This letter recommends Carlos López for a PhD Fellowship from Boehringer Ingelheim Fonds. The letter writer, Simón Méndez Ferrer, is the head of Carlos López's potential PhD lab at Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III. The letter details Carlos López's excellent academic record and notes that he has already conducted promising preliminary research in Méndez Ferrer's lab on signals between leukemic stem cells and mesenchymal stem cells. Méndez Ferrer believes Carlos López's proposed PhD research building on this work could provide novel therapeutic targets for leukemia. He strongly endorses Carlos López's application for the fellowship

1. Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
Melchor Fernandez Almagro 3, E-28029 Madrid, España · Tel. 91 453 12 00 | Fax. 91 453 12 40 · CIF. G82316753
Cardiovascular Development and Repair Department
Fundación Centro Nacional de Investigaciones
Cardiovasculares Carlos III (CNIC)
C/ Melchor Fernández Almagro, 3
28029 Madrid, Spain
Tel.: + 34 914531200
Fax: + 34 914531240
Boehringer Ingelheim Fonds
Stiftung für medizinische
Gurndlagenforschung
Re: Recommendation letter for Mr. Carlos López application
Madrid, September 30th
, 2014
Dear Members of the Board of Trustees:
I write this letter to enthusiastically express my strongest possible support for Mr. Carlos López
application for a PhD Fellowship from Boehringer Ingelheim Fonds.
Mr. López has an extraordinary academic record, personal and professional qualities and specific
lab expertise (despite the early stage of his career) that I believe make him an outstanding candidate
for this Fellowship. We would be extremely happy to accept him as a PhD student in our group so
that he can develop the experimental research project outlined in his proposal.
Mr. López completed his Bachelor in Biology in Emory University (Atlanta, GA, USA), where he
obtained top qualifications, receiving the Dean's List Award for academic excellence. He obtained
several competitive US fellowships that allowed him to participate in summer research programs
and train in the laboratory of Dr. Jacobus de Roode. He decided to return to Spain (where he was
born) for family reasons and is currently finishing his Diploma in Advanced Biotechnology in the
University of La Coruña (Spain), where he is originally from. He will finish his Diploma by La
Coruña University in the upcoming months and has already obtained sufficient credits to apply for a
PhD program in Spain.
We were fortunate that Mr. López decided to apply for a summer stay at the National
Cardiovascular Research Center (CNIC), where our group is based. He wisely chose our institute as
a Center of Excellence in Research (Severo Ochoa Award) and applied to my group based on his
interest in our research track. Over the past 10 years, and based on my PhD background in
neurobiology, we have been interested in the neural regulation of peripheral stem cell niches. We
showed that the brain regulates the bone marrow stem cell niche via the sympathetic nervous
system (Mendez-Ferrer S et al. Nature 2008) and that mesenchymal stem cells expressing the
intermediate filament protein nestin play a key role in regulating haematopoietic stem cells
(Mendez-Ferrer S et al. Nature 2010; Isern J et al. Cell Rep 2013). This association with the
peripheral nervous system is further emphasized by a common origin for peripheral neuroglia and
mesenchymal stem cells with specialized niche functions (Isern J et al. eLife 2014). We have
recently shown that this regulatory network is lost during myeloproliferative diseases, as a
consequence of the inflammatory insult caused in the bone marrow by the mutated haematopoietic
stem cells. However we have also demonstrated that rescue of this neuropathy can rescue the niche,
prevent the expansion of mutated cells and the development of fibrosis (Arranz et al, Nature 2014).
This work has been possible thanks to competitive international funding, such as the International
Early Career Scientist grant of the Howards Hughes Medical Institute. These results have fructified
in a clinical trial awarded as the winner of the Gateway/RTF-CCR/SAKK Research Grant 2014, in
collaboration with multiple hospitals in Switzerland.

2. Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
Melchor Fernandez Almagro 3, E-28029 Madrid, España · Tel. 91 453 12 00 | Fax. 91 453 12 40 · CIF. G82316753
Cardiovascular Development and Repair Department
Fundación Centro Nacional de Investigaciones
Cardiovasculares Carlos III (CNIC)
C/ Melchor Fernández Almagro, 3
28029 Madrid, Spain
Tel.: + 34 914531200
Fax: + 34 914531240
Mr. López wants to build on our recent work to study the leukemic stem cell niche in the bone
marrow. Normal and leukaemic haematopoietic stem cells are regulated by a specialized
microenvironment (“niche”) which contributes to maintain them in a slowly proliferative state that
makes them more resistant to chemotherapy, a major cause of relapse. His proposal (which he has
written with very little help) builds on our new findings that challenge current dogmas in this field:
the identification of different mesenchymal stem cells with non-overlapping functions (skeletal and
hematopoietic stem cell maintenance); cell identity might be reversible in myeloproliferative
neoplasms, where the change of cell fate is pathogenic and can be reverted; our discovery that
mutated HSCs, considered to drive myeloproliferative neoplasms autonomously, can be controlled
by the niche, and are also sensitive to long-distance neuroendocrine signals that could be exploited
for the treatment of myeloproliferative diseases. A main aspect of his proposal builds on his
discovery—as a summer student in our lab—that leukemic stem cells change nestin+ mesenchymal
stem cells to favor their own survival. Mr. López has found that leukemic stem cells depend on
survival signals produced by nestin+ msenchymal stem cells. He has proposed a sophisticated
approach to discover the key survival signals that might represent novel therapeutic targets for the
treatment of these devastating incurable diseases.
Mr. López came highly recommended by his previous advisor and our interactions with him have
surpassed our best expectations. Mr. López is a brilliant student with a high degree of curiosity and
an outstanding commitment to science. He possesses the rare combination of perfectionism in
experimental research with ambition, dedication and productivity. He is a great team player but has
also a clear vision towards which he wants to move his scientific career, despite his early stage. I
would be delighted to accept him as a PhD student. If awarded, the Fellowship from Boehringer
Ingelheim Fonds would critically impact his career and the possibilities of developing this project.
Please do not hesitate if you need any further information for his evaluation.
With best wishes,
Simón Méndez Ferrer, PhD
Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
(CNIC) Planta 3 Sur
Calle Melchor Fernández Almagro, 3
28029, Madrid
Tel 91 453 12 00, Ext. 3310
Fax 91 453 13 04
E-mail: smendez@cnic.es