Zachary Aaron Silver, MD, PhD

Pulmonary & Critical Care Physician–Scientist · UCSF

Uncovering how the innate immune system misfires in the lung — tracing the molecular triggers of STING-driven interferon disease from the bench to the patient at the bedside.

View the research Get in touch

About

A physician-scientist bridging molecules and medicine

Zachary Silver is a physician-scientist in Pulmonary & Critical Care Medicine at the University of California, San Francisco, where he works in the laboratory of Anthony Shum. His path joins molecular science to clinical care: he earned his MD and PhD through the Medical Scientist Training Program at the University of Miami, completed Internal Medicine residency at Duke University, and now trains in pulmonary and critical care medicine at UCSF.

One question runs through all of his work — how the immune system recognizes danger, and what happens when that recognition turns against the body's own tissues. His doctoral research revealed how HIV hides from the immune system; today he studies the mirror image of that problem: how misdirected immune signaling injures the lung.

Research

Immune recognition, and what happens when it misfires

Current focus

Immune-driven lung disease

In the Shum Lab at UCSF, Dr. Silver investigates COPA syndrome and related disorders in which the innate immune sensor STING becomes inappropriately active — flooding the lung with type I interferon and driving interstitial lung disease. Using spatial transcriptomics and single-cell RNA sequencing, he maps how disruptions in the COPI coatomer machinery derail the trafficking of STING, and how those molecular missteps reshape lung tissue. These conditions are rare, but their lessons reach into far more common forms of pulmonary fibrosis and autoimmunity.

Doctoral work

Disarming HIV's shield

His doctoral work in the Desrosiers laboratory examined the virologic determinants of elite control of HIV. He discovered that certain HIV-1 strains elongate a region of their envelope protein and cloak it in O-linked sugars — a glycan shield that hides the virus from an entire class of broadly neutralizing antibodies. The findings help explain viral immune evasion and inform how next-generation antibody therapies might be designed to overcome it.

COPA syndrome STING & type I interferon COPI coatomer Interstitial lung disease Spatial transcriptomics Single-cell RNA-seq Structural & computational modeling HIV immunology

Publications

Selected publications

Selected foundational work in viral immunology and glycobiology; current research on COPA syndrome and STING biology is ongoing.

Discovery of O-linked carbohydrate on HIV-1 envelope and its role in shielding against one category of broadly neutralizing antibodies.
Silver ZA, Antonopoulos A, Haslam SM, Dell A, Dickinson GM, Seaman MS, Desrosiers RC. Cell Reports, 2020;30(6):1862–1869. doi:10.1016/j.celrep.2020.01.056
A highly unusual V1 region of Env in an elite controller of HIV infection.
Silver ZA, Dickinson GM, Seaman MS, Desrosiers RC. Journal of Virology, 2019;93(10):e00094-19. doi:10.1128/JVI.00094-19
HIV and SIV maintain high levels of infectivity in the complete absence of mucin-type O-glycosylation.
Termini JM, Church ES, Silver ZA, Haslam SM, Dell A, Desrosiers RC. Journal of Virology, 2017;91(19):e01228-17. doi:10.1128/JVI.01228-17
The role of MHC class I gene products in SIV infection of macaques.
Silver ZA, Watkins DI. Immunogenetics, 2017;69(8–9):511–519. doi:10.1007/s00251-017-0997-3
HEK293T cell lines defective for O-linked glycosylation.
Termini JM, Silver ZA, Connor B, Antonopoulos A, Haslam SM, Dell A, Desrosiers RC. PLOS ONE, 2017;12(6):e0179949. doi:10.1371/journal.pone.0179949
Geographical distribution of soil-transmitted helminths and the effects of community type in South Asia and South East Asia — a systematic review.
Silver ZA, Kaliappan SP, Samuel P, Venugopal S, Kang G, Sarkar R, Ajjampur SSR. PLOS Neglected Tropical Diseases, 2018;12(1):e0006153. doi:10.1371/journal.pntd.0006153

Practice & Consulting

Clinical expertise & collaboration

Dr. Silver is board-certified in Internal Medicine and licensed to practice medicine in California. Through his medical corporation, Zachary Aaron Silver, M.D., Ph.D., Inc., he offers medical and scientific consulting — pairing clinical training in pulmonary and critical care medicine with a research background spanning immunology, genomics, and computational biology.

For consulting inquiries or research collaboration, please get in touch below.

Contact

Get in touch

For research collaboration, scientific consulting, or correspondence: