LMP student seminars: 6 May

Agile education

Each week during term time, MSc and PhD candidates in the Department of Laboratory Medicine and Pathobiology present their research.

Anyone is welcome. No need to register.

Location: Medical Sciences Building, rooms 4171 or 4279, see below.

As part of the core research curriculum, students taking LMP1001/2/3: Graduate Seminars in Laboratory Medicine and Pathobiology will present their projects. Please see abstracts below.

3. Cardiovascular, Physiology and Metabolism/ Molecular and Cell Biology and Regenerative Medicine

Location: MSB 4279

Nathaniel Vo

Title: Characterization of healthy and obese adipose tissue remodelling by 3D imaging and single cell analysis
Supervisor: Dr. Hoon-Ki Sung

4. Infectious Diseases, Inflammation and Immunology

Location: MSB 4171

Zoya Hussain

Title: Exploring Trogocytosis as the Primary Driver of Antibody-Mediated Immune Suppression
Supervisor: Dr. Alan H. Lazarus

Aideen Shannon Teeling

Title: TBA
Supervisor: TBA

Abstracts

Nathaniel Vo: Characterization of healthy and obese adipose tissue remodelling by 3D imaging and single cell analysis

BACKGROUND: The healthy expansion of white adipose tissue (WAT) is highly dependent on the remodelling of its supporting neurovascular network. Our previous research revealed intermittent fasting (IF) promotes vascular endothelial growth factor A (VEGFA) induction, leading to angiogenesis and brown-fat-like changes in WAT, accompanied by enhanced glucose homeostasis. Similarly, exercise or cold-induced sympathetic nerve growth has been shown to also induce WAT browning and thermogenesis, resulting in metabolic improvements. However, it remains to be elucidated whether IF can also stimulate sympathetic neuritogenesis. This study aims to characterize healthy vs. unhealthy adipose tissue remodelling in terms of its neurovascular architecture and investigate how IF may promote sympathetic innervation and thereby induce WAT browning.

METHODS: We employed diet-induced obesity (DIO) and IF models in C57BL/6 mice, conducting metabolic assessments that included bodyweight monitoring and glucose and insulin tolerance tests. Adipose tissue was analysed using Adipo-Clear for three-dimensional visualization of neurovascular architecture, complemented by mass cytometry for immune profiling and transcriptomic and protein expression analyses.

RESULTS: DIO mice exhibited marked insulin resistance, increased inflammation, and disrupted adipose architecture, characterized by reduced vascular and nerve fibre density, a decline in M2-like macrophages, and increased pro-inflammatory markers. In contrast, short-term IF (4 weeks) not only promoted VEGFA induction and neurotrophic factors like neuregulin 4 but also led to early signs of adipose browning and neurovascular remodelling in inguinal WAT, preceding observable metabolic benefits. Extended IF (16 weeks) further improved glucose tolerance and insulin sensitivity and is associated with increased markers for angiogenesis, sympathetic innervation, and a reduction in adipocyte size.

CONCLUSIONS: Our findings illustrate that maintaining a healthy neurovascular architecture is crucial for adipose function and systemic metabolic regulation. The contrasting impacts of HFD-induced obesity and IF on adipose tissue highlight potential therapeutic targets for metabolic disease interventions, focusing on enhancing adipose tissue quality through neurovascular and immune modulation.

Zoya Hussain: Exploring Trogocytosis as the Primary Driver of Antibody-Mediated Immune Suppression

Hemolytic disease of the fetus and newborn (HDFN) is a severe neonatal disorder occurring when the maternal immune system recognizes paternally-derived antigens on fetal red blood cells (RBCs), resulting in RBC alloimmunization. Prophylactic administration of anti-D, a pooled donor-derived antibody, prevents maternal immune sensitization against RhD-positive fetal RBCs through antibody-mediated immune suppression (AMIS). Despite its efficacy, the mechanisms behind AMIS remain unknown. Recent work from our lab proposes trogocytosis, a cellular process involving antigen removal from a target cell, as the primary contributor to AMIS, rather than phagocytosis. This study investigates the role of antibody quantity on trogocytosis and phagocytosis in a murine model to determine the primary mechanism driving AMIS. We hypothesize that trogocytosis primarily drives AMIS. Using the HEL murine model, in which mouse RBCs are chemically linked to hen egg lysozyme (HEL), RBCs are sensitized under conditions favoring either trogocytosis (antibody 4B7) or phagocytosis (antibodies 4B7+6D7) and incubated with RAW macrophages, after which the level of AMIS is assessed. Phagocytosis and trogocytosis are distinguished through microscopy and flow cytometry, respectively. Findings demonstrate phagocytosis is enhanced when using a blend of monoclonal antibodies as compared to an equivalent amount of a single monoclonal antibody alone. Trogocytosis experimental data demonstrate that the fluorescent membrane lost by RBCs is consistent with the fluorescence gained by macrophages, particularly with the antibody blend. The small particle fluorescence uptake by macrophages indicates that trogocytosis, rather than phagocytosis, is taking place and supports trogocytosis as the primary driver of AMIS. This research offers novel insights on AMIS and anti-D prophylaxis by investigating trogocytosis as a mechanism of AMIS, and may contribute to the development of a recombinant antibody with equal efficacy as anti-D. This would reduce reliance on donor-derived products and associated risks, offering a safer and more convenient alternative to administering blood products to pregnant women.

Aideen Shannon Teeling: TBA

TBA

Contact

No need to register.

Contact lmp.grad@utoronto.ca with any questions