Szirina Ismail, COL ’26, Toronto, Canada
As an aspiring physician committed to global health, I was drawn to the Abdulmalik Lab for its focus on sickle cell disease: an illness that disproportionately impacts vulnerable communities in the Middle East, sub-Saharan Africa, and beyond. With my strong interest in medicinal chemistry and pharmacology, I was particularly inspired by the lab’s emphasis on these fields, where we conduct extensive in vivo and ex vivo experiments to evaluate drug efficacy.
This summer, my project centered on scaling up a delay-time absorption assay to test novel therapeutic candidates for sickle cell disease. The assay measures how long deoxygenated sickle hemoglobin takes to polymerize. Drugs that extend this delay provide hemoglobin more time to reoxygenate in the body, serving an important therapeutic role. Our challenge was to transition from a protocol that tested only a few compounds to one capable of screening dozens simultaneously.
Developing this high-throughput method offers several advantages: minimizing variability between experiments, increasing replicates for stronger statistical reliability, and reducing the volume of valuable reagents required. This is particularly important because purified hemoglobin S, essential for the assay, is difficult to obtain. I spent two weeks purifying a large volume of blood to generate enough hemoglobin S for experimentation, a labor-intensive process requiring careful preparation of buffers at precise pH values.
To optimize the new assay, I standardized reagent volumes, ran control experiments to establish ideal conditions, and redesigned the plate map to minimize cross-contamination. At each stage, I questioned assumptions, isolated variables, and iterated on technical details. This experience taught me to embrace complexity as an opportunity to refine methods and ask better questions. Next steps for this assay include screening additional drug candidates and testing them in mixtures containing hemoglobin F and A, as well as exploring dose-dependent effects of drug-induced hemoglobin modifications.
In parallel, I also optimized a density separation assay to compare the density of healthy red blood cells with that of sickle cells, both untreated and treated with candidate drugs. Using self-forming and mechanically layered gradient solutions, combined with centrifugation, we tested multiple conditions to identify the most effective for evaluating drug effects on cell density.
This summer was valuable in bridging my chemistry background with an in-depth understanding of drug development for a disease that affects millions worldwide. It reinforced my commitment to a career at the intersection of medicine and global health. I am deeply grateful to Dr. Abdulmalik and my lab colleagues for their mentorship, and to the UPenn Career Services Summer Grant for making this research possible.
This is part of a series of posts by recipients of the 2025 Career Services Summer Funding Grant. We’ve asked funding recipients to reflect on their summer experiences and talk about the industries in which they spent their summer. You can read the entire series here
