As an NIH Ox-Cam fellow, Madeline works jointly in the laboratories of Dr. Pamela Schwartzberg, at the NIH, and Professor Ken Smith, at the University of Cambridge. Her work focuses on the role of cellular signaling and communication in the pathogenesis of genetic disorders of the immune system. Work will include investigation of the role of CD8+ T cell signatures in clinical outcomes of primary immunodeficiencies and T cell exhaustion. Utilizing murine models and CRISPR of T cells, the research will examine functional applications of deep phenotyping hits to decipher novel cellular signaling pathways and explore their role in broader immune function. These genetic elements will be further used to screen for drug targets that can modulate genetic signatures in patient samples to offer beneficial effects on disease pathophysiology and clinical outcomes. Through identification and functional analysis of these unknown cellular pathways and cell function states, the research aims to complete pre-clinical and/or phase 1 trials to offer eventual therapeutic benefit to patients suffering from primary immunodeficiencies and autoimmune disorders.
Work prior to the UMN MSTP:
Manoli I, Sysol JR, Epping MW, Li L, Wang C, Sloan JL, Pass A, Gagné J, Ktena YP, Li L, Trivedi NS, Ouattara B, Zerfas PM, Hoffmann V, Abu-Asab M, Tsokos MG, Kleiner DE, Garone C, Cusmano-Ozog K, Enns GM, Vernon HJ, Andersson HC, Grunewald S, Elkahloun AG, Girard CL, Schnermann J, DiMauro S, Andres-Mateos E, Vandenberghe LH, Chandler RJ, Venditti CP. FGF21 underlies a hormetic response to metabolic stress in methylmalonic acidemia. JCI Insight. 2018 Dec 6;3(23). pii: 124351. PMCID: PMC6328030