Mechanisms of signal integration
To form the right connections neurons must navigate long distances, guided by attractive and repulsive signals. These ‘guidance cues’ act like streetlights and street signs, and tell the developing neurons where to go to reach their final destinations. Just like when we are driving our cars, neurons encounter multiple signals along the road. While a number of these neuronal guidance signals have been identified, we still don’t understand how multiple attractive and repulsive cues are interpreted inside the developing neuron. Understanding how these cues are integrated and interpreted inside the cell to trigger a diverse array of developmental events is of critical importance if we are to understand the formation, function and malfunction of the human nervous system. We are investigating how a family of intracellular proteins participates in the establishment of brain circuits. These proteins (Cas family) have the potential to interpret and integrate the multiple signals that neurons receive.
Molecular mechanisms of pruning
The initial assembly of neuronal circuits is carried out by progressive developmental events, like the growth of axons (the main output projection of neurons). During these progressive or circuit-building events, excessive projections, which are unnecessary for the mature circuit, are formed. Subsequently, many brain circuits require refinement of these supernumerary connections via regressive events (e.g. death or devolvement of these byproduct projections) in order to properly function. One such regressive event, axonal pruning, remodels immature pathways by removal of exuberant axonal branches. Disruption of normal pruning events during neural development and circuit maturation has been linked to neurodevelopmental disorders, including autism-spectrum disorders. We are taking a variety of approaches to identify the molecular players critical for axonal pruning.
Targeting reactive astrocytes
Common to virtually all neurodegenerative diseases and brain disorders are changes in a glial cell type in the brain called an astrocyte, which become “reactive”. Astrocytes normally perform critical supportive functions in the brain, but the jury still out on whether reactive astrocytes are beneficial or detrimental for the progression of disease. In collaboration with the Fiacco and Wilson labs we are developing new approaches to study the role of reactive astrocytes during neurological disease.
December 7th, 2022 - Congratulations to Jason on his successful thesis defense!
August 22nd, 2022 - Will and Teresa's paper is now published in Cell Reports Methods. Here is a link. Now also featured here.
August 5ht, 2022 - Wenny and Jason's work is now available as a preprint at bioRxiv.
December 8th, 2021 - Congratulations to Wenny on her successful thesis defense!
October 20, 2021 - Teresa and Tyler's new paper is published in the Journal of Cell Science, and got the cover! Check it out here.
July 28, 2021 - Congratulations to Will on his successful thesis defense!
December 15, 2020 - Congratulations to Tyler on his successful thesis defense!
July 30, 2020 - Our new preprint on the development of a viral-based approach for cell- and time-specific gene expression (ExBox) is now available at bioRxiv.
January 12, 2020 - Martin is now a Keystone Symposia Fellow.
We are looking for postdocs. See the ad here.
August 1, 2019 - The Fiacco, Riccomagno and Wilson Labs are awarded a multi-PI R01 grant from NIDA to investigate the role of reactive astrocytes in different models of chronic inflammation.
June 1, 2019 - The Riccomagno and Fiacco Labs are awarded an R03 grant from NIA to study the role of reactive astrocytes in Alzheimer's disease.
March 11, 2019 - Congratulations to Jason for passing his qualifying exam!
March 8, 2019 - The Riccomagno and Fiacco Labs are awarded an R21 grant from NINDS. The goal of the proposal is to develop a combinatorial strategy to selectively manipulate reactive astrocytes in disease.
January 25, 2019 - Congratulations to Wenny for passing her qualifying exam!
October 11, 2018 - The Riccomagno Lab is awarded a 1-year research grant from the CANCER RESEARCH COORDINATING COMMITTEE.
September 22, 2018 - The Riccomagno Lab is awarded an R21 grant from NIMH. The major goal of this project is to understand the role of caspase-dependent refinement during brain development.
August 29, 2018 - Congratulations to Tyler for passing his qualifying exam!
July 1st, 2018 - The Riccomagno Lab is awarded a Hellman Fellowship. The major goal of the award is to explore the mechanisms that regulate thalamo-cortical axon pruning.
June 15, 2018 - The Riccomagno Lab is awarded an R01 grant from NINDS. The major goal of this 5 year project is to determine the role of adhesion signaling during cortical development.
Earlier 2018 - Congratulations to Jason and Tyler for publishing their papers in Scientific Reports!
Because Science Is Fun!
Honor's Undergraduate Student
Lab Assistant Emeritus
FORMER TEAM MEMBERS
Jason Estep - Research Associate, Arc Institute
Wenny Wong - Scientist III, Thermo-Fisher Cell Biology
Will Agnew-Svoboda - Research Scientist at Akoya Biosciences
Tyler Vahedi-Hunter - Lecturer at Cal State Bakersfield
Punit Bhattachan - Postdoctoral fellow at Albert Einstein College of Medicine
Yiu-Cheung (Eric) Wong - PhD student at Stanford University
Camila Alvarez - PhD student at UC Riverside
Carly Horn - Clinical Laboratory Scientist Program
Sunny Trieu - Pharmacy student of UC San Diego
Nahal Khalkhali (Honor's) - Master's student at UC Irvine
Srinija Maganti - Postbac student at Dartmouth College
Alexis Marquez - Lab Assistant at UC San Francisco
Kieusa Nguyen - Medical Student at Nova Southeastern University
Alexander Taft - Medical Student Arkansas College of Osteopathic Medicine
Brian Loui - Medical student at Loma Linda University
Mandeep Chhokar - Postbac student at UC
Lauren Lopez (Honor's) - Medical student at UC Riverside
Jasmine Pacheco - EMT
Jessica Avalos (MarcU)- Dental Student
Jonathan Argame -Master's student at Southern California University of Health Sciences
Anthony Chen - Clinical Genetic Molecular Biologist Scientist at Ambry Genetics
Abhinandan Singh Pabla - Medical Student at Stritch School of Medicine
THE LAB OVER THE YEARS
Wong, W*, Estep, J.A*, Ubina, T., Jahncke, J.N., Wright, K.M., and Riccomagno, M.M. (2022) An adhesive signaling axis regulates the establishment of the cortical glial scaffold. In Revision. Also bioRxiv https://doi.org/10.1101/2022.08.02.502565 [Preprint]
Estep, J.A, Sun, L.O., and Riccomagno, M.M. (2022) A Luciferase Fragment Complementation Assay to Detect Focal Adhesion Kinase (FAK) Signaling Events. In revision. Also SSRN http://dx.doi.org/10.2139/ssrn.4182286 [Preprint]
Agnew-Svoboda, W., Ubina, T., Figueroa, Z., Wong, Y-C, Vizcarra, E., Roebini, B., Wilson, E., Fiacco, T.* and Riccomagno, M.M. * (2022) A genetic tool for the longitudinal study of a subset of post-inflammatory reactive astrocytes. Cell Reports Methods, 2 (8) 100276
Ubina, T.*, Vahedi-Hunter, T.*, Gupta, A., Wong, W., Agnew-Svoboda, W., Santhakumar, V., and Riccomagno, M.M. (2021) ExBoX: a simple Boolean exclusion strategy to drive expression in neurons. Journal of Cell Science 134 (20). PMC8572001
Rutlin, M., Rastelli, D., Kuo, W. T., Estep, J. A., Louis, A., Riccomagno, M. M., Turner, J. R., and Rao, M. (2020) The Villin1 Gene Promoter Drives Cre Recombinase Expression in Extraintestinal Tissues. Cellular and Molecular Gastroenterology and Hepatology 10:864-867. PMC7573669
Vahedi-Hunter, T.A., Estep, J.A., Rosette, K.A., Rutlin, M.L., Wright, K.M., and Riccomagno, M.M. (2018) Cas Adaptor Proteins Coordinate Sensory Axon Fasciculation. Scientific Reports 8:5996. PMC5902548
Estep, J.A., Wong, W., Wong, Y-C. E., Loui, B. M. and Riccomagno, M.M. (2018) β-Chimaerin regulates cerebellar granule cell development. Scientific Reports 8:680. PMC5766509
Agnew-Svoboda, W., Kolodkin, A.L.*, and Riccomagno, M.M.* (2016) Regressive Phenomena: Refining Connections. D.W. Pfaff, N.D. Volkow (eds.), Neuroscience in the 21st Century. * Authors for correspondence
Riccomagno, M.M. * and Kolodkin, A.L. *(2015) Sculpting Neural Circuits by Axon and Dendrite Pruning. Annual Review of Cell and Developmental Biology. 31: 779-805. * Authors for correspondence
Riccomagno, M.M.*, Sun, L. O.*, Brady, C.M., Alexandropoulos, K., Seo, S., Kurokawa, M., and Kolodkin, A.L. (2014) Cas adaptor proteins organize the Retinal Ganglion Cell Layer downstream of Integrin signaling. Neuron 81:779-786 * Equal contribution
Wang, S-H.J., Celic, I., Choi, S-Y., Riccomagno, M., Wang, Q., Sun, L.O., Mitchell, S., Vasioukhin, V., Huganir, R.L., and Kolodkin, A.L. (2014) Dlg5 Regulates Dendritic Spine Formation and Synaptogenesis by Controlling Subcellular N-cadherin Localization. Journal of Neuroscience 34: 12745-12761
Riccomagno, M.M., Hurtado, A., Wang H., Macopson, J.J, Griner, E.M., Betz, A., Brose, N., Kazanietz, M.G., and Kolodkin, A.L. (2012) The RacGAP β2-Chimaerin Selectively Mediates Axonal Pruning in the Hippocampus. Cell 149: 1594–1606
Pachikara, A., Dolson, D.K., Martinu, L., Riccomagno, M.M., Jeong, Y., and Epstein, D.J. (2007) Activation of Class I transcription factors by low level Sonic hedgehog signaling is mediated by Gli2-dependent and independent mechanisms. Developmental Biology 305: 52-62
Torban, E., Wang, H-J., Patenaude, A-M., Riccomagno, M., Daniels, E., Epstein, D., and Gros, P. (2006) Tissue, cellular and sub-cellular localization of the Vangl2 protein during embryonic development: effect of the Lp Mutation. Gene Exp. Patterns 7: 346-354
Riccomagno, M.M., Takada, S., and Epstein, D.J (2005) Wnt dependent regulation of inner ear morphogenesis is balanced by the opposing and supporting roles of Shh. Genes & Dev. 19: 1612-1623
Kleber, M., Lee, H-Y., Wurdak, H., Buchstaller, J., Riccomagno, M.M., Ittner, L.M., Suter, U., Epstein, D.J. and Sommer, L. (2005). Neural Crest Stem Cell Maintenance by Combinatorial Wnt and BMP Signaling. J. Cell. Bio. 169: 309-320
Riccomagno, M.M., Martinu, L., Mulheisen, M., Wu, D.K and Epstein, D.J. (2002) Specification of the mammalian cochlea is dependent on Sonic hedgehog. Genes & Dev. 16: 2365–2378
Paganelli, A., Ocaña, O., Prat, M. I., Franco, P., López, S., Morelli, L., Adamo, A., Riccomagno, M.M., Matsubara, E., Shoji, M., Affranchino, J., Castaño, E. and Carrasco, A. (2001) The Alzheimer-related gene presenilin-1 facilitates sonic hedgehog signalling in Xenopus primary neurogenesis. Mech. Dev. 107: 119-131