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Iwijn de Vlaminck

Breaking rules to create new diagnostic tools

Professor Iwijn de Vlaminck discusses his work with two graduate students.Iwijn De Vlaminck’s work is in precision and genomic medicine, a new, exciting and rapidly growing area in biomedical engineering. 

De Vlaminck is interested in developing single-cell and single-molecule assays that can find application in diagnostic medicine. His work takes advantage of the sensitivity and throughput of modern DNA sequencers.  De Vlaminck uses DNA sequencers as molecular counters of molecules of cell-free DNA in blood or urine and as rapid profilers of the gene expression levels in individual cells. His goals are to improve the accuracy and to lower costs in molecular diagnostics and to create completely new diagnostic tools.

One immediate application is in the area of organ transplants.

Organ transplants have saved millions of lives since the first successful kidney transplant was performed in 1954. In the intervening 62 years, surgeons have transplanted lungs, pancreases, hearts, livers, small intestines, and kidneys. But not all transplant surgeries are successful. In fact, the immune systems of quite a few patients reject the new organ. Immune systems are evolved to recognize when something ‘foreign” enters the body, and antigens on the cellular surfaces of the transplanted organ can trigger the immune system to attack the organ as an invader.

Over the years, doctors have gotten better at matching the antigens between the transplant recipient and the transplant donor. The closer the match, the more likely the transplanted organ will be accepted by the patient’s immune system. In addition to careful matching, doctors administer drugs that suppress the recipient’s immune system. Even with these advances, rejection is still a major fear and cause of death.

De Vlaminck, who is the Robert N. Noyce Assistant Professor in Life Science and Technology at Cornell’s Nancy E. and Peter C. Meinig School of Biomedical Engineering (BME), has found a better way to identify if and when the process of organ rejection has started. Currently, organ recipients must return for tissue biopsies at regular intervals after receiving a new organ. Small samples of the transplanted organ are removed and biopsied to assess the health of the tissue. “The biopsy method is invasive, often leads to complications and has limited predictive power” says De Vlaminck. “Our non-invasive method can identify rejection sometimes months before the biopsy test can pick it up.”

De Vlaminck’s method requires a sample of blood from the recipient. “We can look at the amount of cell-free DNA released from the transplanted organ in the scope of injury and that gives us a good picture of the health of the organ,” says de Vlaminck. The non-invasive procedure uses a DNA sequencer to identify transplant donor specific DNA in blood and can identify potential rejection early and effectively, in both heart and lung transplants.

De Vlaminck’s assay can also identify infections. Bacterial and viral infections are a huge concern when a patient has received a transplanted organ. As mentioned earlier, transplant recipients are often given immune suppressants so that their body’s defenses don’t attack the new organ. While aiding in the acceptance of the new organ, these suppressants also leave the patient vulnerable to infections their immune systems would ordinarily handle with ease. De Vlaminck’s assay can use cell-free DNA to identify infections by comparing sequences found in the patient’s blood with a ‘library’ of known bacterial and viral DNA sequences. “This method casts a much wider net than traditional tests that can only find an individual infection,” says de Vlaminck.

As an undergraduate, De Vlaminck studied electrical engineering at KULeuven. During his undergraduate studies he was able to join a research lab and help with research into organic semiconductors. “That research experience set me on a different path,” says de Vlaminck. “I found that I very much enjoyed thinking about technical issues and the broader scope of a project. I like that research is a creative and open-ended process. I made up my mind that I wanted to continue on to grad school after that.”

De Vlaminck pursued his graduate studies at KULeuven. At first, he was interested in making nanoscale mechanical and optical devices that could be used as bio-sensors, but he did not know much about biology. He moved into biology and biophysics and studied the mechanical properties of single molecules of DNA with Cees Dekker at TUDelft in the Netherlands. With Dekker, he developed new measurement principles in single molecule biophysics. “Then I learned about genomics and how cheap DNA sequencing was becoming,” say de Vlaminck. 

De Vlaminck took a position as a post-doctoral researcher at Stanford, where he worked with Professor Stephen Quake. At Stanford, De Vlaminck began work on methods for identifying cell-free DNA in a sample of blood with a multidisciplinary team of collaborators, including bioengineers and transplant physicians. De Vlaminck joined the faculty at Cornell in 2015. At Cornell, De Vlaminck’s group has developed a novel assay to probe ultrashort molecules of DNA in blood and urine and his group is using this technique to study host-pathogen interactions in the scope of urinary tract infection. In related work, his group is pursuing a new approach that would allow for the broad diagnosis of organ injury (independent of transplants) from analyses of blood. His lab is further interested in applications of high-throughput single-cell messenger RNA sequencing in pathology, and is developing an imaging process that enables identifying all of the microbes present in a sample. These studies require multidisciplinary innovation in genomics, biophysics and computational biology. 

“I have a lot that I am excited to be working on,” says De Vlaminck, “and Cornell is a great place for me to be. As biomedical engineers we have the wonderful opportunity to have a big impact on human health and I hope that my work will start to have that sort of an impact soon.”