Research & Innovation

“There is a lesson for all of us, which is to ask yourselves if there is something that limits our vision, that limits our capacity to create: And is there a way to enlarge it?”

Research & Innovation

“There is a lesson for all of us, which is to ask yourselves if there is something that limits our vision, that limits our capacity to create: And is there a way to enlarge it?”

Our projects

The need

Pluripotent stem cells (either IPSCs or ESCs) and their tremendous capacity to differentiate to a number of tissues are the holly grail for Regenerative Medicine. Nevertheless, the success of those differentiation protocols is still limited by the insufficient potential of stem cells to survive under challenging conditions, differentiate and maturate to be functional and maintain those properties in the long-term.

The need

Pluripotent stem cells (either IPSCs or ESCs) and their tremendous capacity to differentiate to a number of tissues are the holly grail for Regenerative Medicine. Nevertheless, the success of those differentiation protocols is still limited by the insufficient potential of stem cells to survive under challenging conditions, differentiate and maturate to be functional and maintain those properties in the long-term.

Our first approach

During my last years as senior postdoc, I established the bases of a novel technology that potentiates the differentiation capacity of stem cells. Our team described a method mainly based on the transient exposure to a microRNA that notably enhances the developmental capacity of stem cells (Salazar-Roa et al., 2020)

Our first approach

During my last years as senior postdoc, I established the bases of a novel technology that potentiates the differentiation capacity of stem cells. Our team described a method mainly based on the transient exposure to a microRNA that notably enhances the developmental capacity of stem cells (Salazar-Roa et al., 2020)

Building novel strategies

With this backup, we aim to design now novel technologies to significantly improve the stem potential of the initial material, their survival and their capacity to specialize into mature and functional cells.

Such strategies will reinforce the use of stem cell approaches on fundamental research, generation of disease models and numerous applications in regenerative medicines.

Building novel strategies

With this backup, we aim to design now novel technologies to significantly improve the stem potential of the initial material, their survival and their capacity to specialize into mature and functional cells.

Such strategies will reinforce the use of stem cell approaches on fundamental research, generation of disease models and numerous applications in regenerative medicines.

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 aim 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 may represent an encouraging solution to revolutionize the current state-of-the-art for pancreatic cell replacement.

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 aim 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 may represent an encouraging solution to revolutionize the current state-of-the-art for pancreatic cell replacement.

Advanced Differentiation Therapy in cancer

During my work as senior postdoc, we demonstrated how this miRNA 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 aim 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.

Advanced Differentiation Therapy in cancer

During my work as senior postdoc, we demonstrated how this miRNA 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 aim 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.

For a more detailed information about our ongoing projects, work planning, strategic alliances and ideas for the future, contact us

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

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

DOI: 10.15252/embj.2019104324

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

DOI:10.1038/s41388-019-0746-1

 

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

DOI: 10.15252/embj.201695916

 

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

DOI: 10.4161/auto.7.9.15866

 

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

DOI: 10.4161/auto.5.7.9508

 

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

DOI: 10.1074/jbc.M513737200

 

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