Sarah Ali
BME PhD Proposal Presentation

Date: 2025-09-02
Time: 3:00 PM- 5:00 PM
Location / Meeting Link: IBB Suddath Seminar Room (IBB 1128)/Zoom Link: 

Committee Members:
Aniruddh Sarkar, PhD (Advisor) Ankur Singh, PhD Wilbur Lam, MD/PhD Cheryl Day, PhD Jishnu Das, PhD


Title: Antibody-Omics for Biomarker Discovery and Diagnostic Translation in Tuberculosis

Abstract:
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains the leading cause of death from a single infectious agent. In 2024 alone, approximately 1.25 million people died from TB— primarily in low- and middle-income countries (LMICs) where TB is endemic—despite the availability of effective treatment. The burden of TB is particularly severe among vulnerable populations, including people living with human immunodeficiency virus (HIV), those with Type-2 diabetes mellitus (T2D), and children. A major contributor to global TB-related mortality is the lack of accurate, rapid, and affordable diagnostic tools. While traditional diagnostic approaches often target the pathogen, its antigens, or nucleic acids, antibodies present a particularly attractive alternative due to their abundance and the ease of detection from small sample volumes. However, antibody titer alone has shown limited diagnostic utility across the TB disease spectrum. Recent studies highlight the importance of antibody quality—specifically, the functional properties of the Fc region—as a more nuanced and informative biomarker for differentiating disease states and predicting outcomes across various infections, including TB. Following infection, the Fc region of antibodies undergoes rapid diversification, including changes in glycosylation patterns and Fc receptor binding profiles. These Fc-driven features offer promising diagnostic potential. Yet, current methods for profiling antigen-specific antibody glycosylation—such as mass spectrometry and capillary electrophoresis—are prohibitively expensive, sample-intensive, and technically complex, limiting their feasibility for point-of-care (POC) TB diagnostics, particularly in resource-constrained settings. Given these observations, I propose to develop and translate multiplexed, antibody-based biomarkers for accurate and affordable TB diagnostics. By focusing on Fc glycosylation and Fc receptor -binding properties beyond antibody titer, this work will establish novel detection strategies compatible with POC platforms. Integrating antibody, cytokine, and metabolomic profiling across adult and pediatric TB—including cases with HIV and T2D comorbidities—and applying machine learning and perturbation testing, this research aims to identify biophysical and mechanistic immune signatures and deliver field-ready diagnostic tools tailored for diverse TB-affected populations.