Biotechnology

Cell Reprogramming and Developmental Hematopoiesis

Cell Reprogramming

Epigenetics

Hematopoietic Stem Cell

Dendritic Cell

Immunotherapy


Research lines

Engineering Cell Fates for Regenerative Medicine: Programming Blood Cell Types

Programming, Reprogramming and Developmental Biology

Development of New Therapies

Overview

The focus of our laboratory is to understand the molecular determinants underlying cell reprogramming and hematopoietic specification. In humans, the multiple differentiated cell states are normally stable and inherited through cell division. Under certain conditions, cell fate can, however, be modified or reversed. Cell reprogramming can be achieved experimentally in different ways, including nuclear transfer, cell fusion or expression of transcription factors. The emergent ability to directly reprogram somatic cells into desired hematopoietic cell-types is opening avenues to the discovery of new therapies for immune and blood diseases. Our approach focuses on Hematopoietic Stem Cells (HSCs) for their remarkable regenerative potential and Dendritic Cells (DCs) as key mediators of immunity.

Aims:
• To understand at the molecular level how hematopoietic cellular identities are specified during development employing cellular reprogramming
• To use this knowledge to allow the generation of patient-specific hematopoietic and immune cells for regenerative medicine and immunotherapy

Our research will increase the understanding of the intrinsic determinants underlying hematopoietic progenitor and effector cell developmental specification. This knowledge may allow the re-creation of these unique cell identities from any human cell. Ultimately, we believe that our research will contribute to personalized hematopoietic regeneration by employing human programmed HSCs for patient-specific cell transplantation. In addition, DC reprogramming is allowing us to develop new ways to modulate the immune response. This represents a unique opportunity to merge the field of cell reprogramming and cancer immunotherapy and may result in the development of powerful new therapeutics for cancer and other diseases resulting from a dysfunctional immune system.

Induction of human hemogenesis in adult fibroblasts by defined factors and hematopoietic coculture

Daniel, M.G.; Sachs, D.; Bernitz, J.M.; Fstkchyan, Y.; Rapp, K.; Satija, N.; Law, K.; et al, 2019. FEBS Letters. 3266 - 3287. 23. 593. 2019. http://www.scopus.com/inward/record.url?eid=2-s2.0-85074051202&partnerID=MN8TOARS . 10.1002/1873-3468.13621 . FEBS Letters

Hemogenic Reprogramming of Human Fibroblasts by Enforced Expression of Transcription Factors

Silvério-Alves, R.; Gomes, A.M.; Kurochkin, I.; Moore, K.A.; Pereira, C.-F., 2019. Journal of visualized experiments : JoVE. 153. 2019. http://www.scopus.com/inward/record.url?eid=2-s2.0-85075191300&partnerID=MN8TOARS . 10.3791/60112 . Journal of visualized experiments : JoVE

Understanding and Modulating Immunity With Cell Reprogramming

Pires, C.F.; Rosa, F.F.; Kurochkin, I.; Pereira, C.-F., 2019. Frontiers in Immunology. 10. 2019. http://www.scopus.com/inward/record.url?eid=2-s2.0-85077260284&partnerID=MN8TOARS . 10.3389/fimmu.2019.02809 . Frontiers in Immunology

Is immunotherapy the holy grail for pancreatic cancer?

Andersson, R.; Pereira, C.-F.; Bauden, M.; Ansari, D., 2019. Immunotherapy. 1435 - 1438. 17. 11. 2019. http://www.scopus.com/inward/record.url?eid=2-s2.0-85076450369&partnerID=MN8TOARS . 10.2217/imt-2019-0164 . Immunotherapy

Direct reprogramming of fibroblasts into antigen-presenting dendritic cells

Rosa, Fabio F.; Pires, Cristiana F.; Kurochkin, Ilia; Ferreira, Alexandra G.; Gomes, Andreia M.; Palma, Luis G.; Shaiv, Kritika; et al, 2018. Science Immunology. 30. 3. 2018. http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000452571800002&KeyUID=WOS:000452571800002 . 10.1126/sciimmunol.aau4292 . Science Immunology

Ihor R. Lemischka (1953-2017) Obituary

Ivanova, Natalia; Pereira, Carlos-Filipe; Lee, Dung-Fang, 2018. Cell. 1 - +. 1-2. 172. 2018. http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000419840100001&KeyUID=WOS:000419840100001 . 10.1016/j.cell.2017.12.028 . Cell

Ihor R. Lemischka (1953-2017)

Ivanova, Natalia; Pereira, Carlos-Filipe; Lee, Dung-Fang, 2018. Cell Stem Cell. 16 - +. 1. 22. 2018. http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000419306500008&KeyUID=WOS:000419306500008 . 10.1016/j.stem.2017.12.015 . Cell Stem Cell

Cooperative Transcription Factor Induction Mediates Hemogenic Reprogramming

Gomes, Andreia M.; Kurochkin, Ilia; Chang, Betty; Daniel, Michael; Law, Kenneth; Satija, Namita; Lachmann, Alexander; et al, 2018. Cell Reports. 2821 - +. 10. 25. 2018. http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000452894600018&KeyUID=WOS:000452894600018 . 10.1016/j.celrep.2018.11.032 . Cell Reports

INDUCTION OF HEMOGENIC REPROGRAMMING IN HUMAN FIBROBLASTS

Gomes, A.; Pereira, C. -F.; Chang, B.; Kurochkin, I.; Daniel, M.; Law, K.; Satija, N.; et al, 2017. Haematologica. 102. 2017. http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000404127006340&KeyUID=WOS:000404127006340 . Haematologica

High-throughput identification of small molecules that affect human embryonic vascular development

Vazão, H.; Rosa, S.; Barata, T.; Costa, R.; Pitrez, P.R.; Honório, I.; De Vries, M.R.; et al, 2017. Proceedings of the National Academy of Sciences of the United States of America. E3022 - E3031. 15. 114. 2017. http://www.scopus.com/inward/record.url?eid=2-s2.0-85035214278&partnerID=MN8TOARS . 10.1073/pnas.1617451114 . Proceedings of the National Academy of Sciences of the United States of America

Transient HES5 Activity Instructs Mesodermal Cells toward a Cardiac Fate

Freire, A.G.; Waghray, A.; Soares-da-Silva, F.; Resende, T.P.; Lee, D.-F.; Pereira, C.-F.; Nascimento, D.S.; Lemischka, I.R.; Pinto-do-Ó, P., 2017. Stem Cell Reports. 136 - 148. 1. 9. 2017. http://www.scopus.com/inward/record.url?eid=2-s2.0-85021126795&partnerID=MN8TOARS . 10.1016/j.stemcr.2017.05.025 . Stem Cell Reports

The stem cell niche finds its true north

Agnete Kirkeby; Thomas Perlmann; Carlos-Filipe Pereira, 2016. Development. 2877 - 2881. 16. 143. 2016. https://doi.org/10.1242/dev.140095 . 10.1242/dev.140095 . Development

Hematopoietic Reprogramming In Vitro Informs In Vivo Identification of Hemogenic Precursors to Definitive Hematopoietic Stem Cells

Pereira, C.-F.; Chang, B.; Gomes, A.; Bernitz, J.; Papatsenko, D.; Niu, X.; Swiers, G.; et al, 2016. Developmental Cell. 525 - 539. 5. 36. 2016. http://www.scopus.com/inward/record.url?eid=2-s2.0-84959312876&partnerID=MN8TOARS . 10.1016/j.devcel.2016.02.011 . Developmental Cell

MECHANISMS UNDERLYING HUMAN HEMOGENIC REPROGRAMMING

Gomes, Andreia; Pereira, Carlos-Filipe; Papatsenko, Dmitri; Moore, Kateri Ann; Lemischka, Ihor, 2016. Experimental Hematology. S75 - S76. 9. 44. 2016. http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000382184600129&KeyUID=WOS:000382184600129 . 10.1016/j.exphem.2016.06.144 . Experimental Hematology

ZERO FOOTPRINT INDUCTION OF HUMAN HEMOGENESIS TO STUDY PATHOLOGIC DEVELOPMENTAL HEMATOPOIESIS IN FANCONI ANEMIA

Daniel, Michael; Fstkchyan, Yesai; Gomes, Andreia; Pereira, Carlos-Filipe; Lemischka, Ihor; Moore, Kateri Ann, 2016. Experimental Hematology. S65 - S65. 9. 44. 2016. http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000382184600098&KeyUID=WOS:000382184600098 . 10.1016/j.exphem.2016.06.112 . Experimental Hematology

Reprogramming mouse embryonic fibroblasts with transcription factors to induce a hemogenic program

Daniel, M.G.; Pereira, C.-F.; Bernitz, J.M.; Lemischka, I.R.; Moore, K., 2016. Journal of Visualized Experiments. 118. 2016. 2016. http://www.scopus.com/inward/record.url?eid=2-s2.0-85015946426&partnerID=MN8TOARS . 10.3791/54372 . Journal of Visualized Experiments

Making a Hematopoietic Stem Cell.

Daniel MG; Pereira CF; Lemischka IR; Moore KA, 2015. 2015. http://europepmc.org/abstract/med/26526106 . 10.1016/j.tcb.2015.10.002 .

Tbx3 Controls Dppa3 Levels and Exit from Pluripotency toward Mesoderm

Waghray, A.; Saiz, N.; Jayaprakash, A.D.; Freire, A.G.; Papatsenko, D.; Pereira, C.-F.; Lee, D.-F.; et al, 2015. Stem Cell Reports. 97 - 110. 1. 5. 2015. http://www.scopus.com/inward/record.url?eid=2-s2.0-84937523983&partnerID=MN8TOARS . 10.1016/j.stemcr.2015.05.009 . Stem Cell Reports

DIRECT CONVERSION FROM MOUSE FIBROBLASTS INFORMS THE IDENTIFICATION OF HEMOGENIC PRECURSOR CELLS IN VIVO

Pereira, Carlos-Filipe; Chang, Betty; Niu, Xiaohong; Gomes, Andreia; Swiers, Gemma; Azzoni, Emanuele; Schaniel, Christoph; et al, 2014. Experimental Hematology. S55 - S55. 8. 42. 2014. http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000340344300196&KeyUID=WOS:000340344300196 . Experimental Hematology

'From blood to blood': De-differentiation of hematopoietic progenitors to stem cells

Pereira, C.-F.; Lemischka, I.R.; Moore, K., 2014. EMBO Journal. 1511 - 1513. 14. 33. 2014. http://www.scopus.com/inward/record.url?eid=2-s2.0-84904561142&partnerID=MN8TOARS . 10.15252/embj.201488980 . EMBO Journal

"There will be blood" from fibroblasts

Pereira, C.-F.; Lemischka, I.R.; Moore, K., 2014. Cell Cycle. 335 - 336. 3. 13. 2014. http://www.scopus.com/inward/record.url?eid=2-s2.0-84896884486&partnerID=MN8TOARS . 10.4161/cc.27507 . Cell Cycle

Induction of a hemogenic program in mouse fibroblasts.

Pereira, Carlos-Filipe; Chang, Betty; Qiu, Jiajing; Niu, Xiaohong; Papatsenko, Dmitri; Hendry, Caroline E; Clark, Neil R; et al, 2013. Cell stem cell. 205 - 18. 2. 13. 2013. 10.1016/j.stem.2013.05.024 . Cell stem cell

Zfp281 mediates Nanog autorepression through recruitment of the NuRD complex and inhibits somatic cell reprogramming

Fidalgo, Miguel; Faiola, Francesco; Pereira, Carlos-Filipe; Ding, Junjun; Saunders, Arven; Gingold, Julian; Schaniel, Christoph; et al, 2012. Proceedings of the National Academy of Sciences of the United States of America. 16202 - 16207. 40. 109. 2012. 10.1073/pnas.1208533109 . Proceedings of the National Academy of Sciences of the United States of America

Regulation of Embryonic and Induced Pluripotency by Aurora Kinase-p53 Signaling

Lee, Dung-Fang; Su, Jie; Ang, Yen-Sin; Carvajal-Vergara, Xonia; Mulero-Navarro, Sonia; Pereira, Carlos F.; Gingold, Julian; et al, 2012. Cell Stem Cell. 179 - 194. 2. 11. 2012. 10.1016/j.stem.2012.05.020 . Cell Stem Cell

Using heterokaryons to understand pluripotency and reprogramming

Piccolo, Francesco M.; Pereira, Carlos F.; Cantone, Irene; Brown, Karen; Tsubouchi, Tomomi; Soza-Ried, Jorge; Merkenschlager, Matthias; Fisher, Amanda G., 2011. Philosophical Transactions of the Royal Society B-Biological Sciences. 2260 - 2265. 1575. 366. 2011. 10.1098/rstb.2011.0004 . Philosophical Transactions of the Royal Society B-Biological Sciences

CHD7 targets active gene enhancer elements to modulate ES cell-specific gene expression.

Schnetz, M.P.; Handoko, L.; Akhtar-Zaidi, B.; Bartels, C.F.; Pereira, C.F.; Fisher, A.G.; Adams, D.J.; et al, 2010. PLoS genetics. 7. 6. 2010. http://www.scopus.com/inward/record.url?eid=2-s2.0-79952538205&partnerID=MN8TOARS . PLoS genetics

Jarid2 is a PRC2 component in embryonic stem cells required for multi-lineage differentiation and recruitment of PRC1 and RNA Polymerase II to developmental regulators

Landeira, David; Sauer, Stephan; Poot, Raymond; Dvorkina, Maria; Mazzarella, Luca; Jorgensen, Helle F.; Pereira, C. Filipe; et al, 2010. Nature Cell Biology. 618 - U214. 6. 12. 2010. 10.1038/ncb2065 . Nature Cell Biology

ESCs Require PRC2 to Direct the Successful Reprogramming of Differentiated Cells toward Pluripotency

Pereira, Carlos F.; Piccolo, Francesco M.; Tsubouchi, Tomomi; Sauer, Stephan; Ryan, Natalie K.; Bruno, Ludovica; Landeira, David; et al, 2010. Cell Stem Cell. 547 - 556. 6. 6. 2010. 10.1016/j.stem.2010.04.013 . Cell Stem Cell

Differences in the epigenetic and reprogramming properties of pluripotent and extra-embryonic stem cells implicate chromatin remodelling as an important early event in the developing mouse embryo

Santos, Joana; Pereira, C. Filipe; Di-Gregorio, Aida; Spruce, Thomas; Alder, Olivia; Rodriguez, Tristan; Azuara, Veronique; Merkenschlager, Matthias; Fisher, Amanda G., 2010. Epigenetics & Chromatin. 3. 2010. 10.1186/1756-8935-3-1 . Epigenetics & Chromatin

Short RNAs Are Transcribed from Repressed Polycomb Target Genes and Interact with Polycomb Repressive Complex-2

Kanhere, Aditi; Viiri, Keijo; Araujo, Carla C.; Rasaiyaah, Jane; Bouwman, Russell D.; Whyte, Warren A.; Pereira, C. Filipe; et al, 2010. Molecular Cell. 675 - 688. 5. 38. 2010. 10.1016/j.molcel.2010.03.019 . Molecular Cell

Heterokaryon-based reprogramming for pluripotency

Pereira, C.F.; Fisher, A.G., 2009. Current Protocols in Stem Cell Biology. SUPPL. 9. 2009. http://www.scopus.com/inward/record.url?eid=2-s2.0-65149087887&partnerID=MN8TOARS . 10.1002/9780470151808.sc04b01s9 . Current Protocols in Stem Cell Biology

Hepatocytes and IL-15: A Favorable Microenvironment for T Cell Survival and CD8(+) T Cell Differentiation

Correia, Margareta P.; Cardoso, Elsa M.; Pereira, Carlos F.; Neves, Rui; Uhrberg, Markus; Arosa, Fernando A., 2009. Journal of Immunology. 6149 - 6159. 10. 182. 2009. 10.4049/jimmunol.0802470 . Journal of Immunology

Senescence impairs successful reprogramming to pluripotent stem cells

Banito, Ana; Rashid, Sheikh T.; Acosta, Juan Carlos; Li, SiDe; Pereira, Carlos F.; Geti, Imbisaat; Pinho, Sandra; et al, 2009. Genes & Development. 2134 - 2139. 18. 23. 2009. 10.1101/gad.1811609 . Genes & Development

REST selectively represses a subset of RE1-containing neuronal genes in mouse embryonic stem cells

Jorgensen, Helle F.; Terry, Anna; Beretta, Chiara; Pereira, C. Filipe; Leleu, Marion; Chen, Zhou-Feng; Kelly, Claire; Merkenschlager, Matthias; Fisher, Amanda G., 2009. Development. 715 - 721. 5. 136. 2009. 10.1242/dev.028548 . Development

Satb1 and Satb2 regulate embryonic stem cell differentiation and Nanog expression

Savarese, Fabio; Davila, Amparo; Nechanitzky, Robert; De La Rosa-Velazquez, Inti; Pereira, Carlos F.; Engelke, Rudolf; Takahashi, Keiko; et al, 2009. Genes & Development. 2625 - 2638. 22. 23. 2009. 10.1101/gad.1815709 . Genes & Development

Protein interactions between CD2 and Lck are required for the lipid raft distribution of CD2

Nunes, R.J.; Castro, M.A.A.; Gonçalves, C.M.; Bamberger, M.; Pereira, C.F.; Bismuth, G.; Carmo, A.M., 2008. Journal of Immunology. 988 - 997. 2. 180. 2008. http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000252290000036&KeyUID=WOS:000252290000036 . 10.4049/jimmunol.180.2.988 . Journal of Immunology

Heterokaryon-Based Reprogramming of Human B Lymphocytes for Pluripotency Requires Oct4 but Not Sox2

Pereira, Carlos F.; Terranova, Remi; Ryan, Natalie K.; Santos, Joana; Morris, Kelly J.; Cui, Wei; Merkenschlager, Matthias; Fisher, Amanda G., 2008. Plos Genetics. 9. 4. 2008. 10.1371/journal.pgen.1000170 . Plos Genetics

Protein interactions between CD2 and Lck are required for the lipid raft distribution of CD2

Nunes, R.J.; Castro, M.A.A.; Gonçalves, C.M.; Bamberger, M.; Pereira, C.F.; Bismuth, G.; Carmo, A.M., 2008. Journal of Immunology. 988 - 997. 2. 180. 2008. http://www.scopus.com/inward/record.url?eid=2-s2.0-40449133966&partnerID=MN8TOARS . Journal of Immunology

Acquisition and extinction of gene expression programs are separable events in heterokaryon reprogramming

Terranova, R.; Pereira, C. F.; Du Roure, C.; Merkenschlager, M.; Fisher, A. G., 2006. Journal of Cell Science. 2065 - 2072. 10. 119. 2006. 10.1242/jcs.02945 . Journal of Cell Science

Altered expression of CD1d molecules and lipid accumulation in the human hepatoma cell line HepG2 after iron loading

Cabrita, M.; Pereira, C. F.; Rodrigues, P.; Cardoso, E. M.; Arosa, F. A., 2005. Febs Journal. 152 - 165. 1. 272. 2005. 10.1111/j.1432-1033.2004.04387.x . Febs Journal

Red blood cells as modulators of T cell growth and survival

Arosa, F. A.; Pereira, C. F.; Fonseca, A. M., 2004. Current Pharmaceutical Design. 191 - 201. 2. 10. 2004. 10.2174/1381612043453432 . Current Pharmaceutical Design

Red blood cells promote survival and cell cycle progression of human peripheral blood T cells independently of CD58/LFA-3 and heme compounds

Fonseca, A. M.; Pereira, C. F.; Porto, G.; Arosa, F. A., 2003. Cellular Immunology. 17 - 28. 1. 224. 2003. 10.1016/s0008-8749(03)00170-9 . Cellular Immunology

Red blood cells upregulate cytoprotective proteins and the labile iron pool in dividing human T cells despite a reduction in oxidative stress

Fonseca, A.M.; Pereira, C.F.; Porto, G.; Arosa, F.A., 2003. Free Radical Biology and Medicine. 1404 - 1416. 11. 35. 2003. http://www.scopus.com/inward/record.url?eid=2-s2.0-0344875071&partnerID=MN8TOARS . 10.1016/j.freeradbiomed.2003.08.011 . Free Radical Biology and Medicine

Red blood cells promote survival and cell cycle progression of human peripheral blood T cells independently of CD58/LFA-3 and heme compounds

Fonseca, A.M.; Pereira, C.F.; Porto, G.; Arosa, F.A., 2003. Cellular Immunology. 17 - 28. 1. 224. 2003. http://www.scopus.com/inward/record.url?eid=2-s2.0-0142169441&partnerID=MN8TOARS . 10.1016/S0008-8749(03)00170-9 . Cellular Immunology

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