<![CDATA[Todd Evans Laboratory - Todd Talks - Blog]]>Wed, 14 Jun 2017 06:31:03 -0700Weebly<![CDATA[Science is a marathon...or perhaps a half]]>Thu, 03 Nov 2016 22:34:30 GMThttp://toddevanslab.net/todd-talks---blog/science-is-a-marathonor-perhaps-a-halfIt's true that sometimes doing science can feel like running a marathon. Except a marathon where you run two miles, turn around and run one mile back, and then turn around again and get back on your journey. So maybe it is more like an Ironman!

(See this link for a story about how pushing it to the limit can kind of get out of control....

But an important part of doing science is knowing how to set a finish line. Yes, you can decide where that line lies, or at least suggest a finish line, and then let peer review decide if its appropriate, or you need to keep on going a bit further. To do good science you need perseverance, endurance, and training, much like distance running. Im sure its why you find many runners in science. We needed to really persevere  for a recent study published in Cell Stem Cell, which is a high impact journal that sets a high bar (sorry, didn't mean to analogize into yet another track and field event!). Kudos to our collaborators in the Shuibing Chen laboratory for fortitude and hard work, especially Hui Zeng and Min Guo, for their demonstration using a human ESC model that a specific GWAS-identified diabetes risk allele actually does impair insulin secretion, and for the identification of a candidate drug that can rescue the defect. This is a great example for how we will eventually develop patient-specific drugs to treat metabolic diseases. You can find the paper here:

The reviewers kept the finish line moving, but eventually we nailed it.

Meanwhile, this Sunday is the New York City Marathon, so best wishes for all the runners. Most likely will not be won by a scientist, but I hypothesize that plenty will be running. While members of our lab have run the NYC marathon in the past, more recently we are feeling pretty satisfied with the half. As seen below, from the Jersey City Half, completed about a month ago. Keep running and never give up!

L-R: Ingrid, Bran, Todd, and Kelly at the finish line, Sept. 2016. Bran had to wait a bit for the rest of us!

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<![CDATA[Stem Cells at the United Nations]]>Fri, 29 Jul 2016 18:57:00 GMThttp://toddevanslab.net/todd-talks---blog/stem-cells-at-the-united-nationsOne of the great things about being in New York City is that unique opportunities present themselves that allow you to interact with all sorts of interesting people doing all sorts of interesting things. I had the opportunity in May, along with my colleague Dr. Shahin Rafii, to make a presentation at the United Nations, for a seminar series sponsored by the UN International Women's Forum. The title of our presentation was "The Promise of Stem Cells for Curing Disease". See below:
No, sadly this was not the room for the seminar :(  it was a bit less.....big.
However, we did also get a chance to tour the UN, including visiting this famous room used by the General Assembly, and to wander for a bit among the working ambassadors from all over the world, who for some reason can park basically anywhere they want and never get a ticket....dont get me started on that one.

Anyway, I have lived in NY most of my adult life, and we work just a mile uptown from the UN, but I had never visited. I highly recommend it! It's really like a special museum and has an incredible assortment of gifted art, from countries around the globe. Urns seems to be particularly popular. I prefer the huge tapestries. Lots of important educational information about what is really really bad, and also really really good about the world today.

One of the major topics of our presentation was that stem cell cures are REAL but thus far pretty limited (basically, hematopoietic stem cell transplants), and that much more research is required before additional types of stem cell therapies are going to be ready for the clinic. However, that has not precluded "clinics" from making outrageous claims to new stem cell therapies that can cure most anything (with patient testimonials!!). These fraudulent outfits can do much more harm than good, and can surely give stem cells a bad reputation. Yes, some of them can be found in places like Costa Rico, but you can find them right on Fifth Avenue as well. Our advice was to avoid anything that is not a clinical trial, as those are the only scientifically valid stem cell treatments for the meanwhile outside of HSCs (and HSCs only for replacing the blood system!). I highly recommend the information provided by the International Society for Stem Cell Research, regarding this topic: http://www.closerlookatstemcells.org/stem-cells-and-medicine/

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<![CDATA[Best Talks (ever!)]]>Thu, 26 May 2016 23:15:59 GMThttp://toddevanslab.net/todd-talks---blog/best-talks-everGreat news from the lab front, or more specifically from the lecture circuit! Among the most important responsibilities for a scientist is to get the word out on recent progress and share your results with fellow scientists to get critical feedback and generate some buzz! We have all been busy doing this in Spring 2016, and to some considerable acclaim. Congratulations go out to Emily Mercer for winning the first place prize at the Weill Cornell Annual Vincent du Vigneaud Graduate School Symposium. Emily is shown below accepting the prize from Dean Gary Koretsky, along with a close-up view of the gold-plated plaque. I was present at her talk, and indeed I agree she gave a stunning presentation regarding her recent discoveries for the role of Hspb7 in regulating cardiac morphogenesis and protection. The audience truly grew to appreciate how much they depend on Hspb7, and were amazed at the detective work Emily used to reveal its connection to large sarcomeric protein turnover, via an autophagic pathway. Then, just about a week ago, I was privileged to attend the annual Weinstein Cardiovascular Development Meeting in Durham NC, along with Yahui Lan, who gave an amazing presentation of her poster revealing for the first time the requirement for TET proteins in the development of the epicardium, likely through control of DNA methylation. This is the premier meeting for those of us interested in cardiogenesis and heart regeneration and is attended by many of the top researchers in the world. At the end of the meeting, it was announced that Yahui had received one of the 10 Best Poster Presentation awards (out of at least 200 posters). This is a great honor and even comes with a nice cash bonus award. We will have to see, but perhaps Emily and  Yahui will be taking the lab out for some celebratory libations! 

Although such awards are very nice and terrific validation for all the hard work and smart thinking accomplished by these scientists, the meetings themselves are the most important point. Here we exchange ideas, get new ideas for extending our results, and perhaps discover that some ideas are not worth pursuing (better to find out sooner than later!). More travel later this summer: International Zebrafish Meeting. What could possibly be more fun than Orlando in August??
Left: Emily being recognized for BEST TALK EVER (Emily is not the one with a tie). Right: Emily's gold-plated (I'm pretty sure) plaque, representing a great honor for her and the entire Evans lab. We are all very proud of Emily and Yahui!
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<![CDATA[What's happening in 2016?]]>Mon, 18 Jan 2016 22:27:52 GMThttp://toddevanslab.net/todd-talks---blog/whats-happening-in-2016Well, it has been quite a while since the last post! What's the excuse then, was nothing happening in the lab? Was the lab shut down for 2016? 

No of course not. Remember, science never sleeps, so we have been as busy as ever. In fact, I have been a bit too busy to post blogs over the last few months, doing all the things that a scientist does in academia. Such as? (you might ask). 

Fair question. Such as: Teaching in several courses for graduate and medical school students, serving on study section for the NIH (reviewing and ranking grant applications), presenting our research in seminars here and at other schools, reviewing papers for scientific journals, serving on advisory committees for faculty, postdocs, and especially students,  writing what seems like an endless number of recommendation letters (happy to do it!), and of course meeting with lab members and our collaborators to discuss experimental results and make future plans. And the great thing is, guess how much I get paid for doing all of this......drum roll......NOTHING! Sounds like a great career choice, eh?? (actually there is a very modest stipend provided for NIH service, and often times for outside seminars, but trust me, it's well below minimum wage).

BUT: this does afford the opportunity to do the things that I am paid for (and a pretty fare wage, in my opinion), namely writing and submitting grant applications to fund the research, and writing and submitting manuscripts to describe our research thereby contributing to the literature and the knowledge of mankind. And occasionally, when nobody is looking, I even get to help out on an actual experiment. So, to prove that this recent failure in blogging does not reflect a lack of productivity, let me post about three studies that were recently published, that were each made possible only by a lot of very hard work, and great collaborations with our colleagues in the field.

1) We worked with Mary Goll (Sloan Kettering Memorial Cancer Center) and her terrifically talented student Cheng Li to report how TET proteins (cytosine hydroxylases that are able to demethylate DNA) are essential for the generation during development of hematopoietic stem cells (Cell Reports). Yahui Lan from our lab is continuing this collaboration with a focus on heart development. Mary is an expert in DNA methylation and epigenetics and we have several interesting projects in the works together. Read all about it here: http://www.sciencedirect.com/science/article/pii/S2211124715007652

2) We worked with Amit Verma (Einstein) and Amittha Wickrema (U Chicago) to show that mutations or loss of function for the DOCK4 gene disrupts normal red blood cell differentiation and may be a key mechanism causing a group of diseases called Myelodysplastic Syndromes (PNAS). This involves work in our lab started by Thomas Quenon, when he was a visiting student from Belgium way back in the summer of 2012. Amit and Amittha are leaders in this important field, so it was a great pleasure to work with them. Read all about it here: http://www.pnas.org/content/112/46/E6359.long

3) We worked with Shuibing Chen (WCMC) and other colleagues in our Department to show that human pluripotent stem cells could be used to model defective pancreatic ductal cell function in cystic fibrosis (Stem Cell Regen Med). This was the main project for Dr. Senem Simsek, who has now moved on to a new position at Sabanci University in Turkey. Sorry but the publication link is not yet live, but I'll post it shortly.

Much more coming in 2016, as we expect multiple papers from these and other collaborations, and hopefully they will be duly blogged in a much more timely manner!   Todd


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<![CDATA[Todd's Youtube Interview: Stem cells personalized]]>Tue, 01 Dec 2015 17:09:51 GMThttp://toddevanslab.net/todd-talks---blog/todds-youtube-debut-a-starring-role
Todd and other stem cell experts in a special The Young Turks interview!
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<![CDATA[If it's important...someone else is also working on it! (Panic!!)]]>Tue, 11 Aug 2015 18:00:00 GMThttp://toddevanslab.net/todd-talks---blog/if-its-importantsomeone-else-is-also-working-on-it-panicKaren's recent paper is now available at Developmental Dynamics. Here is the link: http://www.ncbi.nlm.nih.gov/pubmed/25997406

This work is important because it identifies the kinase (called sphk2) responsible for generating a lipid mediator (sphingosine 1-phosphate, S1P) that provides a critical signal for bringing together the early progenitors that form a primitive heart during embryogenesis. Without this signal, this process fails and the embryo generates two "hearts" on either side (cardia bifida) which is, obviously, a bad thing. To do this work, Karen generated a targeted mutation in the sphk2 gene. Gene editing is an amazing technology that is truly revolutionizing science, and soon enough, medicine. More on that to come...

Meanwhile, the point  of this post is not only to highlight Karen's paper, but to mention that shortly after her paper was accepted, an entirely independent study was published in JBC by Kawahara's group, that essentially showed the exact same results, using more or less the exact same strategy. The link to their paper is here: http://www.ncbi.nlm.nih.gov/pubmed/25907554

Is that weird? How could two completely independent groups halfway around the world from each other, carry out the same study? No, it's not weird. Each group's work is the natural extension of a larger body of work focused around this signaling pathway and its role in cardiogenesis, starting back in 2000 when Didier Stainier's laboratory identified the S1PR2 (the receptor) as the mutated gene in the zebrafish miles-apart mutant (back in the day, you found mutants first, and then had to clone the gene to figure out the cause; today we can mutate any gene we want). Here is that link, which is really a tour-de-force and beautiful paper: http://www.ncbi.nlm.nih.gov/pubmed/10910360

So there is a very important lesson to be learned: If nobody else is working on  your project, then you may need to rethink if it's really an important project. The corollary, and more relevant lesson, since you can never prove that nobody else is working on your project, is this: if you are quite sure that your project is important, than you can be completely sure that others are also working on the problem. Does this mean you will get "scooped" and unable to publish your work (and thereby perish!). Well, it can happen (at least the scoop part, and "publish or perish" is certainly true). But usually it does not happen, and it certainly does not mean you are likely to perish. In fact, there are almost always related papers published around similar times. 

Two additional examples from our lab: In 2013, Novikov and Evans discovered that the Tmem88 gene regulates WNT signaling and cardiogenesis in zebrafish (http://www.ncbi.nlm.nih.gov/pubmed/23903195). Back-to-back in the same issue of Development, Murray's group discovered the exact same thing using hESCs (http://www.ncbi.nlm.nih.gov/pubmed/23924634).  Earlier that same year, Gabe and Emily showed in Developmental Biology that two small heat shock proteins regulate early cardiogenesis (http://www.ncbi.nlm.nih.gov/pubmed/23850773) and lo and behold, the exact same thing was shortly thereafter reported in the same journal by Marvin's group (http://www.ncbi.nlm.nih.gov/pubmed/24140541).

So this happens all the time. Although we may worry about being scooped, in fact it is quite reassuring to find other groups are replicating your own discoveries. So then, should you panic, worrying about who is potentially going to scoop your work? Of course you should!! But do so in a productive way, which means heading to the bench and pushing ahead. Keeping close track of the literature and meeting reports. Making sure you are doing the right experiments to complete a publishable study. Don't give up! And ultimately, don't worry. Even if scooped, you will likely have some additional information or alternative perspective to contribute, so that the work can still be published.]]>
<![CDATA[Emily and Su-Yi in New Orleans (working hard!)]]>Tue, 14 Jul 2015 21:21:53 GMThttp://toddevanslab.net/todd-talks---blog/emily-and-su-yi-in-new-orleans-working-hardThe American Heart Association is currently running its Basic Cardiovascular Sciences (BCVS) Scientific Sessions, and this year it is being held in New Orleans. Both Emily and Su-Yi are presenting their research in poster sessions. 

Here is the program: BCVS 2015

A poster session is sort of like a pop-up flea market (a bit more organized) to facilitate the presentation of a large number of studies all at once, allowing meeting attendees to browse around and spend as much time as they wish (or not) looking at the presentations, and also have a chance to speak directly with the lead author. Its also a good opportunity for students and fellows to network and perhaps make connections for future positions. To this day I have colleagues and friends that I met because their poster just happened to be set up next to mine. Below, see Emily after having just set up her poster. Looks like her "neighbor" has not yet arrived.

Posters can be even more challenging to present than a formal lecture, since an entire study needs to be condensed onto a relatively small presentation board (that would be the "poster") in a manner that is clear and comprehensible to a passing audience. It needs to be "catchy" enough so that it grabs the audience's attention, but deliver the message in a clear manner so that one does not need to spend more than about 5 minutes looking it over (unless perhaps its really directly in your area, or even perhaps your competition!). A well done poster can be completely understood, primarily using figures and graphics, rather than text, even if the author is not present to explain it (posters are typically left up for a day or two). It can be exhausting to present a poster, but that would be a good sign (compared to having nobody stop by to discuss it!).

It seems a shame that Emily and Su-Yi had to travel all the way to New Orleans just to spend several days holed up in a convention center doing nothing but talking science. Well actually, ...I suppose they might get a chance to poke around the French Quarter just a bit. I told Emily it was closed this week, but I'm pretty sure she did not believe me. In case that gets out of hand, an early morning visit to Cafe Du Monde should do the trick.

When she returns, Emily will be posting pictures from the lab picnic from last week. 
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Who Dat?? In New Orleans, Emily will present her poster on the role of the HSPB7 chaperone protein in cardiogenesis (her main PhD thesis topic). Su-Yi is presenting her work on generating cardiac Purkinje Cells from embryonic stem cells. Great job guys!!
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<![CDATA[Scientists: usually just 1 degree of separation]]>Wed, 08 Jul 2015 22:04:02 GMThttp://toddevanslab.net/todd-talks---blog/scientists-usually-just-1-degree-of-separation OK, as promised, here you get an idea about the walking lane signs I was so fond of in Helsinki. This was very nicely sent to me by Nicholas Downes, who is carrying out his PhD studies at the University of Eastern Finland. In fact, the specific graphic I was seeing in Helsinki tended to be painted right onto the sidewalk, but you get the idea. The design is the same.

Now, how did Nick happen to find my request for a photo of the walking parent/child image? It could be because our blog is already so world famous, but....probably not. In fact, Nick went to the same College as Emily Mercer a few years back in the UK, and so picked up my request from Emily's Facebook page. (see Emily on our People page).

This is a great thing about science, as there is almost always someone who can help you out and is only 1 or 2 degrees of separation away.  About a week ago, we received the generous gift of a new vector for efficient homologous recombination to create conditional alleles in zebrafish embryos, from David Grunwald in Utah, about which I had seen him discuss at a meeting in California earlier this year.  Julien Ablain, a postdoc from Len Zon's lab in Boston, just promised to send us his new vector for efficiently generating tissue-specific Crispr/Cas knockout/edits in zebrafish. We just sent off a shipment of our transgenic gata4:gfp reporter fish to Leo Kurian's laboratory in Koln, Germany (hope customs is kind to them!). All of these things were swapped without any conditions and simply to promote the success of each others' science. Thanks Nick, David, Julien, and Len.

BTW, I did my postdoctoral training with Gary Felsenfeld, and Gary did his training with Linus Pauling. So my students are only 3 degrees of separation away from the only person in history to win two unshared Nobel Prizes (and we won't go into that whole Vitamin C thing).     Todd

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Not exactly sure what the rules are at this particular spot, but perhaps the walkers and riders share this lane!
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<![CDATA[An international consortium of sorts]]>Fri, 03 Jul 2015 18:54:13 GMThttp://toddevanslab.net/todd-talks---blog/an-international-consortium-of-sortsUnfortunately, the lab picnic was canceled due to an irrational faith in weather forecasters. Try again next week. But we did want to say farewell to Deepika Rajaram, who was visiting on a 6-week internship, from her program at Anna University in Chennai, India. Its very tough to get much accomplished in 6 weeks, but Deepika worked very hard, studying under the mentorship of Ritu Kumar, and I think she learned quite a lot, and also was able to help move along one of Ritu's projects. Keep in touch, Deepika.

Our laboratory is comprised of investigators who hail from all over the world. This includes not only India (Ritu) but also Colombia (Miriam), Spain (Jessica), China (Yahui), Korea (Heejin), Taiwan (Su-Yi), the UK (Emily, Sarah), and even the mysterious kingdom of New Jersey (Ingrid). In the US we also represent the Pacific Islands of Hawaii (Suveg), the Rockies (Bran), the midwest (Alice, Todd), and a scattering of east-coasters (Susanna, Arielle, Karen, Ellen). Of course, this is New York City, so its normal to be around a cosmopolitan mix, but science is truly an international pursuit, and one of the best things about working in a lab is meeting interesting people from all over the world. Importantly, this has a major positive impact on the potluck picnic menu!

You might notice, however, that we are not so well balanced when it comes to gender. You may think that STEM is generally biased against women, and perhaps it is. However, we currently have 14 women and 4 men (and only if you include Nate who is currently in Ithaca, and me, who is rarely allowed to carry out actual experiments). Well, there is no conspiracy here, and lab membership is dynamic and always shifting as people move in and out. We just want good people, and don't care at all how they identify. However, it is true that women are generally quite well represented in our specific field of developmental biology (while it is also true that at the highest levels of academia the balance shifts again to men, for reasons that should be debated). 

Why do women do so well in developmental biology? One could speculate either nature (they have a natural affinity for the discipline) or nurture (they have role models that inspire). Personally (while stupidly wading into a topic on which I have absolutely no qualifications to comment; note to self: really should stick to cardiovascular development) I would argue for nurture. Developmental biology (and related molecular genetics) is a relatively young scientific discipline, and many of the great "mothers" of the field were...women. We can point to brilliant scientists like Hilde "shoulda had Spemann's Nobel" Mangold, Barbara McClintock, Rosa Beddington, and Nicole LeDouarin. Leaders today include Christiane Nusslein-Volhard,  Brigid Hogan, and Janet Rossant. Right here at the Tri-institution we have Alex Joyner, Elaine Fuchs, Kathryn Anderson, Heidi Stuhlmann, Kat Hadjantonakis, Cori Bargmann, Mary Hatten, Liz Lacy, etc. (sorry I don't mean to leave anyone out as Im just free-associating). 

So, while it must have been horribly difficult for the founders, today there are plenty of great women scientists who serve as leaders and can be role models to inspire the next generation. Maybe eventually it will not even be needed, as it becomes less of an issue. Just read their papers, that should be inspiration enough!   Todd
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Barbara McClintock, 1902-1992 Discovered transposable elements (jumping genes). At the time, nobody believed it was true. She believed in her data and she was right. In fact, transposable elements (or really ex-transposable elements) make up a large percentage of our genome! She was awarded the Nobel Prize in 1983. She was a Cornell alum!!
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<![CDATA[Collaboration is really important!]]>Tue, 30 Jun 2015 16:12:09 GMThttp://toddevanslab.net/todd-talks---blog/collaboration-is-really-importantGreat news just in, with a new paper "accepted in principle" at Cell Reports! This work is a collaboration with the laboratory of Dr. Mary Goll,  located across the street at Memorial Sloan Kettering Cancer Center. Like our lab, Mary also uses the zebrafish as an animal model, and she is an expert at studying DNA methylation. We are also interested in how DNA methylation controls gene expression during development, so we worked together on a project studying the function of TET genes, which encode enzymes that can help remove DNA methylation (and thus, perhaps, turn on specific genes). Most of the effort was carried out by Mary's very talented graduate student Cheng Li. More details on this work to follow (after it is officially accepted), but postdoctoral fellow Yahui Lan from our lab helped Cheng show that TET genes are critical for the embryo to produce hematopoietic stem cells (stem cells that make all the blood cells).

Yahui (you may go look her up now!) came to us last year from Hong Kong, where she obtained her PhD working in the laboratory of Zilong Wen. She is second author on Cheng's new paper. But in fact, it's already her second (second) author paper, as she also helped our postdoctoral fellow Karen Mendelson with her paper, which was recently accepted to Developmental Dynamics. This was Karen's second (first) author paper (are you following), which is focused on how the sphingosine phospholipid signaling pathway regulates cardiovascular development. Karen's project is itself a collaboration with the laboratory here at WCMC of Dr. Timothy Hla, who is a world-expert in this pathway, and with whom we have already co-published a number of papers investigating S1P in embryonic development. Karen is also first author on a review we all wrote together last year for Development.

So...in summary...2 recent papers accepted that were made possible because of collaborations with 2 different laboratories. And as you surely recall, collaborations were key to the papers published last month by Su-Yi and Miriam. 

Why is this so? Why don't we just stay hunkered down in our own lab? Science is actually a very creative and collaborative process and different people bring distinct ideas, perspectives, and skill-sets that can all contribute to push the work in new directions and make us all more productive. This is particularly true in academic science, and it is these collaborations that make lifetime connections, working groups, and (added bonus) friendships.

Finally, sorry but I made a mistake in the last post. We moved here to the Department of Surgery at WCMC in 2009, not 2006. Just a typo, but its important in science to always get the facts right, and double-check the numbers!

Todd]]>