From telescope to microscope
A pioneering cancer researcher’s lifelong search for answers
Meet Jordi Petriz, PhD
As a kid fascinated with the night sky, Jordi Petriz once asked his father to explain the origin of the stars. His father’s surprising response reveals how the younger Petriz’s upbringing was a catalyst to becoming a trailblazing scientist. He said he didn’t know.
“He only had a primary school education,” Petriz explains, “and never had the opportunity to learn how to answer these types of questions, so he offered me the opportunity to meet people who were specialists in this field—he helped me join an astronomical society.”
Through that astronomical society in his hometown of Barcelona, Spain, Petriz discovered his lifelong passion for the appreciation and scientific study of space—and by age 12 he had built his own functioning telescope, through which he observed Jupiter, Saturn, and orbiting satellites. Eventually, he acquired a professional telescope, and to this day, Petriz continues to study the heavens. In fact, it was an aspect of this interest in studying the outer world that also led Petriz to discover the inner worlds that became the focus of his career in science.
“I started to collect micrometeorites and analyze them using a microscope,” he says. “I became fascinated with this world. I think this was a key point in my life—when I started to try and discover the microscopic world.”
Thinking small to think big
The turn to the microscopic world was also practical: “One of the main reasons I decided to swap the telescope for the microscope in my career path was because in Spain at the time, there was simply no specific career in astronomy—so I decided to put all of my efforts in the field of biology.”
Petriz began his academic studies in animal biology, which eventually led him to field work in Spain’s Ebro River Delta. Using biochemical techniques to study the effects of pollutants on heron eggs, Petriz became fascinated with how the membranes of cells necessary for the development of an embryo also help protect the embryo from the accumulation of pollutants like PCBs and DDT.
These cell membranes that protect the embryo resist pollutants because of proteins in the cell membrane called multi-drug transporters, which find the toxic compounds and pump them out of the cell. Multi-drug transporters mediate the export of a broad range of these compounds from cells, including antibiotics and anticancer agents.
Petriz says he became “especially fascinated by how cells are able to self-protect against pollutants but also against other types of agents, which is crucial for how cancer cells are able to resist chemotherapy.”
“I think this was a key point in my life—when I started to try and discover the microscopic world.”
When he finished his studies in the university, he obtained a fellowship to do cancer research at a hospital in Barcelona. There, his fascination with the complex and mysterious activity of multi-drug transporters put Petriz on the path to becoming a pioneer in combining the methods of immunophenotyping with functional analysis.
That’s because classical immunophenotyping alone couldn’t answer all of his questions.
“Using immunophenotyping, you can identify many different cell subpopulations, but not their activity,” he explains. “For example, you can attach a specific antibody against one of these transporters, but you cannot measure how the transporter is working. This means that you can detect how cells express transporters, and yet miss important information about how the transporters are working. Functional measurement is fundamental to understanding how transporters are working, and thus to understanding drug resistance.”
Going with flow
The key tool Petriz has used in this groundbreaking research on the behavior of transporters in cell membranes is flow cytometry.
“I was very interested from the beginning in the huge capabilities of flow cytometry to perform functional analysis,” he says. “Flow cytometry is fundamental to making these discoveries possible.” In trying to understand how and why cells express multi-drug transporters, he began to study very primitive subpopulations of stem cells, which lack a specific phenotype—so the only way he was able to identify these primitive subsets was using functional flow cytometry.
Because this functional cytomic research requires working with very rare cells and small sample volumes, a high-sensitivity flow cytometer is essential. Petriz’s cytometer of choice is the Invitrogen Attune NxT Flow Cytometer.
“I believe the Attune NxT instrument is, in fact, the best flow cytometer ever, because of its extraordinary sensitivity,” Petriz says. He explains how this high-sensitivity capability enables detection of the presence of very rare cells, as well as small changes in phenotype, function, and DNA content—which he found impossible using other flow cytometers. “I’ve been really surprised and satisfied with the high sensitivity of the cytometer.”
Looking forward
Currently, Petriz and his team are hoping to publish an article based on their research with patients affected with acute myeloid leukemia. Using Invitrogen Alkaline Phosphatase Live Stain, Petriz was able to measure the activity of enzymes expressed in leukemic stem cells at different time points. Most importantly, his team was able to identify very primitive stem cell subpopulations at the time of diagnosis, and then analyze the activity of these cell subpopulations in relation to the survival rates of patients.
“We are very excited about our results,” he reports. “I hope we will be able to publish very soon.”
“I always love to learn from the people around me. I'm eager for knowledge; it’s so fundamental to progress.”
Petriz’s main advice for other scientists facing challenges in research is quite practical: take good care of your sample.
“Sample manipulation is a big problem, not only in flow cytometry, but in many other research disciplines,” he explains. “It can heavily affect almost everything that you’re measuring. That’s why I suggest to anyone interested in doing research in cancer, and especially those interested in rare cells: avoid sample manipulation as much as possible.”
And his team walks that walk, performing their experiments with the least possible sample manipulation. They acquire the sample, stain it with antibodies and fluorescent probes, and then simply dilute it for analysis on the flow cytometer. Petriz explains that this is fundamental to helping identify very rare cells—because if you’re performing some of the additional steps commonly used in science, you may easily fail to identify the target population.
He also has some less scientific but equally important advice: stay connected. “I always love to learn from the people around me. I'm eager for knowledge; it’s so fundamental to progress,” he says.
While Petriz can’t recall a time when he wasn’t passionate about doing science, his inspiration hasn’t been confined to the lab. He enjoys participating in conferences and bouncing ideas off of his colleagues, but he also likes to talk with people who aren't involved in science at all. His conversations with non-scientists have sometimes led to new research considerations.
He explains that he “once had the opportunity to give some talks about science to ordinary citizens. It was a chance to hear directly from people concerned about members of their families suffering from cancer. They asked some really touching questions. And this is very motivating—it moves me to keep asking new questions and developing new experiments.”