Awardee Profile - Pardis Sabeti

Pardis Sabeti, M.D., D. Phil.

2007 - It’s hardly common to lead a double life as a top scientific researcher and cutting-edge rock musician. But Pardis Sabeti, M.D., D. Phil., who received a Burroughs Wellcome Fund Career Award in the Biomedical Sciences in 2005, satisfies that billing.

On the science side, Dr. Sabeti is an assistant professor of organismic and evolutionary biology at Harvard University who studies the evolution of infectious diseases and their effects on the human genome. Her work already has earned her a spot on a “top 100 living geniuses” list compiled by Creators Synectics, a global consulting firm.

On the music side, Dr. Sabeti is lead singer with the well-reviewed alternative rock band Thousand Days, which has released three albums. In addition, she is creating a series of music videos to spark young people’s interest in science.

“I think the reason I can do as much as I can is that I’m doing things I’m really passionate about,” Dr. Sabeti said.

Dr. Sabeti’s science career began as an undergraduate student at the Massachusetts Institute of Technology, where she majored in biology and worked in the laboratory of genomics pioneer Eric Lander, Ph.D. She then earned a doctorate in biological anthropology at the University of Oxford as a Rhodes scholar, where she specialized in genetic diversity.

While in graduate school, Dr. Sabeti discovered that her interests in genetics and evolution intersected at infectious disease.“I got really excited about the idea that evolution would tell you a lot about infectious disease,” Dr. Sabeti said.“You can see these waves of history—we can find out what infections were major killers thousands of years ago.”

Following her graduation from Oxford, Dr. Sabeti enrolled in Harvard Medical School to improve her understanding of infectious disease. She graduated summa cum laude in 2006, the third women to receive the honor since the school admitted its first group of female medical students in 1945.

At the same time she attended Harvard, Dr. Sabeti was a postdoctoral fellow at the Broad Institute—a joint initiative of Harvard and MIT—working again with Dr. Lander.There, Dr. Sabeti began to probe the link between pathogens and the human genome with a new data set, the HapMap.

The International HapMap project parsed the massive amounts of information hidden in the human genome by identifying common regions of genetic variations called single-nucleotide polymorphisms, or SNPs.

SNPs are sites where the DNA sequence of individuals differs by just one of four nucleotides that comprise the building blocks of genes. For example, some people may have a chromosome with one particular nucleotide at a particular site, while others have a chromosome with a different nucleotide at that site. Research shows that such variations are responsible for person-to-person differences in diseases as varied as diabetes, cancer, depression, and asthma. SNPs also affect a person’s response to infectious diseases and drugs.

There are about 10 million SNPs in the human genome, making the search for specific genetic variations akin to finding a needle in a haystack. But it turns out that SNPs tend to carry many of their chromosomal neighbors along with them as they rise in frequency among a population. These neighborhoods, called haplotypes, are inherited in long connected chunks of DNA.With only a few hundred thousand haplotypes accounting for most of the genetic variation in a population, researchers can quickly zoom in on chromosomal regions most likely to affect disease.

With help from haplotypes, Dr. Sabeti developed a method to measure how long ago a genetic variation arose and to determine how old it is. This provided the ability to identify evolutionary effects in the human genome.

In one study using the technique, Dr. Sabeti and her colleagues discovered three examples of population-specific natural selection based on geographic area. These examples involved genes linked to Lassa virus in West Africa, skin pigmentation in Europe (for lighter hair and paler skin), and hair follicle development in Asia. Now Dr. Sabeti is applying her expertise in medicine and genomics to understanding the interplay between humans and pathogens such as malaria, tuberculosis, and other difficult-to-treat scourges.

Infectious diseases have powerfully shaped the human genome through natural selection, according to Dr. Sabeti. Similarly, human influence is just as apparent in the genomes of disease-causing microbes.

When Dr. Sabeti analyzed the malaria parasite genome, she found genes involved in drug resistance and in evading the human immune system, revealing new treatment routes and clues to the global spread of malaria.

One of the major hurdles in the battle to eradicate malaria is the parasite’s rapidly evolving drug resistance. Chloroquine, the most effective antimalaria drug currently available, worked for just 16 years before widespread resistance developed. Dr. Sabeti and her colleagues are working to identify genetic variations crucial to malaria’s drug resistance and disease severity. The researchers hope to identify vaccine and drug targets, as well as develop an early warning system to detect drug resistance.

And as she embarks on her research career, Dr. Sabeti continues to bring the two sides of her life together, using music to interest children, particularly girls, in science.

With support from the MIT Council for the Arts and a women-in-science program sponsored by L’Oreal, Dr. Sabeti is planning a series of music videos featuring Boston-based science luminaries such as Dr. Lander and artificial intelligence expert Marvin Minsky.

Dr. Sabeti, who was born in Iran and raised in Florida, grew interested in reaching young people after she was awarded a L’Oreal For Women in Science Fellowship.

“L’Oreal started putting me in front of high school students,” Dr. Sabeti said. It’s been great to increase awareness about science to girls and boys.”

The videos, which Dr. Sabeti would like to distribute online, will use pop culture to show that science is cool. Her hope is that young viewers will want to learn more about the people in the videos.

“One thing I’ve noticed, having been caught between the two worlds of music and science, is that there’s such a public fascination with artists and musicians,”Dr. Sabeti said.“But really, scientists are much more fascinating.”

By Becky Oskin, a freelance science journalist based in Chapel Hill, North Carolina.