About

Kathryn Whitehead is a professor in the Departments of Chemical Engineering and Biomedical Engineering (courtesy) at Carnegie Mellon University. Her research focuses on developing drug delivery systems for RNA, proteins, and applications in maternal and infant health. Her lab works on designing lipid nanoparticles that can safely and effectively deliver mRNA to specific organs, including the pancreas and placenta, with the goal of advancing treatments for various diseases. Whitehead's work also explores utilizing breast milk to improve infant drug delivery and developing novel therapies for infant diseases. She obtained her bachelor’s and doctoral degrees in chemical engineering from the University of Delaware and the University of California, Santa Barbara, respectively, before completing an NIH Postdoctoral Fellowship at MIT. Whitehead has received numerous awards, including the NIH Director's New Innovator Award, the DARPA Director's Fellowship, and the ASEE Curtis W. McGraw Research Award. She is an elected Fellow of the American Institute for Medical and Biological Engineering and the Controlled Release Society, where she has also served on the Board of Directors. Her contributions to the field have been recognized through her listing as a Highly Cited Researcher by Clarivate, and her work has been featured in media outlets such as CBS Evening News. Her research aims to reframe RNA delivery by designing vehicles that can work around the immune system’s memory, and she is actively involved in organizing symposia on nucleic acid therapeutics. Whitehead's publications have been cited over 15,000 times, and her patents have been licensed for reagent and therapeutic use. She is committed to advancing the understanding and application of nanotherapeutics and biomaterials in medicine.

Research topics

• Biology
• Chemistry
• Biochemistry
• Genetics
• Immunology
• Virology
• Molecular biology
• Medicine
• Cell biology

Selected publications

• Efficacy of oral micronutrients and online mindfulness for emotional dysregulation in children aged 6–10 (The M&M Trial): Protocol for a randomized, double-blind, placebo-controlled trial

  Nutritional Psychiatry · 2026-01-01

  articleOpen access

  Emotional dysregulation (ED) is increasingly recognized as a transdiagnostic construct associated with significant impairment in children, regardless of psychiatric diagnosis. Both nutritional insufficiencies and poor emotional regulation in early life are linked to adverse mental health outcomes. Evidence supports a multimodal approach to mental health, with mindfulness-based interventions (MBIs) and micronutrient supplementation emerging as promising, complementary strategies. This study aims to evaluate the individual and combined effects of a broad-spectrum micronutrient formula and an online mindfulness program on ED symptoms in children aged 6–10 years. In a randomized, placebo-controlled, 4-arm parallel-group trial, 160 6-10 year old children with ED will be assigned to one of four groups (n=40 per group): (1) micronutrients + mindfulness; (2) micronutrients + active monitoring; (3) placebo + mindfulness; (4) placebo + active monitoring. Micronutrients will be administered as a powdered formulation absorbed via the oral mucosa to enhance bioavailability and tolerability. The mindfulness intervention, MindKiwi, is an online adaptation of the UCLA ADHD mindfulness program, culturally tailored for New Zealand children. Outcomes include changes in ED symptoms, parent-reported mood and stress. Stool and saliva samples will be collected at baseline and post-intervention from a subset of participants, measuring biological markers including microbiome diversity and DNA methylation. We hypothesize that children receiving any active intervention (micronutrients, mindfulness, or both) will show greater improvements in emotional dysregulation compared with placebo + active monitoring control group. We also expect micronutrients, whether delivered alone or alongside mindfulness, will be associated with increased gut microbiome diversity. • Efficacy of Oral Micronutrients and Online Mindfulness for Emotional Dysregulation in Children Aged 6–10 (The M&M Trial): Protocol for a Randomized, Double-Blind, Placebo-Controlled Trial. • Evaluates micronutrients and mindfulness for child emotion dysregulation • Four-arm RCT tests individual and combined intervention effects • MindKiwi provides culturally adapted online mindfulness training • Biological markers examined through microbiome and methylation samples • Targets 6–10 year olds, a key period for emotional regulation development

  PublisherDOI

• Enhanced Epigenetic Modulation via mRNA-Encapsulated Lipid Nanoparticles Enables Targeted Anti-inflammatory Control

  ACS Synthetic Biology · 2026-01-15

  articleOpen access

  . By targeting Myd88, an essential adaptor molecule involved in immunity, our system demonstrates therapeutic efficacy against septicemia in C57BL/6J mice and improves repeated AAV administration by reducing antibody responses. This epigenetic engineering approach provides a platform for safe and efficient immunomodulation applicable across diseases caused by imbalanced inflammatory responses.

  PublisherDOI

• Maternal milk cell components are uptaken by infant liver macrophages via extracellular vesicle mediated transport

  The FASEB Journal · 2025-01-21 · 2 citations

  articleOpen accessSenior authorCorresponding

  Milk is a multifaceted biofluid that is essential for infant nutrition and development, yet its cellular and bioactive components, particularly maternal milk cells, remain understudied. Early research on milk cells indicated that they cross the infant's intestinal barrier and accumulate within systemic organs. However, due to the absence of modern analytical techniques, these studies were limited in scope and mechanistic analysis. To overcome this knowledge gap, we have investigated the transintestinal transport of milk cells and components in pups over a 21-day period. Studies employed a mT/mG foster nursing model in which milk cells express a membrane-bound fluorophore, tdTomato. Using flow cytometry, we tracked the transport of milk cell-derived components across local and systemic tissues, including the intestines, blood, thymus, mesenteric lymph nodes, and liver. These experiments identified milk-derived fluorescent signals in intestinal epithelial and immune cells as well as liver macrophages in 7-day-old pups. However, the minute numbers of macrophages in mouse milk suggest that maternal cells are not systemically accumulating in the infant; instead, pup macrophages are consuming milk cell membrane components, such as apoptotic bodies or extracellular vesicles (EVs). Ex vivo experiments using primary macrophages support this hypothesis, showing that immune cells preferentially consumed EVs over milk cells. Together, these data suggest a more complex interplay between milk cells and the infant's immune and digestive systems than previously recognized and highlight the need for future research on the role of milk cells in infant health.

  PublisherOA PDFDOI

• Enhanced epigenetic modulation via mRNA-encapsulated lipid nanoparticles enables targeted anti-inflammatory control

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-02-28 · 7 citations

  preprintOpen access

  Abstract Temporal transcriptional modulation of immune-related genes offers powerful therapeutic potential for treating inflammatory diseases. Here, we introduce an enhanced zinc finger (ZF)-based transcriptional repressor delivered via lipid nanoparticles for controlling immune signaling pathways in vivo . By targeting Myd88, an essential adaptor molecule involved in immunity, our system demonstrates therapeutic efficacy against septicemia in C57BL/6J mice and improves repeated AAV administration by reducing antibody responses. This epigenetic engineering approach provides a platform for safe and efficient immunomodulation applicable across diseases caused by imbalanced inflammatory responses.

  PublisherOA PDFDOI

• Limiting endosomal damage sensing reduces inflammation triggered by lipid nanoparticle endosomal escape

  Nature Nanotechnology · 2025-08-11 · 42 citations

  articleOpen access
  PublisherOA PDFDOI

• The great lipid hunt

  Nature Chemical Engineering · 2025-12-19

  article1st authorCorresponding
  PublisherDOI

• Protein corona formed on lipid nanoparticles compromises delivery efficiency of mRNA cargo

  Nature Communications · 2025-09-30 · 36 citations

  articleOpen access

  Lipid nanoparticles (LNPs) are the most clinically advanced nonviral RNA-delivery vehicles, though challenges remain in fully understanding how LNPs interact with biological systems. In vivo, proteins form an associated corona on LNPs that redefines their physicochemical properties and influences delivery outcomes. Despite its importance, the LNP protein corona is challenging to study owing to the technical difficulty of selectively recovering soft nanoparticles from biological samples. Herein, we develop a quantitative, label-free mass spectrometry-based proteomics approach to characterize the protein corona on LNPs. Critically, this protein corona isolation workflow avoids artifacts introduced by the presence of endogenous nanoparticles in human biofluids. We apply continuous density gradient ultracentrifugation for protein-LNP complex isolation, with mass spectrometry for protein identification normalized to protein composition in the biofluid alone. With this approach, we quantify proteins consistently enriched in the LNP corona including vitronectin, C-reactive protein, and alpha-2-macroglobulin. We explore the impact of these corona proteins on cell uptake and mRNA expression in HepG2 human liver cells, and find that, surprisingly, increased levels of cell uptake do not correlate with increased mRNA expression in part due to protein corona-induced lysosomal trafficking of LNPs. Our results underscore the need to consider the protein corona in the design of LNP-based therapeutics.

  PublisherOA PDFDOI

• Synthetic Strategy for mRNA Encapsulation and Gene Delivery with Nanoscale Metal‐Organic Frameworks

  Advanced Functional Materials · 2025-05-19 · 6 citations

  articleOpen access

  Abstract Metal‐organic frameworks (MOFs) have evolved from uses in catalysis and gas storage to exciting applications in biomedicine, particularly in drug delivery. Initially, MOFs are primarily used to deliver small molecules, recent innovations have shifted focus toward more complex nucleic acids like DNA, short guide RNA (sgRNA), and short interfering RNA (siRNA). Remarkably, no studies to date have demonstrated the encapsulation and delivery of messenger RNA (mRNA) via MOFs in vitro and in vivo. This study addresses that gap by identifying synthetic conditions to encapsulate and deliver mRNA using zeolitic imidazole framework‐8 (ZIF‐8). Early attempts show mRNA loading in ZIF‐8 but loss of mRNA in biological media. To overcome this challenge, polyethyleneimine (PEI) is incorporated into the formulation, forming a robust polymer complex core‐MOF shell particle. This system stabilizes mRNA complexes and delays their release, resulting in effective protein expression in multiple cell lines and mice, performing on par with commercial lipid‐based systems. Here, the first investigation into thermally stable mRNA storage using ZIF‐8 demonstrates successful protein expression after three months of room‐temperature storage in vitro and one month in vivo. These findings broaden the scope of MOF‐based therapeutic delivery and open new avenues for long‐term mRNA storage and transport.

  PublisherOA PDFDOI

• Designing around immune memory to counter PEG immunogenicity

  Nature Materials · 2025-10-15 · 4 citations

  articleSenior authorCorresponding
  PublisherDOI

• Hydrophobic Ion Pairing for Simple, Non-Toxic Transfection

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-04-28 · 1 citations

  preprintOpen access

  Abstract Although biomacromolecules require intracellular delivery for therapeutic effect, existing transfection agents are often characterized by high cost, low efficiency, and/or cytotoxicity. Here, we describe a new transfection approach based on hydrophobic ion pairing (HIP), which involves the simple mixing of a hydrophobic counterion with charged biomacromolecules. Among tested cargoes (proteins, siRNA, and pDNA), the HIP siRNA system performed especially well, achieving silencing in fibroblasts (80%), T cells (90%), and neurons (70%). HIP siRNA was also highly potent in mice, with tropism dependent on the route of administration. Most notably, intraperitoneal administration enabled ∼40% LAMP-1 knockdown in the pancreas, and intravenous delivery resulted in a remarkable 80% silencing in the heart. Heart delivery was also highly selectively, with no significant knockdown in the liver. Together, these data demonstrate a new, inexpensive approach to biomacromolecular delivery with the potential to target difficult-to-transfect organs, thus expanding the therapeutic potential of nucleic acids.

  PublisherOA PDFDOI

Recent grants

• Diversity Supplement to Fate, Function and Genetic Engineering of Breast Milk Cells for Infant Therapy

  NIH · $2.4M · 2021–2023

• Protein-Piperazine Polymer Conjugates as a New Platform for Oral Protein Therapy

  NSF · $524k · 2018–2021

• NIH Grant F32EB009623

  NIH · $104k · 2012

Frequent coauthors

• Daniel G. Anderson

  Boston Children's Hospital

  31 shared

• Róbert Langer

  Massachusetts Institute of Technology

  28 shared

• Namit Chaudhary

  Carnegie Mellon University

  25 shared

• Katherine C. Fein

  Carnegie Mellon University

  18 shared

• Minglin Ma

  16 shared

• Mariah L. Arral

  Carnegie Mellon University

  14 shared

• Alexandra N. Newby

  Carnegie Mellon University

  13 shared

• Rose Doerfler

  Carnegie Mellon University

  12 shared

Labs

• Whitehead LabPI

  Undergraduate Researchers, ALUMNI, Principal Investigator

Education

• B.S., Chemical Engineering

  University of Delaware

• Ph.D., Chemical Engineering

  University of California, Santa Barbara

Awards & honors

• NIH Director's New Innovator Award
• DARPA Director's Fellowship
• ASEE Curtis W. McGraw Research Award
• Controlled Release Society's Young Investigator Award
• Fellow of the American Institute for Medical and Biological…