Hair Pigmentation

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Carlos Clavel

Carlos Clavel received his BS and MS in Biological Sciences from Saint Louis University in the US. He finished his PhD training in the Cell Therapy lab at the University of Navarra, Spain. Thanks to a collaboration with the laboratory of Dr. Catherine Verfaillie, he had the opportunity of working with Multipotent Adult Progenitor Cells in her groundbreaking laboratories of Minnesota (US) and Leuven (Belgium). At that time, he was focused on the tremendous differentiation potential of human adult stem cells. His research then shifted to understanding how stem cells are instructed to display their potential, and he subsequently joined Dr. Michael Rendl’s laboratory at Mount Sinai School of Medicine in New York where his research focused on the transcriptional control of the hair inducing fate of Dermal Papilla niche cells. Carlos has recently joined IMB as a Project Leader where he is starting up his own research group focusing on understanding the regulation of the hair follicle stem cell niche and its implication in novel therapies for skin pigmentation disorders.

Altered skin pigmentation is one of the most common dermatologic disorders that affect 1 in 3 people worldwide. Among these disorders, vitiligo is one of the most serious conditions due to its visible nature and psychological burden. Recent clinical observations in human skin suggest that hair follicles may provide epidermal melanocytes in the process of recovery from vitiligo. The hair follicle melanocyte stem cell niche is the main melanocyte reservoir of the skin and a better understanding of the mechanisms regulating repigmentation is critical for designing novel strategies for vitiligo therapy. We have developed novel genetic tools to study dermal papilla (DP) cells in the hair follicle stem cell niche. And, we have recently shown how in the hair follicle (HF) the DP-specific gene Sox2 is a key regulator of hair growth by controlling keratinocytes migration through the mesenchymal- epithelial crosstalk between the DP niche cells and the stem cell progeny. Now, we have identified a pigment switch in the pelage of DP-specific Sox2 knock down mice and observed abnormal cell signaling in the DP and melanocytes compartments of the HF. This phenotype, strongly suggests that the DP compartment is a regulator of the melanocyte stem cell niche (MeSC). We seek to gain knowledge on the signaling regulation of the MeSC niche and its possible use in novel therapeutic approaches for skin pigmentation disorders.

Rezza A, Sennett R, Tanguy M, Clavel C, Rendl M. PDGF signaling in the dermis and in dermal condensates is dispensable for hair follicle induction and formation. Exp Dermatol. 2015 Feb 24. doi: 10.1111/exd.12672. [Epub ahead of print] PubMed PMID: 25708924. Link
Sennett R, Wang Z, Rezza A, Grisanti L, Roitershtein N, Sicchio C, Mok KW, Heitman NJ, Clavel C, Ma'ayan A, Rendl M. “An Integrated Transcriptome Atlas of Embryonic Hair Follicle Progenitors, Their Niche, and the Developing Skin.” Developmental Cell 2015 Aug 5. pii: S1534-5807(15)00430-X. doi: 10.1016/j.devcel.2015.06.023.
Sennett R, Rezza A, Dauber KL, Clavel C, Rendl M. Cxcr4 is transiently expressed in both epithelial and mesenchymal compartments of nascent hair follicles but is not required for follicle formation. Exp Dermatol. 2014 Oct;23(10):748-50. doi: 10.1111/exd.12523. PubMed PMID: 25066162. Link
Tsai SY, Sennett R, Rezza A, Clavel C, Grisanti L, Zemla R, Najam S, Rendl M. Wnt/β-catenin signaling in dermal condensates is required for hair follicle formation. Dev Biol. 2014 Jan 15;385(2):179-88. doi: 10.1016/j.ydbio.2013.11.023. Epub 2013 Dec 3. PubMed PMID: 24309208; PubMed Central PMCID: PMC3933391. Link
Grisanti L, Rezza A, Clavel C, Sennett R, Rendl M. Enpp2/Autotaxin in dermal papilla precursors is dispensable for hair follicle morphogenesis. J Invest Dermatol. 2013 Oct;133(10):2332-9. doi: 10.1038/jid.2013.140. Epub 2013 Mar 14. PubMed PMID: 23677168; PubMed Central PMCID: PMC3748178. Link
Grisanti L, Clavel C, Cai X, Rezza A, Tsai SY, Sennett R, Mumau M, Cai CL, Rendl M. Tbx18 targets dermal condensates for labeling, isolation, and gene ablation during embryonic hair follicle formation. J Invest Dermatol. 2013 Feb;133(2):344-53. doi: 10.1038/jid.2012.329. Epub 2012 Sep 20. PubMed PMID: 22992803; PubMed Central PMCID: PMC3530628. Link
Clavel C, Grisanti L, Zemla R, Rezza A, Barros R, Sennett R, Mazloom AR, Chung CY, Cai X, Cai CL, Pevny L, Nicolis S, Ma'ayan A, Rendl M. Sox2 in the dermal papilla niche controls hair growth by fine-tuning BMP signaling in differentiating hair shaft progenitors. Dev Cell. 2012 Nov 13;23(5):981-94. doi: 10.1016/j.devcel.2012.10.013. PubMed PMID: 23153495; PubMed Central PMCID: PMC3500526. Link
Driskell RR, Clavel C, Rendl M, Watt FM. Hair follicle dermal papilla cells at a glance. J Cell Sci. 2011 Apr 15;124(Pt 8):1179-82. doi: 10.1242/jcs.082446. Review. PubMed PMID: 21444748; PubMed Central PMCID: PMC3115771. Link
Roobrouck VD, Clavel C, Jacobs SA, Ulloa-Montoya F, Crippa S, Sohni A, Roberts SJ, Luyten FP, Van Gool SW, Sampaolesi M, Delforge M, Luttun A, Verfaillie CM. Differentiation potential of human postnatal mesenchymal stem cells, mesoangioblasts, and multipotent adult progenitor cells reflected in their transcriptome and partially influenced by the culture conditions. Stem Cells. 2011 May;29(5):871-82. doi: 10.1002/stem.633. PubMed PMID: 21433224. Link
Tsai SY, Clavel C, Kim S, Ang YS, Grisanti L, Lee DF, Kelley K, Rendl M. Oct4 and klf4 reprogram dermal papilla cells into induced pluripotent stem cells. Stem Cells. 2010 Feb;28(2):221-8. doi: 10.1002/stem.281. PubMed PMID: 20014278. Link
Rice CM, Clavel C, Mazo M, Prosper F, Scolding NJ. Multipotent adult progenitor cell isolation and proliferation in cytokine and serum-free medium conditioned by rat B104 cells. Br J Haematol. 2010 Feb;148(3):441-4. doi: 10.1111/j.1365-2141.2009.07986.x. Epub 2009 Nov 30. PubMed PMID: 19961484. Link
Clavel C, Verfaillie CM. Bone-marrow-derived cells and heart repair. Curr Opin Organ Transplant. 2008 Feb;13(1):36-43. doi: 10.1097/MOT.0b013e3282f428d1. Review. PubMed PMID: 18660705. Link
Barajas M, Franchi F, Clavel C, Aranguren XL, Kramer MG, Abizanda G, Merino J, Moreno C, Gárate L, Guitart A, Narvaiza I, Gutiérrez-Perez M, Riezu-Boj JI, Berasain C, Prieto J, Prósper F. Multipotent Adult Progenitor Cells (MAPC) contribute to hepatocarcinoma neovasculature. Biochem Biophys Res Commun. 2007 Dec 7;364(1):92-9. Epub 2007 Oct 2. PubMed PMID: 17931602. Link
Pelacho B, Aranguren XL, Mazo M, Abizanda G, Gavira JJ, Clavel C, Gutierrez-Perez M, Luttun A, Verfaillie CM, Prósper F. Plasticity and cardiovascular applications of multipotent adult progenitor cells. Nat Clin Pract Cardiovasc Med. 2007 Feb;4 Suppl 1:S15-20. PubMed PMID: 17230211. Link
Aranguren XL, Luttun A, Clavel C, Moreno C, Abizanda G, Barajas MA, Pelacho B, Uriz M, Araña M, Echavarri A, Soriano M, Andreu EJ, Merino J, Garcia-Verdugo JM, Verfaillie CM, Prósper F. In vitro and in vivo arterial differentiation of human multipotent adult progenitor cells. Blood. 2007 Mar 15;109(6):2634-42. Epub 2006 Nov 7. PubMed PMID: 17090652. Link