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

Catheter -integrated soft multilayer electronic arrays for multiplexed sensing and actuation during cardiac surgery

Multimodal multiplexed soft sensors and actuators for minimally invasive surgery

WHAT IS KNOWN?

  1. Catheters are widely used for minimally invasive therapies such as atrial fibrillation ablation, intravascular stents, etc. In addition, they are also used for capturing information during procedures such as measuring temperature, pressure, electrograms etc.
  2. However, these catheters are limited by mechanical rigidity, low spatial densities, single function capability necessitating use of multiple catheters to acquire critical information.

WHAT THIS STUDY ADDS?

  1. We have designed a novel flexible, stretchable and tissue conforming electronics device integrated with a balloon catheter that supports simultaneous high-density spatiotemporal mapping of temperature, pressure, and electrograms.
  2. In addition, our device allows for programmable electrical stimulation, radio frequency ablation and irreversible electroporation.
  3. This novel device, the first of its kind, anywhere in the world, will eventually enable physicians to acquire a rich set of physiological information and complete surgeries and deliver therapies in shorter times than currently possible, with a single instrumented catheter system.

LINK TO THE ARTICLE

Mengdi Han*, Lin Chen*, Kedar Aras*, Cunman Liang, Xuexian Chen, Hangbo Zhao, Kan Li, Ndeye Rokhaya Faye, Bohan Sun, Jae-Hwan Kim, Wubin Bai, Quansan Yang, Yuhang Ma, Wei Lu, Enming Song, Janice Mihyun Baek, Yujin Lee, Clifford Liu, Jeffrey B. Model, Guanjun Yang, Roozbeh Ghaffari, Yonggang Huang, Igor R. Efimov, John A. Rogers. Catheter-integrated soft multilayer electronic arrays for multiplexed sensing and actuation during cardiac surgery. Nature Biomedical Engineering (2020). https://doi.org/10.1038/s41551-020-00604-w.

Research in the time of covid-19 (part 2 of 2), July 11, 2020

The COVID-19 pandemic has created a global health emergency upending people’s lives and impacting them socially, economically in addition to being a health and human crisis. From the perspective of scientists, it has disrupted the typical functioning of academic research labs and hampered the ability to do research. For example, researchers who may have been in the process of collecting data to submit with their grant application or a manuscript for publication now could face inordinate delays. For a lucky few, this delay may be annoying but not debilitating to their academic careers. For others, this could result in the window closing on time critical experiments and needing to start all over again, if at all possible. And for the early career scientists, who are especially vulnerable with the tenure clock ticking, this delay could jeopardize their ability to secure tenure. I’d count myself as among the lucky few, who has his own funding for the next few years. In addition, I work in a lab where my mentor also has funding for the next few years. This has allowed me to stay patient and flexible with my plans, while also exploring other ways to be productive. 

As mentioned in an earlier blog post, I have been focused on the major K99 deliverables that include Postdoctoral Training, K99 Research Project, R01 Grant Preparation, Manuscript Publications, and Tenure Track Faculty Job Search. With COVID-19 pandemic, my planned approach for each of the deliverables has changed as follows:

  1. Postdoctoral Training: Over the next year or so, I am hoping to pick up skills in bioinformatics and adipose tissue biology to complement my cardiac electrophysiology and scientific computing & visualization background. The pre-covid19 plan was to spend 4-6 months in each of two mentors’ labs (Bioinformatics: Prof Crandall, Adipose Biology: Prof Li) and learn from them. However, with university and lab closures, the timeline has been delayed. But rather than wait for the labs to open back up, I have been attending online seminars, watching and/or reading online tutorials, textbooks and current literature to get conceptual and theoretical knowledge of these skills. Obviously, this approach is not ideal or perfect, and no substitute for hands on learning. But my hope is that when things open back up, I can use the conceptual knowledge gained now to accelerate the learning in the labs. Current Risk Level: Moderate
  2. K99 Research Project: The pre-covid19 plan was to conduct experiments and generate enough data for validating research hypotheses and eventually publish the results as journal papers. With Covid-19, there has been a delay of at least 4 months, which while concerning has not been debilitating, yet. With the labs opening slowly and in phases, I have been able to restart my experiments, albeit at a slow rate. If things continue to improve, I am cautiously optimistic that the delay will be overcome, and I will get back on track with my project timeline. On the other hand, if the Covid-19 pandemic worsens, it could elevate the risk level for this deliverable. Current Risk Level: Moderate.
  3. R01 Grant Preparation: I will be expected to submit a R01 grant application during my 3rd year of the award, at the earliest, giving me 3 years to prepare the application. As such there is no time sensitive work that needs to be accomplished immediately. Even so, my approach has been to do copious amounts of reading including current literature and attend online seminars and presentations to formulate and flesh out new grant ideas.  Pre-covid19, I would be inclined to attend more conferences in person and talk to resident experts and explore opportunities for future collaborations. This would also be in conjunction with doing proof of concept experiments to gather preliminary data for grant applications. With Covid-19, these activities are on hold. But there is still time and I don’t necessarily feel the pressure to try and force the issue. At this time, I am mostly engaged in lot of reading and thought experiments. Current Risk Level: Mild.
  4. Manuscript Publications: The pre-Covid19 plan was to design and conduct experiments, process and analyze data, present results at conferences and publish findings in peer reviewed journals. Rinse and Repeat. With Covid-19 the inability to conduct experiments has put a damper on this process. Thankfully, there are projects in the pipeline where data was already collected, and I was in the various stages of data processing and analysis, or manuscript preparation and revision. These tasks can still continue, and I have been busy on this front. I am hoping by the time these projects are completed and the findings published, the university and the labs will open up for normal function and I will be able to restart experiments on new projects and repopulate my projects pipeline for the future. Current Risk Level: Mild
  5. Tenure Track Faculty Job Search: Professional networking is a never-ending process. Typically, you meet people at scientific conferences and/or put the word out through your professional networking channels that you are looking for a faculty position in the near future. The best time to look for a job is when you already are employed. Even so, finding the right opportunity is a matter of timing and serendipity. Thankfully, I have couple of years to find a TT faculty position. The COVID-19 pandemic has slowed down the professional networking process. Even so, I have used this time to refresh my social media presence and activated a passive job search process. In addition, my mentors are aware of the tentative timeline and are putting out feelers on my behalf. My role at this point is to stay prepared so that when the opportunity does arrive, I will be ready.  Current Risk Level: Mild.

At the end of the day, these plans are not set in stone. I will continually tweak them as needed until I get the expected results. The concept is similar to an airline pilot responsible for flying from one location to another. The pilot sets the initial destination coordinates and takes off. But during the flight, he/she makes continual course corrections to account for wind, turbulence, and storm patterns and eventually lands the plane safely at its destination. I intend to do the same :).

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 🙂

Scientist, Educator, Entrepreneur