Original Research: Critical Volume of Human Myocardium Necessary to Maintain Ventricular Fibrillation

My co-authored research article titled – Critical Volume of Human Myocardium Necessary to Maintain Ventricular Fibrillation was published in the peer review journal – Circulation. Arrhythmia and Electrophysiology. The article is available in print, in the December 2018 issue of the journal.

Briefly, the manuscript documents evidence using donor human hearts that ventricular arrhythmias (e.g., ventricular fibrillation) is only sustained if the cardiac tissue volume exceeds the cardiac wavelength volume . The article can be accessed here

Research in the time of Covid-19 (Part I) – JUly 01, 2020

The official start date of my K99 award was May 07, 2020 and the official end date for the K99 phase of the award is April 30, 2022. As mentioned in an earlier blog post, the K99 award entails two years of additional training as a postdoctoral fellow followed by transition to a tenure track faculty position with three additional years of funding. The NIH award comes with expectations that include: One, picking up additional technical skills during the first two years of the award and Two, successfully applying for an R01 grant during the latter phase (R00) of the award. It also goes without saying that you need to be productive relative to publications throughout the duration of the award. 

Given the clearly defined NIH expectations commiserate with allocated resources, my planned approach has been twofold: First, chart out the timelines for each of the major deliverables including: Postdoctoral Training, K99 Research Project, R01 Grant Preparation, Tenure Track Faculty Job Search, and Manuscript Publications. Second, keep a daily log to track my progress relative to each of the deliverables. In addition, I also set aside time once a week to evaluate the effectiveness of my approach and make course corrections as needed. (There are lot of free online project management tools you can use to track the progress of your projects, if so inclined )

While the official notification of the award came in May, I had an inkling that my application was likely to be funded back in January, given the overall score assigned to my K99 application and the past history of applications with similar scores receiving funding. As such I had already started the planning process with the intent to hit the ground running. But as Mike Tyson once famously said, “Everybody has a plan until they get punched in the mouth.” My planning did not account for the COVID-19 pandemic. 

 It’s taken a little bit of time to assess the new reality of things and recalibrate my approach and project timelines accordingly. It is likely that there will be project delays and the research and training tasks that were straightforward pre COVID-19 will no longer be that, especially since the universities and research labs have been shut down and are only now beginning to reopen in phases. But as with life, we make do with what we have. The key is to stay nimble and be flexible without losing sight of the overall aim and objective. 

My story: not winning the aha early career award (ECA)… well, not yet :) (June 21, 2020)

I had mentioned during my earlier posts on winning the K99/R00 award that I had a plan B in motion in case I did not get the award. That plan B was applying for the AHA early career award (ECA). The award is designed to fund new faculty appointments (assistant professors) for 3 years. It is equivalent to the R00 phase of the K award, although with a little less money available for research. Even so, getting the AHA ECA is pretty impressive and can fast track your research career.

You would assume that if my plan B was the AHA ECA, I would be fairly confident about getting the award. Well, you would assume wrong :). To put it mildly, I have not had much success with AHA. I have applied for AHA postdoctoral fellowships three different times and gotten rejected every time. The only reason I considered AHA ECA as plan B was the timeline. The K99 application deadline was earlier (July 2019) than the AHA ECA application deadline (Oct 2019).

The documentation required for the AHA ECA is fairly similar to that required for the K99 application. Even so, there are a few things unique to the AHA ECA. First, unlike the K99 award which is given to postdocs, the AHA ECA requires the applicant to be in an independent faculty position (e.g., research assistant professor or such) to be eligible for the award. Second, unlike the K99 award, where the training component is extensive with university courses, lab training etc. , the AHA ECA training focuses primarily on training needed as a research faculty. In other words, its more about how you are going to secure resources to help with your research (e.g., through mentors etc.,). Third, while the K99 application assigns equal weightage to the 5 criteria: candidacy, career development and training plan, research plan, mentors, and environment, my sense is that the AHA ECA assigns a lot more weight to the research plan compared to the other criteria.

I will admit that when I submitted the AHA application I was still recovering from the K99 application submission fatigue as well as adjusting to the life as a father to a beautiful boy. As it was, I repackaged my K99 application for AHA but did not spend too much time customizing it. I would strongly recommend against this approach. While the documentation is similar, there are still enough differences in terms of content requirements that it is best to spend equal amount of time preparing the AHA application as you would a K99 application.

The application was submitted in Oct 2019 and the results were out in June 2020. I did not get the award. To be honest, after finding out that I had won the K99 award, I was not really concerned about the AHA ECA results one way or other. If I had gotten the award, I would have had to decline it as the award cannot run concurrently during the K99 phase of the K-award. However, you can apply for and accept the award during the R00 phase of the K award. That said, I was curious to read the comments from reviewers. Of the 5 criteria, they thought my candidacy, mentors, career development plan, and environment were very strong or exceptional. One of the reviewers brought up the point that I was still a post doc and not an independent faculty, which could be an issue. So of the 5 criteria, I scored strong to exceptional on 4 of them. However, they found my research plan relatively weak and identified from their point of view gaps in my research design that if addressed would make the proposal strong. I am thankful for that feedback as I can now use that knowledge to strengthen my K99 research plan.

I do plan to apply for the AHA ECA in the future. However, it will be for another project as I cannot use the current project which is already funded through NIH to apply for the AHA ECA. They do not allow for double dipping, which is fair. If you have been paying attention, my current success rate with AHA remains at 0% (0/4). However, I have not given up hope yet :). I will continue to refine my grant writing skills, come up with research ideas that I think are awesome and apply again. Hopefully, the next time, I will breakthrough and get the award 🙂

MY STORY: WINNING A K99/R00 AWARD – Part 4 (June 7, 2020)

PART 4 of 4

My first K99/R00 submission did not even make it to the review committee. It got the dreaded “Not Discussed” tag. I did get a summary statement with the critiques from the three reviewers. To put it mildly, they had doubts about the competitiveness of my application and perhaps, rightfully so.

  1. Candidacy: The reviewers acknowledged my publication record as being good but not exemplary. I had 14 publications at the time of my first submission. However, they were more interested in my productivity during the postdoctoral years. As a post-doc, I had 2 first author publications, couple of review articles, couple of book chapters, and a patent submission. I was perhaps competing with other applicants who had one or more nature, science, or cell papers, hence the good but not exemplary remark. Interestingly, one of the reviewers was under the impression that I had no first author publications as a post-doc. Thankfully, I had the opportunity to provide a rebuttal when I submitted the revised application.
  2. Training Plan: The reviewers thought my training plan was not strong enough or novel enough to require 2 years of additional training time. Given my lack of background in molecular & cellular profiling (e.g., western blot, immunohistochemistry etc.,), I had proposed spending time to pick up these skills. However, the reviewers thought the skills could be easily acquired in a few weeks. They suggested that I should focus on picking up techniques outside of my mentor’s lab expertise. This was precisely the kind of feedback I was seeking from my initial submission. To that end, I modified my training plan to focus on getting specialized training in two areas: adipose biology and bioinformatics, which were outside my primary mentor’s research expertise, but still complementary with my research background. I also enrolled two additional mentors to help with my training plan.
  3. Research Plan: The reviewers were particularly brutal in their feedback here, but rightfully so. They felt that my specific aims were more of a fishing expedition rather than a specific project with well defined aims and hypotheses. I had no preliminary data to show project feasibility or back up my hypotheses. However, they did acknowledge a general interest in the research topic. Since I already knew my lack of preliminary data would be an issue, I had begun to acquire data immediately after my first submission. By the time the reviews came back, I had most of my preliminary data ready for the resubmission. I also sought out the program officer (PO) associated with the study section and got feedback on the specific aims. This proved extremely valuable as I got more insights into what the reviewers and the review committee were looking for. This step is often ignored by applicants, not realizing that the PO can be a valuable resource. That said, I would suggest being mindful and respectful of their time and only seek their help after your specific aims have been fleshed out in detail. As it was, I was able to address most of the reviewer critiques in my revised application.
  4. Mentors, Collaborators, and Consultants: The reviewers were not impressed with my mentoring committee as I only had one primary mentor. They suggested that I set up a formal mentoring committee that would provide research and career guidance. Consequently, I set up a formal research advisory committee with 3 mentors and 6 collaborators and/or consultants. All the mentors and consultants /collaborators on my advisory committee were well known and well respected scientists. Looking back, I believe that their reputation played a significant role in how my revised application was scored.
  5. Institute Environment: The reviewers did not really critique the institute environment and agreed that the university and department would be supportive of my training and research needs.

To recap the timeline, my initial application was submitted in October 2018. The summary statement was made available in April 2019. The revised application was submitted in July 2019 and I got the summary statement in December 2019. The advisory council met in Feb 2020 and I got the email notification of grant award (NOGA) in May 2020. The whole process from initial submission to award notification took 17 months and probably 24 months if you include the initial planning period before the first submission. The application process is more like a marathon than a sprint, so plan accordingly 🙂

It was an exhausting journey but thankfully I was one of the lucky ones that got the award. But what if I had not gotten the award? After all, only 1 in 5 applicants are funded. What would have been my Plan B? I had already started the ball rolling on Plan B by applying to the American Heart Association’s (AHA) early career development award. The award is similar to the K99, but only for 3 years and with lot less money. I applied for the grant in Oct 2019 with the start date being April 2020. I have not yet heard back from them. If by chance, they select my application for funding, I will have to decline the award as I already have the K99 award. What if the Plan B also fails and AHA application is not funded? What would have been my Plan C? I had already started work on Plan C by exploring options with my PI to get promoted to a research faculty position within the department so that I could then package my grant application as an R21 or even an R01. Granted, at this point, it would be tough sledding, but I was already preparing along those lines. Fortunately, I did not have to make Plan B or Plan C work. The point being, you cannot afford to put all your eggs in one basket. You have to plan for contingencies.

Now that I have my K99 award, what does that mean for the future? To be honest, things only get more challenging from this point on. Yes, I do have peace of mind, at least for the next 5 years relative to my research projects and funding. On the other hand, I am now expected to be extremely productive relative to publications, be able start my own research lab as a tenure track faculty, hopefully at a Tier 1 research university, and successfully apply for one or more R01 NIH grants. Chances are, my R01 grant applications will be evaluated based on the productivity of my K99/R00 award. If I don’t deliver with a $1 million grant, how can I expect them to give me more money for research? Thus the pressure to succeed and repay their investment in my career. Then again, I would rather be in my shoes than have to execute Plan B or Plan C :). I am confident in my abilities and feel optimistic that I will be able to carve out a successful research career with the resources I have been given.

I hope you have found my K99 journey informative as you plan your own K99 application submission. Feel free to send me comments or questions, if you are so inclined. I will be happy to provide feedback, if I can. Good luck 🙂

My story: winning a k99/R00 award – part 3 (May 31, 2020)

PART 3 of 4

When I started the process of writing the K99 grant application, I knew early on that I would not be able to acquire preliminary data in time to meet the submission deadline (Oct 2018). Not having preliminary data is a major weakness in any research plan. On an average only 20% of K99 applications get funded. Given the ultra-competitive nature of the grant I had no illusions that my application would be funded in its current version. However, I wanted to get a sense of what the review committee thought of my overall application. My submission strategy focused on getting feedback from the review committee on my first submission; address any concerns and gaps in the application as they saw it, and then submit a revised, stronger application.

The K99 application is evaluated on 5 equally weighted factors: Candidacy, Training Plan, Research Plan, Quality of Mentors, and Institute Environment. Briefly, the application review process is as follows.

  1. Your application is first checked for completeness by the scientific review officer (SRO) and then assigned to 3 reviewers on the committee, which can comprise of up to 30 members. One of the 3 reviewers will serve as the primary reviewer and the other two will serve as secondary reviewers. The choice of reviewers is left to the discretion of the SRO. It should also be noted that the reviewers on the committee have varied research backgrounds, interests and areas of expertise, which may or may not overlap with your research topic. As such, there is an element of luck involved and the choice of reviewers can make or break your application. Even so, the SRO does a good job of assigning reviewers who are either familiar or at least have an interest in your field of research.
  2. Each reviewer grades your application on the 5 factors. The scale is from 1 to 9 with 1 being exceptional and 9 being poor. The preliminary scores from the 3 reviewers are averaged and if the application scores high enough (3 or less on each of the criterion ), the application is likely to go to the full 30 member review committee for further discussion. If not, the application is tagged “Not Discussed”. This also means your application likely fell in the bottom 50% of applications and will not be funded. However, you will still receive a summary statement that includes critiques from the 3 reviewers.
  3. Only the top 50% of the applications are selected for further discussion by the review committee, which convenes after all the applications have been given a preliminary score. At the study section, the primary reviewer will lead a 15 minute discussion of your application’s strengths and weaknesses relative to the 5 evaluation criteria. At the end of the discussion, each committee member will assign an overall impact score, which again ranges from 1 to 9. The average of all the impact scores is what constitutes as your application’s overall impact score and determines whether your application will be funded. Every NIH institute has their own internal threshold for fundable overall impact score, which can change from year to year depending on the NIH budget, quality of applications, and the funding cycle. Even so, on an average, if your application receives an overall impact score of 3 or less, you should have a reasonable chance of getting funded. You will also receive a summary statement that includes the overall impact score, summary of what the review committee thought of your application, and also the individual critiques by the 3 reviewers.
  4. The review committee does not make funding decisions. They only evaluate the technical merits of the application. The funding decisions are made by the advisory council that convenes 4-6 weeks after the review committee has done their part. At this meeting, the applications that received fundable impact scores are selected for funding, barring any administrative issues. Moreover, certain applications that fall just outside the threshold may or may not be discussed for funding, especially if the research topic is of strategic interest to the institute. Even so, these are rare occurrences.
  5. If your application has received a fundable score, then 4-6 weeks after the advisory council meeting, you will receive the official notification of grant award (NOGA) and you can officially celebrate 🙂

My initial submission received a “not discussed” tag, which while expected still stung a bit. Even so, I was glad to receive valuable feedback from the reviewers, which were for the most part fair, if a little harsh. It made my revised application that much stronger and ultimately helped secure funding.


PART 2 of 4

Writing a K99 application is an involved process with lots of documentation beyond the research plan. Moreover, each document has a page limit, which if exceeded can lead to rejection of the application. Briefly, the list of documents that make up the application includes:

  1. Cover letter (1 page). The purpose of the signed cover letter is to inform the NIH of your intention to submit the application for review and consideration. Effort level: Easy
  2. Project summary (1 page). Describe the research project and the training plan in approximately 30 lines or less. Effort level: Easy
  3. Project narrative (2-3 sentences). Describe the project in couple of sentences so that the general public can understand the significance of this research. Effort level: Easy
  4. Facilities and other resources (No limit, but generally 2-4 pages). Describe the list of institutional resources available to conduct the research (e.g., computing facilities, imaging facilities etc..). If your PI already has grants, you can repurpose his/her documentation for your application. If not, this will require a little bit of work. However, you cannot skimp on this as Institutional environment is one of the 5 factors that your application will be evaluated on. Effort level: Easy.
  5. Major Equipment (1 page). Describe the list of equipment and resources available in the PI’s lab (e.g., lab & office space, lab equipment etc.,) for your use. Effort level: Easy.
  6. Candidate Biosketch (5 pages). This is similar to your CV. Even so, make sure, you are using the NIH approved template. Your candidacy evaluation will entail quality and quantity of publications, current & past funding, research awards etc. I did not have any past funding to list. On the other hand, I had won a young investigator award and my publication count was 14 at the time of submission. Effort level: Easy.
  7. Budget & Budget Justification (1-2 pages). If your university has a grants administration office, they should be able to help you with the budget, which typically includes: 100% salary, up to $25K in research funding, and 8% indirect costs. If your PI has grants you should be able to repurpose the justification document for your needs. If not, just list your likely expenses (e.g., key personnel, materials and supplies, travel costs, publication costs etc..). Effort level: Easy.
  8. Candidate Background and Training Plan (3-4 pages). Think of this as your personal statement. Briefly describe your research and education background, career goals and objectives (short term and long term), career development and training activities planned during the award period (proposed coursework, lab training, mentoring, education, 5 year timeline of milestones etc.). Needless to say, this will be a key component that your application will be evaluated on. You should plan on spending considerable time working on this document. Perhaps, as much as on your research plan. Effort level: Difficult.
  9. Specific Aims (1 page). This page summarizes your research plan and is rightly or wrongly, the determining factor on how well your research plan will be received and evaluated. The specific aims page should generally include: a paragraph on research motivation, a paragraph on your central hypothesis and findings from preliminary studies you may already have conducted, 2-3 specific aims broken up into K99 and R00 phases, and finally a short paragraph on benefits of completing this study to you and the scientific field at large. If your specific aims are not compelling enough you will be fighting an uphill battle to get funded. Effort level: Difficult.
  10. Research Plan & Bibliography (8-9 pages). Once you have your specific aims page more or less finalized you can begin work on your research plan. The key components of the research plan include: Significance, Innovation, Feasibility and Preliminary results, Research Approach, Scientific Rigor, and Long term outlook. The bibliography is not included in the page constraint and can be as long as needed. I recommend including lots of figures (8-10) to help with the narration. The reviewers are likely to appreciate it more than the text. Effort level: Difficult
  11. Training in Responsible Conduct of Research (1 page). Describe courses, boot camps, and seminars you will attend to complete requirements for responsible conduct of research. Your university should offer such courses, which you can list here. Effort level: Easy.
  12. Description of Institutional Environment (1 page). List the department faculty members who can serve as intellectual resources if needed. You can also include weekly/monthly seminars, journal clubs that you attend to help foster your education. Effort level: Easy.
  13. Letter of Institutional Commitment (1 page). A letter from the department chair supporting your application and hopefully also providing a subtle recommendation of your candidacy. Effort level: Easy.
  14. Resource Sharing Plan (1 page). Describe the data sharing plan including data collected from experiments, custom software etc. as needed. You can also include information conferences you will attend to present your data and submit to peer review. Effort level: Easy.
  15. Authentication of Key Biological and/or Chemical Resources (1 page). If you conduct wet lab experiments and are planning on using antibodies, cell lines etc., you should list the vendors and specific anti-body products you will be using. This will enable other labs to replicate your data in the future. Documentation of general reagents that is widely used is not needed. Effort level: Easy.
  16. Human Subject Research or Vertebrate Animals Research (1-2 pages). If you are planning on conducting clinical studies you will need to include details on sex, age, race as well as plan to maintain patient privacy. You will also need to provide an approved IRB protocol at a later date, if your application is approved. Alternately, if you are planning on conducting animal studies, you will need to include justification on number of animals used and also furnish information on approved IACUC protocol. Effort level: Easy to Medium, depending on whether you need to secure an IRB and/or IACUC approval.
  17. Mentor Statement (6 pages). Your PI will be describe his/her plan in support of your research and training plan. He/she will also ideally praise your skills and accomplishments and help your cause. Your mentors cannot serve as references, so this document provides an opportunity for them to put in a good word on your behalf. You can have more than 1 mentor, but the page constraints still remain. In my case, my PI served as the primary mentor and wrote a 4 page statement. I had 2 other co-mentors and they each wrote a 1 page statement. Your mentor statements will play a key role in how your application is evaluated. On a side note, all the listed mentors will need to provide a biosketch (5 page limit) similar to yours. Effort level: Easy to Medium
  18. Collaborators and Consultants (6 pages / optional). If you have collaborators or consultants, you will need a letter of support from them. In addition, each collaborator will also need to provide a biosketch. However, consultants are not required to provide one. Effort level: Easy to Medium
  19. Reference Letters (3-5 references). NIH has a template that you should send to your referees. The recommendation letter should include information such as candidate’s name, candidate era commons id, FOA number, and a 2 page description of your candidacy including potential to become an independent scientist. It goes without saying, but your reference letters will play a vital role in your candidacy evaluation. Effort level: Easy to Medium

Given the amount of documentation required to submit and K99/R00 application, it is highly recommended that you start the process at least 6 months before the deadline. If you already have the specific aims page written up and preliminary data to go with it, then obviously you are ahead of the game. Even then, I’d set aside 2-3 months to get everything lined up and ready to go.

Scientist, Educator, Entrepreneur