Fights Sickle Cell Anemia and Other Diseases
By Tom Gibson
Born and raised in Sofia, Bulgaria, Peter Vekilov wanted to spend his career in his homeland. “I never thought of anything else,” he relates. As a chemistry buff, he chose to concentrate in the field of phase condensation and crystallization because Bulgaria had the best chemists for that.
“Then, suddenly communism collapsed, and it meant two things,” Vekilov recalls. “I could work in other countries without being considered a traitor. And I couldn’t work as a scientist in Bulgaria because the economy was in bad shape, so there wasn’t much money for science. My choice was either abandon science or move out of the country. I chose to stay in science.”
Vekilov ended up coming to the United States, and the 47-year-old now finds himself as a professor in the Department of Chemical and Biomolecular Engineering at the University of Houston in Texas. Along the way, he has become a pioneer in researching the nucleation and crystallization of proteins, an endeavor that has many applications, including curing diseases such as sickle cell anemia. This highlights the role chemical engineers play in treating and curing diseases and the opportunities it creates for them – even in Houston, they don’t just work at chemical plants or oil refineries.
Why chemistry as a career? Vekilov says he came by it honestly. “I had a very good chemistry teacher in high school. I think she was the best chemistry teacher in our whole country.” He adds, “My mother was a chemistry professor at the University of Sofia. I found it really fascinating that you can use microscopic data — things you can see and measure with a microscope — and then gain information about what the atoms and molecules do.”
When Vekilov went to college, Bulgaria was still under communist rule and occupied by the Russians. “I wish I could’ve gone to Cambridge in England, but I couldn’t. The government wouldn’t support me and wouldn’t allow it. The best place I could go was Moscow State University,” he says. He got a degree from there that combined a B.S. and M.S. in a five-year joint program. He would go on to get his Ph.D. in chemistry from the Russian Academy of Sciences, Institute of Crystallography in Moscow.
Then came the big move to the states. In 1993, Vekilov took a job as a research associate at the University of Alabama in Huntsville. NASA had started a program a year earlier in protein crystallization, and Huntsville became a major center of it. A top scientist there knew Vekilov’s Ph.D. advisor from Moscow, so Vekilov became a post doc for the scientist, and he went on become an assistant professor at the school. After accumulating a quality body of work there, he got recruited by several universities and chose Houston.
In explaining how he chose his specialty, Vekilov says that at Alabama-Huntsville, when he started reading about the nucleation of protein crystals, he found that many open questions existed. “You know, they crystallize crystals in millions of tons every single day in this country for various purposes of chemical industry and pharmaceuticals. It’s a huge problem,” he says. “Protein crystals are a very good model system. You can study the crystallization of proteins and the nucleation of protein crystals and draw conclusions about crystals of other materials that nucleate. That’s what I found fascinating.”
Before Vekilov, nobody had ever directly studied nucleation, and he is shedding light on the fundamental principles of nucleation. He and a co-author took the first photos of individual molecules forming the nucleus of a crystal.
Vekilov works with a research group of seven people, focusing on phase transitions that occur in protein solutions. They take interest in this because proteins in human cells and tissues form condensed phases that cause severe maladies such as sickle cell anemia, cataracts, and Alzheimer’s, among others. They employ many techniques such as the atomic force microscope, light scattering, small angle x-ray scattering, scanning probes, and interferometry.
A Debilitating Disease
Much of Vekilov’s research has focused on sickle cell anemia. With this disease, red blood cells harden into polymers and take an abnormal crescent or sickle shape. This causes obstruction of blood flow and many subsequent symptoms throughout the body, mainly episodes of pain that can last from hours to days. Red blood cells are normally shaped like a disc and pliable, so they maneuver easily through narrow passages like capillaries to supply oxygen to far-reaching parts of the body. This shape change occurs because of a mutated type of hemoglobin called hemoglobin S, hemoglobin being the protein inside red blood cells that carries oxygen.
Sickle cell anemia is inherited from both parents and is much more common in people of African and Mediterranean descent. In the United States, approximately 1 in 5,000 people get it, and about 1 in 500 African American births have sickle cell anemia; more than 7000 Americans have it. No known reliable cure exists. Treatments include medicine and blood transfusions. Bone marrow transplants can cure it but have many risks, including infection and rejection, and patients often can’t find suitable donors. The median life span for patients ranges from the 40s to 60s, but some live into their 70s.
According to Vekilov, the challenge is to find a way to slow nucleation in sickle cell hemoglobin, as this triggers the polymerization. He sees nucleation as the weakest link in the disease, the stage at which it should be attacked.
While Vekilov follows a path and comes from a background that few others have, he has found a like-minded soul almost in his back yard in the form of Anatoly Kolomelsky, associate professor of chemical and biomolecular engineering at Rice University in Houston. From Ukraine, Kolomelsky also studied at Moscow State University, coming four years behind Vekilov. As Kolomelsky recalls, “I heard about this bright new professor who came to the University of Houston chemical engineering.” They met at a meeting at the Texas Medical Center in Houston, where “Peter gave a talk I really liked” on protein nucleation and crystallization.
“We discuss many things, as we have similar backgrounds,” Kolomelsky says. They work together on formal projects and informal ones unsupported by grants. “What I like about him is he is excited about science, and it doesn’t matter if there’s money or not, we still do the work. Science is his passion.” They meet for lunch and at seminars. Rice researchers collaborate closely with those from the University of Houston.
Kolomelsky’s perspective allows him to comment on the role of chemical engineers in curing and treating diseases. “Chemical engineers are the people between fundamental scientists like me in chemistry and physics and the real world. They know the practical problems, but at the same time, they’re well trained scientists. So, I think they’re extremely important. Not all chemical engineers do this. The best ones, in my opinion, work like Peter. They really want to connect the gap.”
Vekilov echoes these sentiments, saying chemical engineers play a significant role that can be separated into two groups. “One is that engineers help design treatment strategies such as drug delivery with all these sustained release materials being designed. This is a very big field of research in chemical engineering. Then there is all the tissue engineering, the science of how wounds heal.” He summarizes: “Chemical engineers help create better tools for treatment of disease and study the fundamentals of the disease. My group is in the second area.”
Efforts Pay Off
Results are starting to come for Vekilov and his crew, as they have proposed a new mechanism of nucleation. They first came up with it in the early 2000s, formulating it only for protein crystals. Then in 2007, they published a paper that shows it also applies to the nucleation of sickle cell hemoglobin polymers. And then in the last several years, this mechanism has been shown to apply for a huge variety of systems. “Sometimes it’s called the Vekilov Mechanism and sometimes the two-step mechanism,” he explains. “It seems that this year this two-step mechanism has been recognized by many people. I’ve been asked to write three review papers for it, and it’s all very exciting.”
“His experiments were quite unusual,” Kolomelsky observes. “When Peter did his experiments on nucleation of proteins, his results were very surprising. He couldn’t describe it by classic nucleation theory, so that was quite controversial. But when we worked it out, we were able to explain his results. What is interesting, people are finding more and more examples that this two-step nucleation mechanism works. So essentially, for all complex molecules, it looks like the two-step mechanism, or multi-step mechanism, is a better way of describing nucleation, the appearance of new phases.”
While a cure for sickle cell anemia may not come soon, at least Vekilov’s work has raised hope. “We just got a paper accepted this summer that identifies a very crucial co-factor for the polymerization of hemoglobin. This is a molecule that if it’s not present in the solution or in the red blood cells, the hemoglobin will not polymerize,” he explains. “So the new target is this molecule, and the new strategy will be ways to reduce its concentration, prevent its synthesis, or find ways to remove it if somehow it’s synthesized in the red cells.”
“He has a clear physical, chemical idea. He proved it, and I think it has a very good chance to work,” Kolomelsky notes. “I may not be objective here. He’s my friend; I like him. But looking at this field, this is the best idea to come for a long time.”
“We still have to figure out the ways to study the removal of this molecule. This will probably take five years, and then you can commercialize this, probably in another five years,” Vekilov says. “My big mission: if someone is born with this disease, they can take a pill or two every day to control it. That’s the plan.”
In reflecting, it appears Vekilov’s decision to come to the states has paid off for him. He has made a name for himself, but he says he also enjoys living in a big city like Houston. “It’s an acquired taste, but I love it. It’s a big city, so it has everything you want to do. It has lots of interesting people. I’m an opera fan, and it has an excellent opera. And every once in awhile, I go to the ballet or the symphony. There are lots of universities here, so you find lots of people to cooperate with.” Such cooperation will hopefully lead the way to finding a cure for sickle cell anemia and other diseases, with chemical engineers playing a major role.
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