Thao P. Phan

I have had the great opportunity to pursue my graduate research work in Andrew Holland’s lab. Our lab is fascinated with cell division and the molecular mechanisms that allow this process to happen precisely every time the cell divides.

My research project focuses on cell divisions that occur during early brain development. Specifically, I was curious as to why mutations in proteins functioning at the centrosome — organelles that help form the bipolar spindle during mitosis, frequently lead to a brain developmental condition called microcephaly. Using mouse models carrying these mutations, I was able to show that during the pathogenesis of microcephaly, neural progenitor cells with centrosome defects take longer to complete mitosis, which in turn activate a signaling axis consisting of 53BP1, USP28 and TP53. Activation of this signaling pathway, collectively referred to as the mitotic surveillance pathway, leads to cell death in the developing brain, resulting in a smaller brain size with fewer neurons. Remarkably, removal of any components of the mitotic surveillance pathway is sufficient to restore neural progenitor proliferation and rescue brain size. These findings suggest that activation of the mitotic surveillance pathway is a central mechanism underlying microcephaly pathogenesis in human patients.

Questions & Answers

Why did you choose Johns Hopkins for your work? I chose Hopkins because of the very friendly and collegial atmosphere here. This was apparent even from my short interview visit: I was immediately impressed with how much every student knew about the research going on in other labs and how invested they were in other people’s projects. I cannot imagine having done many of the experiments for my graduate work without the mentorship and generous feedback from everyone in my department, my thesis committee and the many collaborators we have across campus. What does receiving this award mean to you personally and professionally? Do you have any connection with the particular award you received? I am incredibly honored and humbled to receive the Mette Strand Award. Personally, it means a lot to me that my award is named after a female immigrant scientist who was not only a successful researcher but also a beloved mentor to her students. It is absolutely inspiring! What contributed to your project's success? When I started working in the lab, I had no mouse work experience and very little neuroscience background. Looking back, I feel very lucky and grateful that Andrew trusted me with such a challenging but also very exciting project. Throughout the years, his enthusiasm and mentorship have constantly motivated me to step out of my scientific comfort zone and make the most of my learning environment. I also have to thank the many graduate students, postdocs and faculties in my department and the neuroscience department who spent countless hours training me to perform techniques that no one else in our lab does. I often tell people that I am a great example of what it means to be “raised by a village.” What thoughts do you have about Young Investigators’ Day itself, as a celebration of the roles students and fellows play in research at Johns Hopkins? I think it is an amazing opportunity for young trainees like myself to share my research and get inspired by the science happening all around Hopkins. What has been your best/most memorable experience while at Johns Hopkins? All of the wonderful time I shared with my classmates and labmates is definitely what I will treasure most from my time at Hopkins. What are your plans over the next year or so? I am hoping to graduate within the next couple of months, and then hopefully join a lab somewhere as a postdoc and see where science takes me next. Tell us something interesting about yourself. Both my parents are researchers in the biochemistry field, which I think is rather unique. What often surprises people is that as a kid I wanted nothing to do with science. But I guess the apple didn’t fall far from the tree. And as it turns out, discussing experiments with my parents can be a lot of fun. Maybe except for when my dad tells me my Western blots “have room for improvements.”