Zanyah Shepherd

Zanyah Shepherd

Biography

Zanyah Shepherd is a rising junior chemistry major at Claflin University. Born in
Southeast, DC, and raised in Temple Hills, MD, she was surrounded by family members
in the medical field, which sparked her appreciation for healthcare. After a computational
bioinformatics internship at Howard University focused on protein stability and its role in
diseases like cancer, Zanyah realized her impact could take a different path. Then, through the
Environmental Science Summer Program experience at Claflin University, she developed a
passion for using chemistry to solve health challenges. She now aspires to collaborate across
disciplines to develop innovative methods, tools, and discoveries that aid in the prevention
or cure of developmental diseases through small-molecule research targeting understudied
cancer-related proteins. Zanyah plans to achieve her goals by pursuing a Ph.D., expanding
her network, and seizing opportunities like her current internship at MIT. Beyond science, she
enjoys reading, exercising, and practicing yoga.

Developing A DnaJB6 Chaperone Probe Through G/F1-Derived
Peptide Optimization
Zanyah Shepherd1, Natalie Heitman2, Berenice Estrada Chavez2, Zahmiria Johnson2,
Dr. Oleta Johnson2
1School of Natural Science and Mathematics, Claflin University
2Department of Chemistry, Massachusetts Institute of Technology

DnaJB6 is a chaperone protein that suppresses protein aggregation associated with
numerous diseases, but its regulation remains poorly characterized due to its highly disordered
nature. Nevertheless, it is known to act on clients such as Tau and Polyglutamine-expanded
huntingtin, which are associated with neurodegenerative diseases. Mutant forms of DnaJB6 can
impair its ability to suppress protein aggregation, contributing to disease progression. Notably,
mutations in the G/F1 region cause a muscular disease called Limb-Girdle Muscular Dystrophy
Type D1 (LGMDD1). Previous studies show that DnaJB6 has an autoinhibition mechanism in
which the G/F1 region lies across its canonical J-domain, preventing interaction with Hsp70, a
co-chaperone of DnaJB6. This study leverages that region’s autoinhibitory properties to inform the
design of a high-affinity DnaJB6-specific probe. Accordingly, this work builds on a peptide probe
developed by the Johnson Lab that mimics the G/F1 sequence and binds to the J-domain with 90
uM affinity. To make this probe more experimentally tractable, we synthesized peptides
containing substitutions at the LGMDD1-associated residue F91 that were computationally
predicted to improve binding affinity. Ultimately, this optimization will enable the probe to be
applied to critical investigations of DnaJB6 function and regulation, yielding valuable insights into
its critical roles in proteostasis.