About

Vadim Backman is a professor affiliated with the Interdisciplinary Biological Sciences Graduate Program at Northwestern University. He holds a PhD from Harvard University - MIT. His research focuses on the convergence of physical and biological sciences, specifically on elucidating the function of the human genome and its dysregulation in disease. His work is enabled by the development of new nanoscale imaging and computational technologies, which lead to novel methods for the regulation of global patterns of gene expression and their clinical translation for disease diagnostics and therapeutics. Backman's contributions include advancing nanoscale chromatin imaging, analyzing 4D chromatin organization, understanding disordered chromatin packing and its role in phenotypic plasticity, and exploring the physical and data structure of the 3D genome. His research also involves macrogenomic engineering through modulation of chromatin packing density and label-free imaging of native cellular nanoarchitecture using partial-wave spectroscopic microscopy.

Research topics

• Biology
• Medicine
• Ecology
• Computer Science
• Internal medicine
• Evolutionary biology
• Demography
• Cell biology
• Engineering
• Gastroenterology
• Computational biology
• Biophysics
• Physics
• Immunology
• Telecommunications
• Genetics

Selected publications

• Gene transcription and chromatin packing domains form a self- organizing system

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-17

  articleOpen accessSenior author

  Abstract The human genome organizes into several thousand chromatin packing domains that couple euchromatin and heterochromatin into unified nanoscale volumes. Prior work suggested these domains form by transcriptionally driven loops that guide packing domain assembly. Here, we study the process of transcriptionally driven domain formation and maintenance. By pairing auxin-inducible degron technology with nanoscopic imaging, transcriptomics, and Hi-C, we show that Pol-II regulates conformationally defined interphase chromatin packing domains. Pol-II facilitates nascent domain generation and maintains mature domain integrity through the process of generating transcriptional loops. Mechanistically, Pol-II maintains the packing of intronic and intergenic chromatin within domains by transcribing exons within gene bodies. Consequently, polymerase loss disrupts genome connectivity, in situ packing domains, and gene expression, genome-wide. Our findings suggest chromatin packing domains and RNA synthesis are tightly coupled to optimize transcriptional responses in human cells.

  PublisherOA PDFDOI

• One Chromatin, Many Structures: From Ensemble Contact Maps to Single-Cell 3D Organization

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-21

  articleOpen access

  Understanding how chromatin folds in three dimensions remains challenging because most experimental assays capture low-dimensional projections of an underlying, highly heterogeneous polymer. Here we present an ensemble-based interpretive framework built on the previously introduced Self-Returning Excluded Volume (SR-EV) model, a minimal generator of nucleosome-resolution chromatin conformations based on stochastic return rules and excluded-volume geometry. Despite its simplicity, SR-EV reproduces key experimental signatures across scales: heterogeneous nanoscale packing domains resembling ChromEMT and ChromSTEM observations, sparse and highly variable single-configuration contact patterns analogous to single-cell chromosome conformation capture (Hi-C), and robust ensemble-level contact enrichment consistent with topologically associating domains (TADs). In this framework, Hi-C loop and TAD signatures are interpreted as ensemble-level statistical enrichments rather than invariant features of single-cell conformations. SR-EV is explicitly designed to generate large ensembles of complete three-dimensional chromatin configurations that can be projected consistently onto two-dimensional contact maps and one-dimensional genomic profiles. By introducing architectural-protein effects only through ensemble selection rather than explicit forces, SR-EV supports a separation between intrinsic polymer geometry and regulatory bias and suggests that TAD-like features can emerge as statistical enrichments rather than deterministic three-dimensional structures. Coordination number and probe-based accessibility computed directly from SR-EV provide a unified link between three-dimensional packing, two-dimensional contact maps, and one-dimensional genomic profiles. Together, these results establish SR-EV as a minimal and physically grounded reference framework for interpreting how heterogeneous chromatin ensembles give rise to multimodal experimental observables, while remaining consistent with the fact that chromatin organization is realized in individual cells. SIGNIFICANCE Chromatin domains, boundaries, and contact enrichments are often interpreted as fixed structural entities, even though most experimental measurements average over large and heterogeneous cell populations. The SR-EV framework shows that many of these features can be understood as emerging from minimal geometric rules combined with ensemble-level bias, without requiring explicit molecular interactions or deterministic folding mechanisms. By distinguishing single-configuration heterogeneity from ensemble-level statistical organization – including the emergence of packing domains– SR-EV supports an interpretation in which chromatin organization is realized in individual cells but must be analyzed through ensembles. This perspective clarifies the probabilistic nature of genome architecture and provides a tractable reference framework for interpreting multimodal genomic and imaging data.

  PublisherDOI

• One Chromatin, Many Structures: From Ensemble Contact Maps to Single-Cell 3D Organization

  Biophysical Journal · 2026-05-01

  article
  PublisherDOI

• JoVE Video Dataset

  2026-03-07

  databaseSenior author

  Super-resolution imaging has revolutionized biological research by revealing structural details at the nanoscale. Most optical super-resolution methods rely on fluorescent labeling of biomolecules, which enables specific tagging of molecular species but can disrupt cellular functions, introduce inaccuracies from linker molecules, and fail to provide the consistent high labeling density required for chromatin imaging at the scale of individual DNA molecules. A technology that enables label-free, in situ genomic imaging with nanometer resolution would profoundly impact biology. Here, we present a protocol that harnesses the intrinsic fluorescence of DNA to perform spectroscopic single-molecule localization microscopy (sSMLM). The protocol details sample preparation, data acquisition, and spectral analysis. Briefly, a thin DNA gel is created by depositing a polynucleotide solution onto glass and allowing it to dry for hours. After gel formation, the sample is imaged in the presence of an imaging buffer using sSMLM. The recorded dataset comprises a zeroth-order image, providing spatial localizations, and a first-order image, encoding the emission spectrum of each localization. Spatial reconstructions are generated from the zeroth-order data, after which the corresponding spectra are extracted from the first-order signal. Finally, we demonstrate the feasibility of this approach using multiple excitation wavelengths and DNA molecules with varying lengths, sequences, and compositions.

  PublisherDOI

• DNA spectroscopic photon-localization nanoscopy

  2026-03-04

  articleSenior author
  PublisherDOI

• First-in-human pilot study of broadband optical spectroscopy (BOS) as noninvasive surveillance for necrotizing enterocolitis (NEC)

  Journal of Pediatric Surgery · 2026-02-04

  article
  PublisherDOI

• Spectroscopic Super-resolution Imaging of DNA Molecules using Intrinsic Contrast

  Journal of Visualized Experiments · 2026-03-06

  articleOpen accessSenior author

  Super-resolution imaging has revolutionized biological research by revealing structural details at the nanoscale. Most optical super-resolution methods rely on fluorescent labeling of biomolecules, which enables specific tagging of molecular species but can disrupt cellular functions, introduce inaccuracies from linker molecules, and fail to provide the consistent high labeling density required for chromatin imaging at the scale of individual DNA molecules. A technology that enables label-free, in situ genomic imaging with nanometer resolution would profoundly impact biology. Here, we present a protocol that harnesses the intrinsic fluorescence of DNA to perform spectroscopic single-molecule localization microscopy (sSMLM). The protocol details sample preparation, data acquisition, and spectral analysis. Briefly, a thin DNA gel is created by depositing a polynucleotide solution onto glass and allowing it to dry for hours. After gel formation, the sample is imaged in the presence of an imaging buffer using sSMLM. The recorded dataset comprises a zeroth-order image, providing spatial localizations, and a first-order image, encoding the emission spectrum of each localization. Spatial reconstructions are generated from the zeroth-order data, after which the corresponding spectra are extracted from the first-order signal. Finally, we demonstrate the feasibility of this approach using multiple excitation wavelengths and DNA molecules with varying lengths, sequences, and compositions.

  PublisherOA PDFDOI

• Geometrically Encoded Positioning of Introns, Intergenic Segments, and Exons in the Human Genome (Adv. Sci. 6/2026)

  Advanced Science · 2026-01-01

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Leveraging chromatin packing domains to target chemoevasion in vivo

  Proceedings of the National Academy of Sciences · 2025-07-22 · 3 citations

  articleOpen accessSenior authorCorresponding

  Cancer cells exhibit a remarkable resilience to cytotoxic stress, often adapting through transcriptional changes linked to alterations in chromatin structure. In several types of cancer, these adaptations involve epigenetic modifications and restructuring of topologically associating domains. However, the underlying principles by which chromatin architecture facilitates such adaptability across different cancers remain poorly understood. To investigate the role of chromatin in this process, we developed a physics-based model that connects chromatin organization to cell fate decisions, such as survival following chemotherapy. Our model builds on the observation that chromatin forms packing domains, which influence transcriptional activity through macromolecular crowding. The model accurately predicts chemoevasion in vitro, suggesting that changes in packing domains affect the likelihood of survival. Consistent results across diverse cancer types indicate that the model captures fundamental principles of chromatin-mediated adaptation, independent of the specific cancer or chemotherapy mechanisms involved. Based on these insights, we hypothesized that compounds capable of modulating packing domains, termed Transcriptional Plasticity Regulators (TPRs), could prevent cellular adaptation to chemotherapy. We conducted a proof-of-concept compound screen using live-cell chromatin imaging to identify several TPRs that synergistically enhanced chemotherapy-induced cell death. The most effective TPR significantly improved therapeutic outcomes in a patient-derived xenograft model of ovarian cancer. These findings underscore the central role of chromatin in cellular adaptation to cytotoxic stress and present a framework for enhancing cancer therapies, with broad potential across multiple cancer types.

  PublisherOA PDFDOI

• Multiplexed Chromatin Analysis Using Optical Spectroscopic Statistical Nanosensing

  ACS Photonics · 2025-07-10 · 1 citations

  articleOpen accessSenior authorCorresponding

  In single cells, chromatin packs into organized structures to perform biological functions, such as RNA transcription regulation. Characterizing such structural behaviors, including packing density and mass scaling, is critical in epigenetics research. Partial wave spectroscopic (PWS) microscopy is a label-free, live-cell, high-throughput imaging modality that utilizes optical spectroscopic statistical nanosensing. Rather than resolving the exact chromatin packing structure, PWS extracts statistical packing information from spectroscopic interference signals. In this study, we evaluate its ability to characterize multiplexed chromatin packing density and mass scaling, as well as its spatial confidence interval, using finite difference time domain (FDTD) electromagnetic simulations. We validated the simulation-based analysis algorithm by comparing experimental PWS images against coregistered super-resolution acquisitions, confirming its accuracy in capturing chromatin packing metrics. We then applied this modality to live cells treated with different epigenetic agents, mapping spatial changes in chromatin packing in a high-throughput workflow.

  PublisherOA PDFDOI

Recent grants

• Microvasculature in Colon Field Carcinogenesis: Clinical-Biological Implications

  NIH · $3.3M · 2018–2025

• EAGER: BISH: Biophotonics Technique for Detection of Lung Cancer

  NSF · $300k · 2009–2011

• NIH Grant R21EB003454

  NIH · $366k · 2006

• Cancer Research Training and EducationCoordination

  NIH · $51.1M · 1997–2030

• Nanoscale/Molecular analysis of Fecal Colonocytes for Colorectal Cancer Screening

  NIH · $2.8M · 2012–2018

Frequent coauthors

• Hemant K. Roy

  Baylor College of Medicine

  235 shared

• Hariharan Subramanian

  226 shared

• Dhwanil Damania

  143 shared

• Michael J. Goldberg

  124 shared

• Ramesh K. Wali

  124 shared

• Hemant K. Roy

  117 shared

• Lusik Cherkezyan

  94 shared

• Jeremy D. Rogers

  University of Wisconsin–Madison

  94 shared

Education

• Ph.D.

  Harvard University - MIT