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2015 STEM CELLS Young Investigator Award Winner: Kamil R. Kranc



On the Right Trajectory

An Interview with 2015 YIA Winner Kamil R. Kranc

Kamil R. Kranc, M.D., Ph.D., is the 2015 recipient of STEM CELLS' Young Investigator Award. This $10,000 prize is awarded annually to a young scientist whose paper is judged to be of worldwide significance by a global jury.

Prof. Kranc currently heads up the Haematopoietic Stem Cell Laboratory at the MRC Centre for Regenerative Medicine, University of Edinburgh. His lab focuses on understanding how haematopoietic stem cells (HSCs) choose to self-renew or differentiate, and how these cell fate decisions are affected under pathological conditions to generate leukemic stem cells.

Prof. Kranc was a first author of the paper "Acute loss of Cited2 impairs Nanog expression and decreases self-renewal of mouse embryonic stem cells," published in the March 2015 issue of Stem Cells (SC). This paper caught the attention of the YIA judges and earned him this year's award. Combined with their previous studies, the SC paper helped the Kranc team identify Cited2 as the only known stem cell master regulator that controls embryonic, iPSC, tissue and cancer stem cells by orchestrating distinct pathways.

Understanding how somatic and pluripotent stem cells are maintained and how these functions are perturbed under pathological conditions is of fundamental importance to regenerative medicine and cancer treatment. Prof. Kranc's lab hopes to harness this knowledge to efficiently reprogram and expand somatic stem cells to employ them in regenerative and transplantation medicine, and to eradicate cancer stem cells to achieve curative cancer therapies.

Prof. Kranc obtained his M.D. in Poland (1994-2000) and pre-doctoral research training at the University of Oxford (1998-2000). He was awarded a Ph.D. in biochemistry from Lincoln College at the University of Oxford (2000-2004) where he held a Wellcome Prize Ph.D. Studentship, Overseas Research Studentship and a Keith Murray Senior Scholarship.

He obtained his postdoctoral training at the MRC Human Immunology Unit in Oxford (2003-2007). He was then a junior principal investigator and a Beit Memorial Fellow at the MRC Molecular Haematology Unit at Oxford (2007-2010) and subsequently a group leader at the Paul O'Gorman Leukaemia Research Centre at the University of Glasgow (2010-2013).

Prof. Kranc joined the MRC Centre for Regenerative Medicine in 2013 as a CRUK Senior Fellow and Chair of Molecular Haematology. He is also a member of the Edinburgh Cancer Research Centre.

Prof. Kranc recently talked with SC about his research and what it means to have earned the YIA award.

SC: Please describe, in language intended for a general scientific audience rather than for stem cell researchers, what hypothesis you were testing in the research described in your award-winning paper?

Prof. Kranc: My laboratory at the University of Edinburgh aims to understand how normal stem cells choose to self-renew or differentiate and how these cell fate decisions are perturbed under pathological conditions to generate cancer stem cells. One of the main goals of my laboratory is to identify the key regulatory pathways controlling normal stem cell functions and harness this knowledge for the purposes of regenerative medicine.

As part of this research program, we previously revealed that a transcription factor, Cited2, is critically essential for adult haematopoietic stem cell functions (Kranc et. al, Cell Stem Cell, 2009). In our STEM CELLS paper, we tested the hypothesis that Cited2 plays critical roles in embryonic stem cell functions and is important for reprogramming of somatic cells to induced pluripotent stem cells (iPSCs).

SC: Can you explain why investigating this hypothesis is important to stem cell research?

Prof. Kranc: The identification of the fundamental pathways controlling stem cell behavior is central to our understanding of stem cells and their immense clinical potential. We hope that by manipulating these pathways we will be able to efficiently generate iPSCs for the purposes of regenerative medicine, expand tissue stem cells for transplantation purposes or target cancer stem cells.

SC: Briefly outline the approach you used to test your hypothesis.

Prof. Kranc: In this paper, we genetically deleted the Cited2 gene in embryonic stem cells and found that Cited2 was absolutely required for their proliferation, survival and self-renewal. Mechanistically, we found that Cited2 exerts its functions in embryonic stem cells by controlling transcription of genes that play roles in the regulation of stem cell pluripotency, namely Nanog, Tbx3 and Klf4. So in essence we positioned Cited2 within the pluripotency gene regulatory network.

Finally, we demonstrated that Cited2 is required for and enhances reprogramming of somatic cells to iPSCs.

SC: What does this mean for stem cell biology and its application?

Prof. Kranc: Our findings published recently in Stem Cells, taken together with our previous work, imply that the critical functional requirement for Cited2 in stem cell maintenance is conserved between embryonic and tissue stem cells. The identification of such conserved master regulators of stem cell functions is important, as such regulators are likely to control the key pathways in many stem cell types and thus the concept can be applied across many tissues.

SC: What's the best scenario that you would like to see come out of your study?

Prof. Kranc: While we identified Cited2 as an essential regulator of the stem cell pluripotency network, much work still needs to be done to unravel the molecular pathways through which Cited2 controls normal and cancer stem cell functions. Once we understand exactly how Cited2 functions in different stem cell types, I hope that we will be able to manipulate Cited2-dependent pathways to enhance iPSC generation, improve tissue stem cell expansion or more efficiently target cancer stem cells.

SC: Let's turn the spotlight on you for a bit: Why did you choose to go into stem cell research?

Prof. Kranc: As an M.D./Ph.D. I am very keen on translational "bench to bedside" research. Given that stem cells reside at the top of cellular hierarchies in normal tissues and in cancers and fuel their development, understanding stem cell biology is critical for regenerative medicine and cancer therapy, respectively. Thus it is the fascinating biology of stem cells combined with their immense clinical importance that attracted me to this exciting field.

SC: Can you talk about your training, any mentors who might have influenced you? 

Prof. Kranc: I have always been extremely lucky to work with internationally recognized mentors who strongly supported me. I did my Ph.D. at Oxford with Professor Shoumo Bhattacharya who had enormous and very positive impact on my scientific development, and supported me far beyond my Ph.D. Following a postdoctoral fellowship at Oxford, I obtained a Beit Memorial Fellowship, which allowed me to hold my first PI position at Oxford and the support of Professors Tariq Enver and Sten Eirik Jacobsen was essential. All these great mentors hugely influenced my research career and the way I run my own group and research.

I am extremely grateful to funding bodies and charities supporting our research. In particular, I am indebted to Cancer Research UK for awarding me a Senior Cancer Research Fellowship, which funds my group for six years. Finally, the continuous support and inspiration from my wife, who is also a scientist, and my parents have always been invaluable.

SC: What motivates you today? 

Prof. Kranc: I have always been driven by my curiosity and passion for medical research, and I get excited by every experiment done in my lab. I am motivated by new results that my hard-working group generates every day as we realize we are getting closer to understanding stem cells and applying our knowledge in the clinic.

SC: Tell us a bit about your current position.

Prof. Kranc: I am a Professor of Molecular Haematology and Cancer Research UK Senior Fellow at the University of Edinburgh. The nice thing about my current position is that I have a joint appointment between the MRC Centre for Regenerative Medicine and the Edinburgh Cancer Research UK Centre, which are centers of excellence in stem cell biology and cancer research, respectively. The access to the internationally recognized expertise in these two important fields allows me to conduct multidisciplinary research, maximize the outcomes of our work and enhance its translational value.

SC: Is there anything else that you think is important to bring up about your paper, your work and what you think should happen next?

Prof. Kranc: I would like to emphasize that this work was conducted in collaboration with the teams of Jose Braganca, Tariq Enver, Helen Wheadon, Jenny Nichols and Keisuke Kaji, and our paper is a great example of fruitful interactions between several research groups. We will be happy to develop further multidisciplinary collaborations in order to validate our findings in other types of stem cells and test their translational value.

SC: Why did you select the journal STEM CELLS to publish your paper?

Prof. Kranc: STEM CELLS is a very respected journal with a broad audience and many important findings in the field are published there. This influenced our decision to submit our work to STEM CELLS and we are very happy to have published some of our key findings there. 

SC: How do you think the Young Investigator Award might affect your career?

Prof. Kranc: It will be very helpful. Being recognized by a respected journal is a true honor and I am grateful to STEM CELLS for this prestigious award. It reassures me that our research in this evolving field is on the right trajectory.

Click here to read the best papers from our 2015 Young Investigators.