Vaibhav Tiwari, Ph.D.

The observable universe is estimated to contain hundreds of billions of galaxies and more than 10²² stars. Yet another universe one built at the molecular scale may rival this astronomical complexity: the universe of glycans. Unlike nucleic acids and proteins, whose primary structures are largely dictated by genetic templates, glycans emerge from highly coordinated, non-template-driven biosynthetic networks. Their extraordinary diversity arises from combinations of monosaccharide composition, regio- and stereospecific glycosidic linkages, branching, polymer length, and dynamic chemical modifications. Together, these features generate an immense molecular repertoire, a glycan universe whose structural complexity extends far beyond that encoded by the genome alone.

Among the many inhabitants of this molecular universe, heparan sulfate occupies a singular position. This ubiquitous cell-surface and extracellular matrix glycan is not merely a structural component of the glycocalyx but a dynamic molecular interface that governs cellular communication with extraordinary precision. By encoding information through exquisitely regulated sulfation patterns, heparan sulfate directs developmental signaling, tissue homeostasis, immune surveillance, and host–microbe interactions. Each sulfation motif constitutes a distinct molecular "word" within an intricate carbohydrate language, selectively recognized by growth factors, morphogens, chemokines, extracellular enzymes, and microbial ligands. One of the most compelling examples of this molecular coding is 3-O-sulfated heparan sulfate, a rare glycan modification generated by the heparan sulfate 3-O-sulfotransferase (3-OST) family of enzymes. Although representing only a minute fraction of the total heparan sulfate landscape, this highly specialized structure creates molecular recognition sites with profound biological consequences. Remarkably, it serves as a functional entry receptor for herpes simplex virus (HSV), enabling viral attachment and membrane fusion in the absence of a conventional protein receptor. This paradigm illustrates how subtle alterations in glycan architecture can reshape host susceptibility, dictate viral tropism, and influence disease pathogenesis.

Our laboratory is dedicated to exploring this remarkable Universe of Glycans deciphering the molecular grammar through which complex carbohydrates regulate viral infection, immunity, and human health. We seek to understand how viruses navigate and exploit the glycocalyx, how glycan-mediated interactions govern the earliest events of infection, and how these same molecular principles can be harnessed to create transformative antiviral therapies. By integrating glycobiology, virology, structural biology, chemical biology, computational modeling, and translational medicine, we aim to uncover the fundamental design principles that govern host–pathogen interactions and translate these discoveries into innovative strategies for preventing and treating infectious diseases. At its core, our research is driven by a simple yet profound question: Can the molecular language that viruses have evolved to exploit be deciphered and ultimately rewritten to protect human health?