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Erika Matunis, Ph.D.

Erika Matunis, Ph.D.

Academic Titles: 
Position Title: 
Principal Investigator
410-502-0009 (Office)
410-502-0013 (Lab)
410-955-4129 (Fax)

Department of Cell Biology
Johns Hopkins School of Medicine
725 N. Wolfe Street, G11 Hunterian
Baltimore, MD 21205

Research Topic:  Signals Regulating Stem Cell Self-renewal

What are the signals regulating stem cell fate? 

A major goal in stem cell biology is to understand how the balance  between stem cell renewal and differentiation is controlled.  Signals from neighboring cells are key regulators of stem cells.  However, identifying these signals has proven very difficult in many systems, since the precise location of stem cells is usually unknown. However, by studying stem cells that sustain spermatogenesis in the fruit fly Drosophila melanogaster, we have begun to get a much clearer idea of  stem cell regulation.  In this tissue, germ line stem cells (GSCs,) attach to a cluster of non-dividing somatic cells called the hub.  When a GSC divides, its daughter is pushed away from the hub and differentiates into a gonialblast (GB).  Somatic stem cells called Cyst Progenitor Cells, are also anchored at the hub, and produce cyst cells that form an envelope around each GB to support its development.  We can readily see all of the cells comprising this stem cell niche by confocal microscopy.

Local signaling controls stem cell renewal:

How do GSC divisions produce two cells with such different fates?  The GSC could receive a signal from the hub that allows it to remain a stem cell, while the daughter displaced away from the hub loses the signal, and differentiates. This is thought to happen in many stem cell systems, but has been extremely difficult to prove.  However, we have found that this is how stem cells are renewed in the fly testis, and we have identified the key regulatory signal.  The hub secretes a ligand (called Unpaired), that activates the Janus kinase-Signal transducer and activator of transcription (Jak-Stat) signaling pathway within GSCs. Activation of Jak-Stat within GSCs ensures that they remain stem cells; GB do not receive enough Upd to activate Jak-Stat, and instead differentiate.

Currently we are using genetic and genomic approaches to identify targets of Stat within GSCs, since these genes molecularly define the GSC fate. We are also determining if the hub directly activates Stat in somatic stem cells, or if a different mechanism is operating to ensure their renewal, since little is known of how two stem cell populations are regulated within one niche. We are also asking how the stem cell niche is established during development.

Finally, we have recently found that spermatogonia that have begun to differentiate can reverse their path and de-differentiate to become GSCs. We are very interested in understanding the mechanisms controlling de-differentiation.

Research Interest: 
Molecular genetics of germ line stem cell function
Research Associates and Staff:
Name Position title Email Phone
Margaret (Maggie) De Cuevas, Ph.D. Research Associate decuevas@jhmi.edu 410-502-0013
Lab Members:
Namesort descending Classification Email Phone
Kathy Le Student kle16@jhu.edu 410-502-0013
Katie Conlon Student kconlon1@jhmi.edu 410-955-4145
Kevin Yu Student kyu14@jhu.edu 410-502-0013
Miriam Akeju Student makeju1@jhmi.edu 410-502-0013

Many adult tissues are renewed from small populations of stem cells, which continually replace differentiated cells lost to damage or age.  Since tissue stem cells are highly dependent on signals from their local microenvironments, or niches, understanding how niches work is important for manipulating regeneration.  To answer this question, the Matunis lab combines genetics, live imaging, and genome-wide approaches to understand how the germline and somatic cells in the testis that create and reside in the testis niche cooperatively ensure a lifetime supply of sperm.

Selected Publications:
Zhang W, Zhang X, Xue Z, Li Y, Ma Q, Ren X, Zhang J, Yang S, Yang L, Wu M, Ren M, Xi R, Wu Z, Liu JL, Matunis E, Dai J, Gao G. (2019).  Probing the function of metazoan histones with a systematic library of H3 and H4 mutants.  Dev Cell Feb 11;48(3):406-419.
Greenspan, L.J., and Matunis, E.L. (2018).  Retinoblastoma intrinsically regulates niche cell quiescence, identity, and niche number in the adult Drosophila testis. Cell Reports 25;24(13):3466-3476.  
Greenspan LJ, Matunis EL. 2017. Live Imaging of the Drosophila Testis Stem Cell Niche. Methods Mol Biol. 1463:63-74.
Ma Q, de Cuevas M, Matunis EL. Chinmo is sufficient to induce male fate in somatic cells of the adult Drosophila ovary. Development. 2016 Mar 1;143(5):754-63. doi: 10.1242/dev.129627. 
Greenspan LJ, de Cuevas M, Matunis E. Genetics of gonadal stem cell renewal. Annu Rev Cell Dev Biol. 2015;31:291-315. doi: 10.1146/annurev-cellbio-100913-013344. 
Hasan, S., Hétié, P., and Matunis, E.L. (2015). Niche signaling promotes stem cell survival in the Drosophila testis via the JAK-STAT target DIAP1. Dev Biol 404, 27-39.
Stine, R.R., Greenspan, L.J., Ramachandran, K.V., and Matunis, E.L. (2014). Coordinate regulation of stem cell competition by Slit-Robo and JAK-STAT signaling in the Drosophila testis. PLoS Genet 10, e1004713.
Ma, Q., Wawersik, M., Matunis, EL.  2014.  The Jak-STAT target Chinmo prevents sex transformation of adult stem cells in the Drosophila testis niche. Dev Cell 31, 474-486.  
Li, Y., Ma, Q., Cherry, C.M., and Matunis, E.L. (2014). Steroid signaling promotes stem cell maintenance in the Drosophila testis. Dev Biol 394, 129-141.
Hetie, P., de Cuevas, M. and Matunis, E.  2014.  Conversion of Quiescent Niche Cells to Somatic Stem Cells Causes Ectopic Niche Formation in the Drosophila Testis. Cell Reports 7, 715-721.
Stine RR, Matunis EL.  Stem cell competition: finding balance in the niche.  2013 Aug;23(8):357-64.
Matunis EL, Stine RR, de Cuevas M.  2012.  Recent advances in Drosophila male germline stem cell biology.  Spermatogenesis 2: 137-144.  PMID: 23087833.
Sinden D, Badgett M, Fry J, Jones T, Palmen R, Sheng X, Simmons A, Matunis E, Wawersik M.  2012.  Jak-STAT regulation of cyst stem cell development in the Drosophila testis.  Dev. Biol. 372: 5-16.  PMID: 23010510.
Issigonis M, Matunis E.  2012.  The Drosophila BCL6 homolog Ken and Barbie promotes somatic stem cell self-renewal in the testis niche.  Dev. Biol. 368: 181-92.  PMID: 22580161.
Sheng, X. R., Matunis, E. L.  2011.  Live imaging of the Drosophila spermatogonial stem cell niche reveals novel mechanisms regulating germline stem cell output.  Development 16:3367-3376.
de Cuevas, M., Matunis, E. L.  2011.  The stem cell niche: Lessons from the Drosophila testis.  Development 14:2861-2969.  
Cherry, C.M., Matunis, E.L. 2010.  Epigenetic regulation of stem cell maintenance in the Drosophila testis via the nucleosome remodeling factor NURF.  Cell Stem Cell 6:557-567.
Issigonis, M., Tulina, N., de Cuevas, M., Brawley, C., Sandler, L., Matunis, E. 2009.  JAK-STAT signal inhibition regulates competition within the Drosophila testis stem cell niche.  Science 326:153-6.
Sheng, X.R., Brawley, C.M., Matunis, E.L. 2009.  Dedifferentiating spermatogonia outcompete somatic stem cells for niche occupancy in the Drosophila testis.  Cell Stem Cell 5:191-203.
Sheng, X.R., Posenau, T., Gumulak-Smith, J.J., Matunis, E., Van Doren, M., Wawersik, M., 2009.  Jak-STAT regulation of male germline stem cell establishment during Drosophila embryogenesis.  Dev. Biol. 334:335-344.
Buszczak, M., Paterno, S., Lighthouse D., Bachman J., Plank J., Owen S., Skora A., Nystul T., Ohlstein B., Allen A., Wilhelm J., Murphy T., Levis B., Matunis. E., Srivali N., Hoskins R., Spradling A.  2007.  The Carnegie protein trap library: a versatile tool for Drosophila developmental studies.  Genetics 175:1501-1531. 
Terry, N.A, Tulina, N., Matunis, E., DiNardo S.  2006.  Novel regulators revealed by profiling Drosophila testis stem cells within their niche.  Dev. Biol. 294:246-257. 
Wawersik, M., Milutinovich, A. Matunis, E., Williams, B. Van Doren, M.  2005.  Somatic control of germline sexual differentiation is mediated by the JAK/STAT pathway. Nature 436:563-567.  
Brawley, C, Matunis, E. 2004. Regeneration of male germline stem cells by spermatogonial dedifferentiation in vivoScience 304:1331-1334.
Tulina, N., Matunis, E. 2001.  Control of Stem cell self-renewal in Drosophila  spermatogenesis by Jak-STAT signaling.  Science 294: 2546-2549.