Probing the interaction of SCD and malaria resistance in Ghana

September/October 2024 | Volume 23 Number 5

This page features a photo of Dr. Adel Driss wearing a black suit jacket, pale green shirt, and an African-print tie with a matching pocket handkerchief.

Photo courtesy of Adel DrissDr. Adel Driss of Morehouse School of Medicine

Sickle cell disease (SCD) is a genetic condition caused by a mutation in one of the genes that controls hemoglobin, the protein in red blood cells that transports oxygen. People with sickle cell trait—those who carry one mutated allele of the sickle cell gene—are protected against severe malaria. This unusual interaction between a genetic disease and a parasitical infection transmitted by mosquitoes intrigued Dr. Adel Driss during his 2014 Fogarty Global Health Fellowship.

His fellowship at the Noguchi Memorial Institute for Biomedical Research in Ghana led to his International Research Scientist Development Award (IRSDA) project, which investigated the molecular factors underlying the complex relationship between SCD and malaria resistance.

Molecular deep dive

Driss, an assistant professor at Morehouse School of Medicine, split his IRSDA project time between field research in Ghana and performing lab experiments and data analysis in the U.S. The relationships he established as a fellow helped him in his immersive investigation. Specifically, he investigated how microRNAs, small molecules in the blood that regulate gene expression, may play a role in protecting individuals with sickle cell trait from severe malaria. This study involved collecting blood samples from individuals with various sickle cell genotypes to examine whether microRNA levels fluctuate during malaria infection. (“Sickle cell genotype” refers to the specific abnormal hemoglobin gene a person inherits—there are a few different types.) Driss also conducted lab experiments and mouse model studies to explore how microRNAs affect malaria parasites in red blood cells. “For example, if we increase the expression level of a specific microRNA, will that enhance or inhibit malaria parasite growth?” he explained.

His project, scheduled to run from September 2016 to August 2021, was extended to March 2022 due to COVID-19 disruptions. The early years were productive, with almost 900 samples collected, and progress made on the study’s objectives. Later, pandemic restrictions prevented travel and fieldwork in Ghana and limited lab access in the U.S. Despite challenges, he and his colleagues achieved key milestones. Their findings included identifying differences in microRNA expression across various hemoglobin genotypes. They also showed that malaria parasites in red blood cells derived from donors grew at different rates (in petri dishes) depending on the donor’s hemoglobin genotype.

In the photo on this page, Dr. Adel Driss, who is wearing a white shirt with blue stripes, looks into a microscope

Photo courtesy of Adel DrissDr. Adel Driss’ findings enhance the understanding of the relationship between microRNAs, SCD, and malaria

“Additionally, we identified miR-451a, a microRNA, as a potential new player in the pathogenesis of malaria and SCD,” said Driss. (The 2024 Nobel Prize in Physiology or Medicine honored two scientists for their discovery of microRNA and its role in post-transcriptional gene regulation.) Though Driss is still preparing final results for publication, six articles have already been published in high impact journals. Overall, his findings enhance the understanding of the relationship between microRNAs, SCD, and malaria. Possible long-term outcomes of this work include development of new therapies, interventions, and diagnostic tools aimed at preventing severe malaria and improving the health of individuals with SCD.

Why Ghana?

Conducting research on SCD in Ghana was essential to his study because it is a malaria-endemic country with SCD affecting approximately 2% of newborns, said Driss. (Sickle cell allele prevalence among Ghana’s general population is reported to be 25%.) The West African nation’s rich genetic diversity allowed him to investigate a variety of distinct sickle cell genotypes and their interactions with malaria. His project, a collaboration between Morehouse School of Medicine and the Noguchi Memorial Institute for Medical Research, has benefited the local population and also informed resource allocation in the region. “We've trained students and early-career researchers in both Ghana and the U.S.,” said Driss.

Previously, Driss studied muscular dystrophies in Tunisia, France, and Japan. He’s also conducted research on cancer at Emory University. “Since grad school, I’ve been involved in research all over the world, which is amazing and the best part of my work. I’ve collaborated with various institutions in different countries and trained different students at different career levels.”

Shared lessons

Experience cultivates wisdom and mentorship is crucial for success, says Driss. In a blog post commemorating his late mentor, Professor Dr. Michael David Wilson of the Noguchi Memorial Institute for Medical Research in the University of Ghana, he writes, “Together, we explored how genetic and molecular factors influence disease outcomes, focusing on microRNAs, exosomal signaling, and inflammation. His generosity of spirit, matched with his extraordinary intellect, made him irreplaceable in the global fight against infectious diseases.”

So what does Driss tell his mentees? “Have a collaborative and multidisciplinary vision in mind from the start of a project.” He emphasizes that combining molecular biology, genetics, immunology, and epidemiology helped him explore interactions between malaria and SCD. A similar interdisciplinary approach is essential for addressing other complex global health issues, he notes. Working on a global scale also requires diplomacy: “because it's easy to get lost in translation—be very careful about what you say and don't say.” Finally, he recommends cultivating patience and resilience. “It's not always as easy as it looks… or as it's supposed to be!”