/Prof Phil Darcy and Dr David Gyorki

Remuneration for this prestigious fellowship will be commensurate with qualifications and experience.

For further details please contact Dr David Gyorki (david.gyorki@petermac.org)

Posting 3: The NCI-designated Sidney Kimmel Cancer Center at Thomas Jefferson University in Philadelphia, Pennsylvania

Post-doctoral position available in the laboratory of Dr. Takami Sato in the NCI-designated Sidney Kimmel Cancer Center at Thomas Jefferson University in Philadelphia, Pennsylvania. Our laboratory focuses on translational research using animal models with patient-derived xenograft and established cell lines for metastatic uveal melanoma patients. In addition, our laboratory works on the development of a novel immunotherapy. The applicant should have expertise in cell culture, mouse work, ELISA, ELISPOT and flow cytometry techniques. Interested candidates should send a CV, a short statement describing previous research experience, and contact information of three references to:

Takami Sato, M.D., Ph.D.

K. Hasumi Professor of Medical Oncology

takami.sato@Jefferson.edu

Upcoming Melanoma Meetings

Held at: The Institut Curie, Paris, France on April 27-28, 2017

Washington DC, USA on March 12-13, 2017

Saturday, April 22, 2017

For more about the mission of the March For Science: https://www.marchforscience.com/mission/

To search for a march in your local area or country: https://www.marchforscience.com/satellite-marches/

  • World Congress of Melanoma deadline for abstract submission is 7th May 2017. Please refer to congress website for important information about visa requirements (depending on your country of origin, either an online application or an in-person application at an Australian embassy is required).
  • Society for Melanoma Research abstract submission will open April 10, 2017, the deadline for submission is June 12, 2017. Please stay tuned for further information regarding where to submit your abstracts and the guidelines.

What to expect during the 9th World Congress of Melanoma- Brisbane

Written By: Ken Dutton-Regester

Still deciding on whether to attend the Congress this year? (Answer: Definitely MUST attend). The flight to Australia for most researchers is a big one, so to get you excited about what you can look forward to (besides the great research and networking opportunities), we thought we would highlight Brisbane and Australia over the next series of newsletters. This issue: Brisbane (Brizzy).

Brisbane is the third largest city in Australia located in the South-East corner of Queensland with a population of 2.3 million people. Highly multicultural, approximately 30% of residents were born overseas. Being located in humid subtropical climate it’s pretty warm all-year with an average high/ low of 30°C (86°F) / 22°C (70°F) in the summer and 22°C (71°F) / 10°C (50°F) in the winter. During the meeting the average high/ low is 27°C (81°F) / 17°C (62°F) so don’t forget to pack your swim wear! (known to the locals as swimmers, togs, cossies, or budgie smugglers).

Historically considered a ‘big country town’, significant expansion since the 80’s has seen the city develop a unique culture that has long-since shattered this stereotype. Located along the Brisbane River, the city has a number of iconic bridges and scenic riverfront pathways to explore. One of the most iconic bridges, the Story Bridge, can be climbed for a unique viewpoint (Story Bridge Adventure Climb), and there are plenty of boat tours of the river (pro-tip: jump on the public transport ferry ‘CityCat’ for a cheap and equally rewarding trip).

This year the Congress is located at the Brisbane Convention Center and Exhibition Center located in Southbank (opposite river side of the central city area). Southbank is an iconic Brisbane precinct that was originally established for the 88’ World Expo. Here you will find numerous culinary delights (along Grey st and the waterfront), the Brisbane Wheel, Streets Beach (a man-made beach), and a variety of Museums and Performing Arts Centers.

A short walk across the river you will find the Central Business District and Queen Street Mall that is bursting with shops and restaurants. Some homegrown local favorites are the Noosa Chocolate Factory and hole-in-the wall Doughnut Time. For coffee, head to Brew, located down an unsuspecting alleyway just off Queen St. A number of riverside restaurants are located along Eagle St, including the cocktail bar Jade Buddha, the Bavarian Bier Café, and the contemporary Japanese restaurant Saké. For bowling, head back into Queen St for Strike Bowling (they also have a number of escape rooms).

If nightlife is your thing, you need to check out Fortitude Valley (just north of the CBD). Here you will find pretty much any type of drinking hole or restaurant that tickles your fancy packed into a small area encompassing Brunswick, Ann and Wickham St (perfect for a good o’l pub crawl). Some of the local favorites include Alfred & Constance (Contemporary Australian), the Bowery, Elixir Rooftop Bar and Cloudland (Cocktails), Rics (Dive), the Family, the Met, and Prohibition (Nightclubs). For something a little different check out Netherworld (drinking hole and arcade) or Holey Moley (drinking hole and mini golf).

Other areas of interest that are closeby is West-End (Boundary St right next to Southbank and considered more of a hipster/ alternative area), New Farm (next to Fortitude Valley), and Milton/ Paddington (Caxton St and Latrobe Terrace). At the latter, you will come across the XXXX Brewery that creates the most iconic Queensland lager (XXXX Bitter and XXXX Gold) as well as see some of the classic architecture associated with the region (the Queenslander). While your about, keep an eye out for Jacaranda’s that should be in full-bloom during the conference.

Prominent universities, institutes and hospitals of interest within the area:

QIMR Berghofer Medical Research Institute, Translational Research Institute, University of Queensland (Institute for Molecular Biology), Queensland University of Technology (Institute of Health and Biomedical Innovation), Griffith University, Royal Brisbane and Women’s Hospital, Princess Alexandra Hospital, Mater Hospital (Mater Medical Research Institute)

In the next SMR newsletter, we will cover other parts of Australia you should try and check out while you’re visiting

Expression of Interest- Road Bike Tour of Brisbane During Congress Meeting

Any keen lycra-clad cyclists out there? We’re currently gauging the interest of Congress attendees as to whether a bike tour of Brisbane on an early morning either before, during or after the meeting would be a good idea. If we get enough interest, local organizers would arrange rental road bikes (BYO cycling kit and helmet) for a Brisbane River Loop (classic local route) and/or a Mt Cootha hill climb (short but steep climb, but worth it for the view). At this stage, the cost of bike rentals would be covered by participants. If this sounds of interest, send an email to ken.dutton-regester@qimrberghofer.edu.au

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