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Preparing for the AHA Predoctoral Fellowship Application

In the second year of my Ph.D., I began applying for predoctoral fellowships. There are only a limited number of fellowship programs that I am eligible for as an international student, as I was ineligible for most federally funded research fellowships. My advisor suggested that I apply to the American Heart Association predoctoral fellowship, which is open to any full-time student enrolled in a doctoral degree program (Ph.D., MD, DO, DVM, PharmD, DDS, DrPH, PhD in nursing or equivalent health science doctoral degrees) without any restriction on residence or citizenship. The AHA predoctoral fellowship awards one or two years of NIH-rate predoctoral fellow stipend, funds for health insurance, and an additional $2,000 for project support.

In addition to being a great opportunity to obtain funding support for my research, applying for predoctoral fellowships also helped me polish my grantsmanship and clarify my research directions.  In my fourth year, I was awarded a two-year AHA predoctoral fellowship. Here are some of my tips for preparing for the AHA Predoctoral Fellowship:

  1. Enroll in a grant writing course in your program if your institution has one. Before applying for predoctoral fellowships, I took the grant writing course that was taught by one of the professors in my department. In the course, I was able to obtain feedback on my research grant, not only from experienced professors but also from my peers. Since I had limited experience in grant writing, taking an organized course really helped me navigate the process and build a solid draft. In addition, this experience gave me an opportunity to think deeply and incorporate others’ feedback on my research directions.
  2. Connect with individuals who can write you a stellar recommendation. The AHA predoctoral fellowship application requires three letters of reference, but the proposal sponsor (likely your principal advisor), co-sponsor, collaborator, or consultant cannot serve as a referent. Therefore, you will likely have to reach out to other faculty members, previous research mentors, or other individuals. Staying in touch with these individuals is a great way to ensure their support of your application.
  3. Think of how to convey your research to a broad audience. One of my favorite aspects of the AHA application is thinking about how my work could achieve AHA’s mission to achieve a world of longer, healthier lives. To communicate the value of my research, I wrote a non-scientist summary of my project and outline how my work supports AHA’s mission in my proposal. In fact, this summary to a non-scientist audience is one of the key peer review criteria of the award. Attending courses and workshops on science communication really helped me clarify my writing and avoid scientific jargons.
  4. Update your resume. Like other predoctoral fellowship applications, you will have to document your academic record as well as your prior research experience and/or publications. Don’t forget to update your resume from time to time to make sure you are presenting the best version of yourself.
  5. Don’t give up. I missed the funding mark in my first AHA fellowship application and was only awarded after resubmission. The reviewers’ comments on my first application, which I addressed in my resubmitted application, improved my proposal and research directions in general. Needless to say, resilience is a necessary quality in research!

The deadline for the 2023 AHA predoctoral fellowship is Wednesday, September 7, 2022. Mark your calendar and don’t miss this excellent opportunity!

“The views, opinions, and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness, and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions, or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your health matters. If you think you are having a heart attack, stroke, or another emergency, please call 911 immediately.”

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Combining CAR-T and mRNA Therapeutics to Cure Heart Failure

Heart failure is the leading cause of death in the Western world, causing more than 300,000 deaths per year. Heart failure is also a source of significant economic burden, costing the American healthcare system more than 30 billion dollars in 2012.[i] Cardiac fibrosis is central to the pathology of heart failure. Cardiac fibroblasts are activated in response to injuries. However, when activated fibroblasts fail to quiesce and continue secreting extracellular matrix, cardiac fibrosis occurs, leading to scarring of heart tissues. Ultimately, cardiac fibrosis can lead to fatal heart failure. Fibrotic diseases, including lung and cardiac fibrosis, cause more than 800,000 deaths worldwide per year.[ii]

Researchers from the laboratory of Dr. Jonathan Epstein in the University of Pennsylvania recently showed that mRNA therapeutics can be used to address cardiac fibrosis.[iii] The researchers delivered a modified mRNA coated with T-cell targeting lipid nanoparticles. The mRNA encodes for a chimeric antigen receptor against FAP, a specific protein expressed by activated fibroblasts. This allows for the generation of transient chimeric antigen receptor T (CAR-T) cells that recognize fibrotic cardiac cells.

Successfully delivered, the mRNA was able to reprogram T cells to specifically recognize and eliminate activated fibroblasts. In a mouse model of heart failure, the engineered CAR T cells were able to resolve cardiac fibrosis, restructuring the heart and improving heart function after injury. Unlike ex vivo CAR-T cells generation, this method allowed the generation of CAR T cells entirely in the human body. In addition, these engineered CAR T cells are transient, therefore not compromising the heart’s ability to resolve future injuries through fibroblast activation.

With the recent advances of the COVID-19 vaccines, the use of mRNA therapeutics in other diseases is gaining traction. The possibility of eliminating the disease burden of cardiac fibrosis using mRNA therapeutics is extremely attractive, as it has the potential to reverse cardiac fibrosis and restore heart function. This presents a significant addition to existing antifibrotic agents that only limit or slow down fibrosis progression. This first proof-of-concept study opens a new avenue to optimize the strategy of combining mRNA therapeutics and CAR-T technology to address cardiac fibrosis and fibrotic diseases in general.

References:

[i] Virani, S. S. et al. (2021) Circulation 143: e254–e743

[ii] Hinderer, S. and Schenke-Layland, K. (2019) Advanced Drug Delivery Reviews 146: 77-82

[iii] Rurik, J. et al. (2022) Science 375.6576: 91-96

 

“The views, opinions, and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness, and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions, or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your health matters. If you think you are having a heart attack, stroke, or another emergency, please call 911 immediately.”

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Zooming In: The Impact of the COVID-19 Pandemic on PhD Interviews

The COVID-19 pandemic has brought significant changes to multiple layers of academia, including the biological and biomedical sciences PhD admissions process in the United States. Typically, prospective applicants are selected to interview in-person at the destination campus not only as a part of the evaluation process, but also as an opportunity for the applicants to gauge program fit. The travel disruptions caused by the pandemic put this opportunity on hold in 2020, and for many programs, lasted into the 2021 admissions cycle. As such, many programs opted for virtual interviews instead.

 

Rama Alhariri, a PhD student in the Human Genetics and Molecular Biology program at Johns Hopkins University, was unable to visit the universities she applied to when she was choosing PhD programs in 2020. All her interview processes took place virtually. Although there was slight variation in the format, she had an opportunity to talk to current students and faculty members about their research interests and the PhD program in general. In addition to the interviews, her virtual programs included sessions introduce applicants to the university and the city itself, such as a panel session about things to do in the area and a live virtual tour of the program. However, this experience did not quite resemble the in-person visits.

“I would’ve liked a higher quality of the tour of facilities as some programs lacked that altogether or it was a little unclear. Additionally, I would’ve liked a greater interaction with other interviewees without the presence of upper-class students or faculty so that we can get to know one another better, the way we might if we were in an in-person interview. It is unfortunate because it’s these interactions that also shape how well you might integrate with other students,” she added.

When asked about how she gauged the fit of the PhD program, Alhariri said that she tried to focus on her interactions with the students, faculty, and other interviewees. From these conversations, she was able to get a glimpse into the campus culture and the overall level of formality and professionalism among the faculty members and students.

“Ultimately the program I chose, while it was also the highest ranking one, was the one in which I felt most comfortable with the upper-class students as well as those that could potentially be within my cohort. I sought an environment with a good balance between professional and somewhat relaxed, which would be the best fit for me.”

Although virtual interviews have become more common in the PhD admissions process in the past two year, they are not new. International students who reside in other countries, for example, typically have limited opportunities to travel due to visa issues and a lack of financial reimbursement for long-distance travel. When I was choosing a PhD program to commit to in 2018, I was finishing up my undergraduate studies outside of the United States. Because of that, my campus visits were limited to places that I could afford flying to. Additionally, my virtual interviews were limited to conversations with faculty members, which was not enough to give me a comprehensive picture.

Alhariri shared a few tips for current applicants who are unable to visit campuses in-person, “It’s hard to make a decision on what program you want to choose based off limited virtual interactions. I say trust your gut and try to support your intuition with evidence. I obtained information about living in the city through online searching. Because faith is important to me, I also checked social media sites of the Muslim student faith group – I wanted to know that there was a large enough Muslim community within the city and even within the university at large, not limited to just my program.”

Ultimately, completing a PhD is a long-term commitment, and the decision making to commit to a program looks different from person to person. Self-introspection can help a lot in this case: what is important for you? Will the environment nurture your academic curiosity? Do you like the idea of living in the area for several years? Based on my own experience of interviewing virtually, I would suggest doing the following things. First, try to talk to as many people in the PhD program as you can. Do not hesitate to ask to be connected to faculty members you are interested in working with and current students to get more information about the culture of the university. Second, try to connect with previous applicants who ended up choosing a different program to understand their perspectives and add information to your decision making. Lastly, if you are moving to a new environment, do some research about the area itself – including cost of living and things to do beyond academic work – to ensure that you will adapt well.

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”

 

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Covering #AHA21 as an Early-Career Blogger

It has been a month after the American Heart Association (AHA) Scientific Sessions 2021. Not only was this year my first time attending the conference, but it was also my first time ever covering a scientific meeting as an early career blogger. As a participant in the AHA Early Career and FIT Blogging program, the AHA sponsored my access to the conference and my media pass – so fancy!

My favorite aspect of Scientific Sessions was the balance between basic and translational scientific research. As an early-career PhD scientist who primarily works at the bench, it’s easy to limit myself to the day-to-day routine of basic science work. Attending Scientific Sessions gave me the opportunity to expand my viewpoint: from viewing posters on cellular signal transduction in the morning to attending clinical talks about the latest cardiovascular treatment breakthroughs in the afternoon, the conference really had it all. The opportunity to interact with clinicians and industry partners was particularly meaningful, as it broadens my perspectives on how our basic understanding of human physiology translates into tangible, impactful solutions for patients (check out my coverage of the effectiveness of non-statin therapies in reducing low-density lipoprotein C, the “bad” cholesterol, here). Most importantly, attending sessions on health equity allowed me to reflect on the current challenges of addressing health disparities and informed my research philosophy in my own work.

Being an early career blogger also allows me to network with other early career bloggers on social media (#SciTwitter, anyone?). Due to the diversity of session topics, it was impossible to attend every session. The AHA bloggers’ live tweets and coverage of different conference sessions, however, gave me a pleasant conference experience: if I missed a session, I could read their coverage and check out recorded sessions I might have missed. Beyond the conference, I remain connected to my fellow bloggers on multiple social media platforms, an invaluable opportunity for my own professional development.

The American Heart Association recruits early career bloggers every year for The Early Career Voice, the organization’s platform to amplify the contribution of early career scientists and clinicians. Be sure to apply to the program – we need your insights to shape our conversations on science, mentorship, and professional development!

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”

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Adding to Statins: Achieving Optimum Reduction of “Bad” Cholesterol

Atherosclerotic cardiovascular disease (ASCVD) is the number one cause of death in the Western world.[1] Since 2016, cardiovascular diseases have caused 1 in 3 deaths in the United States, and this trend is expected to continue in the future. There is a well-established relationship between ASCVD and elevated levels of low-density lipoprotein C (LDL-C), often called “bad” cholesterol because of its potential to accumulate in the blood vessels and contribute to the formation of fat plaques.[2] People with familial hypercholesterolemia (an autosomal dominant genetic disease caused by mutations in the LDLR, LDLRAP, APOB, and PCSK9 genes)[3] are also at risk for ASCVD due to their genetic predisposition to high cholesterol levels.

Currently, the standard of care is statin, a group of drugs that inhibits the HMGR enzyme, a key player in the cholesterol synthesis pathway. Over 55% patients undergo statin management to lower their LDL-C levels and consequently reduce morbidity and mortality.[4] However, 7 out of 10 patients on statins do not achieve their LDL-C goal. In addition, patients on statins still have residual risk of experiencing cardiovascular events and premature mortality.[5] This is due to multiple factors: nonadherence to statin management, which typically is consumed daily; drug intolerance due to the development of statin-associated muscle symptoms[6]; heterogeneity in response[7]; and others. As such, patients who are unable to control their cholesterol levels on maximum statin dose typically require an additional therapy.

Exploring additional therapies for patients who are unable to control their cholesterol levels on statins alone is the goal of the Add on Efficacy: Oral, Nonstatin Therapies for Lowering LDL-C Program in Scientific Sessions 2021, presented by Harold Bays, MD (Medical Director and President of the Louisville Metabolic and Atherosclerosis Research Center) and sponsored by Esperion Therapeutics. Until 2020, there was only one FDA-approved oral nonstatin therapy for ASCVD management: a drug called ezetimibe, which inhibits intestinal cholesterol absorption.[8] In 2020, bempedoic acid (Nexletol™) and bempedoic acid plus ezetimibe (Nexlizet™) were approved as adjuncts to diet and maximally tolerated statin therapy for patients with ASCVD or familial hypercholesterolemia who require additional lowering of LDL-C. Bempedoic acid inhibits ACL, a key enzyme in the cholesterol synthesis pathway. By week 12 of treatment, bempedoic acid and the combination of bempedoic acid and ezetimibe led to 17-18% and 38% and mean reduction of LDL-C, respectively, compared to patients given placebo and maximally tolerated statin dose.

Although statins have typically been the first line therapy for the management of ASCVD, current trends point to the need of developing additional and orthogonal therapies to achieve optimal LDL-C levels. To this end, multiple therapies are used clinically, including oral medications like bempedoic acid, ezetimibe, and bile acid sequestrants as well as other forms of therapeutics like PCSK9-inhibiting antibodies.[9] Beyond this session on non-statin therapies, Scientific Sessions 2021 provides other updates on current clinical management and emerging breakthroughs in cardiovascular health – make sure you tune in to other sessions on November 14-15, 2021!

Reference

[1] Nichols M, et al. (2014) Eur Heart J 35:2950–9

[2] Mihaylova, B. et al. (2012) Lancet 380:581–90

[3] Bouhairie, V. E. and Goldberg, A. C. (2015) Cardiol Clin 33.2: 169-79

[4] Bittner, V. et al, (2015) Journal of the American College of Cardiology, 66.17: 1873-1875

[5] Go, A. S., et al. (2014) Circulation 129: e28-e292

[6] Ward, N. C., et al. (2019) Circ Res 124:328–350

[7] Akyea, R. K. et al. (2019) Heart 105:975–981

[8] Miura, S. and Saku, K. (2008) Intern Med 47.13: 1165-1170

[9] Gupta, M. et al. (2020) Expert Opin investing Drugs 29(6):611-622.

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”