Diego Valdes Cavazos
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MIT Department: Biomedical Engineering
Faculty Mentor: Prof. Bryan Bryson
Undergraduate Institution: University of Texas, San Antonio
Hometown: San Antonio, Texas
Website: LinkedIn
Biography
Diego Valdes Cavazos is a Biomedical Engineering undergraduate at the University of Texas at San Antonio, where he was a scholar in the NIH-funded ESTEEMED Program and is currently in the MARC Program. Through the program, he works in Dr. Brey’s Tissue Engineering and Regenerative Medicine Lab, studying extracellular matrix effects on adipose differentiation. During the summers of 2023 and 2024, he interned at the Broad Institute and MIT, working in the Golub and Bryson Labs on cancer cell lines related to Parkinson’s disease and mRNA technology for immune response manipulation, respectively. Diego is the President of his College’s Student Advisory Council and a Senior Ambassador for the IEEE EMBS Student Mentorship Program. He aims to pursue a doctorate in bioengineering, work in private industry, and eventually transition to academia. His vision includes leading a research lab and directing an undergraduate research initiative to support underrepresented students.
Abstract
A Novel mRNA-Based System for Investigating Immune Response in
Primary Macrophages Engineering gene expression in primary human macrophages
Engineered mRNA delivery to facilitate novel studies in primary human macrophages
Diego Valdes Cavazos1 and Bryan Bryson2,3
1Department of Biomedical Engineering and Chemical Engineering, The University of Texas at
San Antonio
2Department of Biological Engineering, Massachusetts Instititute of Technology
3Ragon Institute of Massachusetts General Hospital, MIT, and Harvard
Mycobacterium tuberculosis (Mtb), the causative agentcau of tuberculosis (TB), infects the body’s first line of defense, macrophages, through phagocytosis. Once inside, Mtb secretes effectors to support its survival by that inhibiting phagosome maturation and disturbing macrophage’s intercellular signaling, setting up an Mtb tolerance for favorable intracellular survival. Due to this hijack, cEngineeringreating a system that can dynamically monitor immune responses in primary macrophages while bypassing their phagocytosis is crucial for developing physiologically efficient TB therapeutic strategies. Considering mRNA advancements in recent years, we hypothesized that using mRNA technologies can could facilitate macrophage engineering, providing a novel system to study immune responses like antigen presentation, membrane damage, and signaling. never been done in primary monocyte-derived human macrophages. To test this hypothesis, we began by delivering commercial mRNA encoding green fluorescent protein (GFP) and determined that GFP mRNAs incorporating modified nucleotides facilitated GFP expression. looked at its expression to confirm the translation of our mRNAs. Next, we delivered engineered GFP mRNAs incorporating diverse nucleotides and found that mRNAs incorporating both mRNA of single and combined modifications revealing that modified bases 5-methylcytidine-5′-triphosphate (m-CTP) and 5-methoxyuridine-5’- triphosphate (m-UTP) combined efficientlyreduced production of inflammatory cytokines reduce macrophage’s immune response. Identifying this ideal mRNA formulationcombination, we next demonstrated successful delivery of mRNA-encoded antigens in addition to mRNAs.