New Publication Studies Effectiveness of Anti-Malarial Drugs

Dr. Roland Cooper and Dominican University of California graduate student Jordan Charlton ’21, are co-authors on a new publication in the Journal of Medicinal Chemistry focused on the effectiveness of anti-malarial drugs. The project, led by researchers from Stanford University and University of Central Florida, features work done by Cooper and Charlton in Uganda during summer of 2022.

"Discovery of Potent Antimalarial Type II Kinase Inhibitors with Selectivity over Human Kinases" demonstrates that the experimental kinase inhibitors had excellent potency against Plasmodium falciparum parasites isolated from malaria patients, says Cooper, who teaches advanced genetics, medical parasitology, and research methodology at Dominican.

While progress has been made in the effort to eradicate malaria, the disease remains a significant threat to global health, note the authors.

“Acquired resistance to frontline treatments is emerging in Africa, urging a need for the development of novel antimalarial agents. Repurposing human kinase inhibitors provides a potential expedited route given the availability of a diverse array of kinase-targeting drugs that are approved or in clinical trials. Phenotypic screening of a library of type II human kinase inhibitors identified compound 1 as a lead antimalarial, which was initially developed to target human ephrin type A receptor 2 (EphA2). Here, we report a structure–activity relationship study and lead optimization of compound 1, which led to compound 33, with improved antimalarial activity and selectivity.”

Charlton says working with Cooper in Uganda gave her first-hand insight into the importance of collaboration in a research lab. The project involved working with anti-malaria compounds for a study that also involves scientists from the University of Central Florida, Cornell University and Portland State University.

“From the moment Dr. Cooper approached me with the opportunity I knew that was exactly what I wanted to do,” says Jordan, who earned a BS in Biochemistry from Dominican and is scheduled to graduate this spring from the MS in Biological Sciences program.

Jordan was a member of Dominican’s NCAA Division II women’s basketball team as both an undergraduate and graduate student. During the 2022-23 season she appeared in 15 games with nine starts and 211 minutes played while balancing her work as a graduate research student. In the 2021-22 season she was an academic All-PacWest recipient, appearing in 27 games with 25 starts and 487 minutes played. She scored a career-high 16 points to help lift Dominican to a 93-82 victory at Fresno Pacific.

“Basketball taught me many valuable traits such as, dedication, leadership, communication, teamwork skills and most importantly the true meaning of passion,” she notes. “I say this because my passion for research was sparked when I saw my first DNA sequencing chromatogram on my computer screen. It was not just any DNA sequence it was the same DNA that I had earlier extracted from a living crustacean. As an undergraduate research student, it was an astounding moment that kept me eager to learn new research skills and further understand the important role research plays for the future of medicine .”

After she graduated from Fort Lauderdale High School, she played basketball at St. Thomas University in Miami. She transferred to Dominican from Broward Community College.

“Dominican’s science program seemed very strong, and they had the pre-med mentorship program and that really stood out to me,” says Jordan, a native of South San Francisco. “The biological science program also seemed very strong. I also loved the small class size.”

That allowed her greater access to professors, including Cooper, who earned his PhD from the University of Arizona in Pharmacology & Toxicology and his master’s in public health from the Harvard School of Public Health. He came to Dominican and the School of Health and Natural Sciences to combine his love of research and his commitment to mentoring students. He has been investigating the molecular mechanisms how drugs work against the malaria parasite known as Plasmodium falciparum, for more than 20 years with the help of funding from the National Institutes of Health and several private foundations.

In collaboration with scientists from research institutions across the United States and abroad, Cooper is studying how the Plasmodium parasites become resistant to drugs and how this knowledge guides development of new compounds to treat malaria. Cooper invites Dominican undergraduates and graduates to participate in the malaria research, both in his Dominican laboratory and, during the summer, on field studies in Uganda. He also studies parasites at a laboratory in the west African country of Burkina Faso, where he and his team have started a new research program.

“We learn a lot about anti-malarial drug work and the genetic landscape of the parasite,” Dr. Cooper says. “When the government of Uganda says they are going to use this drug, they follow how malaria changes with the drug remedy. We research and learn a lot about how to give good advice as to what anti-malarial makes sense to use because which malaria chemotherapies to use may need to be reconsidered every few years. There needs to be constant updates in the way it is treated.” 

Jordan brought a basketball – as well as Dominican T-shirts from Dominican Athletics – with her to Uganda. Both proved popular.

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“That ball was bouncing from sunrise to sunset once— we’d be eating breakfast and it would be bouncing,” she says. “We would come home from work, and it would be bouncing. Adults began to play with the basketball, too, and everyone became involved. It got put to good use to say the least!”

“The entire trip was so rewarding,” says Jordan, who would like to pursue a career in translational research to help pave the way for future therapeutics upon completing her Dominican education.

Through his mentorship, students learn to think and work as researchers. He has inspired future MDs and PhDs to not limit their ambitions.

Among the Dominican alumni whose lives Dr. Cooper has impacted include:

Stephanie Huezo, DNP, ’12 BS, ’15 MS spent two summers working with Dr. Cooper in Uganda, before graduating and accepting a position as a technician in a microbiology laboratory at UCSF. She now is a pediatric nurse practitioner at Provider Healthcare. 

Dr. Jordan Rode ’14. The summer before Jordan began working on his medical degree at University of California Davis School of Medicine, he traveled to Uganda with Dr. Cooper to work at Tororo District Hospital studying the evolution of drug resistance in malaria parasites from blood samples from infants. Today Jordan is an emergency medicine physician at University of Utah Health.

After rotating through several research labs at Dominican and completing a summer internship at Stanford, Dimitrios Camacho ’19 was the first Dominican MHIRT fellow to work with a collaborator of Dr. Cooper in Malawi, on a malaria project. Dimitrios received a Minority Health International Research Training Fellowship (MHIRT), funded by the NIH through UC Berkeley’s Center for Emerging and Neglected Diseases in support of his studies abroad. Dimitrios became a PhD candidate in the Merchant Lab in the Department of Molecular and Cell Biology at UC Berkeley.

Stephanie Rasmussen ’15 BS, ’17 MS spent three summers working in Uganda and was the lead author on a paper describing her work, published in Antimicrobial Agents and Chemotherapy plus is a co-author on five additional papers. She graduated from the UC Davis School of Medicine with honors and began the residency program at New York University Grossman School of Medicine.

Frida Ceja BS ’17 has spent three summers in Uganda with Dr. Cooper and has contributed to several important studies and continues to be a co-author on multiple publications. Frida is currently a medical student at Midwestern University in Glendale, AZ.

Sevil Chelebieva ’20, went to Uganda in 2019, also with an NIH-MHIRT fellowship to study malaria. There she worked in the lab to assess the sensitivity of malaria parasites to new antimalarial compounds in blood samples from malaria patients. She has since appeared as a co-author on several peer-reviewed research publications and is currently an ophthalmic technician.