Cancer

Visitor of the Week: Koen Schipper

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Meet Koen Schipper of the Netherlands Cancer Institute. A PhD student in a group led by Jos Jonkers. He is at Cold Spring Harbor Laboratory for his first CSHL meeting – Mechanisms & Models of Cancer – where he presented a poster titled “Actomyosin relaxation enables tumor formation upon loss of E-cadherin expression in the mammary gland”.

What are your research interests? What are you working on?
My current research focuses on the process of tumor initiation in lobular breast cancer. We primarily use mouse models and cell culture approaches to determine the driving forces behind tumor development. 

How did you decide to make this the focus of your research?
I have always found the transformation of a normal cell into a tumor cell very interesting; especially since a small alteration in a single cell can have such tremendous impact on an entire organism. Mouse models are particularly suitable to study tumor development since you have the optimal environment to study the early phases of tumor initiation. 

How did your scientific journey begin? 
I did a bachelor study in bio-pharmaceutical sciences during which I discovered an interest for courses about signal transduction and how it is altered in disease. As a result, for my masters I decided to delve deeper into the signaling routes frequently deregulated in tumorigenesis and, during my research internships, I truly understood how much we still don’t know in this field and how much there is left to discover.   

Was there something specific about Mechanisms & Models of Cancer meeting that drew you to attend?
Several former lab members have been to this meeting and all of them highly recommended it as one of the best meetings they have attended; and so I had to experience it as well. The meeting also has a nice format with a number of short talks giving young scientists ample opportunities to present their work. 

What is your key takeaway from the meeting?
Discussing your research with those outside of your own field is very useful. You are able to see how they interpret your results and think about potential future directions. It can really open up new avenues for your own project. 

What did you pick up or learn from the meeting that you plan to apply to your work?  
The main thing I plan to apply to my research is to broaden how I look at the effects I see in our mouse model in human patients with germline CDH1 mutations. This way, I am able to validate our findings and identify possibilities to prevent cancer development in these families.

If someone curious in attending a future iteration of this meeting asked you for feedback or advice on it, what would you tell him/her?
Just like the people who recommended I attend, I would encourage them to come and experience this great meeting and venue for themselves. 

How many CSHL meetings have you attended?
This was my first CSH meeting but, if I get the opportunity, I will definitely attend future meeting(s) or a course. 

What do you like most about your time at CSHL?
I really liked the atmosphere of the CSH campus. Compared to most institutes located in big cities, it is calm and helps you to relax and think about your research from a different perspective.

Thank you to X for being this week's featured visitor. To meet other featured scientists - and discover the wide range of science that takes part in a CSHL meeting or course - go here.

Photo: Koen Schipper

A Word From: Benjamin Allen & Amy Ralston

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We recently chatted with the Mouse Development, Stem Cells & Cancer course instructors Benjamin Allen and Amy Ralston. Ben and Amy, for a number of years, have been involved with the course in various capacities but this is the first year both are co-lead instructors so we dived right into the benefits of participating in the course.  

Ben: From my standpoint, the students get two important things out of the course. Sure they learn how to do these techniques and practice them a few times while they’re here but, more importantly, they get introduced to the people who are experts in each of those techniques. So even if they walk out of here not an expert in a particular technique, they’re now friends with an expert they can contact. So if they’re doing experiment X and running into technical troubles, they can feel free contact one of the best people in the world to get advice.

Amy: In addition to the professional and scientific opportunities, we’re trying to maximize our students’ networking opportunities. We bring in about 30 additional experts from fields we’re not experts in so the students are exposed to a broad number of topics and taught classes and labs by those experts. One thing that is new to this year’s course is “First Drink”, where the students sign up to host a lecturer of their choice and take the lecturer to the Blackford Bar to buy his/her first drink. I think the students really like it! I’ve asked feedback from the lecturers too, and one comment I heard from a lecturer who has been here several times was that there were interactions that probably wouldn’t have happened otherwise.

Curious as to what other updates were made, we asked the first-time lead instructors if they made any changes to the curriculum. 

Ben: Amy and I replaced a few of the labs with ones that fit more smoothly with the flow of the course and that give the students a fuller grasp of the different stages of mouse development. We also swapped out some of the lecturers.

Amy: Another thing we’ve done, which is in response to survey feedback from last year’s students, is to give the students multiple opportunities to try each experiment rather than offering more experiments with fewer opportunities to practice. So far, I see people mastering things a little bit more and I’ve seen a lot less frustration than in previous years when we were ambitious with the number of experiments we taught.

In addition to the changes made to the course curriculum and lecture lineup, Amy and Ben incorporated a hot new experimental approach into this year’s course. 

Amy: Top secret! No, I’m kidding. It’s CRISPR. The course was originally designed to teach scientists how to make transgenic mice or knock-in mice the old fashioned way. But now that CRISPR exists, we adapted a lot of those same approaches to facilitate CRISPR, which is more efficient than the old approaches but it requires the same skillset.

Ben: CRISPR is the newest and biggest thing we incorporated into this year’s course. Last year was the first year we taught CRISPR and it was successful…

Amy: Successfully CRISPR-ed.

Ben: …we expanded it this year and we’re hoping it will be successful again.

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The Mouse course celebrates its 35th iteration this year. To commemorate the course’s milestone anniversary, the organizers coordinated a special one-day symposium. Trainees of this year’s Mouse course – in between checking in on their experiments, of course – were treated to a full day of talks from scientists who made significant contributions to both the course and to mouse biology. 

Amy: We’re really excited that we were able to invite all 3 of the founders of the Mouse course. They were all present for the Symposium: Brigid Hogan gave a talk at the Symposium, Liz Lacy gave a lecture this week, and Frank Costantini is arriving in a few days. It’s special to have all the founders present to acknowledge the course’s 35th anniversary.

We closed our laughter-filled conversation with their advice for future Mouse course applicants. 

Amy: It’s very important to justify how the Mouse course will enhance their career and research project. When we have a clear understanding that the student is familiar with what happens at the course, then we can be confident that they’ll have a satisfactory experience.

Ben: Also, we would recommend they ask their advisor or letter writers to do the same, to emphasize how the course is going to be a practical benefit. We don’t want this to be an intellectual exercise. Our hope is that students walk out of here trained, to actually use the techniques we’re teaching them here.

Thank you to both Amy and Ben for taking the time to chat with us. For more conversations with our other meeting organizers and course instructors, go here. Also, to gain a trainee's perspective on the Mouse course, read our Q&A with Rebecca Lea. In the meantime, enjoy the results of our rapid-fire photography session with Ben and Amy. 

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A Word From: Dafna Bar-Sagi, Howard Crawford, Tony Hollingsworth & David Tuveson

L to R: Howard Crawford, David Tuveson, Dafna Bar-Sagi, Tony Hollingsworth

L to R: Howard Crawford, David Tuveson, Dafna Bar-Sagi, Tony Hollingsworth

Last week, Cold Spring Harbor Laboratory welcomed 26 trainees, 31 lecturers, and 2 new additional instructors to the biennial Workshop on Pancreatic Cancer. The course, just four iterations young, has substantially grown over the last six years, reflecting the growth in the field. Our conversation with the four instructors Dafna Bar-Sagi, Howard Crawford, Tony Hollingsworth, and David Tuveson illustrates how pancreas cancer research continues to evolve and progress. We also discuss developments that may be game changers, as well as advice for those interested in the field or who wish to attend a future iteration of the course. 

To start, here is a brief history of the course as told by Dafna and David – the two instructors who have been with the course since its premiere. 

David: The pancreas cancer course started in 2011. There hadn’t been an instructional course in pancreatic cancer before that time and Jim Watson felt strongly that that was one of the reasons why the field was going so slowly. He convinced Dafna Bar-Sagi to organize such a course and, around this time, I was engaged with Jim Watson and Bruce Stillman on a number of issues involving pancreatic cancer so they asked me to help Dafna. 
The first course was held that summer with 19 selected trainees who were students, postdocs, junior faculty, as well as some senior faculty. We assembled 19 lecturers to have an intensive workshop at the Banbury Center to go over aspects of pancreatic cancer medicine and science. 
Dafna: We almost ran through the entire research community when we first organized the course. Fortunately, for a lot of reasons – funding, publicity for the disease – there are more investigators studying it so we now have a fantastic resource of people looking at the disease from many different perspectives. Now we have to actually leave out great people because there are so many to choose from.

We opened the discussion with how both the course and the field have changed since 2011: 

Dafna: The thinking now is less about the tumor cell itself and more about the environment, and putting more weight towards what we call the tumor microenvironment. There is a recognition that it’s not just the genetics of the tumor but how the tumor cells themselves talk to cells in the organ that are doing a lot of important things. Talks that address either partly or completely the role of the tumor microenvironment made up a lot of the talks we heard and what I sense to be exciting to our participants. 
David: This year’s course, compared to just six years ago, has more to tell people because in the last six years we’ve learned a lot about pancreatic cancer - not about the medicine but about the science underneath it. We now know genetic events in pancreatic cancer, and we’ve developed methods to study the disease that are much deeper and much more facile than they were even six years ago. 
Howard: Scientifically, we’re definitely up-to-date. That’s the nice thing about having four organizers and making these decisions together. It’s not very difficult to incorporate new science.
Tony: In general, there is more discussion now of opportunities compared to the large number of talks about infrastructure before. In the early days, people were still trying to build programs of research – it was an emerging field – which have come together now. As a result, there’s a lot more collaboration going on and more institutionalized programs are making progress. 
Something else that’s different in the course are the student presentations that have been incorporated into the curriculum. They’re very effective and very good for engaging the young people with the faculty to discuss a lot of ideas that are going on in their labs right now. 
David: The students today are much more informed because they come to the course knowing a lot about pancreatic cancer whereas, in the past, they came to the course to learn what was pancreatic cancer. And so the quality of the students as well as the knowledge of the disease has made it so now we get twice as many applicants as we have spots. 

Our conversation then transitioned to the lecturers, topics presented, and exciting new developments:

Howard: Having our lecturers as part of the audience gives the impression of "no holds barred." As a result, the trainees understand early on that there will be questions and challenges, and that it's alright. They also get more comfortable inside the room to be able to bring up any topic that's in their mind.  
David: There were a number of lectures this week that were extremely exciting. One was by Dieter Saur who is a professor in Munich, Germany. He’s developed the next version of a mouse model of pancreatic cancer where you can turn genes on and off at different times. In fact, he has gone to the level of making the first known pig model of pancreatic cancer, which looks intriguing and promising and a bit scary. 
There was also a lecture by Matthew Vander Heiden who is a well-known biochemist and metabolism researcher. Matthew has identified new pathways that are required by pancreatic cancer to survive. I think his work is groundbreaking and will pave the way for many additional investigators. 
And finally, one of our course instructors, Dafna Bar-Sagi has identified two methods by which pancreatic cancer cells evade therapy and survive in a hostile environment. One is they eat their surroundings to live – that’s where they get their food, by eating what’s around them. And the second is they have a stress pathway they activate to prevent responding to therapies. Both of her observations can lead to brand new therapeutic approaches. 
Tony: There is a coalescence of ideas of early detection that are coming together. I think the basic studies in the field are really making progress. There’s been development of new complementary model systems – organoids and different animal models – to go along with the existing studies. Also, there is more focus on human studies now than there was for a long time.
Howard: I’d like to re-emphasize that. The idea that there are these new models – organoids and new mouse models and such – and essentially everyone knows they’re available. The students don’t just hear about them but get help developing them in their own laboratory. I think that’s huge. The camaraderie of these workshops is one of the biggest selling points. It gives the students things they can take back to the lab, and the connections to help implement them. 
Tony: I think it’s notable that a lot of students from previous workshops are now in faculty positions and are participating in this workshop as lecturers. 
Howard: At least two alumni are presenting this year – Mara Sherman and Jenn Bailey
Dafna: It’s extremely rewarding. Mara Sherman attended as a trainee in 2013 while she was a postdoc in a lab that didn’t work on pancreatic cancer, and she is now an independent investigator in Oregon. We invited her to be a lecturer this year because obviously she’s very driven to do pancreatic cancer research. But Mara will also say herself that attending this workshop was a very reinforcing experience. 

For those interested in applying for the Workshop on Pancreatic Cancer, here is additional insight from two of the instructors: 

Dafna: This is the only existing opportunity in the field of its kind. It is an immersion course in everything that has to do with the disease. The beauty of this course is that in 5-6 days you are exposed to everything you need to know if you are either going into the field or want to understand the evolving trends. A lot of our lecturers talk about unpublished data. The course is a combination of didactic components so people can actually understand the field, but then it gets into things that are new and exciting that very few actually know about. These are things that aren’t talked about at meetings. It’s a comprehensive way of getting to know everything you need to know about pancreas cancer.
David: For people interested in the course, I would recommend they get in line now. The Workshop on Pancreatic Cancer is the rock concert you don’t want to miss. 

Lastly, here are parting messages from Dafna and David for young scientists: 

Dafna: It’s really important to follow your brain and your heart in terms of what it is you want to do. Don’t get sidetracked by the flashiness of a methodology or by the fact that a certain phenomenon has been published in a high-profile paper. Use your creativity and your curiosity to drive what you’re doing. From my experience, that has been the most important ingredient for success and what is ultimately most rewarding. So really think about the interesting questions, don’t shy away from the more difficult questions, rise up to the challenge and do whatever you can to meet it. 
David: If someone’s really interested in pancreatic cancer, they should find people they can start working with and talking with now. They should contact the participants – the course instructors and students – to seek from them any knowledge about the course that could help them on their quest to learn more about pancreatic cancer. And pretty much anyone who’s a lecturer in this course is more than happy to help someone get started on their path. 

Thank you to Dafna, Howard, Tony, and David for taking the time to chat with us. For more conversations with our other meeting organizers and course instructors, go here. Also, to gain a trainee's perspective on the Ion Channels course, read our Q&A with Lee Shaashua.

Lastly, the Workshop on Pancreatic Cancer will return in the Summer of 2019. For updates, visit our course webpage or follow us on Facebook and Twitter.

Visitor of the Week: Holly Algood

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Meet Holly Algood of the Vanderbilt University Medical Center and Department of Veterans Affairs. Holly, an assistant professor as well as the head of her own lab in the Division of Infectious Disease, attended the 2017 meeting of the Fundamental Immunology & Its Therapeutic Potential where she presented a poster. Read on to get her take on the meeting and what she liked most about Cold Spring Harbor Laboratory.

What are you working on?
I am interested in the development and regulation of inflammation during chronic bacterial infections.  

What is your key takeaway from the Meeting?
We (Immunologists) are making some great progress towards finding targets and developing new therapeutic tools to combat immunologically related diseases and cancer. This has progressed much more rapidly with new technologies being coupled with bioinformatics.

How many CSHL meetings have you attended?
Two. My first CSHL meeting was in 2013 and on a different topic - Microbial Pathogenesis. 

Is there another CSHL meeting in your near future?
I am not sure yet. I have collaborators attending the Microbial Pathogenesis and Host Response meeting in September.

Was there something about the Fundamental Immunology & Its Therapeutic Potential meeting that drew you to attend?
The list of speakers for this conference really drew me to this meeting and having been to a CSHL meeting before I knew that the atmosphere is very nice for networking and sharing data. 

If someone curious in attending this meeting asked you for feedback or advice on it, what would you tell him/her?
I would tell them that it's a small meeting where many people are willing to share unpublished data and are open to comments and criticisms from their peers. As a small meeting where the food, housing and meeting are all 'on campus', it provides a great opportunity to network and meet scientists from all over. Interestingly, this meeting was very different from other meetings I have attended with several biotech companies in attendance.

What do you like most about your time at CSHL?
I love the international atmosphere. There are less than 250 people here, yet I have interacted with people from many different countries - including India, China, Sweden, Germany, France, Spain, Italy, Australia, the Netherlands and Brazil.

Thank you to Holly for being this week's featured visitor. To meet other featured scientists - and discover the wide range of science that takes part in a CSHL meeting or course – go here.