Research & Innovation
“My favourite words are possibilities, opportunities and curiosity. I think if you are curious, you create opportunities, and then if you open the doors, you create possibilities.”
Mario Testino
Our projects
Understanding cancer beyond genes: an integrative view from our lab
Cancer is often described with words like heterogeneity, uncontrolled, and complex—and rightly so. Yet behind its chaotic nature lies a disturbing order, a kind of emergent self-organization that makes cancer a dominant and resilient disease. For decades, researchers have sought clarity by defining the so-called “hallmarks of cancer”: a set of functional capabilities that give malignant tumors their identity. But even this framework falls short of fully capturing cancer’s multifaceted reality.
At our lab, we believe cancer cannot be understood solely through its molecular hallmarks. We approach it as a complex biological problem—one that must be explored through the lenses of evolution, development, and ecology. From the stem-like behavior of cancer cells to their adaptation within the body’s microenvironments, we view tumors not just as genetic accidents, but as dynamic systems shaped by ontogeny and selective pressures.
Since establishing the Cancer STEM Lab at Complutense University in 2022, our research has grown along three interwoven lines:
- Cancer as an evolutionary emergent system
- Cancer as a developmental reminiscence
- Cancer as an ecological challenge
All three projects focus on breast cancer as a model and explore tumor differentiation strategies as a therapeutic approach. Our goal is to determine whether guiding cancer cells toward a differentiated state could break their emergent complexity, uncouple their developmental machinery, and ultimately reduce their ecological fitness.
Cancer as an evolutionary emergent system
This first project was conceived to explore tumor cell plasticity as an adaptive, evolutionary trait, allowing breast cancer cells to survive treatment by shifting between stem-like and differentiated states. This dynamic flexibility—a hallmark of evolving systems—poses a major challenge to effective therapy. We aimed to counteract this adaptability by driving tumor cells toward stable differentiation, thereby limiting their escape routes.
Cancer as a developmental reminiscence
This project investigates the deep parallels between tumorigenesis and embryogenesis. During development, cells follow tightly regulated genetic and epigenetic cues to divide, migrate, and differentiate—all processes that are aberrantly reactivated in cancer. This developmental reprogramming underlies tumor cell plasticity and contributes to malignancy.
Cancer as an ecological challenge
This project investigates breast cancer through an ecological lens, focusing on how eco-evolutionary traits shape tumor behavior and adaptability. Tumors act as dynamic ecosystems, where cancer cells compete, cooperate, and evolve within their microenvironment—much like species in nature.
For a more detailed information about our ongoing projects, work planning, strategic alliances and ideas for the future, contact us
Where we come from
Pluripotent stem cells—whether iPSCs or ESCs—are a cornerstone of regenerative medicine due to their ability to generate diverse tissue types. Yet, current differentiation protocols remain suboptimal, with challenges in cell survival, maturation, and long-term functionality.
In my final years as a senior postdoc, I helped develop a novel technology based on transient microRNA exposure, which significantly enhances stem cell developmental potential (Salazar-Roa et al., 2020).
Building on this, we designed new strategies to boost stem cell viability and their capacity to generate mature, functional cells. These innovations aimed to advance fundamental research, disease modeling, and regenerative therapies—particularly in targeting cancer stem cells and treating conditions like Type 1 Diabetes that require tissue regeneration.
Advanced Differentiation Therapy in Type 1 Diabetes
Type 1 Diabetes is one of those diseases that would benefit from regenerative approaches. T1D is devastating, has no cure and can be only managed using lifelong insulin injections. Although promising, regenerative therapies are still showing a number of limitations, specially related to the maturity and survival of the obtained pancreatic cells.
Supported by La Caixa Foundation, MIT LinQ and Global CoCreation Lab, we aimed to use our novel technology to generate MImoPancreas, with mature and functional cells able to efficiently produce insulin in response to glucose and with high survival rates. This strategy represented an encouraging solution to revolutionize the state-of-the-art for pancreatic cell replacement.
Advanced Differentiation Therapy in cancer
During my work as senior postdoc, we demonstrated how miRNA 203 exerts a dual role on the reprogramming/differentiation balance, acting as (i) a potent driver from stemness to expanded differentiation potential, while (ii) blocking reprogramming from somatic to stem cells (Pre-print and Salazar-Roa et al., 2020).
Accumulating evidence has shown that some cancer cells share certain biological and molecular properties with tissue-specific stem cells. Those observations are consistent with the idea that, for tumor initiation, adult cells are required to undergo reprogramming to a progenitor-like fate, suggesting that pluripotency and tumorigenesis entail obvious similar pathways.
Inspired by this general thought and supported by the AECC Scientific Foundation, we aimed to develop novel strategies for anti-tumoral Advanced Differentiation Therapy, to directly confront the tumor-maintaining and regeneration capability of cancer cells.
We anticipate that our Differentiation Technology will drop the stem population in the tumor, in part by unlocking the cellular differentiation programs that are normally inactivated in cancer stem cells and at the same time, blocking the reprogramming from somatic to cancer stem cells. (Nuria García Martínez-Illescas et al. 2023)
Advanced Differentiation Therapy in cancer
During my work as senior postdoc, we demonstrated how miRNA 203 exerts a dual role on the reprogramming/differentiation balance, acting as (i) a potent driver from stemness to expanded differentiation potential, while (ii) blocking reprogramming from somatic to stem cells (Pre-print and Salazar-Roa et al., 2020).
Accumulating evidence has shown that some cancer cells share certain biological and molecular properties with tissue-specific stem cells. Those observations are consistent with the idea that, for tumor initiation, adult cells are required to undergo reprogramming to a progenitor-like fate, suggesting that pluripotency and tumorigenesis entail obvious similar pathways.
Inspired by this general thought and supported by the AECC Scientific Foundation, we aimed to develop novel strategies for anti-tumoral Advanced Differentiation Therapy, to directly confront the tumor-maintaining and regeneration capability of cancer cells.
We anticipate that our Differentiation Technology will drop the stem population in the tumor, in part by unlocking the cellular differentiation programs that are normally inactivated in cancer stem cells and at the same time, blocking the reprogramming from somatic to cancer stem cells. (Nuria García Martínez-Illescas et al. 2023)
Innovation and Tech transfer
The Cancer STEM Lab has a real commitment with transferability. Since 2019, we are proud to participate in prestigious Innovation programs, from Spain and US: our team and project were chosen, trough highly competitive selection processes, to be part of CaixaImpulse 2019 and MIT linQ IDEA2 Gobal 2019.
CaixaImpulse personalized training was developed during 2019 in Barcelona. This program has provided us funding to develop our “Proof of concept” and has offered us the tools we need to improve our valorisation and commercialisation plans.
MIT linQ face-to-face training was also developed during 2019, in Cambridge (Boston). Mentorship and personalized guidance are crucial in this program to efficiently refine our research plans and development strategy, in order to heighten the opportunity to healthcare impact. Our IDEA2 innovation training and individualized mentorship are being extremely helpful for us, to make the right decision in every step of this exciting process.
The Global CoCreation Program at MIT IMES is a high-tech concentrator launched by the MIT (Massachusetts Institute of technology) and sponsored by Miami-Dade County. We are proud to be part of this amazing initiative since 2020, invited by its CSO, Mercedes Balcells-Camps.
Publications
Tumor ecology and the paradox of clean margins in multicentric breast cancer: an exploratory organoid-based functional study
Martínez-Illescas, N.G., Martín-Zapater, E., Quezada-Gutiérrez, C., Yébenes, L., Payo-Payo A., Frías-Aldeguer, L. & Salazar-Roa, M. (2026).
Breast Cancer Research (2026)
https://doi.org/10.1186/s13058-026-02301-z
Transient CB2 receptor activation triggers irreversible luminal differentiation via chromatin remodeling in breast cancer.
Nuria García Martínez-Illescas et al. (Maria Salazar-Roa as corresponding author)
BioRxiv, 2025
DOI: https://doi.org/10.1101/2025.07.29.667375
miR-203 drives breast cancer cell differentiation (read paper)
Nuria García Martínez-Illescas et al. (Maria Salazar-Roa as corresponding author)
Breast Cancer Research 25, 91 (2023)
DOI: https://doi.org/10.1101/2023.01.23.525208
miR-203 drives breast cancer cell differentiation
Nuria García Martínez-Illescas et al. (Maria Salazar-Roa as corresponding author)
BioRxiv, 2023
DOI: https://doi.org/10.1101/2023.01.23.525208
Mammalian CDC14 phosphatases control exit from stemness in pluripotent cells
Carolina Villarroya-Beltri et al. (Maria-Salazar Roa among the senior authors)
The EMBO Journal, 2023
Transient exposure to miR‐203 enhances the differentiation capacity of established pluripotent stem cells
Maria Salazar-Roa et al. (Maria Salazar-Roa as first and corresponding author)
The EMBO Journal, 2020
miR-203 imposes an intrinsic barrier during cellular reprogramming by targeting NFATC2
Maria Salazar-Roa et al.
BioRxiv, 2020
DOI: 10.1101/2020.06.02.131136
Downregulation of Specific Fbxw7 Isoforms with Differential Effects in T-Cell Lymphoblastic Lymphoma
Vazquez-Dominguez, I. et al. (Maria Salazar-Roa among the authors)
Oncogene, 2019
Detection of novel fusion-transcripts by RNA-Seq in T-cell lymphoblastic lymphoma
Pilar López-Nieva et al. (Maria Salazar-Roa among the authors)
Scientific Reports, 2019
DOI: 10.1038/s41598-019-41675-3
Optimization of a preclinical therapy of cannabinoids in combination with temozolomide against glioma
Israel López-Valero et al. (Maria Salazar-Roa among the authors)
Biochemical pharmacology, 2018
DOI: 10.1016/j.bcp.2018.08.023
Therapeutic relevance of the PP2A-B55 inhibitory kinase MASTL/Greatwall in breast cancer
Mónica Álvarez-Fernández et al. (Maria Salazar-Roa among the authors)
Cell death and differentiation, 2018
DOI: 10.1038/s41418-017-0024-0
Programmed mitophagy is essential for the glycolytic switch during cell differentiation
Lorena Esteban-Martínez et al. (Maria Salazar-Roa among the authors)
The EMBO Journal, 2017
Fueling the Cell Division Cycle
Maria Salazar-Roa et al.
Trends in Cell Biology, 2017
DOI: 10.1016/j.tcb.2016.08.009
Dihydroceramide accumulation mediates cytotoxic autophagy of cancer cells via autolysosome destabilization
Sonia Hernández-Tiedra et al. (Maria Salazar-Roa among the authors)
Autophagy, 2016
DOI: 10.1080/15548627.2016.1213927
Competition between members of the tribbles pseudokinase protein family shapes their interactions with mitogen activated protein kinase pathways
Hongtao Guan et al. (Maria Salazar-Roa among the authors)
Scientific Reports, 2016
DOI: 10.1038/srep32667
Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)
Daniel J. Klionsky et al. (Maria Salazar-Roa among the authors)
Autophagy, 2016
DOI: 10.1080/15548627.2015.1100356
Activation of the endomitotic spindle assembly checkpoint and thrombocytopenia in Plk1-deficient mice
Marianna Trakala et al. (Maria Salazar-Roa among the authors)
Blood, 2015
DOI: 10.1182/blood-2015-03-634402
AMBRA1 links autophagy to cell proliferation and tumorigenesis by promoting c-Myc dephosphorylation and degradation
Valentina Cianfanelli et al. (Maria Salazar-Roa among the authors)
Nature Cell Biology, 2015
DOI: 10.1038/ncb3072
AMPK and PFKFB3 mediate glycolysis and survival in response to mitophagy during mitotic arrest
Elena Doménech et al. (Maria Salazar-Roa as corresponding author)
Nat Cell Biol, 2015
DOI: 10.1038/ncb3231
CDK6 as a key regulator of hematopoietic and leukemic stem cell activation
Ruth Scheider et al. (Maria Salazar-Roa among the authors)
Blood, 2015
DOI: 10.1182/blood-2014-06-584417
Loss of Tribbles pseudokinase-3 promotes Akt-driven tumorigenesis via FOXO inactivation
Maria Salazar-Roa et al.
Cell Death and Differentiation, 2015
DOI: 10.1038/cdd.2014.133
Mitophagy in mitosis: More than a myth
Lorena Esteban-Martínez et al. (Maria Salazar-Roa as corresponding author)
Autophagy, 2015
DOI: 10.1080/15548627.2015.1108509
Oncosuppressive functions of tribbles pseudokinase 3
Maria Salazar-Roa et al.
Biochem Soc Trans, 2015
DOI: 10.1042/BST20150124
The new antitumor drug ABTL0812 inhibits the Akt/mTORC1 axis by upregulating Tribbles-3 pseudokinase
Tatiana Erazo et al. (Maria Salazar-Roa among the authors)
Clin Cancer Res, 2015
DOI: 10.1158/1078-0432.CCR-15-1808
The pseudokinase tribbles homologue-3 plays a crucial role in cannabinoid anticancer action
Maria Salazar-Roa et al.
Biochimica Et Biophysica Acta-Molecular and Cell Biology of Lipids, 2013
DOI: 10.1016/j.bbalip.2013.03.014
A Combined Preclinical Therapy of Cannabinoids and Temozolomide against Glioma
Sofia Torres et al. (Maria Salazar-Roa among the authors)
Molecular Cancer Therapeutics, 2011
DOI: 10.1158/1535-7163.MCT-10-0688
Anti-tumoral action of cannabinoids on hepatocellular carcinoma: role of AMPK-dependent activation of autophagy
Diana Vara et al. (Maria Salazar-Roa among the authors)
Cell Death and Differentiation, 2011
DOI: 10.1038/cdd.2011.32
Detecting autophagy in response to ER stress signals in cancer
Maria Salazar-Roa et al.
Methods in Enzymology: Unfolded Protein Response and Cellular Stress, 2011
DOI: 10.1016/B978-0-12-385116-1.00017-0
Loss of striatal type 1 cannabinoid receptors is a key pathogenic factor in Huntington’s disease
Cristina Blázquez et al. (Maria Salazar-Roa among the authors)
Brain, 2011
DOI: 10.1093/brain/awq278
Stimulation of ALK by the growth factor midkine renders glioma cells resistant to autophagy-mediated cell death
Mar Lorente et al. (Maria Salazar-Roa among the authors)
Autophagy, 2011
Stimulation of the midkine/ALK axis renders glioma cells resistant to cannabinoid antitumoral action
Mar Lorente et al. (Maria Salazar-Roa among the authors)
Cell Death and Differentiation, 2011
DOI: 10.1038/cdd.2010.170
The orphan G protein-coupled receptor GPR55 promotes cancer cell proliferation via ERK
Clara Andradas et al. (Maria Salazar-Roa among the authors)
Oncogene, 2011
DOI: 10.1038/onc.2010.402
The role of AMPK in antitumoral action of cannabinoids on HCC
Diana Vara et al. (Maria Salazar-Roa among the authors)
Febs Journal, 2011
WOSUID: WOS:000292333101521
Role of sphingolipid trafficking in cannabinoid-induced autophagy
Sonia Hernández Tiedra et al. (Maria Salazar-Roa among the authors)
Naunyn-Schmiedebergs Archives of Pharmacology, 2010
WOSUID: WOS:000294723000021
The putative cannabinoid receptor GPR55 participates in the control of cancer cell proliferation
Clara Andradas et al. (Maria Salazar-Roa among the authors)
Ejc Supplements, 2010
WOSUID: WOS:000288603100339
Amphiregulin Is a Factor for Resistance of Glioma Cells to Cannabinoid-Induced Apoptosis
Mar Lorente et al. (Maria Salazar-Roa among the authors)
Glia, 2009
DOI: 10.1002/glia.20856
Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells
Maria Salazar-Roa et al.
Journal of Clinical Investigation, 2009
DOI: 10.1172/JCI37948
Cannabinoid receptor 1 is a potential drug target for treatment of translocation-positive rhabdomyosarcoma
Susanne Oesch et al. (Maria Salazar-Roa among the authors)
Molecular Cancer Therapeutics, 2009
DOI: 10.1158/1535-7163.MCT-08-1147
TRB3 links ER stress to autophagy in cannabinoid anti-tumoral action
Maria Salazar-Roa et al.
Autophagy, 2009
Cannabinoids inhibit glioma cell invasion by down-regulating matrix metalloproteinase-2 expression
Cristina Blázquez et al. (Maria Salazar-Roa among the authors)
Cancer Research, 2008
DOI: 10.1158/0008-5472.CAN-07-5176
Down-regulation of tissue inhibitor of metalloproteinases-1 in gliomas: a new marker of cannabinoid antitumoral activity?
Cristina Blázquez et al. (Maria Salazar-Roa among the authors)
Neuropharmacology, 2008
DOI: 10.1016/j.neuropharm.2007.06.021
Glycogen synthase kinase-3beta inhibits the xenobiotic and antioxidant cell response by direct phosphorylation and nuclear exclusion of the transcription factor Nrf2
Maria Salazar-Roa et al.
J Biol Chem, 2006
Persistent penetration of MPTP through the nasal route induces Parkinson’s disease in mice
Ana I. Rojo et al. (Maria Salazar-Roa among the authors)
European Journal of Neuroscience, 2006
DOI: 10.1111/j.1460-9568.2006.05060.x
Regulation of heme oxygenase-1 gene expression through the phosphatidylinositol 3-kinase/PKC-zeta pathway and Sp1
Ana I. Rojo et al. (Maria Salazar-Roa among the authors)
Free Radic Biol Med, 2006
DOI: 10.1016/j.freeradbiomed.2006.04.002
Funding
Ramón y Cajal contract and project funding; 2020; AEI, Spanish Ministry of Science; PI: María Salazar Roa; Complutense University (Spain); 1/08/2022-1/08/2027.
Consolidación Investigadora, CNS2022-135364; “Cannabinoids as breast cancer differentiation drivers: novel strategies for tumor differentiation therapy”; 2022; Spanish Ministry of Science; PI: María Salazar Roa; Complutense University (Spain); 1/07/2023-1/07/2025.
Generación de Conocimiento, PID2022-136508OA-I00; “Exploring the therapeutic advantages of cannabinoids as tumor differentiation drivers in breast cancer”; 2022; Spanish Ministry of Science; PI: María Salazar Roa; Complutense University (Spain); 1/09/2023-1/09/2026.
Financiación de Proyectos de Investigación, plan propio UCM 2022 PR3/23-30841; “Disección molecular de la diferenciación celular por cannabinoides: modelos de terapia dirigida a las células madre del tumor”; PI: María Salazar Roa; Complutense University (Spain); 23/11/2023-23/11/2024.