Thursday, March 23, 2017

Communicating your research effectively

Scientific results are important, but can make little impact on the world without scientific communication - an extremely broad field that encompasses scientific lectures, writings, and reports. The increasing reach of social media in the last 10 years has also increased scientists’ abilities to share their discoveries via Facebook, Twitter, Instagram, Snapchat, and blogging. These platforms are extremely useful and scientists can both share their own research and more importantly explain why these findings matter in an easy and accessible manner.

In fact, clear communication, targeted to a lay or broad audience is a key effective strategy for helping your research make the most impact. Whether you aim to share your research with the general public or with other scientists, the more transparent your statement, the more your audience will understand. Tempting as it may be, overusing technical jargon may alienate your audience. When you are immersed in a topic you may forget which words are general and which are technical, so always pause and think about what your audience might know or not know. This doesn’t mean you must avoid phrases like autophagy or aliquot, but consider explaining technical terms when necessary. Likewise, including a graphical sketch or a nice fluorescence image might help you to catch the reader’s attention, which could guide them to read about your new findings. Short videos explaining your discovery may actually be even more enticing to the reader, and for this reason a lot of scientific journals are implementing them into their press platforms to reach a larger audience. During a workshop I attended recently at the University of Southern California, Carl Marziali, press secretary for the current Los Angeles Mayor, advised the audience to not underestimate the importance of finding a way to reference your published research article on Wikipedia or other widely available and read platforms. For example, as Wikipedia is a free online encyclopedia and one of the most visited portals across the world, citing your work there could definitely increase your visibility across a wider spectrum. Likewise, LinkedIn, a worldwide business and employment-oriented social networking service, allows users (workers and employers) to create profiles and "connections" to each other in an online social network. Posting your discoveries here could also broaden your real-world professional relationships.

But what is the best way to communicate your research? You need to know to whom you are talking. In our field we are used to communicating our research findings primarily to specialized scientists in specific fields at select conferences. Therefore, while we are used to the practice of shrinking down our findings to suit a particular talk time, we unfortunately tend to take for granted that the audience will know a lot of the background scientific knowledge and terminology and as such leave that material behind. For this reason, a major priority nowadays (and also one that ISEH workshops are helping its members to master) is learning how to give a good “elevator pitch.” In these sessions, scientists are challenged to explain the novelty and importance of their scientific project in the time span of 30 seconds to 2 minutes. As an example Steve Palmer, head of press and science communication at Cancer Research UK, during a “media training booth” said that “If you’re talking to a print journalist, explain what you are doing [as if you are talking] to a 12-year-old child… If you’re talking to a TV journalist, you’ve got to explain what you do to a 5-year-old child. This might sound harsh, but it does help scientists condense their research into a 5 minute talk, which is often all the time they get when speaking to print journalists. If you’re on TV, you’ve got to get your spiel down to 45 seconds, hence being able to explain it to a 5-year-old. The main thing scientists need to think about when communicating their research is impact: “What is the impact on society, on all those people who are learning about our work?” or “why did you decide to start doing this in the first place? What did you want to change?” If you can communicate this clearly in about two sentences, you’re all set.”

Moreover, Palmer suggests that all scientists should try to explain their research to their friends, particularly those who are not scientists. “Do they understand roughly what you do? And I don’t mean in a rambling long conversation across a whole Friday night. I mean in 5 minutes. Do they get it? And let them replay it to you. If they’ve got it, you’re fine.” In my experience, this has been a valuable suggestion. I am glad to be surrounded by friends that have expertise in varied fields, like social sciences, anthropology and art. I like to challenge myself to explain my research project and why I am pursuing it to them. It is a good exercise that helps you to summarize your work in an easy and accessible way, and if our friends get the meaning, it rewards you immediately.

Also, it is important to consider that not everyone is a natural communicator or may be better at one type of communication versus another. Every single person has to work on it - Effective communication is a craft, a skill that you have to learn and work to improve. Some are better at oral presentation than others; some are better at writing. Try them all, see which one fits both you and your research best and use that strength to your advantage. Similarly, look for alternative ways to boost your skills, both in areas in which you are a confident communicator and those in which you are not. For example, during my PhD studies I had the opportunity to join a radio station program on a weekly schedule. The topics we covered ranged from science, politics, art, music, environment and technology. I had to learn how to deliver the news in the most accessible and interesting way in order to attract the listeners. Even though most of the time the news was non-scientific, I built up skills to better communicate in a short and proactive way, and consequently this improved my science communication during scientific meetings. Writing something like this blog is another great opportunity to practice effective communication. Being proactive in many different environments or contexts will definitely help shape your skills and abilities for future applications.

Finally, in addition to self-promotion, as described above, to help more effectively communicate your research, take advantage of the press release personnel of your institution as early as possible. When your paper is almost ready to be published, talk to them and try to schedule a press release that highlights the importance of your scientific discoveries. Don’t underestimate the ability of a professional in this area to further the reach of your own discovery – they specialize in translating research to a broad audience and have contacts outside of your institution and field. You worked hard to get to these excellent results, so don’t let their impact slip away without being noticed by the scientific community and general public! It is primarily our duty to contribute more on scientific communication to increase awareness and confidence throughout the population regarding the importance on doing our research, and how this will, in the end, benefit them. You need visibility, because eventually increased visibility can also improve your chances to win a grant to fund your future investigations, help you find a job, recruit new collaborators and propel your research forward, so don’t forget to invest in developing this key component to a successful research program.

“The art of communication is the language of leadership.” James Humes




Novella Guidi, PhD
ISEH New Investigators Committee Member

Postdoctoral Fellow
University of Southern California / Leonard Davis School of Gerontology

Thursday, March 9, 2017

Making the Leap, Part 3: Second Interviews

For academic research institutions in the United States and Europe, it is common (though not an absolute rule) for faculty interviews to feature two separate visits. The first interview, covered in part 1 and part 2 of this series is typically offered to multiple candidates for a position. It offers students, faculty, division and department heads and other stakeholders at the institution an opportunity to get to know each candidate and evaluate strengths and weaknesses, as well as their “fit” within the particular program, based on individual discussions, a seminar, chalk talk (usually), lunches, dinners and other interactions. Depending on how many candidates are invited, the initial interview process can take weeks to months to resolve from broad public searches geared toward interdisciplinary positions or simply premised on casting a wide ‘net’ to see what sort of talent emerges. In other cases, positions are created and tailored to attract specific individuals. If a single top candidate has been identified from the first interview, then the second visit is most often geared toward recruitment with the intention of making an offer. Where multiple candidates have been identified from the first round, the second visit may be geared toward further evaluation of each of the finalists. The latter format is very common for European institutions.

During my faculty search, I was invited back to three of the seven institutions at which I’d interviewed, and all three institutions presented draft offers either at the interview or shortly thereafter. This is not always the case (such as when the institution is still deciding among more than one finalist) and you should feel free to ask about where the institution is in their decision process. Later in the series, we’ll discuss issues related to evaluating offers and negotiating startup packages. Here, we’ll go over some key points on how to maximize the amount of information you obtain in your second visit.

Wining and Dining (and A Lot of Work)
By their very nature, second visits for faculty positions can have a distinctive feel about them. Since the weeding out has essentially already happened, if you are offered a second interview is a very strong indicator that an institution has zeroed in on you as being one of their top choices for a position, if not the top choice. There is less emphasis on you proving yourself to the institution, and more on evaluating how you and your program would fit with that of the rest of the program faculty and the institution demonstrating why you should accept an offer there. This doesn’t mean the interview visit is trivial or easy in any respect; you have much more homework to do beforehand, because it goes without saying that beyond the wining and dining and liberal use of the word ‘collegial,’ by your potential future colleagues, you each need to begin the process of coming to an informed decision on whether that institution is a correct fit for your needs and research goals.


Make a Wish (List)
If you have not already done so beforehand, make a ‘wish list’ that contains both the essential equipment and resources you need to conduct your current line of research, as well as those you may need based on any new direction(s) your research program may go. The goal is to have a set list of equipment and resources that you need to successfully carry out your research program, including microcentrifuges, freezers, tissue culture hoods, flow cytometers with specific capabilities, 96- or 384-well qRT-PCR machines, microscopes and the like. It should also include more run-of-the-mill common items including cold rooms, fume hoods, ice machines, ultracentrifuges, and bacterial shaker incubators. The purpose of the list is to identify your needs to the faculty handling your recruitment; they in turn can (if they’re doing their homework) tell you if someone else already has these items nearby, where those equipment items are, and whether other labs can use them. This could save you from spending startup money on redundant capital resources. This ‘shopping list’ can help you to look for items near your lab space during the visit itself (and can utilize when you actually start your lab), and provides both you and the institution a detailed picture of what your startup needs are, which in turn will form the basis for future negotiations that determine the size and shape of the proposed startup package. I also put together a spreadsheet that contained my projected needs in terms of personnel and core facility usage. Once again, the goal is to provide the institution with as clear a picture as possible of what you need to be successful. I sent these lists to each institution, by their request, prior to the second meeting. Their responsiveness to the list in terms of crafting the startup package varied, which is something that I will touch upon in future posts.


Maximize your meetings
At this point you need to be thinking seriously about what a career at the institution will be like, so you can make an educated decision. Consider your second visit a fact-finding mission. Do you use animal models? Ask to meet with the head of the vivarium facility and get a tour. Find out about per diem costs and space for the number of animals you expect to require in your first five years. Ask questions to evaluate how compatible your current experimental approaches are with institutional animal care policies and resources. Ask about what pathogens are excluded or included in SPF facilities. Find out how well the IACUC works with researchers and how protocols are evaluated. Do you use flow cytometry? Ask to meet with the director(s) of the facility. Find out more about the analytical and sorting instruments available, how much they cost to use, whether professional operators are provided (or required), and ask to see recent schedules to find out how open instruments are. Same strategy goes for genomics and sequencing, microscopy, pathology, transgenic animals or any other specialized facility you absolutely require for your work. These meetings were crucial for me to identify areas where I may need to enter negotiations to ensure my work would be successful. In one institution, the only user-friendly sorter available was tucked away in a BSL3 facility, where it was never used. My conversation laid the groundwork for a decision to relocate the sorter outside of the facility if I accepted the position. In another case, the per diem charge for animal housing at one institution was over 35% more than that of any of the others. My startup offer was eventually enlarged to compensate. Lastly, you may wish to ask what personnel costs are at the institution, with benefits included. Institutions vary somewhat widely in how much technicians, graduate students, and postdocs cost and their associated fringe rates. Indeed, simply because a postdoc salary is pegged to NIH rates doesn’t mean benefits packages are entirely the same. Based on the information I obtained, I made a spreadsheet detailing projected personnel and core facility resource costs for the first five years (typically referred to as the ‘startup’ period) of my position at each candidate institution. This allowed me to directly compare between them, and was useful for downstream negotiations.


You can also ask to meet with faculty with whom you may be interested in collaborating. Such meetings can be worthwhile to gauge their interest and perhaps lay general groundwork for such interactions. You may also want to meet or begin identifying potential mentors, as well as obtaining more detailed information from department heads about the tenure process, including requirements for tenure and promotion, the standard timeline for progression and how you will be evaluated during the process. The mentorship issue is particularly important if you have a career transition award that requires a mentoring committee with a certain mix of expertise, but is also relevant regardless - setting up a lab is challenging, and you will need dedicated mentors who provide you with the assistance and insight required to do the job well. The ultimate goal is to leave your second visit with a reasonably solid idea of who your potential mentors and collaborators will be, and importantly, how well set up the institution is (in terms of resources and expertise) to serve as a platform for your research program. Being the first experimental hematologist to set foot in an institution could mean more time is needed to establish protocols that may be second nature somewhere else. The reverse (and equally important) side of the argument is that if you are the fourth or fifth faculty member with the same expertise, you may find your lab is quicker to be up and running, but the internal pool of collaborators who could make use of your expertise (e.g., your ‘uniqueness’) may be less robust.

See Your Space
During a second interview visit, I also made sure that I was given a tour of my potential lab space. It may sound silly, but I wanted to be certain it was actually there, and available for me to move in. Beware of “this space is similar to yours” or  “I’m sure Dr. X will be moving from his/her space in time for you to start.” Such phrases may indicate that lab space is not currently set aside for you, and this may require some additional negotiation and work later on to ensure you aren’t thrown into a dark basement corner upon signing your letter. On those same grounds, be absolutely certain there is office space near your lab space that has already been identified and allocated for the position. It should be no trouble for the faculty member spearheading your visit to show you these locations and to be forthright about their status. Keep in mind that ultimately, verbal promises (and sometimes even offer letters) from individuals at the institution are not necessarily binding. Do not take a verbal promise as a definitive ‘yes’ on anything, as you may find such promises have no weight once you’ve signed a formal offer letter, particularly if that information was not included in writing.


A Key Opportunity
Altogether, second visits such as these are really your golden opportunity to educate yourself as much as possible on whether the institution really is the great fit you thought it was after your initial visit. You will have met more faculty, core facility directors, and you will undoubtedly have follow-up meetings with the department, center or division head(s) managing your recruitment where they might well show you the draft of your startup package, which you will subsequently receive as a written document. Through it all, stay engaged, listen and ask questions, particularly if you are being shown a draft offer. Do not make commitments you can’t (or eventually won’t) want to keep. It may seem awkward, but you can comment positively and feel enthusiasm about an institution without making a commitment to start your lab there. I was also open about what other institutions I was considering, and if I had a concern about a resource or core facility, I was equally open about it; expressing concern and/or being affirmative about an issue of importance to the success of your research program and career, and being polite and respectful are not mutually exclusive. In fact, I personally found (and still find) that being genuine, rather than cagey or insincere, was the best strategy to approach these discussions, both in the second visit and in the negotiations that followed.


In the next post, we’ll discuss issues relating to family, including addressing the ‘two-body problem’ for dual-career couples.





Eric Pietras, PhD
ISEH New Investigators Committee Member
 
Assistant Professor
Division of Hematology at the University of Colorado Anschutz Medical Campus
Aurora, CO, USA


Thursday, February 23, 2017

Superwoman doesn’t exist- qualities of a successful woman in science (and why they help with success).

Superwoman woke up at 5am. She’d been up most of the night feeding and settling her three-month old baby, but she didn’t really need much sleep, did she? She jumped out of bed and got ready for her gym session (despite being Superwoman, those last few pounds post-baby were proving difficult to get rid of after having her fourth child).

After the gym, she returned home to get the older children fed and ready for school. Her husband, Superman, was heading off to save the world again, so she took care of most things on the home front. After seeing the three oldest safely to school and taking the youngest to childcare, she made her way to the lab to start her work day.

Another busy day-- It was grant season, and she was putting two in this round. She also had a manuscript to submit, two manuscripts to review and a draft of a PhD student’s thesis to finish reviewing- they were going to discuss it this afternoon. In between, she needed to pump milk for her baby every three hours, catch up on some of the lab’s recent data in lab meeting later in the morning and attend a number of different meetings associated with her various leadership roles at the University. Then she had to prepare her seminar for next week.

She read her e-mail while drinking her coffee. Two more manuscript review invitations had arrived since she first glanced at her e-mail from home this morning- she couldn’t really say no, she knew how hard it was to get good reviewers to accept these invitations. There was also an invitation to present at an international conference (I will have to either take the baby with me or wean her prior to attending, she thought). She also had to complete her COIs for the grants allocated to her study section (only 150 grants this time…not too bad).

Not long into her e-mails a call came from childcare. Her baby was very unsettled and it might be easier if she took her home. No problem, she just Skyped in for her meetings and juggled her work from home, all while settling the baby at regular intervals. She managed to get everything done in time to pick the children up from school, help them with homework, settle some sibling disputes, and play with the baby for a while. She even had enough time afterwards to cook a gourmet three-course dinner to share with Superman after his very busy day (the children were still fussy with food, so she cooked them separate meals).

After bathing and putting the kids to bed for the night, she snuggled up to Superman on the couch, listening intently as he told her all about his day saving the world. After relaying his latest achievements in keeping the world a safer place, he asked her, “And how was your day, dear?” “Oh, it looks like we found a cure for cancer today” she murmured satisfactorily. “Excellent, dear, excellent...” replied Superman “and what are your plans for tomorrow?”.

If only we could all be Superwomen but the reality of it is that Superwoman doesn’t exist (nor does Superman for that matter!). Household equality is improving and women are gaining traction in professional settings. Although this old-fashioned view of the woman who does it all is evolving, there are common qualities that do significantly help to make a woman super successful in her career (regardless of whether or not she has children). Much can be learned from those ladies that pushed their way to the top of their scientific fields and refused to take “no” for an answer. They don’t possess superpowers, but do share common attributes of successful men and women. Recently, Stephen Sykes (Assistant Professor, Fox Chase Cancer Center) along with other members of the New Investigator’s committee, wrote a great piece for the January/February ISEH Connections entitled “Combating Gender Disparity in Academic Science.” It is a great scholarly piece providing a broad perspective on the current state of gender equality across the world and what scientists are proposing to do to make a change. Here, we will discuss some of the characteristics that help women (and men) succeed in their scientific career.

Ambition
Ambition is the desire to accomplish something requiring determination and hard work. Graduate and medical schools are filled with determined and hard working individuals who strive to push the envelope and make a difference. Ambition is a feature shared by most scientists, male and female, junior and established. However, ambition alone is not enough - the keys to successfully achieving your ambitions and reaching your goals resides in the characteristics listed below. Furthermore, if your ambition outweighs your willingness to work hard and achieve excellence then desire alone will not be enough to achieve your goals.


Vision/Goals
From childhood, people talk about what they want to be, and what they want to have when they grow up. This announcement marks the beginnings of desire, a stepping stone to ambition, but success only comes when you have a true vision for what you want to accomplish. Connie Eaves, Distinguished Scientist, Terry Fox Chase Laboratory, past ISEH president and the next Editor-in-Chief of Experimental Hematology (the first woman to ever hold this post) shared this hint: “be realistic about your goals, recognise and accommodate your constraints. Aim to achieve what you need to feel successful (fulfilled/happy) on all fronts.” (Note that if your goal is to be awarded a Nobel prize, you will likely never be happy with your career achievements!)”. Pamela Stanley, Professor and Horace W. Goldsmith Chair, Albert Einstein College of Medicine, also shared her perspective, “Successful women take the long view, pick their battles, speak up so their presence is felt, and persevere in the face of difficulties. In addition, successful women are very flexible, patient and manage their time well. Being flexible and resolute in the face of mini-catastrophes are key qualities for long-term success.” Being highly organized is one way to keep your sanity and achieve your goals. Try not to leave things to the last minute to complete as often something unexpected will come up and disrupt your schedule!


Passion
Hopefully passion is one thing that everyone has for her/his chosen career. Yet many people do not openly share their passion for what they do with others, potentially in part due to other issues such as confidence (discussed further below). Don’t be ashamed to show your passion for what you do- it will often get you noticed by your peers and by those in more senior positions to you. It could lead to career opportunities that might not otherwise be as forthcoming, especially in the junior stages of your career.


A scientific career is like a rollercoaster- full of ups and downs, and while it is also a rollercoaster for men, the downs can be steeper for women (see section on confidence below). Passion also contributes significantly to your inner strength, and can be a major force in helping you to survive those tough times, when the rollercoaster is in a sharp decline.

Persistence
Nothing worth having comes easy. Ambitions can only be achieved with persistence and a strong work ethic. Scientists are trained to deal with failures -- like when your single-cell RNA-seq library prep fails the first (or twentieth) time or your long-term cultures become contaminated just days before your final analysis. We are taught how to troubleshoot these technical things from the time we learn how to pipette, but knowing how to respond when your paper is not accepted or your grant is not funded, takes a bit longer to learn. Self-confidence and persistence are just as important to overcome these career hurdles. Margaret “Peggy” Goodell, Professor and Director of the Stem Cell and Regenerative Medicine Center, Baylor College of Medicine and past president of ISEH, shared a story to illustrate this point: “For example, an editor of a well-respected journal in the field once told me that according to her statistics, women senior authors were less likely to rebut a “reject” decision than their male counterparts. I realized hearing this that perhaps I should also be more assertive in defending my work from negative reviewers. This did embolden me to, on occasion, argue an editorial decision. From my experience as both an editor and an author, I can say this rarely works, but it does on occasion. So, the lesson is “know thyself” and try to counteract your own weaknesses. In this case, I learned to do a better job in defending my lab's work.”  Dr. Stanley also commented that, “As a woman trying to juggle a lab of graduate students and postdocs, teaching and administrative responsibilities, and family life, I have found that so many things do not go as planned: trainees have personal and family problems, motivation flags, people -children, babysitters and lab members- get sick, cells get contaminated; Just when a project is going well, the lead researcher decides to leave. Being calm and determined has really helped me. For example, some time ago two colleagues told me they were way ahead of us on two different projects. In each case, my lab ploughed ahead anyway and we managed to publish before each of them! That was very fortunate and satisfying of course, but also a good lesson for me, and my trainees, to keep our eyes on lab goals until they are achieved.”


Perseverance
Life, as in science, doesn’t always go as planned. Dr. Eaves shared her story of bias and perseverance that turned into a blessing: “I was accepted as a postdoc at the Ontario Cancer Institute by Dr. E. A. McCulloch coming from a Ph.D. in Manchester on the basis of references, my academic record and publications. It did not occur to me that being pregnant might be an issue. My arrival two months before I was due, clearly elicited a huge surprise, and an immediate change in supervisor to Dr. J. E. Till. Thereafter, I worked closely with both, but my intellectual proximity to Jim was a wonderful gift and it influenced much of my approach to science thereafter.” Despite the potential for setback, Dr. Eaves embraced the change and pushed forward with her science. The takeaway message is to not let small (or large) slights knock you off course. What may initially be seen as being a negative (or less welcome) step in your career most often turns into a huge positive, especially if you embrace it and let it become one. In Dr. Eaves’ own words- “Do not take ‘no’ for an answer- turn it into a challenge or an opportunity.”


Confidence/Inner Strength
In order to persevere, one must be confident. While self-reflection can be good from time to time for personal growth, self-deprecation is a sure path to failure. Eleanor Roosevelt said it all when she stated, “No one can make you feel inferior without your consent.” The sad truth is that when comparing women to men, one of the biggest differences is that women often lack the confidence (or will be less likely to pretend to be confident) of their peers. One example of the difference in confidence between men and women is the disparity in the number of female applicants for faculty positions. In a 2010 study by the National Research Council, they found that women make up less than 20 % of the applicant pool for faculty positions1. This number is in stark contrast to women receiving nearly 50% of STEMM doctorate degrees2.


While others can boost your ego, true confidence needs to come from within. Be aware of the imposter syndrome, the fear of high-achieving individuals of being exposed as a "fraud". Believing in yourself, and not being afraid to show that you are confident in yourself and your ability will do wonders for your career. Having said that, there is a difference between confidence and arrogance- know what the difference is and aim to be the former and not the latter! Emmanuelle Passegue, Professor and Director of the newly-formed Columbia Stem Cell Initiative, Columbia University Medical Center, places ‘confidence’ as one of the top qualities of a successful woman in science.

Related to confidence is the ability to handle constructive criticism. No one likes criticism, but internalization of harsh critiques can destroy your self-assurance (or what remains of it). As mentioned above, “know thyself”, don’t let others dictate who you are or where you take your science. Read grant and/or paper critiques, listen to mentors’ advice, but don’t let any of it tear you down. Take what is constructive from the comments and leave behind the parts that feel like personal attacks. Dr. Goodell noted that, “Tenacity and pride are important, and women are more likely to be self-deprecating and internalize harsh scientific criticism, rather than fighting for what they really believe. This manifests in various ways that can slow women down.”  Remember the phrase “What doesn’t kill you makes you stronger” applies to your research career just as much as in life!

Ability to delegate or say “no”
This characteristic is less often discussed, but it can slow down your career just as critically: the ability to delegate, or even saying “no” (which in turns delegates the job to someone else) is a key attribute of a successful scientist. Women have a tendency to think they can and should do it all (see superwoman story above). Successful women do not do it all themselves, they learn to delegate. Ana Maria Cuervo, Professor and Robert and Renee Belfer Chair for the Study of Neurodegenerative Diseases, Albert Einstein College of Medicine, notes, “For many women, “delegating” equals asking for help because we are not able to do something, when for most men it means a sign of leadership. Most of us, still feel this need to show that we are able to do everything ourselves to avoid being perceived as weak. Unfortunately that ends up with us doing double or triple the work, and eventually may impact on our overall productivity (there are only so many hours in a day….).” Learning to delegate and lead at work and at home will lead to a more productive and likely more fulfilling career. Sharing tasks allows you to focus on the things that you need and want to do, rather than extra work that just needs to get done (it also helps others develop their own skill set!).


One final note of advice is to seek out mentorship. Having a great, supportive mentor (male or female) is something that can assist you in your career development and achieving your goals. If you do not have a mentor or even if you do but feel you could use another perspective, reach out to someone you feel you would learn from and ask them if they would mentor you. Not everyone is the mentoring type (and no one has the time to mentor an extensive list of mentees) but there are many people around who would make excellent mentors. Mentors can help you find the tools and the path to achieve your vision and fulfil your passion.

These lessons are not restricted to women. To succeed, one must be confident, ambitious, and persistent to accomplish your vision. Stay away from self-deflating habits, and learn to “lead” rather than only “do”. One take away from interacting with the successful women for this piece is that we are not alone. Weaknesses are human, but recognizing, learning, and growing from life lessons helps us to counteract those weaknesses and thrive. Dr. Eaves noted one last thing to always remember, “Keep a sense of humor” – that is good advice for life and career!

We would like to thank Drs. Connie Eaves, Peggy Goodell, Pamela Stanley, Emmanuelle Passegue and Ana Maria Cuervo for taking the time to share some of their opinions (and anecdotes) on qualities of successful women in science and Drs. Trista North and Eirini Trompouki for their thoughtful comments on the piece.

For our next session we have the opportunity to ask Prof Connie Eaves and Prof Thalia Papayannopoulou about their journeys in research, including how to thrive in a two-scientist household. We are encouraging you to submit any questions you might wish to ask them for us to pass on to them to answer. Please submit your questions to Louise (lpurton@svi.edu.au) or Teresa (teresa.bowman@einstein.yu.edu) by the 9th of March. Be proactive- this is a great chance to learn from two of our most prominent senior female researchers in the hematology field!
  1. Council NR. Gender Differences at Critical Transitions in the Careers of Science, Engineering, and Mathematics Faculty 2010.
  2. Shen H. Inequality quantified: Mind the gender gap. Nature. 2013;495(7439):22-24.



Teresa V. Bowman, PhD
Publications Committee Member
Former Chair, New Investigators Committee


Assistant Professor, Department of Developmental & Molecular Biology
Assistant Professor, Department of Medicine (Oncology)
Albert Einstein College of Medicine
Bronx, NY





Louise E. Purton, PhD

Associate Director, St. Vincent's Institute of Medical Research
Co-Head, Stem Cell Regulation Unit 
Associate Professor, Dept. of Medicine SVH, The University of Melbourne

Melbourne, Australia







Thursday, February 9, 2017

Navigating Career Development Awards

For young scientists on the brink of independence, attaining a career development grant can be pivotal for a successful job search.  Establishing a trajectory of external funding early in your career demonstrates not only your capability for grantsmanship, but also your ability to navigate funding opportunities.  In some cases, a career award can bring you to a specific institution or even (back) to a specific country.  It also provides you with an unparalleled opportunity to scope out and define the pathway(s) for your future independent research, and lay out a tentative plan that will prove invaluable when you prepare research statements for job applications. 

Although it is arguable that scientists these days spend too much time writing grants, there are definitely benefits to the process. Grant writing provides the rare chance to catch up on relevant literature, formalize research objectives, and think about future directions.  This is particularly true for young scientists, who still spend the majority of their time at the bench.  While many young scientists may have had some experience with grant-writing that involved collaborations with their mentors, writing a career development grant often represents one of the first times that this endeavor is taken on independently.

In this article, we have outlined a few things that we found helped the process of writing and applying for a career development award progress relatively smoothly.  We also include tips for submitting a successful application.

Identify Opportunities
Many funding opportunities exist, and your first goal is to find the opportunity that is the right fit for you. The best starting point is to search granting agencies in your country (or the country you plan to move to) and determine what career development programs they offer.  Ask fellow colleagues or mentors about their experiences attaining career development funding (they may even be willing to share their successful application with you!). Find out if your institution or neighboring institutions offer workshops for identifying and preparing career development awards. Search for funding opportunity databases and check if your institution has a http://pivot.cos.com subscription. Note funding that is listed in the acknowledgement slides of talks at meetings.  Keep your eyes open! Funding opportunities may also be available from non-government and private agencies but may take a little more legwork to find.

Start early
This is the most important point of all. If you start early, you can put a lot of thought into the structure of the proposal before you start typing a lot of text or get overly committed to a specific line of investigation or approach. You’ll have time to search the literature and revise the proposal based on feedback. Research your particular funding opportunity and be sure to identify all of the required components and any specific eligibility requirements.  It is good to inquire about reference letters and scientific advisory committee participation early, as last-minute requests can be viewed as inconsiderate by senior investigators. It may even be advisable to plan some time “off” from experiments to focus on grant writing.

Make a checklist
Many career development awards involve a lot of “bits and pieces”.  Navigating the guides to these proposals is not always straightforward, so staying organized is instrumental.  Make a checklist of all the required components to keep track of your progress towards the deadline (K99 example: http://bit.ly/2hLzRCU).  Depending on your institution, you may be able to get help from administrative staff or grant coordinators.  If one of your colleagues has submitted a similar application before, looking at their example can be particularly helpful (especially if it was awarded!). Some components may need specific input from your current PI and/or collaborators, so remember to provide sufficient time for them to schedule work on your application as well.

Ask for advice
It is extremely useful to assemble a “reading committee”, a few fellow postdocs or faculty mentors who provide critical feedback. It is helpful if you can plan a meeting where everybody explains their comments, as the resulting synergy and discussion will often pinpoint what you should focus on to improve the proposal. Ideally, this meeting would occur a month or more before the deadline so you have time to make changes.

Identify your own direction

For those at the later stages in their training (approaching independence), it is essential that your grant identify a path for your future research that is distinct from your mentor’s current research.  Depending on what kind of lab you’re in and what you’ve been working on, this may be very straightforward, or may take extra time (see “Start early”, above) and several discussions with your PI to parse out.  It is important that your mentor expands on or clarifies this point in their letter within the grant application package.  Having your mentor delineate their support for your independence can be an significant factor in attaining funding. As mentioned above, this important step can also be fundamental in helping you carve out your future directions as part of a job application.


Assemble a mentoring / scientific advisory committee
For many career development grants, review committees want to see interactions with and guidance from more than just your primary mentor. It is highly beneficial to establish mentoring relationships with people whose expertise will specifically benefit your career trajectory and/or your proposed research, either within your same institution or at different institutions. Are you planning to learn an exciting new technique to investigate your question of interest?  Identify a mentor with expertise in that technique, and incorporate visits to their lab as part of your proposed training.  Are you planning to expand your training into a slightly different field as part of your career development?  Find a mentor that is an expert within that field to guide your training and with whom to discuss your research outcomes. While it may take several tries to get the mentors your desire, making these additional connections will greatly benefit your career in the future.  Additionally, be prepared (and always offer) to provide draft letters for your mentors, specifying their contribution to your career development and/or research proposals.  This will not only save your prospective mentors time (which they will surely appreciate) but will also allow you to craft letters that closely match the focus and aims of your grant. 

Contact your funding source

It is a good idea to reach out to your fellowship office or program officer to seek feedback  as soon as you have a draft of your specific aims. Be sure that the draft or summary page you submit is refined enough to provide the funding agency with a clear vision of your aims.  The purpose for this can be as basic as ensuring that your application is a good fit for the agency, and it also initiates contact.  For example, the translational implications you propose may be a poor fit for that particular funding opportunity, or a National Institute of Health program officer may suggest you submit your application to another institute instead. Knowing these things early on can save you a lot of time.  Once your application is submitted, your contact within the funding agency will be able to answer questions about the review process, and will often be able to help you interpret your reviews after you’ve received them.  They can provide invaluable feedback for your resubmission, since often times they are present during the review of your proposal.

After submission
Hopefully you were funded on your first submission!  If not, read through your reviews carefully and identify areas that the reviewers collectively felt could use improvement. Don’t get too discouraged, as the vast majority of grants are not awarded on the first try. Instead, focus on how you can better shape your application based on the feedback.  Certain areas - like research statements and career objectives - will be easier to re-shape.  Other parts of your application, such as applicant biosketch, may be more difficult -but not impossible- to address directly.  For example, if publication record is a weakness, one might consider waiting until you have published a relevant paper before resubmitting your application.  Your goal is to identify the comments that you can work with, and most importantly, to make sure the reviewers know in your resubmission exactly how you addressed their concerns and improved your application.  Career grant writing is a great opportunity to start honing those perseverance skills necessary to become a successful grant writer and independent scientist! 





Anna Beaudin, PhD
ISEH Publications Committee Member

Assistant Professor
UC Merced




Peter van Galen, PhD
ISEH Publications Committee Member

Postdoctoral Fellow
Massachusetts General Hospital / Broad Institute of MIT and Harvard

Thursday, February 2, 2017

Making The Leap, Pt. 2: Some Strategies for Interview Success

“Eric, I’m going to ask you some hard questions now. Give your nobel prize speech, in 50 words or less. Go.”
-Interviewer at an academic institution


This post is the second in a series relating to making the leap between postdoc to faculty. The goal is to relate some of my insights into the process based on my experience, both then and now, from the other end of the desk. In this post, we’ll explore some strategies to master the main components of interviews: meetings, the seminar and the chalk talk.

Know who you’re meeting with: If you’ve applied to an institution, then it’s a fair bet that you’ve already identified potential collaborators or people of interest who you will want to speak to while you are interviewing. Often (though not always), institutions will ask you if you want to meet with specific people. If they don’t ask you about specific meetings you’d like to have, it doesn’t hurt for you to ask the faculty member or admin handling your visit about some individuals you have in mind. Once your itinerary is settled, it will be forwarded to you. Beyond looking carefully at the details about how you are to get from the airport to the hotel, and from hotel to the interview, note closely the people you are meeting with. Depending on the position and department/division to which you are applying, you may meet almost entirely with people whose work you are familiar with.  It is also likely that you will meet with others who have either identified you as a potential collaborator, or who are stakeholders in your hiring (deans, department and division heads, CEOs or VPs). One interview itinerary for a biology department had me meeting with specialists in raptor behavior as well as inflammation. My industry interview put me in rooms with a physical chemist and a medicinal chemist. Regardless, I looked these people up, read their papers or websites beforehand, and expanded my horizons. Why? The raptor specialist and physical chemist had just as much voting power on my hire as the immunologist. I was probably not going to collaborate with him, but it would be worth knowing about his work, operationally out of respect and ability to have a two-way conversation, but in reality also as a way to learn something new.  Where potential synergies exist with a particular faculty member, it’s worth discussing these in your one-on-one meeting with them. In meetings with deans or department heads, I anticipated that I would be discussing my work with these busy people concisely, from the high-altitude viewpoint, and with emphasis how it would integrate with and enrich their organizational unit as a whole. They were not going to be concerned with my HSC transplantation strategy either during or after the interview. Importantly, if you are interviewing for a position associated with a graduate program, do not underestimate the importance of lunches or meetings with students. They may seem like they’re mostly eager to discuss their work or asking you mentorship-related questions, but keep in mind they are evaluating your potential in these areas and typically report their views to the faculty search committee. As a last point, it’s okay to ask multiple people the same questions. You may think you sound like a broken record, but relating to the first post, it’s a good idea to get multiple viewpoints on key issues relating to the environment and resources integral to your success. Have such key questions composed in advance of your interviews to ensure you aren’t losing key opportunities by making it up as you go along.

A last point to make: academic one-on-one meetings tended to be somewhat freewheeling. They were often centered around potential collaborations or questions relating to the science I do and how it might fit into the department. The discussions largely (if indirectly) related to evaluating my potential as a collaborator, as a citizen of the department, and potential as an independent investigator and mentor. My industry interview on the other hand was highly structured. Individual team members had specific pre-determined sets of questions relating to my ability to sequence projects, problem-solve, identify priorities, deal constructively with superiors, provide leadership to direct reports, and work dynamically on multiple projects. Questions also related to whether I was able to drop a project and move on if required. These questions required me to provide specific examples relating to these topics as well. The interviewers took detailed notes as I talked with them. My discussion with the head of the unit was mostly related to my interest in an industry career.

Give your TED talk: Seminars are actually fun if you are prepared and confident. For the seminar, make sure you have a connection for your laptop and the projector, and your talk on a flash drive.  I remember at least two institutions did not have their own adapters at the seminar room. I also bought my own laser pointer/PowerPoint remote for the same reason; not every institution had a laser pointer in place on the podium. In both cases, these preparations make life easier for you and win optics points for preparation and professionalism. Most institutions also did not have an AV person present to set up the computer. Learning the idiosyncrisies of your machine’s relationship with projection equipment ahead of time could save you from turning your seminar into a second chalk talk, and the flash drive allows you to load your talk onto another computer. Keeping a PDF version on the drive also insulates you from Mac/PC image compatibility issues. Know how to speak into and position both lavalier (clip-on) and lectern microphones before your seminar. Ensure your shoes are broken in and comfortable and have water nearby (avoid placing it where it can spill onto your laptop).

Regarding content, your goal is to get your concepts across, not to describe in depth every supplemental figure from your last publication. Begin broadly, identify the scientific problem and its significance, and do not be afraid to have several introductory slides to get the conceptual framework across. Show key pieces of data, explain complex assays with cartoons, and do the same with the models. In your conclusion, re-address the scientific problem and how your data impact the problem and the field. Importantly, the seminar is not just about your past (or current) work under your mentor. You should spend at least 5-10 minutes discussing what you plan to do next as an independent investigator apart from your mentor, and identify how your work and resources or faculty at that particular institution can synergize. Leaving this part out raises questions as to what you plan to do and therefore your independence. Reiterating from Dan’s blog post, do not assume that everyone at your seminar will be at your chalk talk. People should leave the seminar with a clear idea as to your scientific intent. Keep additional data slides after your acknowledgement slide as a resource. Do not go over time. For my industry talk, what I would do as an independent investigator was a moot point. I spent more time in background discussing the relevance of my work to specific indications where there are ongoing drug development efforts, and discussed at the end how my work and skill set could fit into the company’s interests and lead to initiation of projects for new indications.

Put your ideas on the board: Chalk talks were probably my favorite part of the academic interviews. When else do you get to visit another institution to obtain free advice on your first R01 from experts in the field who are potentially interested in hiring you? For me, this was an exciting opportunity, and the conversations were great. I was challenged, in one case intensely by a faculty member from an institution that later offered me a position. The individual’s critique was legitimate; I kept my cool, acknowledged that the questioner was correct, and offered my appreciation and ways to strengthen the approach. Many of the suggestions and critiques I received at chalk talks have since been extremely useful. Some other points: remember how I mentioned packing my own dry-erase markers in part 1 of the series? Fully half of the chalk talk rooms had no markers, off-colors (brown and orange in one room) or non-working markers. It was an easy optics point to score with faculty who were saved from having to scramble to find markers. Copies of your research prospectus and/or a one-page summary of your aims (preferably with a good conceptual cartoon) can also be of use; I brought copies of the former to my chalk talks and left them near the door for faculty who were filing in. Importantly, if your itinerary does not include 10-15 minutes to prep the chalk talk board beforehand, ask for it. This allows you to get your overall aims/subaims or themes, and maybe a conceptual diagram, up so that you can spend more time talking and less writing. I kept a notepad with my chalk talk talking points mapped out as a sort of scratch pad for ideas, but rarely used this during the chalk talk itself. Make sure you also know how to write legibly on a dry-erase board. Chalk talks will also range in attendance. Attendees to mine ranged from two faculty to about twenty faculty, postdocs and graduate students. Chalk talks at industry interviews are largely atypical.

If you are generally nervous giving seminars or chalk talks, practice and build confidence beforehand. Since becoming faculty member, I have been in faculty meetings where excessive nervousness during a candidate’s talk was mentioned as a potential issue by some of my colleagues. When you are comfortable, invite faculty at your current institution who are known to ask tough questions and not back down to these practice talks. Learn how it feels to be under pressure and you will gain confidence in dealing with it without becoming either defensive or downtrodden.

Taking questions: A key point for every component of the interview process—don’t answer questions impulsively without understanding what is being asked. Paraphrase the question back to the questioner if needed. It gives you time to think it over, and ensures you have processed the question. If you aren’t sure what is being asked of you, politely ask for clarification. Once you understand, then proceed to offer an answer, and keep it to the point. The question at the top of the post? It was less asking for something beginning with “Your Majesties and distinguished guests” and more about soliciting a succinct, 30,000-foot view of my research program and its importance. Taking the time to figure out the intent of the question is the antidote to stumbling over words in front of people making a decision about hiring you.

Plus, real Nobel speeches are always more than 50 words.

Coming up in the third part of the series, we’ll discuss second interviews and starting the process of choosing an institution.





Eric Pietras, PhD
ISEH Member and Simply Blood Contributor 

Assistant Professor
Division of Hematology at the University of Colorado Anschutz Medical Campus
Aurora, CO, USA


Thursday, January 26, 2017

Making The Leap, Pt. 1: Interview Preparation

“Hm. Here’s my suit…now where’s my belt??”
-Me, at the hotel getting ready for an interview

During my job search in 2015, I interviewed at seven academic institutions and one biotech company. In the end I was offered positions at the company as a scientist and at three universities as tenure-track faculty. Each interview was its own unique story. One interview location was a long morning haul to the institution via rental car for a first-thing-in-the morning seminar. A blizzard during a different interview left me stranded in the town the day before I was supposed to fly to Keystone for a conference. The biotech interview was nothing like the academic interviews. Ultimately the process was certainly intense, but also fun and extraordinarily valuable for a young scientist. It’s your first chance to essentially ‘go on tour’ with your own scientific identity. This post is the first in a series relating to making the leap between postdoc to faculty. The goal is to relate some of my insights into the process based on my experience, both then and now, from the other end of the desk. Importantly, if you’ve not read Dan Lucas’ and Isabel Beerman’s posts on academic interviewing (Part 1 and Part 2) they are a fantastic resource and go into great detail on how these interviews are structured. In this first segment, I’ll discuss some logistical strategies and basic principles to keep in mind as you prepare for the interview.

What to bring: Packing for an interview has a few subtleties. Forgetting something, whether it’s an item of clothing or your laptop, is a confidence-killer. You should assume that you won’t have time to replace items you don’t bring. You should also remember that if you are flying and have everything in a checked bag, there is a small (but not insignificant) chance your bag will not be on a carousel. I kept my laptop and power supply, remote/laser pointer, notepad, dry-erase markers, and video adapter in my carry-on shoulder bag, along with a pair of trousers, tie and button-down shirt just in case. The unappetizing thought of showing up to the next morning’s interview in jeans and a t-shirt and having to explain why all day made this a sensible move. Also, regarding clothing, go business formal. It’s a matter of respect and professionalism. I wore a suit the first day, for the second day I dressed down slightly to what I had in my shoulder bag. For second interviews, I ditched the suit but still kept it professional. I also learned how to properly fold those items into a bag to minimize wrinkling. At one interview, I arrived at the hotel at midnight local time and needed to be up at 6 am the next morning and drive to the interview, hopefully beating a blizzard in the process. Half an hour of ironing would not constitute a good use of my time. Lastly, cases where you need to do your own driving (as was the case for two of my interviews), have a smart phone with GPS (or a stand-alone GPS device) and a charger handy and be sure you know where you’re going.

Basic survival: Interviews are fun, but also intense. Most of mine lasted one full and one half day, with the flight in the afternoon before, and flight out the afternoon of the second day. All first visits had a seminar the first day. All but two academic interviews had the chalk talk on the second day of the first visit; one had the chalk talk directly after the seminar, and one had the chalk talk during the second interview. You will likely have no time to yourself from about 7am to 9pm on the first day of the interview. You will also likely not have time or ability to finish meals; they are often with students (typically at lunch) or a faculty member or two, and are conversation-heavy. On interview days, I kept energy bars and a bottle of water in my shoulder bag to keep hydrated and fed. Also: at the height of the process I was traveling roughly 3 of 4 days per week for over a month. Depending on your schedule you may need to temper your expectations of what you can accomplish back in the lab. Also consider your need to stay physically and mentally healthy. Illness, fatigue and interviews do not mix well.

Optics matter: Hires are made not just based on your scientific acumen. You were invited because the faculty hiring committee found your CV to be interesting. Now they have the opportunity to see whether they want to work with the person behind the CV. How you come across during the interview process, ranging from how you handle the initial contacts to the travel logistics to your interaction with every student, postdoc, technician and faculty member can impact the outcome of the interview. Respond promptly and precisely to emails from individuals at the institution regardless of their position. Be respectful of everyone you meet. During your talk and chalk talk, respond respectfully to questions, even if they are either off the mark or aggressive. At meals, mind your manners, and do not over-imbibe. The bottom line is to be yourself (appearing insincere or inauthentic is an easy disqualifier), but maintain professional standards of conduct at all times so you don’t become their ‘worst interviewee ever’ story instead of their next hire. Avoid discussing potentially polarizing issues outside of science, and remember that issues like spousal hires, real estate, startup package and the like are usually better left for second interviews, when the institution is moving to actively recruit you and is ready to consider such matters. Conversely, questions from faculty or other interviewers related to your family and marital status, religion, race, medical issues and/or gender are often illegal and as such you need not provide an answer. Lastly, and importantly, when the interview is finished it’s probably worth it to individually thank via email each person you met with, as well as the admin(s) who took care of the logistics. It is to me a matter of respect for their time and efforts on my behalf, and in nearly every case elicited a response, always positive. I typically drafted these on the plane ride home so they were sent in a timely manner. Such emails also open the door for further correspondence if you didn’t get to ask a key question.

Interviews are not a one-way evaluation: Interviewing for positions in a highly competitive job market should not interfere with the important point that you should be evaluating the institution just as much as they evaluate you. Are their people (particularly recent hires) happy, productive and well funded? Are their research facilities cutting-edge and in good order? Did the interview seem well organized or slapped together at last minute? Did you like the people whom you met? Were your seminars and chalk talks well attended? Did departmental/unit leadership seem interested in you and your work? Did the students and/or staff appear of high caliber? Are the potential collaborations promising? Do they have what you need to set up your research program? Good mentorship, availability of qualified students, technicians, postdocs and clinical fellows to staff your lab, good faculty collaborators, balanced teaching loads, appropriate resources for your research program and evidence of institutional and departmental support for faculty are critical for the success of new investigators. These are important areas that you should make a point to ask about, and to ask multiple people for their input. During a Skype pre-interview, I declined an in-person interview invitation after finding out about a lack of proper sorting facilities; likewise, I found out that another institution didn’t have appropriate mouse facilities and offered no teaching protection for faculty during their first year. These were both dealbreakers for me, and it was better to find out at the first interview than on day one of my faculty job. The bottom line is that as much as you want the institution to love you, you need to love them back in order to have a productive career there.


Coming up in the second part of the series, I’ll discuss some insights into how to approach one-on-one meetings, seminars and chalk talks during job interviews.



Eric Pietras, PhD
ISEH Member and Simply Blood Contributor 

Assistant Professor
Division of Hematology at the University of Colorado Anschutz Medical Campus
Aurora, CO, USA

Thursday, January 19, 2017

2017 ISEH Journal Club: Q&A with Jeff Bernitz

The New Investigators Committee is excited to announce a new ISEH Journal Club for 2017. We will be starting with an exciting publication by Jeff Bernitz, Kateri Moore and colleagues, entitled Hematopoietic Stem Cells Count and Remember Self-Renewal Divisions, recently published in CELL.
 
This first ISEH Journal Club will run 23rd-30th January. During this time, Jeff Bernitz will be answering any questions you have about the paper on the ISEH Facebook page. Please join the ISEH Facebook group, post your questions and join the discussion!
 
To help introduce this paper and start the discussion, we conducted a Q&A with paper’s first author, Jeff Bernitz. Jeff is a current PhD student with Kateri Moore at the Icahn School of Medicine at Mount Sinai.
 
Question 1. What are the key findings of your paper?
Jeff: I think there were several key findings in the paper, but in the end these can be boiled down to two. The first is that cells within the HSC compartment are capable of maintaining a record of their divisional history, and this impacts on both their future regenerative potential and cell cycle progression. This memory also appears to instruct how HSCs accumulate with age. The second is that the stem cell compartment is heterogeneous, with the minority of these cells possessing LT-HSC function, and this is especially true when considering the aging HSC compartment. I think this is something that the field already knew, but what is nice about our work is that we were able to show that this functional heterogeneity can be correlated to divisional history.
 
Question 2. What was the motivation for this line of research?
Jeff: I wish I could say that there was a direct line of logic that motivated the work, but the truth is the study came together largely out of serendipity. A previous graduate student in the lab had placed 30-40 of our label-retaining mice on doxycycline, but never analyzed the mice before she left. This left us with several cages of mice that had been on dox for 9-12 months by the time I started. When I came into the lab I initially didn't have a project, so my first task was to analyze some of these mice that had been on dox for over a year just to see if we could find any label-retaining cells left in the HSC compartment. Of course, we were surprised when we found label-retaining cells after a year on dox, so we started doing transplants and the study slowly began to evolve and reveal itself to us from there.
 
Question 3. In your opinion, how will your story impact the blood field? What new questions does it open up?
Jeff: I hope the story will get people to begin considering how divisional history may play a role in defects associated with drug treatments, stress, and (in our case) aging. I also think that a major implication of our work may extend to understanding HSC expansion for clinical use. The field has been attempting to expand stem cells ex vivo for decades, but has been largely unsuccessful. I think our work provides clues as to why these efforts have not worked: divisional history directly relates to HSC regenerative potential, and the more a cell divides the less regenerative potential it contains. Thus simply forcing HSCs to “self-renew” may not be possible. Obviously this opens a Pandora’s box of questions on how HSCs maintain their divisional history counter, and by extension how we can reset this memory to aid in expanding HSCs without sacrificing function.
 
Question 4. Are there members of our ISEH community that contributed to the context for your paper? How did he/she contribute to your research question?
Jeff: Yes, there are several. Isabel Beerman and Derrick Rossi demonstrated nicely that increasing HSC divisional history via serial 5-FU injections induces several cellular and molecular changes associated with aging HSCs. This work was followed up on by Dagmar Walter and Amelie Lier from Michael Milsom’s group, where they demonstrate serial rounds of pI:pC induced proliferative stress leads to DNA damage accumulation in HSCs, which in the context of Fanca-/- mice results in a premature aging phenotype associated with Fanca mutations in humans. Together, these studies showed that the accumulation of divisional history may underlie several defects associated with HSC aging. Additionally, Ryo Yamamoto and Hiromitsu Nakauchi showed that the phenotypically identifiable HSC compartment contains cells that, upon transplantation, only generate myeloid cells. This work directly inspired our limiting dilution transplantation studies in the paper. As it is known that myeloid output from the HSC compartment increases with age we wanted to see if this was in part due to an over-representation of myeloid-restricted progenitors, and whether these cells correlated with an extensive divisional history.
 
Question 5. Who would you particularly like to read your paper?
Jeff: If I could have anyone read the paper, that person would be Christa Muller-Sieburg. I worked in Christa’s lab as an intern during undergrad, and my time in her lab heavily influenced how I view and interpret HSC research. In some ways I feel this directly contributed to how our paper came together. Her husband, Hans Sieburg, collaborated with us on this work, and both Teri and I view the paper as the culmination of my time and experiences between the two labs. Christa had one of the most beautiful minds I’ve ever seen. When we had journal club and lab meeting, she would pick out flaws in logic and reason that no one else perceived. She was sharp as a knife. I would particularly like her to read the paper, in part, because I know she would shred it to pieces – which can be devastating, but in the end I think this makes us better critical thinkers and scientists. Though more than anything, I just hope that the work would make her proud.

Thank you to Jeff Bernitz for kicking off our 2017 ISEH Journal Club.  Please visit the ISEH Facebook page from 23rd-30th January to submit your questions and join the discussion.



Adam Wilkinson, PhD
ISEH New Investigators Committee Member

Postdoctoral Research Fellow
Institute of Stem Cell Biology and Regenerative Medicine
Stanford Medicine
CA, USA