Skip to main content
Sign In

Joseph A. Brzezinski IV, Ph.D.

Assistant Professor of Ophthalmology

Director, CellSight Laboratory    of Developmental Genetics


Special Thanks to:

  • National Institutes of Health
  • The Boettcher Foundation
  • Department of Defense
  • The Glendorn Foundation
  • The Lyda Hill Foundation
  • The LGA Family Foundation
  • The New L Family Fund
  • Research to Prevent Blindness, Inc.



The retina is a thin nervous tissue that lines the back of the eye. It is responsible for detecting and relaying light stimuli to the brain. The retina is made up of seven principal cell types arranged into three layers (Figure 1). These include rod and cone photoreceptors; amacrine, bipolar, and horizontal interneurons; retinal ganglion cells (RGCs); and Müller glia. Rod photoreceptors detect dim light stimuli, mediating night vision. They are the most abundant cell type in the human retina and are located closest to the back of the eye, near the retinal pigmented epithelium (RPE). Cone photoreceptors are responsible for high acuity vision (like reading) and color discrimination. There are three types of cones in the human retina, each attuned to a specific wavelength of light (blue, green, red). Photoreceptors send their signals via bipolar interneurons, which are then relayed to the brain by the ganglion cells. Signaling between photoreceptors, bipolars, and ganglion cells is further modified by horizontal and amacrine cell interneurons. The retina-spanning Müller glia maintain retinal neuron health and establish a blood-retinal barrier between the vasculature and the neurons.

On a per weight basis, the retina is the most metabolically active tissue in the body. To satisfy this need for nourishment, the retina is perfused by blood vessels that form three planar layers (plexi). One plexus is on the inner surface of the retina and two capillary plexi are located deeper inside the retina (Figure 1). These vessels are made up of vascular endothelial cells and mural cells. Retinal astrocytes coat the surface of the retina and form a blood-retinal barrier with the surface vasculature (Figure 1).


Millions of Americans have vision loss caused by diseases that affect the retina (Figure 2). These diseases can affect neurons directly or other structures in the eye such as the vasculature or the RPE. If the disease process causes the death of retinal neurons, permanent vision loss can occur since neurons do not regenerate. For example, age-related macular degeneration (AMD) results in permanent loss of photoreceptors and significant visual impairment due to RPE and/or vascular alterations (Figure 2). Figure 2 Patients with glaucoma (Figure 2) permanently lose their ganglion cells and cannot relay photic information to the brain. Less commonly, there are diseases caused by defects in genes that control the development and/or function of specific populations of retinal neurons. For example, some genetic mutations cause retinitis pigmentosa, where photoreceptors are progressively lost (Figure 2). Restoring vision in these patients is our long-term goal (see CellSight). One promising way to do this is to replace lost retinal neurons with those grown from stem cell sources. The key to accomplishing this type of treatment is understanding the genetic instructions that tell retinal neurons how to form during development.



All retinal neurons are formed before we are born. The retina starts out as a population of progenitor cells (similar to stem cells). These progenitors are multipotent, that is they can become any of the seven major cell types of the retina. Over time, these progenitors permanently exit the cell cycle (stop dividing) and differentiate (mature) into neurons and glia. Different cell types are formed at different times. For example cones are formed early and bipolar cells are formed late in development. While there is a trend to when each cell type is formed, there is considerable overlap such that multiple cell types are forming at any given time. How do these progenitors decide which type of cell to become? Development is regulated by genetic programs that dictate a cell’s behavior. Our goal is to understand how these genetic programs control retinal development. This could then be applied to produce cone photoreceptors from stem cells, which may restore vision in patients with diseases like AMD (see CellSight).


We are interested in uncovering the mechanisms that regulate mammalian retinal development and applying this knowledge to inform novel stem cell based treatments (see CellSight) that restore vision.  We primarily use the mouse as a model system, as its development is similar to human (Figure 3), and because there is a wealth of genetic resources we can utilize.

Mechanisms of Cell Fate Determination: 
How does a seemingly homogeneous population of retinal progenitor cells diversify into the myriad cell types in the retina? These cells must choose between multiple possible cell fate outcomes at any given time in development. What are the molecules that regulate fate choice? We are currently investigating transcription factors (genes that regulate other genes) for their role in retinal development. One factor of interest is Blimp1 (Prdm1). This zinc finger transcription factor is expressed transiently in the retina and is important for the choice between photoreceptors and bipolar cells (Figure 4). When Blimp1 is deleted, supernumerary bipolar cells form at the expense of photoreceptors (Figure 4). This phenotype is not caused by a failure of photoreceptors to form, but instead, photoreceptor identity is lost and superseded by bipolar identity. We are currently investigating the mechanisms by which: (1) Blimp1 stabilizes photoreceptor fate choice, (2) molecules promote bipolar cell identity, and (3) other factors regulate photoreceptor development.

Gene Regulatory Networks:
Transcription factors bind to DNA regulatory sequences around or within genes, where they can activate or repress expression of a gene. Transcription factors play a critical role in regulating retinal development, but little is known about the positive (enhancer) and negative (silencer) regulatory sequences that are important. It is often difficult to determine what is upstream of a given gene. By carefully examining regulatory elements of key retinal transcription factors, we can identify upstream factors and thus the earliest events in the cell fate choice cascade. Currently, we are examining the regulatory factors that drive Blimp1 and several other genes expressed during retinal development (Figure 5).

Principal Investigator

Brz 200.jpgJoe Brzezinski, Ph.D.
Assistant Professor of Ophthalmology

Joe grew up in the Niagara Falls region of upstate New York. He went to college at SUNY Fredonia and got a B.S. in Recombinant Gene Technology. In 1999, he went to the University of Michigan for Graduate School. Joe studied retinal development with Dr. Tom Glaser in the Department of Human Genetics. In 2006, he went to Northwestern to study cortical development with Dr. Anjen Chenn. In 2007, he joined Dr. Tom Reh’s lab at the University of Washington. There, he continued his studies of retinal development. Joe joined the Department of Ophthalmology at the University of Colorado Denver in 2012.


Laboratory Staff

Ko.jpgKo Uoon Park, M.S.
Professional Research Assistant and Laboratory Manager

Ko was born in Seoul, South Korea and came to the United States in 2003 to study biology. She graduated with a B.A. degree in Molecular Cellular and Developmental Biology from the University of Colorado Boulder. Ko then went to the University of Southern California, where she studied with Dr. James Ou. She obtained her M.S in Molecular Microbiology and Immunology in 2010. Her thesis was on, “The effect of cofilin on Hepatitis C virus (HCV) core protein association with lipid droplet (LD) and LD redistribution in HDV infected cells”. Ko joined the lab as a Professional Research Assistant in 2012.


GoodsonNoah Goodson, M.S.
Neuroscience Graduate Student

Noah grew up in eastern North Carolina. He graduated summa cum laude from Appalachian State University in 2011 with a B.S. in Exercise Science, and minors in Chemistry, Biology, and Psychology. He worked in Dr. Bräuer’s geomicrobiology lab during undergraduate studies. He began graduate work in 2014 and studied neurophysiology in an Ichthyology Lab, receiving the prestigious Bachelors Fellowship and earning a Masters of Marine Science from Nova Southeastern University in 2015. He joined the Brzezinski lab in 2016 where he is head of meme development and dad-joke product testing.


Ko.jpgMichael Kaufman, M.S.
Cell Biology, Stem Cells, and Development Graduate Student

Michael is originally from Los Angeles. He received his B.S. from UC Riverside in 2006, followed by earning a M.S. in Neurobiology at CSU Northridge in 2010. Prior to arriving at the UC Denver Anschutz campus, Michael spent five years in a hematopoietic gene therapy lab at UCLA, researching ADA-SCID and Sickle Cell Anemia. His current scientific interests include stem and progenitor cell fate specification and teaching data science.


Former Lab Members:
  • Joy Abraham
  • Joseph Adewumi
  • Vismaya Bachu
  • Stephanie Bersie
  • Tatiana Eliseeva
  • Sergio Groman Lupa
  • Taylor Mills
  • Jhenya Nahreini
  • Emma Office
  • Eric Pace
  • Grace Randazzo
  • Sophie Schneider
  • Michael Schwanke
  • Brittney Tamayo

Peer Reviewed Publications

For a complete list of publications, please click here.

  1. Brown NL, Patel S, Brzezinski J, Glaser T. Math5 is required for retinal ganglion cell and optic nerve formation. Development (Cambridge, England). 2001; 128(13):2497-508. NIHMSID: NIHMS10447 PubMed [journal] PMID: 11493566, PMCID: PMC1480839.
  2. Brzezinski JA 4th, Brown NL, Tanikawa A, Bush RA, Sieving PA, Vitaterna MH, Takahashi JS, Glaser T. Loss of circadian photoentrainment and abnormal retinal electrophysiology in Math5 mutant mice. Investigative ophthalmology & visual science. 2005; 46(7):2540-51. NIHMSID: NIHMS10448 PubMed [journal] PMID: 15980246, PMCID: PMC1570190.
  3. Akimoto M, Cheng H, Zhu D, Brzezinski JA, Khanna R, Filippova E, Oh EC, Jing Y, Linares JL, Brooks M, Zareparsi S, Mears AJ, Hero A, Glaser T, Swaroop A. Targeting of GFP to newborn rods by Nrl promoter and temporal expression profiling of flow-sorted photoreceptors. Proceedings of the National Academy of Sciences of the United States of America. 2006; 103(10):3890-5. PubMed [journal] PMID: 16505381, PMCID: PMC1383502.
  4. Saul SM, Brzezinski JA 4th, Altschuler RA, Shore SE, Rudolph DD, Kabara LL, Halsey KE, Hufnagel RB, Zhou J, Dolan DF, Glaser T. Math5 expression and function in the central auditory system. Molecular and cellular neurosciences. 2008; 37(1):153-69. NIHMSID: NIHMS38894 PubMed [journal] PMID: 17977745, PMCID: PMC2266824.
  5. Brzezinski JA 4th, Lamba DA, Reh TA. Blimp1 controls photoreceptor versus bipolar cell fate choice during retinal development. Development (Cambridge, England). 2010; 137(4):619-29. PubMed [journal] PMID: 20110327, PMCID: PMC2827615.
  6. Ghiasvand NM, Rudolph DD, Mashayekhi M, Brzezinski JA 4th, Goldman D, Glaser T. Deletion of a remote enhancer near ATOH7 disrupts retinal neurogenesis, causing NCRNA disease. Nature neuroscience. 2011; 14(5):578-86. NIHMSID: NIHMS279319 PubMed [journal] PMID: 21441919, PMCID: PMC3083485.
  7. Brzezinski JA 4th, Kim EJ, Johnson JE, Reh TA. Ascl1 expression defines a subpopulation of lineage-restricted progenitors in the mammalian retina. Development (Cambridge, England). 2011; 138(16):3519-31. PubMed [journal] PMID: 21771810, PMCID: PMC3143566.
  8. Brzezinski JA 4th, Prasov L, Glaser T. Math5 defines the ganglion cell competence state in a subpopulation of retinal progenitor cells exiting the cell cycle. Developmental biology. 2012; 365(2):395-413. NIHMSID: NIHMS364804 PubMed [journal] PMID: 22445509, PMCID: PMC3337348.
  9. Hufnagel RB, Riesenberg AN, Quinn M, Brzezinski JA 4th, Glaser T, Brown NL. Heterochronic misexpression of Ascl1 in the Atoh7 retinal cell lineage blocks cell cycle exit. Molecular and cellular neurosciences. 2013; 54:108-20. NIHMSID: NIHMS451170 PubMed [journal] PMID: 23481413, PMCID: PMC3622171.
  10. Brzezinski JA 4th, Uoon Park K, Reh TA. Blimp1 (Prdm1) prevents re-specification of photoreceptors into retinal bipolar cells by restricting competence. Developmental biology. 2013; 384(2):194-204. NIHMSID: NIHMS531998 PubMed [journal] PMID: 24125957, PMCID: PMC3845674.
  11. Vincent SD, Mayeuf-Louchart A, Watanabe Y, Brzezinski JA 4th, Miyagawa-Tomita S, Kelly RG, Buckingham M. Prdm1 functions in the mesoderm of the second heart field, where it interacts genetically with Tbx1, during outflow tract morphogenesis in the mouse embryo. Human molecular genetics. 2014; 23(19):5087-101. PubMed [journal] PMID: 24821700.
  12. Wilken MS, Brzezinski JA, La Torre A, Siebenthall K, Thurman R, Sabo P, Sandstrom RS, Vierstra J, Canfield TK, Hansen RS, Bender MA, Stamatoyannopoulos J, Reh TA. DNase I hypersensitivity analysis of the mouse brain and retina identifies region-specific regulatory elements. Epigenetics & chromatin. 2015; 8:8. PubMed [journal] PMID: 25972927, PMCID: PMC4429822.
  13. Brzezinski JA, Reh TA. Photoreceptor cell fate specification in vertebrates. Development (Cambridge, England). 2015; 142(19):3263-73. PubMed [journal] PMID: 26443631, PMCID: PMC4631758.
  14. Park KU, Randazzo G, Jones KL, Brzezinski JA 4th. Gsg1, Trnp1, and Tmem215 Mark Subpopulations of Bipolar Interneurons in the Mouse Retina. Investigative ophthalmology & visual science. 2017 Feb 1;58(2):1137-1150. PubMed [journal] PMID: 28199486, PMCID: PMC5317276.
  15. Mills TS, Eliseeva T, Bersie SM, Randazzo G, Nahreini J, Park KU, Brzezinski JA 4th. Combinatorial regulation of a Blimp1 (Prdm1) enhancer in the mouse retina. PLoS One. 2017 Aug 22;12(8):e0176905. doi: 10.1371/journal.pone.0176905. eCollection 2017. PubMed PMID: 28829770; PubMed Central PMCID: PMC5568747.
  16. Groman-Lupa S, Adewumi J, Park KU, Brzezinski IV JA. The Transcription Factor Prdm16 Marks a Single Retinal Ganglion Cell Subtype in the Mouse Retina. Investigative ophthalmology & visual science. 2017 Oct 1;58(12):5421-5433. PubMed [journal] PMID: 29053761, PMCID: PMC5656415.
  17. O'Sullivan ML, Puñal VM, Kerstein PC, Brzezinski JA 4th, Glaser T, Wright KM, Kay JN. Astrocytes follow ganglion cell axons to establish an angiogenic template during retinal development. Glia. 2017; 65(10):1697-1716. NIHMSID: NIHMS888834 PubMed [journal] PMID: 28722174, PMCID: PMC5561467.
  18. Goodson NB, Nahreini J, Randazzo G, Uruena A, Johnson JE, Brzezinski JA 4th. Prdm13 is required for Ebf3+ amacrine cell formation in the retina. Developmental biology. 2018; 434(1):149-163. NIHMSID: NIHMS930527 PubMed [journal] PMID: 29258872, PMCID: PMC5785448.

Book Chapters

  1. Brzezinski JA IV, Reh TA. Encyclopedia of the Eye. Dartt DA, Besharse JC, Dana R, editors. Boston, MA: Elsevier; 2010. Chapter 4, Retinal Histogenesis. pp.73-80.