Faculty Contact Info
OFFICE: 909 S Wolcott
4051 COMRB
PH #: (312) 996-1048
EMAIL: spinho@uic.edu
Sandra Pinho, PhD
ASSISTANT PROFESSOR OF PHARMACOLOGY
B.S., Faculty of Sciences, University of Porto; Biology (2003).
Faculty of Medicine, University of Porto; Molecular and Cellular Biology (2005).
PhD, Imperial College School of Medicine, London; Epigenetics and Stem Cell Biology (2010).
Postdoc, Albert Einstein College of Medicine, New York; Hematopoietic Stem Cell Biology (2016).
Research Interests
The Pinho Lab is interested in understanding how hematopoietic stem cells (HSCs), which are able to self-renew and differentiate into all functional types of blood and immune cells are regulated. In homeostasis, HSCs are located within the bone marrow where they are tightly regulated by cells and factors that constitute the bone marrow microenvironment, also known as the niche. Several HSC niche regulatory cells have been identified, including both non-hematopoietic (e.g., mesenchymal stem and endothelial cells) and HSC-derived progeny (e.g., megakaryocytes). With age, HSCs suffer a decline in their regenerative capacity leading to impaired immune responses and possibly contributing to the development of bone marrow failure and hematopoietic malignancies.
Using the mouse bone marrow as a model and taking advantage of cutting-edge HSC imaging techniques our current focus is on the regulation of the stem cell microenvironment in aging and in malignancies of the hematopoietic system. Overall, our long-term goal is to design novel rejuvenation technologies for aged HSCs and develop strategies that will improve cancer therapy and open novel opportunities in regenerative medicine.
In the mouse bone marrow small hematopoietic stem cells are closely associated with large perivascular megakaryocytes.
Selected Publications
Toboz P, Amiri M, Tabatabaei N, Dufour CR, Kim SH, Fillebeen C, Ayemoba CE, Khoutorsky A, Nairz M, Shao L, Pajcini KV, Kim KW, Giguère V, Oliveira RL, Constante M, Santos MM, Morales CR, Pantopoulos K, Sonenberg N, Pinho S, Tahmasebi S. The amino acid sensor GCN2 controls red blood cell clearance and iron metabolism through regulation of liver macrophages. Proc Natl Acad Sci U S A. 2022 Aug 30;119(35):e2121251119. doi: 10.1073/pnas.2121251119. Epub 2022 Aug 22. PubMed PMID: 35994670; PubMed Central PMCID: PMC9436309.
Pinho S, Wei Q, Maryanovich M, Zhang D, Balandrán JC, Pierce H, Nakahara F, Di Staulo A, Bartholdy BA, Xu J, Borger DK, Verma A, Frenette PS. VCAM1 confers innate immune tolerance on haematopoietic and leukaemic stem cells. Nat Cell Biol. 2022 Mar;24(3):290-298. doi: 10.1038/s41556-022-00849-4. Epub 2022 Feb 24. PubMed PMID: 35210567; PubMed Central PMCID: PMC8930732.
Zhang D, Gao X, Li H, Borger DK, Wei Q, Yang E, Xu C, Pinho S, Frenette PS. The microbiota regulates hematopoietic stem cell fate decisions by controlling iron availability in bone marrow. Cell Stem Cell. 2022 Feb 3;29(2):232-247.e7. doi: 10.1016/j.stem.2021.12.009. Epub 2022 Jan 21. PubMed PMID: 35065706; PubMed Central PMCID: PMC8818037.
Marchand T, Pinho S. Leukemic Stem Cells: From Leukemic Niche Biology to Treatment Opportunities. Front Immunol. 2021;12:775128. doi: 10.3389/fimmu.2021.775128. eCollection 2021. Review. PubMed PMID: 34721441; PubMed Central PMCID: PMC8554324.
Pinho S, Frenette PS. Haematopoietic stem cell activity and interactions with the niche. Nat Rev Mol Cell Biol. 20:303-320, 2019. Review. PMCID: PMC6483843.
Nakahara F, Borger DK, Wei Q, Pinho S, Maryanovich M, Zahalka AH, Suzuki M, Cruz CD, Wang Z, Xu C, Boulais PE, Ma'ayan A, Greally JM, Frenette PS. Engineering a haematopoietic stem cell niche by revitalizing mesenchymal stromal cells. Nat Cell Biol. 21:560-567, 2019. PMCID: PMC6499646.
Pinho S, Marchand T, Yang E, Wei Q, Nerlov C, Frenette PS. Lineage-Biased Hematopoietic Stem Cells Are Regulated by Distinct Niches. Dev Cell. 44:634-41, 2018. PMCID: PMC5886750. (Journal Cover)
Maryanovich M, Zahalka AH, Pierce H, Pinho S, Nakahara F, Asada N, Wei Q, Wang X, Ciero P, Xu J, Leftin A, Frenette PS. Adrenergic nerve degeneration in bone marrow drives aging of the hematopoietic stem cell niche. Nat Med. 24:782-91, 2018. PMCID: PMC6095812.
Bruns I*, Lucas D*, Pinho S*, Ahmed J, Lambert MP, Kunisaki Y, Scheiermann C, Schiff L, Poncz M, Bergman A, Frenette PS. Megakaryocytes regulate hematopoietic stem cell quiescence through CXCL4 secretion. Nat Med. 20:1315-20, 2014. PMCID: PMC4258871. (*co-first authors)
Mizoguchi T, Pinho S, Ahmed J, Kunisaki Y, Hanoun M, Mendelson A, Ono N, Kronenberg HM, Frenette PS. Osterix marks distinct waves of primitive and definitive stromal progenitors during bone marrow development. Dev Cell. 29:340-9, 2014. PMCID: PMC4051418.
Hanoun M, Zhang D, Mizoguchi T, Pinho S, Pierce H, Kunisaki Y, Lacombe J, Armstrong SA, Duhrsen U, Frenette PS. Acute myelogenous leukemia-induced sympathetic neuropathy promotes malignancy in an altered hematopoietic stem cell niche. Cell Stem Cell. 15:365-75, 2014. PCMID: PMC4156919.
Pinho S, Lacombe J, Hanoun M, Mizoguchi T, Bruns I, Kunisaki Y, Frenette PS. PDGFRα and CD51 mark human nestin+ sphere-forming mesenchymal stem cells capable of hematopoietic progenitor cell expansion. J Exp Med. 210:1351-67, 2013. PMCID: PMC3698522.
Kunisaki Y, Bruns I, Scheiermann C, Ahmed J, Pinho S, Zhang D, Mizoguchi T, Wei Q, Lucas D, Ito K, Mar JC, Bergman A, Frenette PS. Arteriolar niches maintain haematopoietic stem cell quiescence. Nature. 502:637-43, 2013. PMCID: PMC3821873.