Sara Cotto Ortiz
University of Puerto Rico, Rio Piedras
Faculty Advisor: Prof. Matthew Shoulders
Research Supervisor: Michael Xiong
Department: Chemistry
Biography
Sara Mia Cotto Ortiz is a rising sophomore majoring in chemistry at the University
of Puerto Rico, Rio Piedras. Sara has always been interested in science, which she explored
in high school, presiding over her school’s science club, graduating with High Honors,
and receiving the Gregor Mendel Medal for excelling in biology. In summer 2024, Sara
participated in a brief summer program at the University of Puerto Rico, Humacao, where she
rotated labs and was introduced to coding and pipetting. At the end of the program, she worked
alongside Dr. Nicholas Pinto, using electrospinning to create polymer nanofibers infused
with antibiotics to treat wounds, and presented her work to the faculty. During her MSRP
experience, Sara worked in the Shoulders lab under Michael Xiong, where she helped test for a
technology that tags secretory pathway proteins for degradation. Sara aspires to pursue a PhD
in Pharmacy and serve her country.
A PROTAC-Based Approach for targeted degradation of secretory pathway
proteins using CATCHFIRE
Sara Mia Cotto Ortiz¹, Michael Xiong², Dr. Matthew Shoulders²
¹Department of Chemistry, University of Puerto Rico, Rio Piedras Campus
²Department of Chemistry, Massachusetts Institute of Technology
The Endoplasmic Reticulum is an important organelle where secreted and lysosomal proteins
pass through. These proteins can get misfolded and accumulate, causing various diseases.
Targeted protein degradation technologies, such as PROTACs, have been created to combat
these problems. However, none have been successful for ER proteins. As a solution, the lab
proposed ERAD-TACs, a technology that uses a linker to bind OS9, a chaperone protein
important in ER-associated degradation. In this project, we tested a new method for the design
of ERAD-TACs using Chemically Assisted Tethering of a Chimera by Fluorogenic-Induced
Recognition (CATCHFIRE). CATCHFIRE uses two amino acid chains, FIRE-tag and FIREmate,
that, when bound with Match 550, emit fluorescence. We transfected HEK293 cells with
a plasmid containing the CATCHFIRE components and OS9 and split them into 4 different
conditions: no treatment, dox-promoter treatment, Match 550, and one with both. Comparison
of the fluorescent signal between the third and fourth conditions confirmed that dimerization
occurred. Through a Western blot, we hope to see if dimerization led to degradation of the
FIRE-mate. Success will open a new form of targeted protein degradation in the ER, which
will help prevent diseases that result from the failure of protein degradation
