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An Interview with Jeanne Loring

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By Carla Mellough

This month’s feature investigator, Jeanne Loring, is an established stem cell researcher and founding director of the Center for Regenerative Medicine at The Scripps Research Institute in La Jolla. Prior to this, Jeanne was a faculty member of the Burnham Institute for Medical research and played an instrumental role in the establishment of their human embryonic stem cell program.

What was your original motivation for pursuing a career in stem cell research? How has this motivation evolved?

A long time ago, I was accepted as a graduate student in a type of program that was new at the time- a Research Institute in Molecular Biology. The faculty were almost all newly arrived, a lot of them senior researchers from highly prestigious East Coast universities who decided together to escape their stifling old fashioned scientific environments and move to the “wild west” of Oregon. I picked up on their spirit. I started out working in a hard-core biochemistry lab. The work was straightforward and I could see the end; I would have my PhD in 3 years. Then I started hanging out with the guys down the hall, at night when only graduate students and the custodians were around. The guys down the hall were working on neural crest stem cells in the chick embryo. It was not at all clear what could be done, and how long it would take. I fell in love with the idea of not knowing what I might discover. I switched labs, developed a project on my own on neural crest stem cells, and it took me 5 years to finish. It was a great decision- I loved the adventure and the risk- I still do.

 

What was it about the molecular governance of pluripotency and differentiation that initially grabbed your interest, leading you to focus much of your work on this?

My work in biotechnology showed me the value of having really great technology. I started combining the best technology with the most interesting cells in the world, and here I am.

 

loringfig2Much of your work has focused on the study of the transcriptional control of stem cells. In your opinion, what has been your most exciting discovery, and why? What might be the potential implications of this discovery?

There is no other type of cell that is pluripotent, has unlimited capacity to reproduce, and manages to keep its DNA relatively normal through all of this. The only other cell types that don’t senesce in culture are cancer cells and transformed cells, and they survive because of multiple lesions in their genomes that cause the cells to lose control. Human pluripotent stem cells have some powerful molecular controls that we need to understand- the information will help us understand cancer cells, human diseases and human development.

 

Some excellent recent papers reveal that the epigenetic profile of embryonic stem cells is quite different to that of induced pluripotent stem cells. In your opinion, how important do you think these differences are? How do you think this might affect the applicability of iPSC in the treatment of human disease?

Our latest work shows that both human ES and iPSC have variable gene expression profiles and variable epigenetic profiles. We can find two hESC lines that are more different from each other than an hESC line and an iPSC line. That’s the value of analyzing 300 lines rather than two.

 

What is your understanding of successful research?

Discoveries that make a difference, that are solid and never get old. Usually these are not projects that get funded by traditional granting agencies or get accepted the first time they’re sent to journals; the first ES cells in 1981, homologous recombination to make knockout mice, Yamanaka’s reprogramming of somatic cells.

 

Can you reflect on what you feel was one of the most important experiences or defining moments in your education, career, or life that has contributed to your success as a researcher? How do you think this has this affected your work and/or career?

There weren’t a lot of women in my field when I started. As an undergraduate, I was one of three women in my biochemistry class of a couple of hundred. It fuelled my competitiveness - I usually got the highest grade in the class, and I finished my BS degree in 3 years after spending my first year as a comparative literature major. I like to win, and now I like for people in my lab to win.

 

How easy or difficult do you find it to keep abreast of the vast volume of new literature in the field?

My postdocs and graduate students are my sources of new information.

 

What do you feel is the most challenging aspect of your job?

Getting funding for novel work. I long for an endowment or some other funding that would allow me to stop writing grants for a year or so and just do science.

 

How important is a collaborative approach in your research and how multidisciplinary has this been/is this becoming, in your experience?

It’s absolutely essential to my research, and I’ve never liked working alone. It’s more fun to brainstorm with others and find compatible people whose expertise complements mine.

 

What would your words of advice be to young researchers trying to find their way in the stem cell field and obtain funding in this highly competitive field and under the current economic climate?

I try to teach my researchers the multiple skills they’ll need; critical thought, the ability to communicate clearly, how to write, to never publish anything that isn’t solid and substantial, that they need to find and keep great colleagues and collaborators. I can teach them and give them confidence but the motivation to succeed can’t be taught.

 

It seems that the barrier is always being raised for the achievement of success in publishing manuscripts and obtaining funding. What effect do you think this has on the research that is being undertaken and the way in which it is conducted?

Rudolf Jaenisch said a couple of years ago that this field is “overheated”. I agree, and think that much too much weak science is being published in this field because of the novelty and excitement.

 

loringfig1How do you think the current funding situation will affect the progression of stem cell research in the short and/or long term?

The current funding situation is affecting all biological research as scientists who have been comfortably funded for their entire lives are now unable to get any funding. I believe in funding young researchers, but not at the expense of the excellent scientists who are their teachers. I think the future is in collaboration, in real partnerships.

In answer to your question, I can take the long view. I know that funding won’t grow, may shrink, and I try to convey that to my postdocs and grad students, telling them they should be flexible and learn to land on their feet. I hope it works.

 

There has been a huge shift in public thinking about the use of stem cells for research and to ameliorate human disease. In your opinion, what are the main barriers that still remain for the clinical translation of hESC, and iPSC? How do you foresee these being overcome?

There is a great need for translational research, the merger of well-controlled, careful studies with the clear consideration of how the basic science can be applied to understanding disease and developing drugs that work. Researchers and clinicians need to find common ground.

 

In your opinion, what do you consider to be the most important advance in stem cell research over the past 5 years?

That’s easy. Yamanaka’s reprogramming of somatic cells to pluripotency. That taught us that the fundamental state of pluripotent or differentiated cells is governed by set-points that are controlled by a set of molecular characteristics that can be understood.

 

What are your hopes for the future stem cell research and clinical translation in your specialist area?

Endless.

 


Read a Featured Reviewed Article by Dr. Loring's Lab

Reprogramming: what’s next?
A commentary on a recent mRNA reprogramming paper by Loring Lab Researchers: 
Trevor Leonardo, Ileana Slavin and Ha Tran