Sam Singer
BME MS Thesis Defense Presentation
Date: 2026-03-18
Time: 11:00 AM
Location / Meeting Link: EBB 3029 / https://teams.microsoft.com/meet/27899382084638?p=QHoEfVRYYDHOXZ00Pv

Committee Members:
Marian Ackun-Farmmer; Joscelyn Mejias; Ankur Singh; Julia Babensee


Title: Nanoparticle Mediated Immunomodulation Of Dendritic Cells Through Receptor Targeting

Abstract:
Autoimmunity is the third most common cause of disease in the United States, yet at this point no cure has been developed. Autoimmune disease is often described as a loss of immune tolerance and can occur when antigen-presenting cells, such as dendritic cells, present self-antigen in combination with inflammatory signals, resulting in immune cells attacking healthy tissues. Dendritic cells regulate expression of these inflammatory signals through pattern recognition receptors, which bind to microbial pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). C-type lectin domain family 12 member A (CLEC12A), also known as CLL1 or MICL, is a pattern-recognition receptor expressed on myeloid cells that has been shown to express an immunoreceptor tyrosine-based inhibition motif (ITIM), which dampens activation of immune cells by downregulating co-stimulatory molecules and inflammatory cytokines. Owing to the role that CLEC12A plays in immune modulation, we aimed to develop a targeted nanoparticle system using a peptide designed to bind CLEC12A, engaging the receptor to treat autoimmune disease. Building on previous work showing that CLEC12A-targeting nanoparticles are taken up via receptor-mediated pathways at high ligand density, we tested the hypothesis that CLEC12A-targeted nanoparticles would activate the CLEC12A receptor, inhibiting inflammation. To evaluate immunomodulatory potential of these targeted nanoparticles, mouse bone marrow was collected and induced to differentiate into dendritic cells, which were then treated with soluble targeting peptide, nanoparticles, or targeted nanoparticles for 2 and 24 hours and assessed for binding and co-stimulatory molecule expression. Soluble peptide showed no preferential binding to CLEC12A and induced slight downregulation of CD80. Untargeted nanoparticles upregulated CD40 expression and showed an unexpected increase in binding in CLEC12A-expressing dendritic cells. CLEC12A-targeted nanoparticles were found to induce significant downregulation of CD80 and CD86 expression in dendritic cells expressing CLEC12A, indicating potential for this platform to be used as a therapeutic to modulate the immune system in autoimmunity.