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Ophthalmology and Visual Sciences

Miesfeld Laboratory

The Miesfeld Laboratory is interested in understanding the gene regulatory networks associated with development and disease of the neural retina, with a focus on retinal ganglion cells (RGCs), the pathogenic target in glaucoma. Through comparisons of natural retinal development with genetic perturbations of genes and cis regulatory elements of interest, we elucidate the mechanisms leading to congenital and adult-onset retinal diseases. The laboratory combines a variety of techniques (biochemistry, histochemistry, molecular biology, microscopy, CRISPR/Cas9 genome editing, etc.) and model systems (mouse, zebrafish, cell and tissue culture) to explore the mechanisms responsible for retinal homeostasis.
Miesfeld Lab_Intro

Research Areas

Retinal Ganglion Cell Genesis and Survival
Retinal ganglion cells are the first-born retinal neurons, important for driving retinal progenitor cell proliferation and their axons form the optic nerve, which serves as a path for migrating astrocytes that promote development of the definitive retinal vasculature. Disrupted RGC genesis is a major cause of congenital blindness. RGCs are essential for vision because they transmit all visual stimuli from the eye to the brain and are the pathogenic target in glaucoma. It is important for vision scientists to understand the mechanisms controlling RGC birth and survival, in order to generate RGCs in vitro for cell transplantation (restoring vision) – and RGC maintenance, in order to prevent degeneration (protecting vision). For this, our lab is investigating the transcription factors, co-activators, co-repressors, and chromatin modifiers contributing to the neural retina/RGC gene regulatory network.

 Miesfeld Lab_embryo_retinal ganglion cell
 Embryonic day 14.5 mouse cryosection labeling retinal progenitor cells, Atoh7+ cells, and RGC axons.
 Miesfeld Lab_Retinal Ganglion cell Pax6enh
 Identification of Pax6+ and Atoh7+ cells in the developing zebrafish retina.

Glaucoma
The Glaucomas are a complex group of ocular neurodegenerative diseases affecting the health of the optic nerve and RGC survival, resulting in blindness from optic nerve atrophy. Most people who develop glaucoma have no known genetic link and do not always share the same set of common risk factors, making it difficult to predict who will develop the disease. Therefore, it is important to assess the susceptibility to develop RGC degeneration using unique combinations of known glaucoma risk factors, such as high intraocular pressure and RGC number. To do so we are utilizing our Atoh7 allelic series, which results in a diminished RGC genesis and ultimately a significant reduction of mature RGCs accompanied by secondary defects to retinal vasculature and axon fasciculation.

Miesfeld Lab_Glaucoma_P30
 RGC axons (green) and retinal vasculature (magenta).
Glaucoma Figure 2 P30 rbpms flat
 Loss of Rbpms+ RGCs in the Atoh7 allelic series. Adapted from Miesfeld et. al. PNAS 2020.

Laboratory Photos

Miesfeld Lab
Miesfeld Lab

Meet Our Team

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Joel B. Miesfeld, PhD

Assistant Professor of Ophthalmology & Visual Sciences; Assistant Professor of Cell Biology, Neurobiology and Anatomy

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Antonia Amidon

Graduate Student

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Darby Bennett

Year Entered MCW: 2023

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Alex Gallo

Graduate Student

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Richard Rausch

Research Technologist I

Our Alumni

Mariah Rossebo
Mason Thao

Funding

The Miesfeld lab is proudly conducting its ongoing research with past and present funding from the NIH/NEI and E. Matilda Zeigler Foundation for the Blind Inc. The NEI supported project “Atoh7 cis regulation and gene regulatory network analysis during retinal ganglion cell development,” seeks to investigate the structure and function of the ATOH7 gene and its enhancers, along with other retinal ganglion cell fate determinants, to better understand the pathogenic mechanisms for human nonsyndromic retinal nonattachment (NCRNA) disease. Our project investigating RGC number as a risk factor for glaucoma was launched from support by the E. Matilda Zeigler Foundation for the Blind Inc.

Get Involved

Support the Miesfeld Laboratory

The Miesfeld Lab could not exist without the generosity and support of many foundations, federal agencies and individual donors. Funds donated to the program are used to acquire new equipment and research consumables, to help train students and fellows, to enable the presentation of our research findings at scientific meetings and to fund positions for support staff.

Join our Team

We are always looking for enthusiastic candidates with strong communication skills and lab experience. We encourage high school students, undergraduate students, graduate students, post doc, and medical students to browse our website and learn more about our research. We also have available positions for laboratory and animal technologists.

Current Openings
We do not have any open positions at this time. Please check back soon!

Resources for Interested Candidates

High School
Research Opportunity for Academic Development in Science (ROADS) program
Undergraduate
Program for Undergraduate Research Experience (PURE)
Summer Program for Undergraduate Research (SPUR)

Graduate
School of Graduate Studies (PhD Program)

Medical
Medical Student Summer Research Program (MSSRP)
Physician Scientist Pathway

Other area institutions
Marquette University, Milwaukee School of Engineering, University of Wisconsin, Milwaukee. These institutions offer collaborative undergraduate and graduate research programs.

Recent Publications

  • (Davis ES, Voss G, Miesfeld JB, Zarate-Sanchez J, Voss SR, Glaser T.) Dev Dyn. 2021 Jun;250(6):807-821 PMID: 32864847 PMCID: PMC8907009 08/31/2020

  • (Miesfeld JB, Ghiasvand NM, Marsh-Armstrong B, Marsh-Armstrong N, Miller EB, Zhang P, Manna SK, Zawadzki RJ, Brown NL, Glaser T.) Proc Natl Acad Sci U S A. 2020 Sep 01;117(35):21690-21700 PMID: 32817515 PMCID: PMC7474671 08/21/2020

  • (Clark BS, Miesfeld JB, Flinn MA, Collery RF, Link BA.) Front Cell Dev Biol. 2020;8:608112 PMID: 33634099 PMCID: PMC7900515 SCOPUS ID: 2-s2.0-85101223534 02/27/2021

  • (Miesfeld JB, Brown NL.) Curr Top Dev Biol. 2019;132:351-393 PMID: 30797514 02/25/2019

  • (Cox AG, Tsomides A, Yimlamai D, Hwang KL, Miesfeld J, Galli GG, Fowl BH, Fort M, Ma KY, Sullivan MR, Hosios AM, Snay E, Yuan M, Brown KK, Lien EC, Chhangawala S, Steinhauser ML, Asara JM, Houvras Y, Link B, Vander Heiden MG, Camargo FD, Goessling W.) EMBO J. 2018 Nov 15;37(22) PMID: 30348863 PMCID: PMC6236334 SCOPUS ID: 2-s2.0-85055253100 10/24/2018

  • (Miesfeld JB, Moon MS, Riesenberg AN, Contreras AN, Kovall RA, Brown NL.) Sci Rep. 2018 Jul 05;8(1):10195 PMID: 29977079 PMCID: PMC6033939 07/07/2018

  • (Hiscock TW, Miesfeld JB, Mosaliganti KR, Link BA, Megason SG.) Development. 2018 May 04;145(9) PMID: 29678815 PMCID: PMC5992593 SCOPUS ID: 2-s2.0-85046850961 04/22/2018

  • (Miesfeld JB, Glaser T, Brown NL.) Gene Expr Patterns. 2018 Jan;27:114-121 PMID: 29225067 PMCID: PMC5835195 12/12/2017

  • (Miesfeld JB, Gestri G, Clark BS, Flinn MA, Poole RJ, Bader JR, Besharse JC, Wilson SW, Link BA.) Development. 2015 Sep 01;142(17):3021-32 PMID: 26209646 PMCID: PMC4582179 SCOPUS ID: 2-s2.0-84940754780 07/26/2015

  • (Porazinski S, Wang H, Asaoka Y, Behrndt M, Miyamoto T, Morita H, Hata S, Sasaki T, Krens SFG, Osada Y, Asaka S, Momoi A, Linton S, Miesfeld JB, Link BA, Senga T, Shimizu N, Nagase H, Matsuura S, Bagby S, Kondoh H, Nishina H, Heisenberg CP, Furutani-Seiki M.) Nature. 2015 May 14;521(7551):217-221 PMID: 25778702 PMCID: PMC4720436 SCOPUS ID: 2-s2.0-84929315796 03/18/2015

  • (Miesfeld JB, Link BA.) Mech Dev. 2014 Aug;133:177-88 PMID: 24560909 PMCID: PMC4138299 SCOPUS ID: 2-s2.0-84908158843 02/25/2014

  • (Clark BS, Cui S, Miesfeld JB, Klezovitch O, Vasioukhin V, Link BA.) Development. 2012 May;139(9):1599-610 PMID: 22492354 PMCID: PMC3317966 SCOPUS ID: 2-s2.0-84859297815 04/12/2012

Publications of from the

Contact Us

Miesfeld Lab

(414) 955-7836

jmiesfeld@mcw.edu

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