Shaheen Kabir

Presented by Titia de Lange

B.S., Haverford College

Investigating Mechanisms of Telomere End-protection

Despite being young, Shaheen Kabir’s life has already involved five continents. Born to Pakistani parents, Shaheen grew up in beautiful Tanzania. She went to Australia to study biology, theater, and dance in Melbourne, and then came to the U.S. to go to Haverford College, where she graduated with a major in biology and a minor in theater arts.

Before Shaheen joined our graduate program, she worked as a technician with Jay Chaudhuri, who had then just joined the faculty of Memorial Sloan Kettering Cancer Center. After helping him set up the lab and getting the first results published, she joined The David Rockefeller Graduate Program in 2008.

When Shaheen started in our lab, she joined postdoc Agnel Sfeir and former graduate student Megan van Overbeek in their quest to understand the role of Rap1 in shelterin, the complex that protects our chromosome ends. Agnel and Megan had been working on various approaches, including gene knockouts, to figure out what Rap1 was doing at telomeres. Disappointingly, they had found that Rap1 was not doing anything at telomeres at all. Shaheen, however, within a few months of joining the lab, showed that Rap1 is required to prevent telomeres from exchanging DNA sequences with each other.

Having established the function of mouse Rap1 at telomeres, Shaheen wanted to address two major questions. She wanted to understand why Rap1 was a highly conserved telomeric protein even though its role at telomeres did not seem to be critical for survival since mice without Rap1 are alive and well. She also wanted to know what the function is of human Rap1, because there were several papers that argued that human and mouse Rap1 were quite different.

Shaheen decided to address these questions by knocking out human Rap1 with TALENs. Since the CRISPR explosion, TALEN gene knockouts are now to genome editing what the iPhone 4 is to the Apple Watch. But the TALENs worked, and Shaheen found that human Rap1, like mouse Rap1, is not essential. Furthermore, the work provided her with the fascinating insight that we have a protein hanging onto our telomeres that is mostly conserved because it is moonlighting as a transcriptional regulator.

Shaheen has now joined the lab of Jennifer Doudna at the University of California, Berkeley. This choice possibly reflects her enthusiasm for the ease of genome editing with CRISPR compared to TALENs. But I suspect that her move to the Bay Area may also have to do with the location of her husband, Alex Bolze, whom she met when he was a student here at Rockefeller. Since Alex is French, their wedding in Paris brought the fifth continent into Shaheen’s life.