Tom Arnold, MD

Assistant Professor, Pediatrics
M_PEDS-CRITICAL CARE
+1 415 476-1034

The Arnold lab is interested in the communication between blood vessel and brain progenitor cells (radial glia) during brain development, and how this communication is altered in pediatric brain diseases, including congenital hydrocephalus, germinal matrix hemorrhage and cerebral palsy. To this end, out lab uses a combination of transcriptomic analysis and mouse genetics to discover novel roles for endothelial cells in brain and blood brain barrier development. We are particularly interested in the role of two factors wich appear to “couple” brain progenitor cell growth and differentiation with vascular development.

  1. We discovered that the integrin aVb8 on radial glia promotes both endothelial and microglia maturation by activating a “feed forward” TGFb circuit. Mice and humans with genetic deficits in this signaling pathway develop spontaneous brain hemorrhage, hydrocephalus and microglia activation, resulting in downstream neuromotor symptoms highly similar to humans with germinal matrix hemorrhage, congenital hydrocephalus and cerebral palsy.
  2. We developed a mouse model for a genetic form of congenital hydrocephalus called proliferative vasculopathy and hydranencephaly-hydrocephalus (PVHH) or Fowler Syndrome (OMIM 225790), and discovered that the heme transporter, Flvcr2, regulates endothelial heme and vascular sprouting in the brain. Our lab continues to investigate the role of integrins, TGFb, and unique transporters such as Flvcr2 in brain vascular development and human brain diseases.

Publications

Dysregulation of FLVCR1a-dependent mitochondrial calcium handling in neural progenitors causes congenital hydrocephalus.

Cell reports. Medicine

Bertino F, Mukherjee D, Bonora M, Bagowski C, Nardelli J, Metani L, Zanin Venturini DI, Chianese D, Santander N, Salaroglio IC, Hentschel A, Quarta E, Genova T, McKinney AA, Allocco AL, Fiorito V, Petrillo S, Ammirata G, De Giorgio F, Dennis E, Allington G, Maier F, Shoukier M, Gloning KP, Munaron L, Mussano F, Salsano E, Pareyson D, di Rocco M, Altruda F, Panagiotakos G, Kahle KT, Gressens P, Riganti C, Pinton PP, Roos A, Arnold T, Tolosano E, Chiabrando D

Dynamic fibroblast-immune interactions shape wound healing after brain injury.

bioRxiv : the preprint server for biology

Ewing-Crystal NA, Mroz NM, Chang AA, Merrill ED, Caryotakis SE, Teo L, Larpthaveesarp A, Tsukui T, Katewa A, Pennington R, McKinsey GL, Nelson S, Ciesielska A, Dahlgren MW, Paidassi H, Jain S, Aghi MK, Bourne JA, Paz JT, Gonzalez FF, Sheppard D, Molofsky AV, Arnold TD, Molofsky AB

Type-I-interferon-responsive microglia shape cortical development and behavior.

Cell

Escoubas CC, Dorman LC, Nguyen PT, Lagares-Linares C, Nakajo H, Anderson SR, Barron JJ, Wade SD, Cuevas B, Vainchtein ID, Silva NJ, Guajardo R, Xiao Y, Lidsky PV, Wang EY, Rivera BM, Taloma SE, Kim DK, Kaminskaya E, Nakao-Inoue H, Schwer B, Arnold TD, Molofsky AB, Condello C, Andino R, Nowakowski TJ, Molofsky AV

APOE4 impairs the microglial response in Alzheimer's disease by inducing TGFβ-mediated checkpoints.

Nature immunology

Yin Z, Rosenzweig N, Kleemann KL, Zhang X, Brandão W, Margeta MA, Schroeder C, Sivanathan KN, Silveira S, Gauthier C, Mallah D, Pitts KM, Durao A, Herron S, Shorey H, Cheng Y, Barry JL, Krishnan RK, Wakelin S, Rhee J, Yung A, Aronchik M, Wang C, Jain N, Bao X, Gerrits E, Brouwer N, Deik A, Tenen DG, Ikezu T, Santander NG, McKinsey GL, Baufeld C, Sheppard D, Krasemann S, Nowarski R, Eggen BJL, Clish C, Tanzi RE, Madore C, Arnold TD, Holtzman DM, Butovsky O