Biology subjects

Hawiger, D.

Publications and source records attributed to Hawiger, D..

2 recordsLinked to original sources

bioRxiv2026

Comprehensive transcriptomic profiling uncovers an inflammatory maturation program conserved in human and mouse dendritic cells

Conventional dendritic cells (cDCs) integrate signals to balance tolerance and immunity, but how steady-state cDC programs are changed during inflammatory maturation remains incompletely resolved. Here, using Seqtometry-based analysis of mouse and human cDCs, we identify distinct steady-state cDC1 gene programs enriched for either tolerance-associated or immune response-associated (pre-immunogenic) transcriptomic features that are present under homeostatic conditions in fully differentiated cDCs with divergent predicted immune functions. Under inflammatory conditions, the tolerance-linked features are reduced, whereas the pre-immunogenic program is extended in response to type I interferon signaling and is selectively impaired by Ifnar1 deficiency. This core inflammatory program is conserved across mouse and human cDC subsets, and while retaining disease-specific transcriptomic features, it is detected in infection, cancer, and autoimmunity. Together, these findings establish a gene program-based framework for cDC inflammatory maturation that extends beyond a binary immature-versus-mature classification and supports the identification of disease-associated cDC biomarkers.

immunology↗

bioRxiv2024

EPISOMAL VECTORS FOR STABLE PRODUCTION OF RECOMBINANT PROTEINS AND ENGINEERED ANTIBODIES

There is tremendous interest in the production of recombinant proteins, particularly bispecific antibodies and antibody-drug conjugates for research and therapeutic use. Here, we demonstrate a highly versatile plasmid system that allows rapid generation of stable Expi293 cell pools by episomal retention of transfected DNA. By linking protein expression to puromycin resistance though an attenuated internal ribosome entry site, we achieve stable cell pools producing proteins of interest. In addition, split intein-split puromycin-mediated selection of two separate protein expression cassettes allows the stable production of bispecific antibody-like molecules or antibodies with distinct C-terminal heavy chain modifications, such as an antigen on one chain and a sortase tag on the other chain. We also use this novel expression system to generate stable Expi293 cell pools that secrete sortase A {Delta}59 variant Srt4M. Using these reagents, we prepared a site-specific drug-to-antibody ratio of 1 antibody-siRNA conjugate. We anticipate the simple, robust, and rapid stable protein expression systems described here being useful for a wide variety of applications.

bioengineering↗