About

Sergei Vinogradov is a Professor of Biochemistry and Biophysics at the University of Pennsylvania's Perelman School of Medicine. His research is focused on the development of advanced probes for microscopy and imaging applications, encompassing the chemistry of porphyrins and other pyrrolic dyes, energy and electron transfer in multichromophoric systems, spectroscopy, and imaging. His group specializes in creating new techniques for biomedical research, with a main focus on optical imaging of oxygen in biological systems, including the chemistry of imaging probes, phosphorescence lifetime imaging instrumentation, image reconstruction methods, and various applications of phosphorescence. Additionally, his research interests include bio-analytes such as pH and metal ions, optical energy upconversion, and magnetic field effects on luminescence for imaging applications. Dr. Vinogradov collaborates broadly with laboratories worldwide, contributing to studies in cellular metabolism, neuroscience, stem cell biology, cancer therapy, tissue engineering, and ophthalmology.

Research topics

• Computer Science
• Neuroscience
• Data science
• Psychology
• Biology

Selected publications

• Erythroid precursors regulate local oxygen tension and repair outcomes in the bone marrow niche

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-01-11 · 6 citations

  preprintOpen access

  Abstract Oxygen tension dynamically regulates stem cell fate and tissue regeneration, yet how local oxygen availability is controlled within the bone marrow niche remains poorly understood. While bone marrow injury, such as by bone fracture, disrupts marrow vasculature, the consequences on local oxygen tension remain unclear. Here, we show in mice that while the tissue oxygen tension in bone marrow is low (25 mmHg, ∼4% O 2 ), intracellular oxygenation is heterogeneous and erythroid cells are high in oxygen. Bone fracture elevates oxygen tension in the injured bone marrow (>55 mmHg, ∼8%), which persists for over a week post-injury. This oxygen elevation results not from angiogenesis, but rather from localized expansion of erythroid precursor cells in the injured bone marrow. The activated erythroid precursors synthesize hemoglobin and accumulate oxygen, acting as local modulators of oxygen tension. Blocking transferrin receptor 1 (CD71)–mediated iron uptake impairs hemoglobin synthesis, reduces local oxygen levels, and enhances bone regeneration through increased angiogenesis and osteogenesis. These findings identify erythroid precursors as active regulators of local oxygen availability in the bone marrow niche, which may be targetable to enhance tissue regeneration.

  PublisherDOI

• Carbonic anhydrase inhibitors prevent presymptomatic capillary flow disturbances in a model of cerebral amyloidosis

  Alzheimer s & Dementia · 2025-03-01 · 4 citations

  articleOpen access

  INTRODUCTION: Disturbances in microvascular flow dynamics are hypothesized to precede the symptomatic phase of Alzheimer's disease (AD). However, evidence in presymptomatic AD remains elusive, underscoring the need for therapies targeting these early vascular changes. METHODS: We employed a multimodal approach, combining in vivo optical imaging, molecular techniques, and ex vivo magnetic resonance imaging, to investigate early capillary dysfunction in C57BL/6-Tg(Thy1-APPSwDutIowa)BWevn/Mmjax (Tg-SwDI) mice without memory impairment. We also assessed the efficacy of carbonic anhydrase inhibitors (CAIs) in preventing capillary flow disturbances. RESULTS: Our study revealed capillary flow disturbances associated with alterations in capillary morphology, adhesion molecule expression, and amyloid beta (Aβ) load in 9- to 10-month-old Tg-SwDI mice without memory impairment. CAI treatment ameliorated these capillary flow disturbances, enhanced oxygen availability, and reduced Aβ load. DISCUSSION: These findings underscore the importance of capillary flow disturbances as early biomarkers in presymptomatic AD and highlight the potential of CAIs for preserving vascular integrity in the early stages of AD. HIGHLIGHTS: Uncovered early capillary dysfunction in a presymptomatic Alzheimer's disease (AD) mouse model. Evidence linking capillary stalls and capillary dysfunction with oxygen delivery issues in AD. Novel use of carbonic anhydrase inhibitors to prevent early capillary flow disturbances in AD.

  PublisherOA PDFDOI

• ECgo: All-Optical Induction of Single Endothelial Cell Injury and Capillary Occlusion in the Brain

  Proceedings of the National Academy of Sciences · 2025-05-30 · 1 citations

  preprintOpen access

  ABSTRACT The ability to induce endothelial cell (EC) damage in the mouse brain with high spatial precision is invaluable for mechanistic studies of brain capillary injury and repair. Here, we introduce an optical method, termed ECgo, that utilizes a new two-photon-excitable porphyrin-based photosensitizer ( Ps2P ) to selectively obliterate single ECs within the brain microvascular network. Using the developed approach, we were able to induce occlusions of single capillaries with high spatiotemporal control, while preserving the surrounding tissue. Combined with longitudinal two-photon imaging, ECgo enables studies of morphological and functional consequences of targeted single capillary EC injury in vivo under healthy and diseased conditions. SIGNIFICANCE STATEMENT Brain capillary injury is a common feature of aging and many neurological disorders. While a single capillary lesion may appear inconsequential, the cumulative effect of repeated and spatially dispersed capillary insults can lead to substantial brain dysfunction. Understanding how single capillary injuries contribute cumulatively to long-term brain damage requires tools that can precisely target individual capillaries in the living brain. Here, we introduce an optical method that uses a new light-activatable compound to selectively injure single brain capillaries with high spatial accuracy. Our method enables detailed, longitudinal studies of capillary repair, blood flow recovery, local oxygen dynamics, and glial responses following microvascular injury.

  PublisherOA PDFDOI

• Global hypoperfusion leads to a mismatch in oxygen delivery and consumption in the cerebral watershed area

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-06-17

  preprintOpen access

  ABSTRACT Despite the pivotal role of pial collaterals in maintaining cerebral blood flow during focal brain ischemia, it is largely unexplored how the microvascular blood flow and oxygenation in the watershed “pial-collateral territory” differ from those in the territory supplied by the major arteries during chronic global hypoperfusion. To answer this question, we applied 2-photon microscopy and Doppler optical coherence tomography to investigate the changes in cerebral microvascular blood flow and partial pressure of oxygen (PO 2 ), induced by bilateral common carotid artery stenosis (BCAS). The measurements were performed in the somatosensory cortex that is supplied by the middle cerebral artery (MCA), and in the adjacent watershed area in the awake, head-restrained C57BL/6 mice, via the chronic cranial window. The results showed that the BCAS induced a larger decrease in capillary red blood cell (RBC) flux in the watershed area than in the MCA territory, especially in the subcortical white matter. Besides, PO 2 in the pial collaterals was significantly lower than that in the upstream MCA segments under control conditions. However, the PO 2 changes in the arteries and veins under global hypoperfusion displayed different trends in the two interrogated regions, resulting in a significant increase in oxygen extraction fraction in the watershed area. These findings suggest a mismatch between oxygen supply and demand in the watershed area due to global hypoperfusion and increased subcortical white matter vulnerability. We have also observed dilation of the pial collaterals after BCAS, which might suggest a compensatory mechanism to improve the blood flow in the watershed under hypoperfusion.

  PublisherOA PDFDOI

• Charge engineering controls cooperative assembly and loading in protein host–guest complexes

  Journal of Materials Chemistry B · 2025-01-01 · 1 citations

  articleOpen access

  ferritin. Guided by molecular dynamics (MD) simulations and computational protein design, experiments confirmed that GFP charge magnitude and distribution dictate capsule assembly and loading efficiency. These data provide the first example of cooperative assembly with a ferritin capsule. Finally, we established a strategy for generating stoichiometric 1 : 1 protein host-guest complexes, confirmed by time-resolved fluorescence anisotropy. This provides a blueprint for designing ferritin host-guest complexes with enhanced homogeneity and functionality.

  PublisherOA PDFDOI

• Author response for "Reactivity of organic photocatalysts displaying thermally activated delayed fluorescence (TADF): rationalizing unexpected differences between rates of quenching of the lowest singlet and triplet states"

  2025-09-22

  peer-review
  PublisherDOI

• Synthesis and Optical Properties of Unsymmetric Aromatically π-Extended BODIPY

  The Journal of Organic Chemistry · 2025-09-09

  articleOpen access

  A series of unsymmetrically substituted BODIPY dyes featuring fused benzo- or naphtho-fragments on one pyrrolic unit were synthesized from the corresponding pyrrolic precursors. The synthetic route was optimized using a modular approach based on the condensation of formylpyrroles with alkylpyrroles, enabling the identification of precursor combinations that minimize byproduct formation and improve preparative yields. The resulting benzo- and naphtho-fused BODIPYs display intense fluorescence in the red region, with emission maxima spanning 590-680 nm and fluorescence quantum yields ranging from 0.27 to 0.84. Their two-photon absorption (2PA) properties were studied both experimentally and computationally. An increase in the two-photon absorption cross-section with an increase in the size of the π-conjugated system was observed, reaching 80 GM for the naphthoBODIPY derivative. These findings demonstrate the potential of π-extended BODIPY scaffolds as NIR-active fluorophores with enhanced nonlinear optical properties.

  PublisherOA PDFDOI

• Author response for "Reactivity of organic photocatalysts displaying thermally activated delayed fluorescence (TADF): rationalizing unexpected differences between rates of quenching of the lowest singlet and triplet states"

  2025-09-04

  peer-review
  PublisherDOI

• Arylphthalimidoporphyrins: New Approaches to High-Resolution Imaging of Tissue Environmental Parameters

  ECS Meeting Abstracts · 2025-07-11

  articleSenior author

  Previously, we have reported the synthesis and photophysical properties of free-base (H 2 ), Zn(II), Pt(II) and Pd(II) of di-arylphthalimidoporphyrins (DAPIP) and tetra-arylphthalimidoporphyrins (TAPIP), including their multiphoton absorption spectra. Using a combination of phosphorescent Pt complexes of TAPIP and DAPIP we are designing a sensor for pH and oxygen, termed pHOx, which operates by measuring ratios of phosphorescence lifetimes. Unlike all existing pH sensors, measurements by pHOx are not affected by optical heterogeneities of the medium and provide unbiased pH readings in vivo simultaneously with pO 2 . Pd complexes of TAPIP have been shown to emit both phosphorescence and thermally activated E-type delayed fluorescence, providing means for optical sensing of temperature. However, to make the temperature readings unobstructed by tissue optical heterogeneities, a PdTAPIP-based probe is supplemented by a probe system, based on H 2 DAPIP, which emits prompt fluorescence at the same wavelengths and can serve as a correction standard for temperature measurements.

  PublisherDOI

• Exciton Coupling and Charge Transfer Dynamics in Zn(II) Complexes of π-Extended Dipyrrins

  The Journal of Physical Chemistry B · 2025-06-13 · 1 citations

  articleOpen accessCorresponding

  -dipyrrin complexes constitute a versatile model for studying exciton coupling and associated energy and charge dynamics.

  PublisherDOI

Recent grants

• A molecular probe for high-resolution dual imaging of temperature and oxygen in vivo

  NIH · $464k · 2018–2021

• NIH Grant R01EB007279

  NIH · $1.2M · 2012

• Oxygen imaging by phosphorescence quenching

  NIH · $1.6M · 2019–2024

• NIH Grant R24NS092986

  NIH · $1.2M · 2019

• NIH Grant R21EB003663

  NIH · $367k · 2006

Frequent coauthors

• Sava Sakadžić

  106 shared

• David A. Boas

  83 shared

• Anna Devor

  Boston University

  80 shared

• Andrei V. Cheprakov

  Lomonosov Moscow State University

  76 shared

• Tatiana V. Esipova

  66 shared

• David F. Wilson

  60 shared

• Brian W. Pogue

  Dartmouth College

  50 shared

• Artem Y. Lebedev

  Lomonosov Moscow State University

  47 shared