Meet Biomedical Sciences alum Tim Czajka, PhD
Tim Czajka is making an impact in the field of cell and gene therapy research at Regeneron. During his PhD program in the Department of Biomedical Sciences, he took inspiration from emerging COVID treatments to develop treatments for ricin poisoning. Czajka recently published a first-author paper in Biochemistry titled “A Biparatopic Intrabody Renders Vero Cells Impervious to Ricin Intoxication”. In this paper, he and his collaborators showed that bispecific (Biparatopic) antibodies were able to prevent cytotoxicity after ricin exposure in vitro.
Czajka found his passion early on in the Mantis lab. Looking back, Czajka says he benefited from the broad perspective UAlbany’s Department of Biomedical Sciences provided through its connection with clinical and public health labs.
He cautioned PhD students against pigeon-holing themselves, instead encouraging fellow scientists to widen their perspectives.
“Whether you want to stay in academia or go into industry, the field is constantly evolving. It is important to stay on top of these discoveries because they really do change the world and can have impacts that you don’t anticipate,” he said.
Holding a big-picture perspective helped prepare him for working in the multi-faceted pharmaceutical industry.
Between finishing his PhD and joining the Regeneron team, Czajka noticed how the race for drug development during COVID paved the way for new technologies that could be applied in a clinical setting. Czajka explained that both COVID and ricin treatments have a shared concern, as they apply genetic material as a drug to target the lungs. His research is unique in the ricin research field because he focused on genetic material while most other ricin research focuses on conventional (protein-based) treatment strategies. Unlike COVID, ricin is largely researched for biodefense purposes. Since ricin can be used as a bioweapon, it’s vital to prepare fast and effective treatments - particularly when there may not be adequate time to vaccinate and wait for an appropriate immune response (like can be done for COVID).
“The problem is that vaccines are more of a long-term solution and ricin isn’t always long-term problem” Czajka explained. “However, just like COVID vaccines, mRNA might soon be a fast and effective delivery method for ricin toxin treatments.”
These potential mRNA treatments may someday encode for antibody fragments derived from camelids that can target ricin for neutralization intracellularly. These VHH camelid antibodies are about a tenth the size of conventional antibodies with small binding surfaces. This makes them ideal for quick delivery and wedging into enzymatic active sites. Czajka and his colleagues used a VHH heterodimer made of two antibody subunits. Each subunit can neutralize ricin toxin on their own by grabbing and holding on to different spots on the ricin toxin. When combined they bind up ricin toxin surprisingly effectively.
“When we did this, the effect was more pronounced than we expected. Cells were almost completely protected from toxin,” said Czajka.
In the future, Czajka would love to see intracellular antibodies (or intrabodies) get the love they deserve. They have enormous potential for therapeutics and biotechnology. Intrabodies have improved binding strength and specificity compared to biomedical tools that rely on small molecules. Intrabodies could also be used for intracellular labeling in live cells or even protein-level knockdown experiments.
“There’s a lot of biology left to learn with the right set of tools,” said Czajka.