Assistant Professor, Baylor College of Medicine
B.S., University of Idaho, Moscow, 2002
Ph.D., Washington University School of Medicine, 2007
Postdoc, Harvard University, 2014
Retina: The right model for the job
Neurons and glia form the road map that defines who we are and what we experience. We seek to understand how this road map is established and why it often fails in disease and old age. To find these answers, we focus our studies on discovering molecules important in determining neural identity and proper connectivity. Disruptions in this connectivity are thought to underlie many of the physiological changes that accompany normal neural aging as well as disease. Thus, we also study how cell identity and wiring change in neural diseases, such as cancer.
The neural retina processes visual information and relays it to the brain. It provides an excellent system for many of our studies for several reasons: 1) the visual system undergoes complex developmental patterning as well as clinically significant age-associated decline; 2) much is known about retinal circuit formation; and 3) retinal neurons themselves are accessible to study in vivo.
There are five general neuron types in the retina. Photoreceptors detect visual stimuli. Interneurons (horizontal, bipolar and amacrine cells), process these signals, and retinal ganglion cells (RGCs) integrate this information and send it to the brain. Retinal neurons can be further subdivided into ~70 distinct functional subtypes. While this number of subtypes is comparable to that of other brain regions, markers for a majority these cells have been well defined only in retina. Moreover, specific types of retinal neurons pattern and connect in precise nuclear and synaptic layers.
Because the circuitry of the retina is well understood, molecular, cellular and functional studies can be completed in parallel and readily interpreted. This is more challenging in the brain where cells and synapses of many types are closely intermingled.
Daffis S, Samuel MA, Keller B, Gale M Jr, Diamond MS (2007) Cell-specific IRF-3 responses protect against West Nile virus infection by interferon-dependent and independent mechanisms. PLOS Pathogens 3:1005-1015.
Samuel MA, Wang H, Siddharthan V, Morrey JD, Diamond MS (2007) Axonal transport mediates West Nile virus entry into the central nervous system and induces acute flaccid paralysis. Proceedings of the National Academy of Sciences USA 104:17140-17145.
Daffis S, Samuel MA, Suthar MS, Gale M Jr, Diamond MS (2008) Toll-like receptor 3 has a protective role against West Nile virus infection. Journal of Virology 82:10349-10358.
Daffis S, Samuel MA, Suthar MS, Keller BC, Gale M Jr, Diamond MS (2008) Interferon regulatory factor IRF-7 induces the antiviral alpha interferon response and protects against lethal West Nile virus infection. Journal of Virology 82:8465-8475.
Szretter KJ, Samuel MA, Gilfillan S, Fuchs A, Colonna M, Diamond MS (2009) The immune adaptor molecule SARM modulates tumor necrosis factor alpha production and microglia activation in the brainstem and restricts West Nile Virus pathogenesis. Journal of Virology 83:9329-9338.
Diamond MS, Mehlhop E, Oliphant T, Samuel MA (2009) The host immunologic response to West Nile encephalitis virus. Frontiers in Bioscience 14:3024-3034.
Parameswaran P, Sklan E, Wilkins C, Burgon T, Samuel MA, Lu R, Ansel KM, Heissmeyer V, Einav S, Jackson W, Doukas T, Paranjape S, Polacek C, dos Santos FB, Jalili R, Babrzadeh F, Gharizadeh B, Grimm D, Kay M, Koike S, Sarnow P, Ronaghi M, Ding SW, Harris E, Chow M, Diamond MS, Kirkegaard K, Glenn JS, Fire AZ (2010) Six RNA viruses and forty-one hosts: viral small RNAs and modulation of small RNA repertoires in vertebrate and invertebrate systems. PLOS Pathogens 12:e1000764.
Samuel MA, Zhang Y, Meister M, Sanes J (2011) Age-related alterations in neurons of the mouse retina. Journal of Neuroscience 31:16033-16044.
Samuel MA, Valdez G, Tapia JC, Lichtman JW, Sanes JR (2012) Agrin and synaptic laminin are required to maintain adult neuromuscular junctions PLOS One 7:e46663.
Hussmann KL, Samuel MA, Kim KS, Diamond MS, Fredericksen BL (2013) Differential replication of pathogenic and nonpathogenic strains of West Nile virus within astrocytes. Journal of Virology 87:2814-2822.
Samuel MA, Voinescu, EP, Lilley BN, deCabo R, Fortez M, Viollet B, Pawlyk B, Sandberg MA, Vavvas DG, Sanes JR (2014) LKB1 and AMPK regulate synaptic remodeling in old age. Nature Neuroscience 17:1190-1197.
Melanie Samuel, Ph.D.
Huffington Center on Aging
Baylor College of Medicine
One Baylor Plaza N910
Houston, TX 77030
Tel: (713) 798-1561