LMP student seminars: 21 January
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.
Group 2: Cancer, Development and Aging
Location: MSB 4171
Rohin Chakraborty
- Title: Role of Natural Killer T Cells in Inducing Pre-tumor Cell Growth to Initiate Medulloblastoma
- Supervisor: Dr. Valerie Wallace
Group 1: Brain and Neuroscience
Location: MSB 4279
Sofia Gentile
- Title: Investigating Neuroinflammation and Immune Activation in Neurodegenerative Proteinopathies using Imaging Mass Cytometry
- Supervisor: Dr. Naomi Visanji & Dr. Michael Pollanen
Abstracts
Rohin Chakraborty: Role of Natural Killer T Cells in Inducing Pre-tumor Cell Growth to Initiate Medulloblastoma
The role of the microenvironment in modulating initiation and progression of cancer growth in not properly understood for CNS tumors, such as medulloblastoma (MB). The loss of action of a Wnt factor, Norrin (Ndp) on the endothelial cells of the leptomeninges show a higher degree of pre-neoplastic lesion (PNL) growth in a Sonic hedgehog-driven Smoothened (SmoA1+/-) MB model. We observed infiltration of CD3+ NK1.1+ indicating likely presence of Natural Killer T (NKT) cells, expressing CCL5 and Arginase 1 in the cerebellum meninges during the growth of PNLs. Loss of function experiments by delivery of anti-NK and anti-CD3 depleting antibodies into the 4th ventricle by intra cisterna magna (i.c.m.) injections limited the growth of PNLs in SmoA1+/- NdpKO mice. Furthermore, in presence of Norrin signalling, there is no considerable presence of lymphoid CD3, NK1.1 cells. As a gain of function, we administered poly I:C, a viral mimetic that recruited T, NK and NKTs into the meninges, known to induce an interferon response led to further PNL growth in SmoA1+/- NdpWT mice. Similarly, delivery of recombinant interferon gamma (IFN-γ) by i.c.m. in SmoA1+/- NdpWT mice promoted PNL growth. We postulate the recruitment of NKTs which produce IFN-γ, in conjunction with CXCL12, act on the granule progenitor pre-tumor cells to induce their proliferation thereby contributing to the formation of PNLs.
Sofia Gentile: Investigating Neuroinflammation and Immune Activation in Neurodegenerative Proteinopathies using Imaging Mass Cytometry
Background: Neurodegenerative proteinopathies are a heterogeneous class of neurological disorders affecting cognitive and motor capabilities due to the aggregation of pathological proteins in the brain, leading to progressive loss of neurons in the central nervous system. Tauopathies (e.g. Nodding syndrome (NS) and Progressive Supranuclear Palsy (PSP)), are defined by the aggregation of insoluble hyperphosphorylated Tau deposits (p-tau), whereas synucleinopathies, (e.g. Lewy Body Disorders (LBD), including Parkinson’s Disease (PD)), involve the aggregation of insoluble α-synuclein. The presence of chronic inflammation and immune activation in proteinopathies is increasingly recognized, however, the contribution to disease pathogenesis is not yet fully understood.
Objective: To perform a quantitative mapping of immune system involvement in neurodegenerative proteinopathies using multiplexed analysis of post-mortem brain tissue of patients with LBD, PSP, and NS.
Methods: Human post-mortem brain tissues were stained using Imaging Mass Cytometry (IMC). IMC is a novel multiplexed technology which utilizes metal-conjugated antibodies and mass cytometry principles to enable the visualization and analysis of 40-plus markers on single tissue slides.
Results: A custom IMC panel containing 38 metal-tagged antibodies of interest was designed, including targets for vasculature, neurophenotyping, immune, and inflammatory markers. Immune markers were picked to define and localize subsets of myeloid cells, lymphoid cells, and components of the complement system (C1q, C4a) in disease tissue. Preliminary panel optimization staining, performed on control AD tissue, and disease tissue staining, performed on LBD, PSP, and NS tissue, shows colocalization of relevant markers.
Conclusions: Future work will apply quantitative measures and spatial analysis of markers of interest in relation to pathogenic protein aggregates and vasculature.
Contact
No need to register.
Contact lmp.grad@utoronto.ca with any questions.