Event
MS Thesis Defense: Smriti Thomas
Monday, March 30, 2026
9:30 a.m.
AJC 4104
Debbie Chu
301 405 8268
dgchu@umd.edu
Title: Engineering Bivalent Single-Domain Antibodies Targeting TGF-β2
Committee Members:
Dr. Kimberly Stroka, Chair
Dr. Jinny Liu
Dr. William E. Bentley
Abstract:
Transforming Growth Factor β (TGF-β) is a signaling protein found in various tissues and cells within the body. It is essential for wound healing, tissue homeostasis, and regulates several cellular processes including proliferation, differentiation, and apoptosis. However, when irregularities occur within the signaling process, it contributes to the pathogenesis of inflammation, fibrogenesis, and other detrimental diseases. One such disease is ocular fibrosis, a condition in the eye due to irregular healing processes that causes irreversible damage. Inflammation, fibroblast activation, and extracellular matrix (ECM) deposition are characteristics of this disease, and are processes regulated by TGF-β. One isoform, TGF-β2, is found to have elevated levels in the occurrence of ocular fibrosis, and is the main target molecule of this project.
This thesis presents single-domain antibodies (sdAb) engineered to bind to TGF-β2, with a potential to disrupt the signaling of the cytokine. The first research aim investigates whether bivalent sdAbs have better binding affinity when compared to monovalent sdAbs. It also investigates different configurations, by altering the number of GS linkers connecting the sdAbs. The second aim investigates whether hetero-bivalent or homo-bivalent constructs have better affinity to TGF-β2. Finally, the strongest binders found in these aims are compared to each other to determine the construct with the highest binding affinity to TGF-β2.
Dr. Kimberly Stroka, Chair
Dr. Jinny Liu
Dr. William E. Bentley
Abstract:
Transforming Growth Factor β (TGF-β) is a signaling protein found in various tissues and cells within the body. It is essential for wound healing, tissue homeostasis, and regulates several cellular processes including proliferation, differentiation, and apoptosis. However, when irregularities occur within the signaling process, it contributes to the pathogenesis of inflammation, fibrogenesis, and other detrimental diseases. One such disease is ocular fibrosis, a condition in the eye due to irregular healing processes that causes irreversible damage. Inflammation, fibroblast activation, and extracellular matrix (ECM) deposition are characteristics of this disease, and are processes regulated by TGF-β. One isoform, TGF-β2, is found to have elevated levels in the occurrence of ocular fibrosis, and is the main target molecule of this project.
This thesis presents single-domain antibodies (sdAb) engineered to bind to TGF-β2, with a potential to disrupt the signaling of the cytokine. The first research aim investigates whether bivalent sdAbs have better binding affinity when compared to monovalent sdAbs. It also investigates different configurations, by altering the number of GS linkers connecting the sdAbs. The second aim investigates whether hetero-bivalent or homo-bivalent constructs have better affinity to TGF-β2. Finally, the strongest binders found in these aims are compared to each other to determine the construct with the highest binding affinity to TGF-β2.
