For this Grant Warrior: Third Time's the Charm

It is challenging to secure federal research funding. Perhaps "challenging" is not the right word. It can feel downright impossible, hopeless, and soul crushing. For sure, it tests one's mettle.

In 2020, the NIH funded only about 20% of the 55,038 applications it received. Many researchers spend as much as 50% of their time writing grants. So, the return on investment is low.

But all is not lost. Just ask Laura Cheney, M.D., Ph.D., instructor in the department of medicine's division of infectious diseases, who received the competitive K08 Career Development Award on her third attempt. She received funding from the National Institutes of Mental Health to support, "Antiretroviral Therapy Impacts Autophagy in Astrocytes, and May Contribute to HIV-Associated Neurocognitive Disorders."

Her perseverance and fortitude should win its own award. Here's why.

A Conversation with Dr. Cheney

What is your research about?

I'm studying how HIV-associated cognitive disorders develop in people with HIV who are taking antiretroviral therapy. It's a very complex process and not wholly understood. But it causes significant morbidity in patients. Even in 2022, when there have been so many advances in the treatment of HIV, neurocognitive impairment is an independent risk factor for death.

I am interested in seeing how antiretrovirals may be contributing to the process of neurocognitive decline, specifically how they affect an intracellular process called autophagy, the cell's self-cleaning mechanism.

What is happening in the brain?

It's a spectrum of abnormalities that includes cognitive deficits, motor abnormalities, behavior, and mood changes. Before antiretroviral therapy, the predominant clinical manifestation was dementia. While we are seeing less dementia now with the availability of antiretroviral therapy, more mild manifestations of the illness persist. These range from subclinical, where it is picked up on testing, but the patient isn't feeling any effects, to where it interferes with their activities of daily living -- relationships, employment, decision-making, etc.  

Without autophagy, cells die. In astrocytes, which are major support cells of the brain, disruption in autophagy has been identified in a lot of neurodegenerative conditions like Parkinson's, Alzheimer's, Huntington's, and ALS. So, there is some literature to support my hypothesis that autophagy is disrupted in the brain in people with HIV that contributes to neurocognitive impairment. There's also literature to support that antiretrovirals may be impacting autophagy.

My goal is to better understand what the drugs are doing in autophagy. Once we know, we can design new antiretrovirals that don't affect autophagy or design modulators of autophagy that could counteract the effects of antiretrovirals or even design antiretrovirals that impact autophagy in a beneficial way.

When did you first apply for a K08 grant?

With the help and support of my mentor Dr. Joan W. Berman (professor in the department of pathology and in the department of microbiology & immunology), I submitted my first application in September 2019 and learned in April 2020 that I did not get the grant. We didn't expect to receive funding at that time. Most people don't get it the first go-round. The point of doing it even though you don't expect to be successful is to receive feedback on how to improve not just the grant writing part but the science itself.

I resubmitted my application in January 2021 where I felt that I addressed all the reviewer's comments, questions, and concerns, and my score improved but just by a little, so we knew again that it wasn't going to be in the fundable range. This is where mentorship is so important. Along the way, Joan guided me—she talked to people, we spoke with the program officer, asked the right questions, read between the lines of the reviewer's answers. We re-grouped.

For lack of a better phrase, "you have to play the game," understand the whole process­—the known and the lesser known, the said and the unsaid—and if you don't have proper mentorship, you're never going to learn how to play. I hate to phrase it that way. But that's the reality. I benefited enormously from Joan's vast knowledge. Rejection is not easy, and Joan was the ultimate cheerleader as was my other mentor Dr. Liise-anne Pirofski (chief of the division of infectious diseases). They both kept me in the game when I had serious doubts. Anyone who has put their blood, sweat, and tears into writing a grant knows the emotional letdown, the bruise to your self-esteem. It's then that you need to summon the emotional reserves to start again.

The third submission in September 2021 was a considered a new application—not to me of course—but to the NIH. So again, I addressed all their concerns. I learned a little bit more about what was being said in between the lines by the program officer and polished up the application. And my score improved significantly. But it was still borderline, which was devastating.

So, with that borderline score, speaking to the program officer again, and doing other things that would help gain the attention of the review committee, I revised the application. It took several months but I finally found out that I would be getting the award.

What would you advise others who are getting discouraged by the process?

I have a few things to offer. It feels very personal, but you have to try not to take it personally because it's not personal. Be open to the feedback in the criticism. And take and learn what it is people have to say. You might initially get some feedback that you think is ridiculous. But there's something to be learned. Maybe it's that you didn't make yourself clear enough. Or you said something in a way that wasn't what you meant.

You need to be open to hearing things that come from what may initially seem like a bad opinion. Growth happens in our most uncomfortable moments. We have to work hard at putting personal, uncomfortable, defensive feelings aside to be open to input so that we can grow.

Equally important is that if this is your passion you must keep going. For those of us earning M.D.s and Ph.D.s, we've worked way too long and way too hard to feel unfulfilled and unsatisfied with where we're at in our careers. So, keep pushing. Find the right mentors. Everybody needs multiple mentors who are going to help and support them and teach them the tools they need to be successful.

I scored high in the mentor department—and on the first go-round. And I can't thank them enough.

Her Mentors Respond

Dr. Joan Berman

"Laura is both an outstanding scientist and clinician. She has extraordinary intellect and compassion, and the drive and tenacity to accomplish truly great things. It is important to note that Laura performed much of the research for and writing of her KO8 application at the height of and during this ongoing pandemic, when her clinical demands were intense. She was undaunted, positive, gracious, and fiercely committed. She is a role model to us all in her ability to get things done, to stay focused on what is important, and to move forward even when challenged, while still fulfilling other significant obligations, all so pleasantly. I am thrilled that Laura’s hard work and creativity has been rewarded, and know the best is yet to come for her! I am delighted to have Laura as a highly valued colleague and friend."

Dr. Liise-anne Pirofski

"From the moment she interviewed to join our fellowship, Laura had her sights on a career path as a physician-scientist. I am delighted that she found her way to Joan Berman who provided her with the scaffold to develop a project that was recognized by the NIH in funding her career development award (K08). I am ever so happy for and proud of Laura for taking on and tackling the challenges of this very important journey."