Interview with the Faculty: Pamela Stanley

This is a guest post from Yan Zheng, an F1000Specialist. Yan graduated from Albert Einstein College of Medicine with a PhD in the Biomedical Sciences. Currently, Yan is doing a postdoc at New York University’s Langone Medical Center.

Here, Yan interviews Pamela Stanley about her career path that led to her current research interests.

Pamela Stanley is a professor of cell biology and the Horace W. Goldsmith Foundation Chair at Albert Einstein College of Medicine. In 2014, she received the annual Marshall S. Horwitz, M.D. Faculty Prize for Research Excellence. Dr Stanley is also an F1000Prime Faculty Member in Cell Biology.

Q: What are you working on at the moment?

My lab is interested in understanding the function of sugars, the most abundant post-translational modification. Currently, there are two projects in my lab. One focuses on Notch signaling: the extracellular domain of Notch receptors is covered with sugars, and getting rid of even one class of glycans compromises Notch signaling. We are trying to understand the functions of Notch receptor sugars and the mechanisms by which these sugars mediate Notch signaling. The other project is to reveal the role of N-glycans in spermatogenesis. We cloned the gene that converts simple N-glycans into complex ones. Conditional knockout of this specific gene in spermatogonia leads to fused spermatids and infertile mice. We are trying to understand how sugars are important for spermatogenesis and to identify a subset of glycoproteins that are most important during this process.

F1000 Faculty Member Pamela Stanley

F1000 Faculty Member Pamela Stanley

How did you get interested in sugars?

My PhD study on influenza virus glycoproteins attracted me to the field of membranes and membrane proteins. The lab I joined for my postdoc training pioneered somatic cell genetics in mammalian cells, and I worked on membrane-interacting proteins named lectins. As a result, I got a bunch of sugar synthesis mutants that were defective in lectin binding, and the years spent sorting out these mutants led me into the field of glycobiology. The reason I stayed in the field was because we discovered dominant mutants which turned on genes rather than inactivated them. These were completely new aspects of sugar synthesis that were unknown at the time.

Of which achievement are you most proud?

My first thrill was demonstrating that the M protein was not exposed on the surface of influenza virus during my PhD study. But I am most proud of my study on the function of sugars in Notch signaling. We were the first to show that knocking out the enzyme that puts fucose onto Notch results in a broad, global Notch signaling defect in mammals. We followed this up and revealed that getting rid of the fucose on just one of the key ligand binding domains of the Notch1 receptor caused a Notch signaling phenotype. All these exciting results suggested critical roles for glycans in Notch signaling.

What’s the riskiest move you’ve made in your career?

Every move is risky, but my riskiest move was setting up my own lab. My husband is also a scientist, and we wanted to start our labs in a big city like New York. I liked Albert Einstein College of Medicine right away because scientists cooperated and shared equipment, which allowed researchers to use their grant money to support people and supplies. I also liked people’s enthusiasm about their work and that they all wanted to do first-rate science. This turned out to be a very good choice.

What is the most interesting question in the biomedical sciences?

Within my field, one of the biggest challenges is to define the molecular details of how various sugars and glycan binding proteins are regulated. Experts in the field hypothesize that, when glycan binding proteins and sugars are present on the cell’s surface, they form lattices that regulate signaling. It is a big challenge to identify these lattices and define their specificity. A more general challenge for biological scientists today is getting information out of big data. There is so much information out there that can help set up models and suggest validation experiments. Getting models, projections, and algorithms to analyze big data is the most interesting and challenging step in biomedical sciences.

Who inspired you? Was there someone who was instrumental in the development of your career?

I have always liked science but I had never thought of doing a PhD until a very good friend invited me to visit a scientific institution in Australia. I met a lot of scientists and was offered a graduate student position in one of the labs. This friend was a very good advisor. Also, my husband, Richard, who is also a scientist, and my PhD and postdoc advisors, were all very supportive of my career. At Einstein, I was inspired by influential women scientists, like Ora Rosen and Lucy Shapiro. Over 40% of the faculty were women when I joined. These women were very serious scientists, very ambitious and enthusiastic. They were good role models.

What’s the best piece of advice you’ve ever received?

My first lab experience was with a biochemist, who taught me very good bench technique and to be highly organized. At Albert Einstein, there is a culture of sharing great advice, especially when reading each others’ grants and papers, and I’ve learned a lot from colleagues over the years. One piece of advice is to not react quickly to criticism. For example, when you receive a review of what you consider to be the best paper you’ve ever written, and it says there are 16 things you have to do, just put it aside and read it more carefully the next day. Another good piece of advice is to write emails without the address listed, so that it will not be sent by accident before you intend to.

Do you have any advice for young people embarking on a research career?

The most important thing is take ownership of your projects as soon as possible. Don’t operate in “student mode” and hope that your advisor will lead you through the process. I encourage people to maximize their time in gathering data because they are responsible for putting the full effort into their experiments. Titrate your time wisely so you are efficient in the lab and maximize your productivity. Don’t forget to read and go to seminars – educate yourself broadly, so that your training will give you more choices when you go on to become a postdoc. The most important piece of advice is to be proactive; take the ball and run, and play your best tennis.

In the current economic climate, would you still make the same decision to become a scientist?

I would. When I was looking for jobs, it was also very competitive. Things go up and down in science. My advice is if you like science, go for it. It is a demanding career, but extremely enjoyable and rewarding. The exciting thing in biology is that even at the very end of your career you can discover something! As long as you have an enjoyable life, go for it.

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