Research

Experience 1:  Musah Lab, Duke University  

Date: January 2020 – April 2023 (500+ hours)

Advisor:  Dr. Samria Musah

Summary:  

During freshman year, I was introduced to tissue engineering after joining Dr. Samira Musah’s lab at Duke University. Affiliated with Biomedical Engineering and School of Medicine, our lab focuses on integrating stem cell biology with engineering to model and understand kidney development and disease mechanisms. For the past 3.5 years, I have been developing a kidney glomerulus organ-on-a-chip with a biomaterial membrane to model blood filtration and kidney disease. Organ-on-a-chips are microfluidic devices containing two overlapping channels separated by a membrane. Cells are seeded in both channels to form monolayers along both sides of the membrane, creating a structurally complex microenvironment that better mimics what cells experience in vivo. Some of this work was published in Bioengineering (https://doi.org/10.3390/bioengineering9050188) and presented at the 2022 Northeast Bioengineering Conference and the 2022 Annual BMES Meeting. 

Experience 2:   Duke International Genetically Engineered Machine (iGEM)

iGEM

Date: September 2020 – October 2022

Advisor: Dr. Cameron Kim 

Summary:  

Duke International Genetically Engineered Machine (iGEM) is an undergraduate-led synthetic biology research group. Clinical glioblastoma treatment is limited by the lack of a scalable, physiologically relevant model for drug testing. To address this, we are developing a brain organoid-based drug screening platform to characterize treatment efficacy in IDH1-mutated patient-derived glioma cells. A plasmid reporter system is used to quantify the concentration of D-2-HG, an oncometabolite upregulated by IDH1, as a readout for tumor growth. When a drug that reduces D-2-HG levels is added to the system, the fluorescence or luminescence levels in the glioma cells will decrease. We designed the fluorescent and luminescent reporter plasmids, synthesized the constructs using PCR and Gibson Assembly, and transfected them into HEK 293T cells. Additionally, we electroporated commercially available plasmids into primary glioma cells as a proof-of-concept for integrating our own plasmids into these cells. We are working on finalizing our reporter constructs, integrating them into our co-culture system, and testing the efficacy of therapies using our platform. We published our project as a website, were awarded the 2021 iGEM Team Impact grant, presented at the 2021 iGEM Giant Jamboree, and won a silver medal at the 2022 iGEM Grand Jamboree.   

Experience 3: Delcassian Lab, Amgen Scholars Program at UC Berkeley

Date: June 2022 – August 2022

Advisors: Dr. Derfogail Delcassian

Summary:  

I was selected as a 2022 Amgen Scholar at the University of California, Berkeley. I led a project developing a lymph node organ-on-chip of dendritic cell migration and activation of T cells for modeling adaptive immune response to mRNA vaccines. Vaccines often fail during clinical trials due to poor efficacy or unpredicted toxicity. Preclinical testing is currently performed in cell culture and animal models, which do not adequately model the complex microenvironment of the human lymph node. I developed a lymph-node-on-chip device for more physiologically accurate vaccine screening. Dendritic cell (DC) migration from the periphery to the lymph node upon mRNA vaccination is critical to initiate the adaptive immune response. Activated DCs upregulate the chemokine-receptor CCR7, which allows them to migrate towards the chemokine CCL19-secreting lymph node and activate T cells. We developed a lymph node-on-a-chip that recapitulates chemokine-mediated DC migration to the lymph node paracortex and T cell activation. The microfluidic device is fabricated in poly(dimethylsiloxane) (PDMS) using soft-lithography and can generate CCL19 concentration gradients via a hydrogel embedded within the PDMS microchannels. Future work will aim to demonstrate chemotaxis of activated DCs along the CCL19 concentration gradient and the activation of T cells, as evidenced by increased CD69 expression, an early activation marker, and IL-2 secretion. Overall, this lymph node-on-a-chip has the microstructure necessary for modeling the antigen exposure and immune cell activation stages of adaptive immunity, providing a new tool for evaluating mRNA vaccine efficacy and toxicities in vitro. This work was presented as a poster presentation and oral presentation at the 2022 UC Berkeley Amgen Scholars Symposium.