About

Shana Kelley is the Neena B. Schwartz Professor of Chemistry and Biomedical Engineering at Northwestern University. Her research group employs a highly multidisciplinary approach to develop new tools for disease diagnosis and therapy. Her projects focus on the development of biomolecular sensors, phenotypic screening platforms, and molecular delivery vectors, utilizing cutting-edge techniques including CRISPR screening and cellular engineering. Kelley’s work aims to create innovative solutions for biomedicine, impacting areas such as diagnostic development and therapeutic strategies. Throughout her career, Kelley has generated over 200 publications, mentored approximately 50 Ph.D. students and postdoctoral fellows, and founded three companies based on her research technologies. Her scientific background spans chemistry, biology, engineering, and other fields, enabling her to lead diverse research initiatives. Kelley has received numerous recognitions, including fellowships, awards, and honors from prestigious institutions such as the Royal Society of Canada, Harvard University, and the American Institute for Medical and Biological Engineering. Her contributions significantly advance the fields of biomedical engineering and chemical biology.

Research topics

• Chemistry
• Materials science
• Nanotechnology
• Chromatography
• Organic chemistry
• Chemical engineering
• Optoelectronics
• Computer Science
• Composite material
• Engineering
• Virology
• Biochemistry
• Biochemical engineering
• Biological system
• Combinatorial chemistry
• Ecology
• Inorganic chemistry
• Molecular biology
• Biology
• Crystallography

Selected publications

• Metabolic programming promotes cellular uptake of extracellular vesicles and boosts in vivo therapeutic efficacy

  Cell Biomaterials · 2026-03-19 · 1 citations

  articleOpen access
  PublisherDOI

• Amino acid supplementation enhances in vivo efficacy of lipid nanoparticle–mediated mRNA delivery in preclinical models

  Science Translational Medicine · 2026-03-11 · 2 citations

  articleCorresponding

  Lipid nanoparticles (LNPs) play a critical role in the delivery of therapeutic messenger RNA (mRNA). Despite extensive efforts to optimize lipid formulations for in vivo delivery, efficacy of mRNA by LNPs remains suboptimal in many organs. Here, we demonstrate that LNP delivery efficacy is influenced by cellular metabolism, with the physiologic metabolome imposing constraints on mRNA expression from LNPs. Using an in vitro system, we found that simulated physiologic metabolic conditions led to the down-regulation of certain amino acid metabolic programs. Supplementation with an optimized formulation of methionine, arginine, and serine as an amino acid supplement (AAS) enhanced the uptake of LNPs and the expression of delivered mRNA cargo in epithelial cells in vitro. Coadministration of AAS with LNPs led to a 5- to 20-fold improvement in mRNA expression across various cell types and lipid formulations in vitro by promoting clathrin-independent carrier-mediated endocytosis. Delivery of mRNA by LNPs coadministered with AAS by multiple routes enhanced in vivo mRNA expression in preclinical models. Delivery of mRNA encoding growth hormone by LNPs with coadministration of AAS improved the liver growth hormone expression and the therapeutic outcomes in a model of inflammatory liver damage. Delivery of gene editing materials by LNP and AAS through an intratracheal route increased lung-targeted in vivo gene editing efficiency compared with LNP alone. The addition of an optimized AAS as a codelivered agent with LNPs may provide a simple strategy to broadly improve the efficacy of mRNA-based cell and gene therapies.

  PublisherDOI

• Biomolecular Condensates as Protein Degradation Tools for Intracellular Targets

  Nature Communications · 2026-05-13

  articleOpen accessSenior author

  Targeted protein degradation harnesses endogenous cellular machinery to eliminate disease-causing proteins, yet achieving phenotype-specific degradation across diverse cell types remains challenging. Here we show that antibody-enriched biomolecular condensates formed by liquid–liquid phase separation function as intracellular protein degradation tools, combining cytosolic trafficking with direct proteasome recruitment for targeted substrate clearance. These nanoscale condensates incorporate a short proteasome-targeting motif into phase-separation precursors, preserve antibody activity, enable direct proteasome recruitment, and improve delivery uniformity. When loaded with a mutation-specific antibody, these condensates selectively degrade oncogenic KRAS G12V without affecting wild-type KRAS in heterozygous cells, and suppress tumor growth in a KRAS G12V xenograft model. This strategy provides a modular platform for intracellular protein degradation that can be readily adapted by exchanging antibodies, without requiring genetic modification of cellular system. Targeted protein degradation has huge potential, but phenotype-specific degradation remains a difficulty. Here, a phase-separation biomolecular condensates as an intracellular degradation agent is developed, combining antibody-guided recognition with direct proteasome recruitment to enable phenotype-selective protein clearance.

  PublisherDOI

• AI-Guided CRISPR Screen Accelerates Discovery of New Drug Targets

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-02-28

  articleOpen access

  Abstract Psoriasis affects over 125 million people worldwide, yet the mechanistic understanding of keratinocyte-driven inflammation remains incomplete, limiting therapeutic innovation beyond costly systemic biologics that are prone to side effects. Here, we performed the first genome-wide CRISPR knockout screen in primary human adult epidermal keratinocytes to systematically identify regulators of IL-17 receptor A (IL17RA), a central node in psoriatic inflammation. To prioritize therapeutically tractable targets from over 19,000 screened genes, we integrated a large language model – VirtualCRISPR – trained on functional genomics data, identifying arachidonate 5-lipoxygenase (ALOX5) and oxytocin receptor (OXTR) as high-confidence novel hits with minimal prior association with psoriasis. Multi-omics validation revealed that ALOX5 and OXTR regulate IL17RA expression through distinct signaling pathways – ALOX5 through lipid mediators that stabilize the receptor at the cell surface, and OXTR through calcium signaling that reprograms cellular metabolism. Topical delivery of their inhibitors Zileuton (ALOX5) and Cligosiban (OXTR) exhibited therapeutic efficacy comparable to systemic anti-IL17RA antibody in the imiquimod-induced psoriasis model, suppressing pathogenic Th17/Tc17 responses, polarizing macrophages toward anti-inflammatory phenotypes, and normalizing epidermal hyperproliferation. Proteomic profiling in human 3D organotypic skin and murine models confirmed on-target pharmacology and revealed convergent suppression of neutrophil-keratinocyte inflammatory circuits. The use of VirtualCRISPR significantly shortened the timescale from screen to the identification of druggable hits with robust validation, and this work establishes a blueprint for integrating AI-driven target prioritization with functional genomics to accelerate therapeutic discovery.

  PublisherDOI

• Resilient nanostructured bioanalytic microneedle longitudinally monitors preclinical renal and hepatic drug clearance and dysfunction

  Science Translational Medicine · 2026-04-01 · 2 citations

  article

  Wearable microneedle biosensors promise real-time molecular monitoring for precision medicine but are limited by low sensitivity and tissue abrasion. Overcoming these challenges, we recast electrode functionality not merely as a sensing substrate but as a mechanism for resilient, high signal-to-noise ratio (SNR) measurements in tissue. Our microneedle-based resilient nanostructured bioelectrode (RNB) is fabricated using a bilayer process that strengthens the electrode with a micrometer-thick gold adhesion layer and reduces fabrication-induced stress through controlled dealloying. The resulting RNBs are corrosion resistant, stable over a wide potential window, and have an artifact-free, nanocavity-textured interface. They integrate receptor-based electrochemical biosensors with enhanced SNR through increased active area, diffusion, and antifouling while remaining abrasion immune in megapascal-stiff tissues. The RNB extended in vivo biosensor lifetime for pharmacokinetics monitoring to 6 days in a freely moving rat. Paired with a blood-interstitial fluid equilibrium-based bioanalytical framework, the RNB accurately derived blood-equivalent pharmacokinetic parameters, enabling not only precision dosing of narrow therapeutic index drugs but also the direct assessment of hepatic and renal clearance. In hepatic studies, the RNB revealed delayed clearance of a chemotherapeutic (irinotecan) in liver-damaged models. In renal studies, RNB recordings correlated with blood antibiotic pharmacokinetics across chronic kidney disease severities. The RNB detected renal impairment earlier than conventional biomarker thresholds through drug clearance quantification and captured recovery under therapeutic intervention. These results establish the RNB as a viable microneedle platform for high-fidelity in vivo deployment of electrochemical biosensors, enabling minimally invasive, longitudinal monitoring of low-concentration analytes and real-time assessment of organ function.

  PublisherDOI

• Wearable biomolecular sensing nanotechnologies in chronic disease management

  Nature Nanotechnology · 2025-10-01 · 19 citations

  reviewOpen access
  PublisherOA PDFDOI

• Implantable Cardiac Patch Continuously Monitors Acute Heart Failure Biomarkers In Vivo and Ex Vivo

  JACC Basic to Translational Science · 2025-02-11 · 5 citations

  articleOpen accessSenior author
  PublisherDOI

• 33 Unresolved Questions in Nanoscience and NanotechnologyArticle link copied!

  RWTH Publications (RWTH Aachen) · 2025-01-01

  article
  Publisher

• Mesothelioma cell heterogeneity identified by single cell RNA sequencing

  Scientific Reports · 2025-03-13 · 2 citations

  articleOpen access

  Mesothelioma cell heterogeneity encompasses diverse morphological and molecular characteristics observed within tumors, significantly impacting disease progression, treatment outcomes, and the development of targeted therapies. This heterogeneity has long posed challenges for accurate diagnosis and effective treatment, but understanding its complexities offers the potential for novel diagnostic modalities and therapeutic interventions. This study employed single-cell RNA sequencing (scRNA-seq) to investigate mesothelioma cell heterogeneity from various sources, including cell culture (CC), peritoneal lavage (Lav) from the tumor microenvironment, and circulating tumor cells (CTC) in murine models. Gene set enrichment analysis was used to identify distinct gene signatures for each subpopulation. The results revealed unique characteristics for mesothelioma cells depending on their origin. In the CC group, up-regulated genes were primarily involved in tumor cell cycle control, proliferation, and apoptosis. In the CTC group, up-regulated genes were associated with cancer cell stemness. The Lav group showed up-regulated genes facilitating interactions between tumor cells and the microenvironment, such as epithelial-mesenchymal transition and immune responses mediated by IFN-α and IFN-γ. Some pathways were shared among all tumor cells, suggesting the potential for transitioning between functional states under specific conditions. This may be the first study to explore circulating mesothelioma cell heterogeneity using scRNA-seq. The distinct gene signatures identified in each mesothelioma cell subpopulation likely play critical roles in tumor initiation and progression, offering potential novel targets for therapeutic intervention. These findings could help inform the development of more effective, personalized treatments for mesothelioma, ultimately improving patient outcomes.

  PublisherOA PDFDOI

• Toward Reagentless and Universal Biomolecular Sensing: Molecular Pendulum-Based Bioanalysis

  Accounts of Chemical Research · 2025-11-07 · 2 citations

  articleSenior authorCorresponding

  Continuous monitoring of physiologically relevant analytes remains an unmet need of high interest to the medical community. Complex biological environments, slow-release affinity receptors, and short sensor lifetimes are just some of the many challenges that stand in the way of delivering real-time analysis for disease diagnosis, prevention, and treatment. Electrochemical biomolecular sensors are poised to address many of these challenges, given their demonstrated ability to detect a wide range of analytes, from proteins to small molecules, in various in vivo applications. Our laboratory has a strong interest in developing electrochemical biomolecular sensors for long-term continuous health monitoring with the ultimate goal of achieving a universal sensing platform.In this Account, we summarize our group's efforts to develop a universal, reagentless continuous monitoring platform for a multitude of biologically relevant targets. We first introduced the molecular pendulum (MP) sensing approach in 2021, which enabled the detection of a variety of essential protein analytes in their physiologically relevant ranges. In subsequent work, we have addressed some limitations to MP universality, first by expanding the analyte scope to include viral particles and electroactive small molecules. We further demonstrated that the MP platform could be integrated with a variety of target receptors, including antibodies, nanobodies, and aptamers, further expanding the receptor space and analyte range of this platform. To address one of the most significant challenges facing the biomolecular sensing community─the inability to overcome strong receptor binding and continuously monitor analytes─we developed an active-reset method for the MP, enabling the continuous detection of proteins through oscillatory receptor regeneration. To integrate sensors into bioelectronic interfaces, we have demonstrated MP function in various microneedle platforms capable of interstitial fluid sampling and monitoring. This platform enabled our laboratory to begin performing a wide range of in vivo tests, as we look forward to new implantable and wearable form factors. Combining all the above factors, we have started to utilize our MP sensing systems to gain critical insights into physiological mechanisms such as inflammation and circadian rhythm disruption by monitoring molecular fluctuations. Given the success of the MP system in targeting a large variety of analytes with high sensitivity, receptor modularity, and in vivo compatibility, we believe that MP sensing can be expanded further and has high potential to serve as a model for universal biomolecular sensing.

  PublisherDOI

Recent grants

• Programmable electrochemical gene circuit sensors for infectious disease detection

  NIH · $300k · 2018–2021

• Development and validation of nanoparticle-mediated microfluidic profiling approach for rare cell analysis

  NIH · $824k · 2017–2021

• NIH Grant R21CA097945

  NIH · $471k · 2005

• NIH Grant R21CA114135

  NIH · $305k · 2008

• NIH Grant R01GM063890

  NIH · $1.2M · 2007

Frequent coauthors

• Edward H. Sargent

  University of Toronto

  266 shared

• Eric Bakker

  University of Geneva

  189 shared

• J. Justin Gooding

  UNSW Sydney

  189 shared

• Antonella I. Mazur

  University of California, San Diego

  185 shared

• Michael J. Sailor

  University of California, San Diego

  185 shared

• Maarten Merkx

  Eindhoven University of Technology

  185 shared

• Lanqun Mao

  Beijing Normal University

  182 shared

• Heather A. Clark

  182 shared

Labs

• Kelley LaboratoryPI

Awards & honors

• Fellow, Royal Society of Canada, 2021
• Order of Ontario, 2021
• AFPC Pfizer Award, 2020
• Distinguished Visiting Fellow, Rowland Institute, Harvard Un…
• ACS Nanoscience Award, 2017