Anti-Drug Antibodies
Over 30 years after the first therapeutic monoclonal antibodymAb) was approved clinical use, the mAb industry has seen remarkable growth, becoming the fastest expanding class of pharmaceuticals. Although mAbs promise significant advancements in human health, their repeated administration can lead to the of unwanted Anti-Drug Antibodies (ADAs), which hinder or negate the drug's effectiveness. The presence of ADAs can also trigger serious clinical side effects, as changes in drug pharmacokinetics and bioavailability, reduced efficacy, cross-reactivity with endogenous proteins, and allergic reactions, among other safety. Nonetheless, the mechanisms behind ADA induction and their molecular composition remain largely unclear. TNFα antagonists are commonly prescribed for certain forms of arthritis, inflammatory diseases, and psoriasis. However, as many as 40% of patients treated may lose their response to the medication due to ADA development. Using Infliximab and Adalimum as model drugs, we investigated the molecular factors involved in ADA formation We created a novel immunoass to measure ADA levels and their neutralizing effects, utilizing a modified drug version to detect serum ADAs while minimizing background interference. Additionally, we observed that drug infusion a vaccine-like response, characterized by a rapid increase in lymphocytes 7- days post-infusion. Isolated lymphocytes and drug-specific serum antibodies following drug infusion were analyzed for their repertoire features through Next Sequencing and shotgun bottom-up proteomics.
Maternal-Infant Immunity
Many vaccine-preventable infections—such as influenza, pertussis, and tetanus—pose serious risks to pregnant women, newborns, and young infants. Vaccinating during pregnancy can protect infants by transferring maternal antibodies across the placenta, but the underlying immunobiology remains poorly understood. Pregnancy alters immune function, yet most vaccines were developed and tested in non-pregnant adults. As a result, we still lack clear data on how antibody responses differ in pregnancy and how maternal immunity shapes protection in early life.
Our research addresses these gaps by comparing the antibody repertoires of pregnant and non-pregnant vaccine recipients and by examining how the placenta selectively transfers vaccine-specific antibodies to the fetus. Using deep sequencing and proteomic analyses, we study antibody diversity, germline gene usage, and somatic hypermutation in maternal and cord blood to define how pregnancy programs the humoral response.
At the same time, we extend this work to the mucosal immune system—a major but understudied site of B-cell activity. Human milk provides a unique, noninvasive window into maternal mucosal immunity. By characterizing B cells and antibodies in milk, we investigate how maternal immunity helps shape the infant’s early mucosal environment, supports microbial colonization, and contributes to immune education during the first months of life.
Together, these studies reveal how maternal antibodies function not only as passive protection, but as active regulators of the infant’s developing ecosystem and immune trajectory. Insights from this work could guide improved maternal vaccine design, optimize early-life immunity, and inspire new therapeutic strategies that harness antibody–microbiota interactions to support lifelong health.
Anti-Bacterial Theranostics
The global rise of multidrug-resistant (MDR) bacterial pathogens is a growing public health threat. Extensive antibiotic use—particularly in high-income countries—has accelerated the selection of MDR strains, forcing reliance on increasingly costly broad-spectrum drugs.
Monoclonal antibodies (mAbs) offer a promising alternative. Their development has expanded rapidly, and antibacterial mAbs are emerging as potent therapeutic candidates. Unlike traditional antibiotics, mAbs do not impose broad selection pressure, preserve the beneficial microbiota, and can be used as single-dose treatments or in combination with existing antibiotics for improved outcomes.
Our work aims to develop a novel monoclonal antibody targeting MDR bacteria and to define its mechanism of action using in-vitro and in-vivo models. In parallel, we are developing mAb-based biosensors capable of rapid, accurate detection of both the infecting pathogen and its antibiotic-resistance profile. These diagnostic tools will enable tailored, effective treatment strategies and help curb the spread of resistant infections.
Tumor Infiltrating B cells (TIL-B)
Tumor-infiltrating B cells (TIL-B) are increasingly recognized as an important component of the tumor microenvironment across multiple cancer types. Yet their contribution to disease progression and patient outcomes remains unclear, with studies reporting beneficial, detrimental, or no measurable impact. B cells may influence tumor immunity through antibody production, antigen presentation, and interactions with T cells, including effects on the PD-1/PD-L1 axis. Despite this emerging importance, TIL-B biology in solid tumors is still poorly understood.
Our project aims to define the role of B cells within the tumor microenvironment and uncover the mechanisms driving their antitumor activity. Using next-generation sequencing and RNA-seq, we profile TIL-B repertoires and transcriptional programs to identify pathways that may guide the development of new B cell–based therapeutic strategies.