Mayar Mossad Allam

BME PhD Proposal Presentation

Date:2022-05-25
Time: 12pm-2pm
Location / Meeting Link: https://bluejeans.com/4663416548   McIntire Room in UAW. 

Committee Members:

Ahmet Coskun, Ph.D. (Advisor) Ankur Singh, Ph.D. Shu Jia, Ph.D. Wilbur Lam, M.D. Ph.D. Kavita Dhodapkar, M.D.

Title: Deciphering spatial immune interactions in health and disease using multiplexed imaging tools

Abstract:
High parameter imaging is an essential tool for the study of human diseases and the discovery of human biosystems. Imaging Mass Cytometry (IMC) is a recently developed technology that can visualize up to 40 biomarkers simultaneously on the same clinical sample at a subcellular resolution of 1 µm. Several studies are limited due to the use of traditional imaging techniques that are prone to data variability, subjective interpretation, and low signal-to-noise ratio. This includes deciphering the tumor microenvironment in cancers. Lung cancer remains to be one of the leading causes of death worldwide with poor prognosis and low drug response rates. Without a comprehensive knowledge of the immune and the stromal components of patients’ tumors, it could be challenging to design treatment plans with high efficacy and minimal off-target toxicity. Further, the immune-rich microenvironment in the secondary lymphoid organs is another example study that will greatly benefit from highly multiplexed spatial studies. Lymph nodes, tonsils, spleen, and Peyer’s patches constitute the secondary lymphoid organs, and they function to trap pathogens in the lymph fluid, blood, and external ingested materials. Their variant systems select for and proliferate immune cells involved in the adaptive immune response. However, we still don’t fully understand the positional interactions and their crosstalk among cell types in these tissues. Thereby, the objective of this study is to fill this gap by mapping the immune microenvironment in lung tumors and secondary lymphoid organs using multiplexed imaging technologies. We will fulfill the objectives with the following specific aims: 1) Quantifying major immune phenotypes in lung cancer including macrophages, T-cells, and B-cells in relation to the disease clinical outcomes. 2) Investigate the immune-rich microenvironment in secondary lymphoid organs that leads to B-cell differentiation, follicle development, and germinal center response. 3) Build perturbative, dynamic 2D cell culture systems to further study the interactions among major immune cell types (ex: macrophage, T-cells) at the proteomic and the metabolic level. These aims could help identify unique cellular phenotypes and their crosstalk which can open the door for more drug discovery.