Two Doctoral Candidates Receive AHA Fellowships

By Dirk Hoffman

The purpose of the fellowships is to enhance the integrated research and clinical training of promising students who are matriculated in predoctoral or clinical health professional degree training programs.

Applicants must also be intending careers as scientists, physician-scientists, or related careers aimed at improving global cardiovascular, cerebrovascular and brain health.

The Jacobs School awardees are:

• Tyler Rolland, a trainee in the doctoral program in physiology and biophysics, who is mentored by Brian R. Weil, PhD, assistant professor of physiology and biophysics
  
• Namrata Deka, a trainee in the doctoral program in microbiology and immunology, who is mentored by Chelsie E. Armbruster, PhD, associate professor of microbiology and immunology
  

Rolland’s project is titled “Mechanisms of Mitochondrial DNA-Mediated Immune Activation in Post-Cardiac Arrest Syndrome.”

“I embarked on this research path driven by a deep interest in understanding the mechanisms underlying cardiovascular health and disease, particularly the complications following cardiac arrest,” he says.

“I was inspired by the complexity of post-cardiac arrest syndrome (PCAS) and the significant impact it has on patients and their families, coupled with the lack of effective therapeutic strategies to improve outcomes.”

According to American Heart Association data, the annual incidence rate of out-of-hospital cardiac arrest is approximately 375,475 adults, with a resuscitation rate of 24.9% percent, an improvement from the rates seen in the 1990s and early 200os.

However, the rate of patients who survive to discharge remains stagnant at only 9.3%, and a mere 7.5% of these survivors retain good neurological function, Rolland says.

Rolland says his previous research experiences in developing therapeutics, understanding innate immune responses and studying cardiovascular physiology provided him with a solid foundation to investigate the biological processes in PCAS and their potential clinical applications.

“I focused on the gap between successful resuscitation and survival to discharge. Recent studies have characterized PCAS and highlighted how post-resuscitation inflammation impacts patient survival,” he says. “There has been a lack of investigation into whether innate immune activation by mitochondrial DNA (mtDNA), a known inflammatory trigger, plays a critical role in PCAS.”

Rolland’s research aims to use the Weil laboratory’s established porcine model of PCAS to:

• elucidate mechanisms of cellular mtDNA release following brief whole-body ischemia, also known as sudden cardiac arrest
  
• identify specific pathways through which cell-free mtDNA activates innate immune cells
  
• determine if mtDNA-mediated immune cell activation is a viable therapeutic target in PCAS
  

“This interdisciplinary approach holds the potential to uncover novel therapeutic targets in PCAS, ultimately aiming to enhance patient care and improve outcomes after cardiac arrest,” Rolland says.

Rolland says receiving the AHA Predoctoral Fellowship Award “is an incredible honor and a significant milestone” in his career.

“It is immensely gratifying to have my research recognized at a national level,” he says. “This award will provide me with invaluable resources and opportunities, including funding for my research, access to a network of leading experts, and platforms to share my findings with the broader scientific community.”

Rolland says Weil is an exceptionally effective mentor due to this vast experience, unwavering support and genuine dedication to fostering the growth of his mentees.

“Dr. Weil’s commitment to collaborative learning and his emphasis on the importance of translational research have profoundly influenced my approach to scientific inquiry,” he says.

“His encouragement and belief in my potential have been incredibly motivating, making him not just a mentor, but also an inspiring role model in the field of cardiovascular research.”

Deka’s research focuses on studying the phenotypic and genotypic changes in Proteus mirabilis during catheter-associated urinary tract infections (CAUTI) in long-term nursing home patients.

Urinary tract infections are some of the most common infections in health care settings, with CAUTIs being particularly concerning due to the risk of spreading to the bloodstream and causing sepsis.

Her project is titled “Impact of Host Adaptation of Proteus Mirabilis Pathogenic Potential and Risk of Urosepsis.”

Deka says the bacteria Proteus mirabilis (Pm) is responsible for up to 45% of CAUTIs and can lead to serious secondary bloodstream infections.

“Pm is especially problematic because it causes kidney stones, renal failure and urosepsis,” she says.

Armbruster’s lab conducted a longitudinal study where urine samples were collected and cultured weekly for 10 to 30 weeks from 10 nursing home residents with long-term indwelling catheters.

“We found that Pm can be present in the urine of patients for many weeks even after catheter changes and antibiotic use,” Deka says. “When bacteria persist like this, they become more drug resistant and are a reservoir for invasive infection.”

“I am studying how Pm adapts while persisting within the urinary tract of the host and how this adaptation impacts the ability of Pm to cause invasive disease, increasing the risk of urosepsis and mortality,” she adds. “Urosepsis is a serious, life-threatening consequence of complicated UTI and can progress to severe multi-organ dysfunction.”

The specific aims of Deka’s research are:

• to determine the impact of persistence on P. mirabilis pathogenic potential by studying the progression of CAUTI and sepsis in a mouse model
  
• to examine the contribution of specific mutations to P. mirabilis pathogenic potential by looking at its genotypic profile
  

“By the end of our studies, we will have identified the changes in the bacteria’s characteristics and genes that help it persist during long-term colonization and how these changes affect its ability to cause serious infections like bacteremia and sepsis,” Deka says.

“Understanding the genetic lineages of Proteus mirabilis will reveal trends in its harmful traits and mutation rates.”

Deka says as an international student studying in the U.S., she is unable to apply to many of the fellowships available due to her citizenship status. She says she was particularly happy to learn the AHA predoctoral fellowships are open to all students conducting research in the U.S.

“I am very grateful to have been funded for two years, as this is a tremendous boost to my doctoral career,” she says. “This award also allows me to be a part of a research community at the American Heart Association which opens up avenues to meet and network with distinguished scientists in the field.”

Deka says Armbruster creates a very supportive environment for the trainees in her lab, making them feel valued and understood.

“She is a very encouraging mentor, helping me to stay focused and driven to achieve my goals,” she says. “She is attentive to our aspirations and provides clear and practical guidance to help reach them, and she tailors her advice to our individual needs.”

Deka says she wants to learn bioinformatics skills in addition to the bench work in the bacteriology lab.

“Dr. Armbruster has been very supportive of these goals and has helped me collaborate with scientists with those specific skills,” she says. “She mentors with an attention to detail to ensure that my work is of the highest quality, and her support for our career development is invaluable as she listens to our goals and helps seek out opportunities and networks.”