Trainees Earn American Heart Association Fellowships

The AHA is the largest not-for-profit funding source for cardiovascular and cerebrovascular disease research next to the federal government.

“Congratulations to these Department of Microbiology and Immunology trainees for successfully securing coveted AHA fellowships,” says Allison Brashear, MD, UB’s vice president for health sciences and dean of the Jacobs School of Medicine and Biomedical Sciences.

“It is a testament to the outstanding quality of students, faculty mentors and programs in the Jacobs School’s Department of Microbiology and Immunology,” she adds.

Emily Blair Ivey, a third-year student in the doctoral program in microbiology and immunology, is funded for $63,072 over two years on an AHA predoctoral fellowship for her proposal titled “Elucidating the Antiviral Role of LGALS3BP against SARS-CoV-2.”

She is mentored by Spyridon Stavrou, PhD, assistant professor of microbiology and immunology, and her work focuses on how the galectin 3 binding protein LGALS3BP, also known as 90K, is able to block the COVID-19 virus.

Severe acute respiratory coronavirus 2 (CoV-2) is the causative agent of COVID-19 and the current global pandemic. CoV-2 infection is characterized by a plethora of symptoms including respiratory distress, extensive cardiovascular damage, and extrapulmonary pathology.

During infection, CoV-2 stimulates a cell intrinsic immune response characterized by the production of host antiviral genes known as restriction factors.

“Our restriction factor of interest, 90K, has been previously shown to restrict biosynthesis and incorporation of the HIV envelope protein, however, the mechanism of restriction is unknown,” Ivey says.

“Our preliminary data indicate that 90K prevents the production and viral incorporation of the CoV-2 spike protein. Spike is required for CoV-2 binding and entry and targeting spike production is a promising avenue for antiviral therapies,” she adds. “In these studies, we will determine the mechanism of 90K restriction on CoV-2.”

Ivey says her research will aim to determine if 90K is directly binding CoV-2 spike and which domains of 90K are involved in its antiviral activity and will also aim to determine the global impact of 90K on the coronavirus family.

“Understanding the way that viruses interface with the host has important implications in the prevention of and response to future emerging viruses,” Ivey says. “This is especially notable because the climate crisis is driving the increased zoonotic emergence of viral pathogens.”

“The antiviral factors that our lab studies have functions in limiting zoonotic viral transmission,” she continues. “Additionally, the factor that I work on, has negative implications in cancers and is an active target of drug development, some of which could have antiviral functions.”

Ivey, a native of Katonah, New York, earned a Bachelor of Science degree in biology on the microbiology track from the University of Rochester and a Master of Science degree in immunology, microbiology and virology from the University of Rochester School of Medicine and Dentistry.

She reveals that she has an interesting path in how she landed in microbiology.

“My mother is ‘vaccine-hesitant.’ As a child, I would read as much as I could in preparation for pediatrician appointments so I could try to convince her to let me get my shots,” she says. “This was what initially drew me to microbiology and infectious disease.”

Ivey says when applying to doctoral programs, she was looking for a collaborative environment with a healthy level of competition.

“I also really wanted a program that placed emphasis on lab work, where classes and qualifying exams were not treated as a major hurdle where students had to prove themselves,” she said.

“I felt like the Jacobs School was exactly that, and thankfully, that was an accurate assessment.” Ivey adds. “The re-worked PPBS (PhD Program in Biomedical Sciences) curriculum felt worthwhile and we weren’t just expected to memorize and regurgitate information.”

When looking for a lab, Ivey says she wanted an environment where she felt challenged and supported.

“Dr. Stavrou is an incredibly hands-on mentor without hand holding his trainees and this was the perfect balance for me,” she says. “He is incredibly invested in his students and everything that goes on in the lab and tailors his mentorship to what different trainees need.”

“Even as I was submitting my AHA proposal, he was in Greece visiting family, but he still made the time to go over my application with me multiple times,” Ivey adds.

She says Stavrou “has fostered an amazing and supportive lab environment where we are all invested in each other’s success and projects.”

Murat Can Kalem, is a trainee in the doctoral program in microbiology and immunology, who works in the lab of John C. Panepinto, PhD, professor of microbiology and immunology and director of recruiting and admissions for PPBS.

A native of Istanbul, Turkey, he completed two bachelor’s degrees — in cell and molecular biology, and biochemistry — at the University of Minnesota–Duluth.

Kalem says he was drawn to the doctoral program in microbiology and immunology at the Jacobs School because of the department’s focus on eukaryotic pathogens.

He was awarded a one-year AHA predoctoral fellowship of $32,000 for his project titled “Role of Arginine Methylation by Rmt5 on lncRNA Biology in Cryptococcus neoformans.”

Cryptococcus neoformans is a ubiquitous environmental fungus and a human pathogen that causes cryptococcosis in people living with organ transplants and immune system defects. 

C. neoformans can adapt and survive under different and challenging conditions, both in the human body and the environment, Kalem says

“Current antifungals are toxic, hard to administer, and drug resistance issues are emerging,” he adds.

“My research broadly focuses on understanding the molecular biology and genetics of this pathogenic fungus that causes devastating infections in immunocompromised people, including heart transplant patients,” Kalem says.

Kalem is investigating an enzyme that modifies proteins, called Rmt5. He says he wants to know which proteins are modified and how these modifications help control gene expression because he believes that this modification may be common in proteins that interact with ribonucleic acid (RNA). 

“I will find out which proteins are modified by Rmt5 and study how protein modifications change when we remove Rmt5. Then, I will explore how modified proteins are interacting with RNAs,” he says. “This interaction of proteins with RNAs may control various functions of the cell.”

“The overall goal of my research is to identify properties of the fungal cell that can be targeted for therapeutic interventions,” Kalem adds.

Kalem says Panepinto “has been a fantastic mentor.”

“He has been extremely supportive. He tailors his mentoring style to each student and makes sure that each person has what they need,” he says.

“Dr. Panepinto provided me with the resources, mentoring, and opportunities to develop an independent and a creative research project,” Kalem says. “It has been invaluable to have such a supportive mentor who has been selflessly guiding me to become a better and a more critical scientist and a person.”

“Dr. Panepinto not only prepared me so well for my next step in academia, but has shown me that I can count on him for guidance, advice and wisdom for the rest my career.” 

Manmeet Pal Singh Bhalla, PhD, is a postdoctoral fellow in the lab of Elsa Bou Ghanem, PhD, assistant professor of microbiology and immunology.

Bhalla is originally from India and earned his bachelor’s and master’s degrees there before earning a doctoral degree in microbiology and immunology from the University of Otago in New Zealand.

He says his initial decision to attend the Jacobs School was mainly driven by his inclination to join Bou Ghanem’s lab.

“I really liked the work she had previously done, and I wanted to venture into the field of neutrophil biology. However, soon after joining the lab, I realized that UB has a lot to offer to the postdoc community,” he says. “The Department of Microbiology and Immunology itself is very supportive and welcoming. The faculty and administrative staff are very helpful. They have supported my intellectual ideas and are appreciative of my research.”

“The overall environment at the department is healthy and student-friendly,” Bhalla adds. “UB provides a collaborative environment dedicated to training of postdocs and doctoral students.”

He describes Bou Ghanem as a “highly enthusiastic and excellent mentor.”

“I have always seen her as a welcoming and humble person, which helps the entire lab to learn more from her,” Bhalla says. “Her inputs and support over the last three years have tremendously helped me with my confidence and problem-solving abilities.”

“With Dr. Bou Ghanem’s support and guidance, I started a new area of research in her lab where I am investigating the role of neutrophils in pneumococcal endocarditis,” he adds. “She gave me the freedom to take ownership of this project from the beginning. Most importantly, she has involved me in the paper and grant-writing process which has proved to be an extremely valuable experience.”

Bhalla’s AHA postdoctoral fellowship is funded for $137,000 over two years and is based on his study titled “Role of Extracellular Adenosine Pathway and Neutrophils During Infective Endocarditis Induced by S. Pneumoniae.”

Streptococcus pneumoniae (pneumococcus) is a serious bacterial infectious threat globally and mainly targets the elderly, he says.

“The disease caused by this bacterium mainly manifests as pneumonia with more invasive pneumococcal strains capable of reaching blood and causing endocarditis and meningitis with a high mortality rate,” Bhalla says. “This organism disproportionally impacts individuals older than 65, where it is increasingly becoming a nuisance in terms of hospitalization rates and treatment costs.”

He says researchers want to know why elderly people are more susceptible to pneumococcal infections and which signaling pathways go bad with age, which decreases the immune response to S. pneumoniae.

One such pathway is the extracellular adenosine (EAD) pathway, which gets dysregulated with age. This dysregulation lowers the capacity of host immune cells, especially neutrophils, a type of white blood cells, to fight Streptococcus pneumoniae, thus making the host highly susceptible to invasive infections. 

“As a part of the main question of the lab, I am trying to understand why aging is associated with reduction in adenosine signaling on neutrophils and exploring various strategies to boost the host immune response against invasive pneumococcal infections using aged mice model,” Bhalla says.

The other focus of his research involves exploring the role of neutrophils and the EAD pathway in bacterial endocarditis.

“S. pneumoniae has the capability to reach blood and then infect the heart, thus causing endocarditis, which is a serious condition with a high mortality rate,” Bhalla says.  “The heart in these patients gets damaged because of the immune response from the body. I therefore want to understand why immune cells damage the heart during these bacterial infections.”

He says neutrophils can move freely into any tissue and help the body fight and clear infections, but when neutrophils reach the heart, instead of helping, these cause serious heart damage.

“Does the EAD pathway play any role in controlling the damage done to the heart by neutrophils?” Bhalla asks. “By studying this, we hope to use the immuno-modulatory agents which target adenosine to fight infection, prevent or limit the extent of heart damage and help patients recover faster.”