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Discovering meaning in a massive amount of random-seeming data is nothing new to Todd Edwards, PhD, a genetic epidemiologist.  His career has made meaning out of many disparate parts, beginning with six years in the US Army as a Print Journalist, pre-med and biology classes in college, and a job in biotech developing kits to sequence human drug metabolism genes, all of which eventually led to a master’s degree in applied statistics and a PhD in genetics at Vanderbilt.  Or, as he puts it, “I stochastically wandered through life and ended up here.”

“Here” is PI of an R21 investigating genetic causes of high blood pressure in African Americans and co-PI of a U01 examining calcium-gene interactions in colon cancer, as well as a strong collaborator with his wife, Digna Velez Edwards, PhD, working to understand the genetics of uterine fibroids.  As if that weren’t enough, he is also the Associate Director of Graduate Studies for Vanderbilt’s PhD program in epidemiology.

Although busy, he says it’s the most fun he’s had in his career.  “Now is an optimistic time to be a geneticist at Vanderbilt,” he says, citing the hiring of Dr. Nancy Cox, who recently arrived from the University of Chicago to head the genetics institute.  And he and Dr. Velez Edwards “have had some successes”—both were on K awards and became independent investigators in the last year—and expect more in the near future.  Dr. Edwards recently finished evaluating a new statistical method he developed to detect genetic variants with effect modifiers through effects on trait variability.  “We believe the approach is really interesting and is one that people will want to use,” he says.  At the same time, the fibroids team is in the middle of analyzing an immense amount of genetic and imaging data from BioVU and a network of collaborators across the country.  “No one has ever even come close to the magnitude or the quality of the data that we have for this analysis, so we really expect to make some novel discoveries,” he notes.  These discoveries may include an explanation for why African American women have a much higher incidence of fibroids than women of other ethnicities, a question researchers have been asking for some time.

Of course, it’s not always been so fun.  Dr. Edwards had to submit many grant applications—multiple cycles with multiple R01s—before he had success.  “I remember there was a cycle in 2013 where I had submitted three grants the previous June as PI while also submitting multiple grants that February.  The week before my grants were due, my other grants from the earlier cycle got scored, and all three of them were not discussed.  On top of that, a paper that had gone through two revisions at Nature Genetics got rejected—all within three days.  And I was in the midst of the crucial, final time to prepare all these applications and get them submitted.  It was devastating.  You’re working so hard—late nights, long days—and you get all this bad news right when you need to be the most focused.

“I tell this story to emphasize that you’ve got to stay mentally organized and focused on what you’re doing.  It’s easy to get discouraged or lose your motivation or get distracted by other things.  But it’s really key to devote yourself to the process of writing the grant.”  It worked for him—he was awarded the R21 and U01 he put in during that cycle.

Edwards also swears by organized, team-based editing: Everyone in a room with the grant up on a projector, editing sentence by sentence.  As well, he advises, “A lot of the time what makes the difference between a successful R and a not so successful R isn’t necessarily the quality of the ideas, but the evidence you can provide that supports why you’re doing what you’re doing, demonstrating some productivity in the area, showing that you have the experience with the resources that you plan to use.  All of those things dispel the common criticisms reviewers like to write about incoming applications.”

Finding signals in the noise requires a lot of hard work, but as Dr. Edwards has found, the work can be its own reward.

For Dawn Newcomb, PhD, writing a grant is like running a marathon.  As a veteran of six marathons since she moved to Nashville in 2007, she should know.  “You have to be in it for the long haul and pace yourself well,” she says.  She found the CTSD grant pacing workshops, which include a 16-week plan, helpful for that.  “A lot of races have a 16-week training period, so it was a timetable I was accustomed to.”

Dr. Newcomb, who recently received an R01 from NHLBI, studies the role of sex hormones estrogen and progesterone in severe asthma.  Currently, she uses cells that circulate in the blood from patients with severe asthma and healthy individuals as well as a mouse model to study the mechanism by which these hormones regulate the production of a protein, IL-17A, that mediates the inflammation in this particular type of asthma.  In this way, she hopes to discover a mechanism to explain exactly why women are more likely to have severe asthma than men as adults.

“Asthma used to be thought of as this big umbrella,” she says.  “If you had asthma, you were going to be treated with the same medications, regardless of what kind of asthma you had.”  However, asthma varies widely among sufferers, from those who have to go to the ER when they get a cold to those who may simply have to use an inhaler once or twice during the week.  In the past, asthma medications have been tested on patients within a broad category, and many of these patients did not have the type of asthma the medication targeted. Newcomb hopes her research findings will lead to a more precise understanding of mechanisms leading to inflammation in severe asthmatics and will help determine which patients may respond to different therapeutics targeting severe asthma.

Newcomb’s focus on sex hormones and asthma developed as a way to optimally position herself for funding.  She had been working broadly to discover exactly how IL-17 causes asthma.  When the Building Interdisciplinary Research Careers in Women’s Health (BIRCWH) K12 called for applications in 2012, she knew she wanted to apply, but had to make her work relevant to the grant’s stated focus on sex and gender differences.  She wondered if IL-17 might work differently in men and women, and ran assays to determine if there was a difference in IL-17A production between CD4+ Th17 cells from women and men.  “Lo and behold, there was a significant increase in IL-17A production in CD4+ Th17 cells from women compared to men.”  This difference was the cornerstone of her successful BIRCWH application, and guided her research in the direction of her current R01.

In the midst of grant-writing and research, Newcomb finds that marathon training, and exercise in general, keeps her sane.  When you’re in it for the long haul, you have to figure out “ways to clear your mind, loosen your shoulders” and concentrate on other things for a while.  As well, support from those around her, including her husband, Jeff, her family, her friends, and mentor, Stokes Peebles, makes the process survivable—even when that support is to have a draft come back so marked up it’s hard to read.

“Understand everyone’s trying to help you.  No one’s trying to diminish your intelligence, your work, or your research.  It’s hard to remember this advice when a draft comes back with more red ink than black ink on it.  So I just stick it in my bag for a day or two and pull it out at a time when I’m not as close to it.”  The corollary to that, she notes, is that you have to give mentors and others time to read and help.  And, much like plotting out a race training schedule, you have to give yourself time “to pull it all apart and put it back together.”

Writing a big grant isn’t a sprint.  But like a marathon, with proper pacing and good support, you can cross the finish line.

For Dawn Newcomb, PhD, writing a grant is like running a marathon.  As a veteran of six marathons since she moved to Nashville in 2007, she should know.  “You have to be in it for the long haul and pace yourself well,” she says.  She found the CTSD grant pacing workshops, which include a 16-week plan, helpful for that.  “A lot of races have a 16-week training period, so it was a timetable I was accustomed to.”

Dr. Newcomb, who recently received an R01 from NHLBI, studies the role of sex hormones estrogen and progesterone in severe asthma.  Currently, she uses cells that circulate in the blood from patients with severe asthma and healthy individuals as well as a mouse model to study the mechanism by which these hormones regulate the production of a protein, IL-17A, that mediates the inflammation in this particular type of asthma.  In this way, she hopes to discover a mechanism to explain exactly why women are more likely to have severe asthma than men as adults.

“Asthma used to be thought of as this big umbrella,” she says.  “If you had asthma, you were going to be treated with the same medications, regardless of what kind of asthma you had.”  However, asthma varies widely among sufferers, from those who have to go to the ER when they get a cold to those who may simply have to use an inhaler once or twice during the week.  In the past, asthma medications have been tested on patients within a broad category, and many of these patients did not have the type of asthma the medication targeted. Newcomb hopes her research findings will lead to a more precise understanding of mechanisms leading to inflammation in severe asthmatics and will help determine which patients may respond to different therapeutics targeting severe asthma.

Newcomb’s focus on sex hormones and asthma developed as a way to optimally position herself for funding.  She had been working broadly to discover exactly how IL-17 causes asthma.  When the Building Interdisciplinary Research Careers in Women’s Health (BIRCWH) K12 called for applications in 2012, she knew she wanted to apply, but had to make her work relevant to the grant’s stated focus on sex and gender differences.  She wondered if IL-17 might work differently in men and women, and ran assays to determine if there was a difference in IL-17A production between CD4+ Th17 cells from women and men.  “Lo and behold, there was a significant increase in IL-17A production in CD4+ Th17 cells from women compared to men.”  This difference was the cornerstone of her successful BIRCWH application, and guided her research in the direction of her current R01.

In the midst of grant-writing and research, Newcomb finds that marathon training, and exercise in general, keeps her sane.  When you’re in it for the long haul, you have to figure out “ways to clear your mind, loosen your shoulders” and concentrate on other things for a while.  As well, support from those around her, including her husband, Jeff, her family, her friends, and mentor, Stokes Peebles, makes the process survivable—even when that support is to have a draft come back so marked up it’s hard to read.

“Understand everyone’s trying to help you.  No one’s trying to diminish your intelligence, your work, or your research.  It’s hard to remember this advice when a draft comes back with more red ink than black ink on it.  So I just stick it in my bag for a day or two and pull it out at a time when I’m not as close to it.”  The corollary to that, she notes, is that you have to give mentors and others time to read and help.  And, much like plotting out a race training schedule, you have to give yourself time “to pull it all apart and put it back together.”

Writing a big grant isn’t a sprint.  But like a marathon, with proper pacing and good support, you can cross the finish line.

Digna Velez Edwards, PhD, can’t remember never doing science. Whether through research initiatives or attending science programs as a child, she always sought to feed her love of nature and observational science. After working in a zebrafish lab as an undergraduate student, she hoped to find an area of study that was more translational, which led her to a human genetics graduate school program. Her research eventually took her to the study of uterine leiomyomata, or fibroids, which are the most common female [noncancerous] pelvic tumor and, as she notes in a recent Human Genetics article, have prevalence rates of up to 77%, especially in women near menopause.

Fibroids are very heritable, she notes, but also are extremely understudied.  With her recently funded R01 devoted to determining the genetics behind fibroid development, Dr. Velez Edwards aims to change that.  She describes her methods as “agnostic”—i.e., she doesn’t start with a belief, or hypothesis, and then chase down a candidate gene or pathway; instead, she scans the genome by way of genotyping or sequencing to identify the strongest associated risk factor.  Then she looks in pathways related to that gene and digs into what that says about the biology.  Because of this approach, “Anything I find may be potentially interesting,” she says.  “That’s the thing with human genetics research: You kind of are in the hypothesis-generating step in the experimental phases.  In animal models, you have a target. In human genetics, you’re looking for targets.  So you kind of work backwards.”

In this backwards science, Dr. Velez Edwards appreciates the collaborative aspect of human genetics research, which allows her to interact with people from all over the world and across disciplines. “Biostatisticians, epidemiologists, basic scientists are all part of the team.” And meeting with these international team members has allowed her to do a lot of traveling in Africa and Europe, including one of her favorite locations, Italy. Visiting a collaborator in Rome affords her the opportunity to work with Italian researchers in the field of human genetics.

In writing her R01, Dr. Velez Edwards took the advice of those who’d gone before her. “You’ve got to keep writing grants,” she says, quoting her own mentor. “The only way to learn to write grants is to write more grants.”  She tries to write a new grant every cycle, in fact.  She also notes that even when fellow colleagues don’t have the time to give input on an entire grant, even just getting the polished aims page out there for feedback is a step in the right direction. “Don’t assume ‘my idea is brilliant,’” she says. “Get input.”

Other ways she got input were through VICTR Studios, the Edge Review mock study sections, and weekly work in progress meetings held by the K12 she was on, Building Interdisciplinary Careers in Women’s Health Research (BIRCWH).

Finally, she says, “Don’t wait till the last minute to write grants.” Referencing her mentor Dr. Katherine Hartmann’s personal pet peeve about work-life balance, Velez Edwards suggests making the NIH grant timeline your own. “Write a grant at your own pace…your life might not always stick to the NIH’s timeline. If you can write a grant that is due in October in July, write it in July.”

Not so backwards advice from the woman working backwards for new discoveries.

As the most common chronic diseases of childhood, asthma and other allergic diseases represent a “substantial burden on children in terms of quality of life, missed school days, and impact on the family in terms of financial costs as well as having to miss work,” according to Kecia Carroll, MD, MPH.  As a pediatrician who regularly sees the tremendous effect of these diseases in her patients, she wants to understand what factors influence their development, perhaps eventually learning how to prevent it.  Her current R01-supported project takes a close look at exposures during pregnancy, specifically dietary factors such as folate intake, and maps their effect on whether children in two different cohorts develop asthma.

“I think we understand now that if you really want to work to prevent illnesses, you have to think about what’s happening during pregnancy, or even before pregnancy, to the mom.  The time when your lungs are developing, your immune system is developing, is what we call a ‘critical window,’ when you can have influences that shape your risk of disease when you’re older,” she says.  Once identified, these factors can potentially be modified, which is what makes them so intriguing.

The mystery is why Dr. Carroll enjoys research.  “It’s almost like a puzzle, trying to understand what’s behind some of the diseases that we see,” she says.  She discovered her interest in it while working as a Research Assistant in Pediatric Infectious Diseases at Vanderbilt before attending medical school, also at Vanderbilt.  Inspired by watching physicians who balanced research, clinical work, and teaching, she finds the same balance herself, noting that research is “a nice complement to clinical care,” as the relationships she develops with patients motivate her to investigate ways to keep more children from developing asthma.

And so one of the keys to writing a successful grant, in Carroll’s opinion, is finding an area you’re passionate about.  The more you enjoy your topic, the easier it is to do the extensive preparation it takes to get the proposal ready, and then of course spend years doing the research itself.  Carroll credits the protected time she had as part of her K award with allowing her to explore related areas and develop her research question.

She also adds that making time for every possible resource Vanderbilt has to offer was essential, especially when it came to CTSA support.  After making some progress on her proposal, Carroll took it to a VICTR Studio to have experts “poke holes in it” and raise questions that reviewers might come up with.  She also used VICTR funding for pilot studies that demonstrated she and her team were going to be able to get the samples necessary to run the study.  And when she finished writing, she submitted her grant to an Edge Review, which she says gave her the opportunity to see what a real review experience is like, as well as where to strengthen and clarify the grant.  “Sometimes when you’re working on a grant, you’re in the literature, you know exactly what you mean and what you want to say,” she cautions, but “it’s good to hear perspectives” of expert researchers who have varying familiarity with the topic.

Getting these outside perspectives made Carroll competitive at the real NHLBI study section.  And her R01 funding will help her puzzle out factors behind the development of childhood asthma, eventually, she hopes, allowing doctors and scientists to reduce the substantial burden it places on children and their families.

Pingsheng Wu, PhD, likes playing with numbers.  She combs through large amounts of data, such as hospital records and surveys, seeking the causes of disease.  Although she has worked with data related to several diseases, her current research centers on asthma.  No primary prevention strategy exists for asthma, so in determining the causes of this disease, she hopes to find ways to preclude its development.

Of special interest are prenatal factors such as maternal smoking.  Dr. Wu’s research questions don’t lend themselves to double-blind clinical trials—after all, she can’t randomize a set of patients and tell some to start smoking—so instead she performs observational studies using medical records from thousands of people to get a picture of which factors, in what combination, lead to the disease she’s studying.  Maternal smoking during pregnancy, for instance, contributes to asthma in the child.  Other exposures in the womb and after birth, infections, and genetics all play a role.

As an example of the power of observational studies, Wu cites her first project at Vanderbilt as a postdoctoral fellow.  She and her mentor, Dr. Tina Hartert, knew that infants born in the fall are more likely to have asthma, but no one understood why.  One possible influence was that infant bronchiolitis, an infection caused mostly by respiratory syncytial virus (RSV), is also more common in fall babies, because they reach three or four months old during the winter.  Many typically begin day care or leave the house for extended periods at this time, which is also when the virus is most common.  Using Tennessee Medicaid data, their team was able to demonstrate the causal connection between the infection and development of asthma, thus determining one cause of the disease and solving a long-standing riddle.  Of course, this is only the beginning; Wu recently received R21 funding from NHLBI to study the effects of immunoprophylaxis on RSV morbidity and asthma in healthy preterm infants, another of many steps on the path to preventing childhood asthma.

Wu credits much of her success to the “tremendous” resources available to early career faculty at Vanderbilt, as well as to strong mentoring by Dr. Hartert and others.  “I used everything” while preparing her R21 and her R01 on the effectiveness and safety of long-acting beta agonists in asthma, she says.

In addition to formal programs like VICTR Studios and Edge Reviews, she presented her work at weekly Building Interdisciplinary Research Careers in Women’s Health (BIRCWH) work in progress meetings and discussed her ideas with anyone who would listen.  For her R21, she called her mentors and potential collaborators together to talk about the RFA soon after it came out, and over two hours, the group helped her hash out specific aims from her original idea.  Since she received a second percentile score on the application, she must be doing something right.  “So I’m going to continue to bug people!” she says.

Earlier in her career, Wu worried about where new ideas would come from.  Now, with several grants under her belt, ideas generate ideas.  She knows she’s found her niche, and has plenty of things to study as well as many people around to bounce ideas off of.  For her next study, she plans to look at the effects of products like the nicotine patch on pregnancy outcomes and childhood asthma.  As always, she’ll play with numbers, and keep using these mathematical methods to probe the causes of disease.

It sounds counter-intuitive, but working at a bustling coffee shop can be less distracting than working in a quiet office.  The change in environment also stimulates creativity, and chance encounters spark new ideas and connections.

In the following article from FastCompany, Family Records founder Wesley Verhoeve writes about his experience working from a coffee shop while being between offices, why he continues to keep a coffee shop day every month, and tips for making the most out of the experience.

While team Family Records was in between offices in early 2012, we had 6 weeks to bridge until our new space was ready. During that time we were fortunate enough to be taken in as guests by awesomecompanies for stretches of time, and for the remainder we took over corners of coffee shops all over Brooklyn and Manhattan. The experience of working out of coffee shops was so positive that even after we moved into our new home, I made sure to get in a few “coffee shop days” each month. For carpal tunnel related reasons alone, I would not recommend working out of coffee shops every day, but here are some reasons why it might be great to try it for one or two days every month.

A change of environment stimulates creativity. Even in the most awesome of offices we can fall into a routine, and a routine is the enemy of creativity. Changing your environment, even just for a day, brings new types of input and stimulation, which in turn stimulates creativity and inspiration.

Fewer distractions. It sounds counter-intuitive, but working from a bustling coffee shop can be less distracting than working from a quiet office. Being surrounded by awesome team- and officemates means being interrupted for water cooler chats and work questions. Being interrupted kills productivity. The coffee shop environment combines the benefit of anonymity with the dull buzz of exciting activity. Unlike working at home, with the ever-present black hole of solitude and procrastination, a coffee shop provides the opportunity of human interaction, on your terms.

Read more at FastCompany.

On a recent Monday, Kevin Ess found himself in the operating room helping guide a brain resection procedure for one of his patients with epilepsy.  Earlier that day, he collected skin samples from two other children with a genetic form of epilepsy, then took them back to his lab to reprogram the skin cells to stem cells. These would later be differentiated into neurons and used to study neuronal function using patient-specific cells.

Though he spends the majority of his time in the lab, this transit between clinical medicine and basic science is not uncommon for Dr. Ess, an MD/PhD who specializes in developmental neurobiology with a specific focus on epilepsy and autism.  The field, he says, “put it all together” for him: A PhD in developmental biology and a residency in child neurology allowed him to combine his interests into an area that offers plenty of opportunity to solve basic science problems that have clear clinical relevance.  In fact, finding these problems, especially in fields like his where relatively few physician-scientists do translational work, has been the centerpiece of his career.

“The modern academic environment is difficult on every level, and you really have to have a smart career plan,” he says.  “You have to figure out what you’re good at and passionate about and make it work for you.”

Ess has made his interests work for him and has received multiple grants, including a recent R01 from NINDS to study genetic aberrations that allow abnormal brain development in children with Tuberous Sclerosis Complex. The hope is this research will allow a greater understanding of this disease and lead to the development of more effective therapies for these patients.

How does he survive the grant-writing process?  Practice.  “Writers write, right?  Grant writers also need to write,” he insists.  He recommends taking opportunities to review manuscripts and grant proposals written by other people, as long as the time commitment is reasonable, because it benefits you—seeing multiple examples of the type of writing you need to do can be invaluable—and the organization that asks for your help.

As well, he urges new writers of grant proposals to “know the alphabet of key people at NIH.  Know the PO and the SRO and the focus of individual study sections. You can talk to these people, and they are there to help you, so you shouldn’t be shy.  Scientists can send them the specific aims portion of your grant, and they’ll help guide you to the most appropriate study section.  The study section that’s best to evaluate your work will go a long way toward success.”

But don’t stop with your proposal itself.  You need the background material about yourself available too.  Ess states that “in this day and age, you are really required to have an active, up-to-date web presence.  When someone does a Google search about you, for example, they should find you pretty easily,” along with your research expertise, publications, and other pertinent information.  This can alter the success of a grant proposal, because as Ess says, “If I’m on a study section, I may search for information about an applicant to understand better what they are doing and why.”.

Words of wisdom from the man who likes to put it all together.

“Why?” is Rizwan Hamid’s favorite question.  Why does one sibling get high blood pressure while another with the same genetic background doesn’t?  Why do people respond so differently to the same treatment for leukemia?

As a clinical geneticist, Dr. Hamid asks his why questions of the TGF-β and BMPR2 pathways.  He calls them “a small piece of the puzzle” why some patients with acute leukemia do much better than others despite having the same therapies, and why some people develop pulmonary hypertension while others do not.  Because “it’s essentially the same pathway, as we look at both of these models, we provide parallel insights” into both diseases, using information gained from one pathway to investigate the other, he says.

Hamid received a $454,000 R01 award last year, but he started preparing for his application more than two years before the deadline.  Once he had a good idea of where his project was headed, he says, he “spent an inordinate amount of time trying to identify the right study section.”  He researched different NIH study sections by examining their rosters and reading the NIH Reporter to identify the types of grants specific study sections tended to fund.  When he started writing his grant a year out from the funding cycle he targeted, he could tailor the proposal’s focus and language to that particular study section.

Eighteen months from his February deadline, he received a small pilot grant to generate more preliminary data.  Based on his results, he “actually wrote a proposal, essentially a full, complete proposal,” and used a VICTR Studio to get feedback.  “We could’ve sent it [to the NIH] six months earlier” than the deadline, he says, but instead he spent the time polishing every sentence, reference, and figure, as well as sending it to an outside editor to make sure no errors slipped through the cracks.

“The other thing I did for my grant, which I think is going to be very important going forward,” Hamid says, “is to not propose to do everything myself.  My grant by design…was a collaborative effort.  I identified other investigators at Vanderbilt who were experts in the techniques I was going to use, and in my grant I had them as co-investigators…even though my lab could do some of those techniques.”  Though he is the PI of the project, he explains that having other investigators with effort in his grant demonstrated his ability to collaborate and seek out expertise, which “my reviewers indicated that they liked.”

In addition to collaboration on project work, Hamid touts the virtues of national conferences for networking purposes.  Even three or four years before your potential deadline, he advises, “you need to be out there presenting your stuff in meetings…even if you have to spend money out of your own pocket to go.”  Senior investigators at conferences will be the ones reviewing your grants and articles, “so if they can say not, ‘Who is this guy from Vanderbilt?’ but, ‘Oh, I remember this guy, I met him at the meeting last year in San Diego,’ [then] even though your grant is still going to be reviewed on its merit, if you make a reasonable impression on these people, you get some subconscious benefit from that.”

Thanks to his thorough preparation and expert networking, Rizwan Hamid will be asking his why questions for many years to come.