A research project to create a new generation of medicines that more accurately target disease while reducing side effects is underway in the lab of Chemical Engineering Associate Professor Maryam Raeeszadeh-Sarmazdeh.
Sarmazdeh and her team are building new therapeutic proteins by modifying naturally occurring proteins to better recognize and target disease.
“Research like Dr. Sarmazdeh’s demonstrates the power of engineering to address some of society's most pressing challenges,” Engineering Dean Tom Weller said.
Keri Ryan, head of Engineering’s School of Civil, Environmental and Chemical Engineering, echoed that sentiment, emphasizing the broad impact engineering can have across disciplines.
“Engineering can help solve challenges in nearly every area of society, including health,” Ryan said. “We’re proud to support Dr. Sarmazdeh’s research, which applies engineering principles to the development of new medical therapies.”
This research is supported by a five-year National Institutes of Health (NIH) Maximizing Investigators' Research Award (MIRA) announced last summer that will provide approximately $2 million in funding.
NIH’s MIRA awards are meant to support a researcher’s entire research program, rather than an individual project. For Sarmazdeh, who has focused on protein engineering research for the past decade, this award is an opportunity to push the boundaries of protein science.
“The NIH MIRA program is designed to support bold, innovative research with the potential for long-term impact," Josh Baker, UNR Med’s associate vice president for research, said. "Dr. Sarmazdeh's work is expanding the frontiers of protein engineering and creating new opportunities for the development of more precise therapies to address complex diseases."
A new protein, inspired by nature
Very basically, Sarmazdeh and her group are designing a new protein using parts of naturally occurring proteins combined with engineered components. The goal is to create a new protein that would block harmful proteins from damaging the extracellular matrix, the body’s natural support structure for cells.
“This work is about learning from nature, then going beyond it — using engineering and computation to design the protein scaffolds that evolution never had the chance to make, but that could form the foundation of safe and more effective therapies,” she wrote.
Sarmarzdeh and her team are designing this new protein through an exhaustive process that involves both directed evolution, improving proteins through repeated testing and selection, and machine learning, in which large language models learn from each round of experiments to guide smarter designs.
At the end of the MIRA award’s five-year funding period, Sarmazdeh aims to deliver something like a blueprint of a molecule engineered to act only on certain, targeted specific signaling molecules and enzymes, those that could malfunction and cause disease. Critical non-pathological molecules within the extracellular matrix would remain untouched, meaning fewer side effects for the patient.
"We want to make a beautifully tuned molecule that goes in, does its job, and doesn't interact with anything that disturbs normal cell function," Sarmazadeh said. "Avoiding side effects is one of our major goals. We're not just trying to make a more efficient drug; we want one with as few side effects as possible."
Potential treatment for diseases
In general, Raeeszadeh-Sarmazdeh's research focuses on engineering proteins to create new tools and materials, including medical treatments. More specifically, her current work centers on designing a protein that could one day help prevent several diseases driven by these pathological enzymes and molecules. Over the past decade, much of her research has involved laboratory experiments to engineer and design these protein-based therapeutics, then test them in biochemical and cell-based assays, allowing her team to study how cellular damage can be inhibited and drug delivery improved. While the work is still at an early, foundational stage, its long-term impact could be significant, opening the door to safer, more targeted therapies for some of medicine's most stubborn diseases where no efficient therapy currently exists.
