A Word From: Scott Lowe, Senthil Muthuswamy & M. Celeste Simon

The fourth biennial meeting on the Biology of Cancer: Microenvironment & Metastasis was held at Cold Spring Harbor Laboratory October 10-14, 2017. One of a handful of CSHL meetings focused on cancer research, we spoke with the co-organizers, Scott Lowe, Senthil Muthuswamy, and M. Celeste Simon, about the unique aspects of their meeting. 

To kick off the discussion, Senthil---one of the meeting’s founders---shared his vision for the inaugural 2011 meeting and how it’s evolved over the last six years. 

Senthil: The idea was to have a Cold Spring Harbor-style meeting that focused on cancer biology as a whole, a small-meeting version of AACR that covers microenvironment, metastasis, imaging for detection, trials, and sometimes therapies as well. The more clinical and translational aspects have since been removed because there is a clinical trials companion meeting for the first time this year (Next Generation Cancer Clinical Trials). We are therefore concentrating mostly on biology in this meeting, and will probably stay like this as long as the companion meeting continues.

Also, this year we introduced a career session, a talk given by Bruce Zetter followed by a dinner organized by CSHL. Bruce has been giving career talks to Harvard students and Damon Runyon Fellows about topics like funding in cancer research. I’ve heard positive reactions about the talks, so I thought it would be good to invite Bruce here and couple his talk with the career dinner.

Next, we discussed the research developments they’re most excited about: 

Celeste: Because of combinatorial approaches to therapy, we're starting to hear of ways to broaden what’s working for some patients. Obviously, there’s a very reasonable and appropriate emphasis on the immunology therapy right now but, like every other approach, it doesn’t benefit everybody. So how can we combine things in a way that more patients durably respond? It goes without saying that the more you know, the more tools you can bring to the table. But we now have so many tools: It’s not that there aren’t enough treatments, there may almost be too many and we don't know who to treat with them or how to best combine them. By understanding all the different mechanisms and interactions between cells and the tumor environment, I think we can logically design trials that will more likely be successful.

Scott: In contrast to CSHL’s other major cancer meeting, (Mechanisms & Models of Cancer) which originated from cancer genetics, this meeting concentrates on the tumor microenvironment. Here, you get a lot more epigenetics and things that are not simply or directly derived from gene mutations. One thing we’ve seen over and over again, a very interesting and somewhat terrifying aspect of cancer, is this sort of plasticity cells have that isn't driven so much by gene mutations, but is maybe enabled by them to change cell fate. This has long-range implications not only for cancer evolution but therapy response as well. We heard from Cory Abate-Shen's talk, for example, of cells that can become resistant to a target of drugs by changing their natures so they no longer care about that target. I think that’s surprising and a really important result.

Senthil: Along the same lines, a highlight of this meeting is to understand how a tumor cell uses its microenvironment to adapt, and how it dictates or actually learns from it. This bears out in some of the talks we’ve heard where genetics of the tumor dictate the immune interactions. I think this meeting helps bring together these diverse topics and pockets, and then connect them together -- which is hard to do at a large or specialized meeting.

Historically, graduate students and postdoctoral fellows make up approximately 50% of the meeting’s attendees each year, so we were curious about how young scientists benefit from participating in this meeting. 

Scott: Beyond the fact that the vast majority of talks are selected from the abstract submissions and feature new results, this has always been a really interactive venue. People tend to stay on campus and see each other in the poster sessions, at Blackford, and in the bar, so there’s always a lot of discussion. That’s what I think really makes this meeting great.

Celeste: Each one of our sessions is a meeting unto itself quite frequently. For me, I’m catching up on a lot of the latest things that I’m a little bit out of date on, like some of the immunology we heard this year. These are very fast-moving fields that would be difficult to catch up on at more specialized or larger meetings. I think everybody benefits. We’ve got PIs, postdocs, students, and even somebody very august like Richard Hynes. He isn’t an invited speaker and I don’t know if there’s anyone from his lab here this year, but he just showed up to learn.

Scott: That’s a great validation of the meeting.

Senthil: Exactly.

Scott: I agree that everybody benefits. It’s a great meeting to come to if you’re a senior graduate student interested in cancer but don’t yet know what to specialize in. This meeting will expose you to really cutting-edge work and help you decide what you want to do as the next step. There are a lot of students here thinking about what to do for their postdocs, and that’ll be true in the future too.

Celeste: Another thing I thought was interesting: I saw at least two people say, “By the way, I’m on the job market for a faculty position.”

Senthil: It happens very frequently, it’s a continued trend.

Celeste: That’s good! I heard a couple of talks here that I’m going to definitely notify our search committee about.

Closely related, this year’s meeting debuted a new element called “Junior Stars Sessions,” which featured talks by early-career investigators.

Scott: The sessions highlighting young, rising junior faculty seem to have been a success. The science has been great.

Senthil: Lots of work in emerging fields, interesting topics that are not mainstream in some places.

Scott: It’s an evolution of what’s special about Cold Spring Harbor meetings. One reason I like the meetings here is that historically, most of the talks come from the abstract submissions. What you're getting is the people who actually did the experiments often are the ones presenting the work and, in many cases, this is the first chance they’ve had to give a big talk. The general philosophy of Cold Spring Harbor meetings is that this is the place where people get to talk about their work at an early stage in their careers. So in addition to disseminating science, we're helping early-stage investigators make a name for themselves. For me, that’s what I want to accomplish as a meeting organizer.

Celeste: There are many challenges to launching a lab, but one is being really seen as independent. Many junior stars are kind of at that point where they are just far enough out from their mentors’ labs – who are usually pretty well established. The Junior Stars Session is just a great forum I’d like to see more of, frankly. I’d like to see it become a tradition because of the positive response it’s received; people have come up to me and said they thought it was great. It can really be helpful for those who, in another few years, will be coming up for tenure; this can help them make the connections.

Senthil: For students and postdocs to hear a scientist who is up-and-coming, it’s inspirational for them. They don’t just see the big names talking -- they see people who are not too far from where they are being recognized as “Junior Stars.” I think that’s inspirational.

The Biology of Cancer: Microenvironment & Metastasis meeting returns to the Laboratory in late September 2019. If you’re looking for a meeting in the years that Biology of Cancer: Microenvironment & Metastasis is not at CSHL, the Mechanisms & Models of Cancer meeting is a great alternative.  

For more conversations with other meeting organizers, check out the rest of our A Word From series. 

Photo: Constance Brukin

A Word From: Edith Heard, Tom Misteli & David Spector

Earlier this month, Cold Spring Harbor Laboratory hosted the tenth biennial meeting on Nuclear Organization & Function. We sat down with three of the four organizers -- Edith Heard, Tom Misteli, and David Spector -- to chat about how the nucleus continues to stay at the forefront of molecular biology and why this meeting should be on the radar of every specialist. The conversation opened with how the meeting and field have evolved since 1998:

David: When the meeting started, it mostly looked at specific proteins or genes, studying their dynamics in 3D, and learning about the dynamics and interactions of various nuclear bodies. Over the past two decades, the meeting has evolved to where the questions are now more centered on genome-wide analysis, whether it be by chromosome painting, Hi-C, or RNA-Seq techniques. We’re now looking at the nucleus in a more global sense: how functions take place in the nucleus, how the genome is organized, and how dynamics are altered upon changes in various physiologic states.

Edith: Since I first participated in this meeting in 2006, I have seen the evolution David mentioned. Before, it was still quite descriptive: types of bodies, types of RNAs in the nucleus, etc. There has indeed been a shift to the more genome-wide approaches that look at how chromatin is organized. People are also using all sorts of nice tricks to look at mutants and see whether these bodies, structures, and RNAs matter in more developmental and disease-type situations. And the imaging is just amazing now. It’s extraordinary how far one can go with these super resolution approaches, where the live imaging goes really well with the genomic information. To me, we’re seeing the beginning of a whole new era where we can visualize the 4D aspect of the nucleus.

Every time we discuss whether we should organize another nucleus meeting, we wonder if maybe things have gone beyond the nucleus. But actually the nucleus keeps being very much at the forefront when it comes to the questions that interest a wide community.

Tom: I first attended this meeting as a postdoc in 1998 so I see its evolution very differently. What’s the same is the realization that the nucleus is very complicated. I think we’ve made a lot of progress over the last twenty years but it still feels like we’re just scratching the surface. We have much better tools now, there’s no question about it, but it’s interesting that the tools are in a way similar: biochemistry and imaging…

Edith: And genetics.

Tom: And genetics. These have evolved and are now very powerful. Twenty years ago, I don’t think we ever felt we were going to solve this problem but now, because of the tools, there’s hope that we can actually do it. Something that struck me this year was the confluence of people thinking about different things. In the past, it was rare for somebody to talk about chromosomes, and then talk about lamins, proteins, or nuclear bodies. But now people think in a more holistic way.

David: Unlike most other meetings which focus on one aspect of the biology like chromatin, RNA, or nuclear export, this meeting encompasses all of those areas and more. It’s a more systemic evaluation and study of nuclear organelles, looking at all aspects and how they communicate with each other. It brings people from different fields together and so there’s a lot of cross talk at this meeting that, in and of itself, will provide avenues for advances.

Collectively, David, Edith, and Tom have attended eighteen CSHL Symposia. We were curious to hear their thoughts on the similarities and differences between their meeting and our annual symposium.

Edith: The symposia are one-offs that each explores a different topic, whereas this meeting is about continuity and community. Some of the postdocs who come to the meeting end up as PIs who eventually help run it.

David: Both have their advantages. The symposia are structured whereby speakers are all invited and are leaders in the field. It’s good to go to a meeting like that because a leader in a particular field will present very differently than a student or postdoc; there’ll be a lot of big picture insights into how the field should move ahead, so there’s a lot to be learned from that type of meeting. Here, the predominant speakers are students and postdocs. That’s also important because it gives them an opportunity to present their data and get exposure to PIs and colleagues. Attending and presenting at this meeting is sort of, in a way, preparation for having their own lab.

We next asked the organizers who they think should attend this meeting and why:

Tom: This is not a field dominated by a single expertise that will give you all the answers. Not everyone can do everything. So a geneticist probably doesn’t do biophysics, but they need to know the biophysics and that’s why I think this meeting is so important. Even though you yourself are a specialist, learning about other fields that are relevant to what you’re doing is absolutely beneficial.

Edith: The attendees all come here from different angles. They’re not necessarily nuclear experts, but they clearly share interests in understanding how the nucleus behaves and the influences that can happen in more in vivo settings.

David: In addition to initiating this meeting, I started a Cold Spring Harbor course called “Immunocytochemistry, In Situ Hybridization & Live Cell Imaging” in the 1990s. The course has evolved over the past 25 years and is now called Quantitative Imaging, but it’s still running. That course and this meeting go hand-in-hand. When those trainees participate in this meeting, they are able to see how the techniques they learned are being applied to answer biological questions.

Edith: Another aspect is that there aren’t many other nucleus meetings. And so this is a community of people who like to come back to the same place and re-connect with colleagues they met last time. People are attracted to this meeting and Cold Spring Harbor because of the community.

David: As Joe Gall always reminds me, this meeting is the home of the nucleus field.

Tom: It’s also very focused on students and postdocs. It’s a Cold Spring Harbor tradition to have a lot of postdoc and grad student speakers, so that’s a reason for especially students and postdocs to attend. This is also a great meeting for people who are not directly in the field to learn about the field. We’re seeing a lot of physicists, chemists, engineers who build microscopes, all getting into this field. I think this has something to do with the complexity and diversity of the question. So this is a great place for people to find out what the biological problem is and how they can apply their expertise and contribute. It really takes a village.

Edith: That’s true, how many other fields have attracted the mathematicians, physicists, and chemists? In biology? Not that many and yet they’re flocking to attack this particular set of biological questions.

We concluded our chat by asking about recent scientific developments they’re most excited about: 

Edith: Right now I’m most excited by the ability to get both genomic and imaging information out of a single cell, and hopefully combine those to really look at the dynamics of nuclear function at every level from the molecule right through to the phenotype. The single cell approaches -- whether it’s imaging or extracting transcriptomes, Hi-C maps, or epigenomes -- the combination of the two is very exciting. You can suddenly see stuff that you suspected (or didn’t suspect!) was there.

Tom: Related to that, the appreciation of heterogeneity and variability between individual cells is exciting. As we said before, this is a very complex problem and so to study it, you simplify. But we’re beginning to realize that every cell is a little bit different and there’s no one way to organize the chromosomes. Because of technologies like single-cell biochemistry and imaging, we’re going to learn a lot about the fundamental principles of how these biological systems work. I think that’s where we’re going and I find that exciting.

David: I would like to see more work on disorder and plasticity. Most people always think, “This has to be super organized, it has to do this to work.” But I don’t think the cell works that way; from a human evolutionary perspective, that would be very dangerous. So I would like to see more of the general neighborhood that things can take place in, how much leeway is there, and what does it all look like in real cells and tissues, rather than in cultures that have been growing in a dish for 25 years. I think more work in that regard would be extremely insightful.

Edith: And a kind of hierarchy as well, to ask if a gene in a particular part of the nucleus at a particular time matters. We used to just watch and say, “Oh look it’s there!” But now we can address the question mechanistically and I think that’s amazing.

David: And “What if it was here, would it still work?”

Edith: Yes.

Tom: Also, we’ve been so busy looking at the fundamentals that we haven’t really applied the knowledge we have to disease models. We use disease as a model system, as natural experiments, but we haven’t truly explored nuclear structure in the context of disease, or in a systematic and focused manner that you can take into the clinic. There’s a lot to be discovered there.

On behalf of the organizers, we hope to see everyone back at CSHL for the 2020 Nuclear Organization & Function  meeting taking place from April 28 to May 2. 

For more conversations with other meeting organizers, check out the rest of our A Word From series. 

Photo: Constance Brukin

Visitor of the Week: Sunil Bhattarai

Meet Sunil Bhattarai of the Neuroscience Institute at Hackensack Meridian Health JFK Medical Center. A postdoctoral researcher in the Laboratory for Stroke Research and Noncoding RNA Biology led by Ashutosh Dharap, Sunil is on campus for the 2018 Regulatory & Non-Coding RNAs meeting. It is his first meeting at the Laboratory and he commemorated it with by presenting a poster entitled “Expression of LncRNAs in post-ischemic mouse cortex”.

What are your research interests? What are you working on?
I am exploring the roles long non-coding RNA (lncRNA) plays during ischemia. We recently reported hundreds of new lncRNA in a post-ischemic mouse brain, and are now attempting to understand the functional roles of lncRNA in post ischemic brain.

How did you decide to make this the focus of your research?
My interest towards neural disorder and neuroscience led me to this work where the overarching role is to find the long non-coding RNA mediated neuroprotective therapy in a post-stroke brain. 

How did your scientific journey begin? 
The major event that really piqued my interest in science was a spinal cord injury suffered   by one of my family members. This was when I first realized the difference in regeneration capability of neurons in the central nervous system and peripheral nervous system. This incident eventually led me to join a lab studying neural injury and regeneration. 

Was there something specific about Regulatory & Non-Coding RNAs meeting that drew you to attend?
I was drawn by the opportunity to meet the people  working exclusively in the RNA field. I met and spoke with one of the meeting speakers, Dr. Angela K. Cruz from the University of Sao Paulo in Brazil who is also studying long non-coding RNAs. We discussed our research and shared ideas on a way to probe functional roles of long non-coding RNAs. We exchanged e-mails and will definitely be in touch to continue discussing our work.

What is your key takeaway from the meeting?
One of the key takeaways from the meeting is how tricky and difficult long non-coding RNA can be to work with.

What did you pick up or learn from the meeting that you plan to apply to your work?  
I had the opportunity to meet people doing similar work and learned about the technique you can use to study the nuclear organization in space in a high-throughput manner.

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?
I would definitely encourage anyone to attend the meeting here in CSHL. Unlike some other big meetings that I have been to, the attendees here are closely knit so you are more likely to interact and have an opportunity to collaborate with them. Additionally, you are more likely to get a thorough look at the work in the field and possibly identify the next place or lab you might be interested to work. Furthermore, it is compelling to attend a meeting in a place fertile in scientific discoveries and achievements. 

How many CSHL meetings have you attended?
This is my first CSHL meeting, and I will be definitely attending others in the future.

What do you like most about your time at CSHL?
The ability to meet and make contacts with colleagues working in my field ; and I had the chance to talk with one of the eminent people in the field: Dr. Samie Jaffrey. Although my work is not directly related to the work being done in his lab, it was great to converse with him, get his advice on career development, and listen to his insights about the RNA field. 

Thank you to Sunil 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.

Photograph provided by Sunil Bhattarai

Visitor of the Week: Brunilda Balliu

Meet Brunilda “Bruna” Balliu of the Stanford University School of Medicine. The Albanian-Greek national is a postdoctoral fellow in Stephen Montgomery’s lab in the Department of Pathology. Bruna returned to campus for The Biology of Genomes meeting where she presented a poster entitled “Longitudinal study of gene expression and regulation during a critical period of the aging process”.

What are your research interests? What are you working on?
I am a biostatistician by training and my research interests focus on the development of novel statistical methods for high-dimensional genomic data. Scientifically, I am interested
in aging and am currently profiling changes in transcription regulation that occur during advanced aging in humans.

How did you decide to make this the focus of your research?
After finishing my PhD, I wanted to extend my statistical background into translational genomics research that more directly impact human health. I am fortunate that my postdoctoral advisor, Stephen Montgomery is involved in numerous collaborations because there were plenty of potential projects to select from when I joined his lab. The project on aging jumped out at me for several reasons. First, aging in an undeniably interesting subject. Second, we had access to a first-of-its-kind data set of functional genomics from individuals in their seventies, eighties, and eventually from those in their nineties. Finally, I have a standing interest in statistical methods for longitudinal data. 

How did your scientific journey begin? 
I did my undergraduate studies in Statistics in Athens, Greece, when the country’s financial crisis began. As I approached graduation, I started looking for a Masters in Finance program but, thankfully, my professors encouraged me to also look for PhD positions in biostatistics. I took the PhD route and the rest is history! 

Was there something specific about The Biology of Genomes meeting that drew you to attend?
This meeting is world-renowned for excellent talks presented by leaders in the field and on their latest work. Since this is a new area for me, I was very excited to attend and gain a broader view of what my colleagues are working on. 

What is your key takeaway from the meeting?
In the past few years, there has been huge progress in both sequencing technology and computational capacities that has allowed researchers to move from observational to large-scale interventional studies. I was impressed by the number of talks presented here based on experiments across multiple species, cell types, environmental conditions etc.     

What did you pick up or learn from the meeting that you plan to apply to your work?  
It’s a great place to network since the structure of the meeting encourages people to interact. I’m going back home full of ideas. After seeing Julien Ayroles and Amanda Lea's work on the impact of genetic and environmental perturbations on molecular co-regulation, and talking to Julien, I’m excited about extending my work to understand the impact of aging on gene-gene interactions in humans. 

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?
This is one of the busiest meetings you will ever attend so get some sleep the week before and leave some room to recover afterwards.

How many CSHL meetings have you attended?
This is my second meeting here. I attended the Probabilistic Modeling in Genomics in 2015 and will be attending that same meeting this November.

What do you like most about your time at CSHL?
It's definitely the conversations. This meeting gives you a lot of time for discussions, and that is a key component of a successful meeting for me. 

Thank you to Bruna 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.

Photograph provided by Bruna Baillau

Visitor of the Week: Aridni Shah

Meet Aridni Shah of the National Center for Biological Sciences, a part of the Tata Institute of Fundamental Research (India). Aridni is a member of Axel Brockmann’s lab, and she made her first trip to CSHL to attend the 2018 Biology & Genomics of Social Insects meeting where the graduate student presented a talk entitled “Egr-1, a candidate molecular player involved in time-related learning and memory processes in honey bees?”

What are your research interests? What are you working on?
I am interested in understanding the molecular processes underlying behavior. Currently, I am working on honey bee foraging behavior to identify the different molecules that might underlie the learning and memory processes during this behavior. So far, I have identified a molecule, Egr-1 that seems crucial for foraging and foraging-related time memory.

How did you decide to make this the focus of your research?
I was keen on understanding how behaviors are brought about by underlying molecules and a short training in the lab made me realize that honey bees are an excellent model to look at behavior and hence the molecules could be identified easily with such strong behaviors.

How did your scientific journey begin? 
My late father was my greatest inspiration. He loved science and, when we were young, used science to show us “tricks” like making a needle float or constructing a steam engine model for a science project. His inquisitiveness helped nurture mine and so I have been very fascinated by science from a young age and always wanted to get into the field to make new discoveries and to answer certain yet-to-be answered questions.  

Was there something specific about the Biology & Genomics of Social Insects meeting that drew you to attend?
Validation and feedback from the social insects community were my incentives for attending this meeting because it is a major meeting on the molecular basis and mechanism of sociality attended by eminent scientists and colleagues working on sociality. At this meeting, I had the opportunity to present my work and discuss it with an international community and get valuable feedback that would help me pinpoint any shortcomings in my current work plan. Also, I was also able to assess the impact of my work which is helpful when it comes to setting a more defined direction for further progress

What is your key takeaway from the meeting?
That social insects are very versatile - the level of sociality can range from solitary to subsocial to incipiently social to advanced eusocial, can have single queen or multiple queens, and can have various forms of reproduction like thelytoky and arrhenotoky - therefore, there is a system which can be used to study these variations and the genes involved with it.

What did you pick up or learn from the meeting that you plan to apply to your work?  
This meeting was extremely helpful for me in many ways. As my first meeting with the social insects community, I met a lot of colleagues with similar interests. I had enlightening conversations with Guy Bloch, Hagai Sphigler, Daniel Friedman, Mehmet Döke, and Manuel Nagel from whom I learnt of a new technique he is establishing, in situ sequencing, that I would like to implement in my future work as it will help me study multiple genes at a time. Discussions about my future work with Guy and Hagai on manipulations of the circadian clock has helped me refine my experiments that I hope will result in meaningful outcomes. 

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?
I would say that he/she should definitely attend the meeting. It is small but since it is attended by all the major scientists working in the field, it provides the right environment to get to know one another and each other’s work very well. The environment was very friendly and you can easily walk up to anyone and start a conversation. 
 
What do you like most about your time at CSHL? 
I enjoyed the meeting a lot. The place is beautiful, and the people are amazing. I was able to put faces to names whose work, until now, I had only read about, and I engaged in a lot of amazing conversations, both scientific and non-scientific, with people I met. And yes, the lobster was great!

Thank you to Aridni 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.