About

Laura Segatori, PhD, is a Professor of Bioengineering, Chemical & Biomolecular Engineering, and Biosciences. She completed her Ph.D. in Chemical Engineering at The University of Texas at Austin in 2005. Following her doctoral studies, she was a Postdoctoral Fellow in the Department of Chemistry at The Scripps Research Institute from 2005 to 2007. Prior to her graduate education, she studied Industrial Biotechnology in Bologna, Italy, in 2000. Her professional contact includes her email segatori@rice.edu and a Google Scholar profile. The information provided does not include specific details about her research focus or key contributions.

Research topics

• Computer Science
• Computational biology
• Biology
• Artificial Intelligence
• Cell biology
• Genetics
• Biotechnology
• Risk analysis (engineering)
• Physics
• Biochemical engineering
• Chemistry
• Optoelectronics
• Medicine
• Engineering

Selected publications

• Establishing an RNA Sensor with High Sensitivity and Dynamic Range Utilizing a Signal Amplifier Platform

  ACS Synthetic Biology · 2026-03-27

  articleOpen accessSenior authorCorresponding

  Precise control of gene expression in a cell-state-specific manner is essential for effective therapeutic interventions in complex and dynamic disease microenvironments. Traditional targeting strategies that rely on surface markers or cell type-specific promoters often assume static cellular identities, limiting effectiveness in context such as cancer and inflammation, where cell states are highly heterogeneous and dynamic. RNA sensors, such as RADAR (RNA sensing using Adenosine Deaminases Acting on RNA), provide a modular, programmable, and nonintegrating platform for classifying cell states. However, it is also characterized by low sensitivity and dynamic range, which limits its applications in detecting low-abundance transcripts. In this work, we integrate RADAR sensors with a signal amplification circuit to enhance sensitivity and dynamic range. We demonstrate that this combined RADAR-amplifier platform enables real-time monitoring of subtle changes in the abundance of endogenous transcripts under physiological conditions. Our results demonstrate the utility of this platform for fundamental biological studies and the development of precision therapeutic strategies.

  PublisherDOI

• Novel Approaches to Label the Surface of <i>S. aureus</i> with DBCO for Click Chemistry-Mediated Deposition of Sensitive Cargo

  Bioconjugate Chemistry · 2025-05-21 · 2 citations

  article

  The strain-promoted alkyne–azide cycloaddition (SPAAC) reaction can be used to modify the surface of bacteria for a variety of applications including drug delivery, biosensing, and imaging. This is usually accomplished by first installing a small azide group within the peptidoglycan and then delivering exogenous cargo (e.g., a protein or nanoparticle) modified with a cyclooctyne group, such as dibenzocyclooctyne (DBCO), for in situ conjugation. However, DBCO is comparatively bulky and hydrophobic, increasing the propensity of some payloads to aggregate. In this study, we sought to invert this paradigm by exploring two novel strategies for incorporating DBCO into the peptidoglycan of Staphylococcus aureus and compared them to an established approach using DBCO-vancomycin. We demonstrate that DBCO-modified small molecules belonging to all three classes─a sortase peptide substrate (LPETG), two d-alanine derivatives, and vancomycin─can selectively label the S. aureus surface to varying degrees. In contrast to DBCO-vancomycin, the DBCO–d-alanine variants do not adversely affect the growth of S. aureus or lead to off-target labeling or toxicity in HEK293T or RAW 264.7 cells. Finally, we show that, unlike IgG3-Fc labeled with DBCO groups, IgG3-Fc labeled with azide groups is stable (i.e., remains water-soluble) under normal storage conditions, retains its ability to bind the immune receptor CD64, and can be successfully attached to the surface of DBCO-modified S. aureus. We believe that the labeling strategies explored herein will expand the paradigm of specific, nontoxic SPAAC-mediated labeling of the surface of S. aureus and other Gram-positive bacteria, opening the door for new applications using azide-modified cargo.

  PublisherDOI

• Generating tolerance through in situ recruitment of regulatory T cells for allogeneic cell transplantation in a bioengineered lymphoid platform

  Materials Today Bio · 2025-10-30

  articleOpen access

  Cellular therapies aim to treat or manage disease by introducing living cells that integrate into the host and restore or eliminate dysfunctional tissues. Despite their promise for clinical success, the host immune response to cellular treatments remains a challenge since traditional approaches for abrogating immune rejection involve systemic immunosuppression, which results in severe off-target toxicity. One alternate strategy for restraining immune responses involves harnessing the natural immunomodulatory capabilities of regulatory T cells (Tregs), a specialized subset of T cells that suppress inflammatory immune responses and can promote induction and maintenance of transplant tolerance. Here we propose using the NanoLymph platform, an implantable subcutaneous device for continuous localized recruitment of Tregs, to achieve immunological tolerance free of systemic immunosuppression. The NanoLymph features a dual-reservoir system for the sustained release of immunomodulatory agents through a nanoporous membrane and a vascularized compartment that supports cell homing and allograft integration with the host. This work demonstrates robust vascularization of the NanoLymph by four weeks post-implantation, along with sustained in vivo elution of immunomodulatory agents for up to one month that selectively recruit and expand Tregs. Finally, we demonstrate that NanoLymph prolongs cell persistence in a bioluminescent allogeneic transplant model. Overall, the NanoLymph represents a versatile platform to generate a safe and localized tolerogenic microenvironment relevant for cell transplant therapies.

  PublisherDOI

• Localized delivery of corticosteroids via in <i>situ</i> modification of gut commensals using a synthetic stem peptide prodrug

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-01-14

  preprint

  SUMMARY Oral colonic drug delivery systems (CDDSs) are oftentimes associated with a short duration of action and poor tissue specificity. To address these challenges, we engineered an oral prodrug that leverages the engraftment and semi-permanence of gut commensals to create a long-acting colonic drug depot. We show that two synthetic stem peptide probes can be stereoselectively incorporated onto the surface of gut bacteria in C57BL/6 mice following oral administration. We then show that a prodrug consisting of budesonide, a corticosteroid with otherwise limiting side effects used to treat ulcerative colitis (UC), conjugated to one of these probes via a hydrolyzable ester is significantly less bioactive and is cleaved over a period of days to weeks in simulated physiological fluids. This prodrug can be integrated into the bacterial peptidoglycan in vitro and be cleaved into free budesonide over time, thereby improving drug localization and potentially rendering it safer for longer-term use. GRAPHICAL ABSTRACT SIGNIFICANCE Corticosteroids are highly effective anti-inflammatory drugs used in the treatment of a variety of conditions. Unfortunately, long-term corticosteroid ingestion can lead to a host of dangerous and undesirable side effects including osteoporosis, glaucoma, and a higher risk of infection, among others. Topical corticosteroids delivered via inhalation (chiefly, budesonide and fluticasone) are the primary long-term treatment modality for chronic asthma symptoms. In contrast to oral corticosteroids, they are considered safer for long-term use when given in moderation because they are directly applied to the airways and exhibit low systemic bioavailability. We sought to apply this successful paradigm to another autoimmune-related disease, ulcerative colitis (UC). We developed a drug delivery system that combines the weakly targeting method of ingestion with a highly specific parameter, microbe prevalence along the gastrointestinal tract, to help improve the specificity and colonic retention of the corticosteroid budesonide, which is currently limited to being used as a short-term treatment for moderate-to-severe UC. Our approach utilizes a largely inert prodrug that can be incorporated into the peptidoglycan of commensal bacteria found at high densities in the colon. After tethering to the bacterial surface via a synthetic stem peptide, the prodrug passively hydrolyzes (cleaves) to release the active, unadulterated form of the drug into the local area, whereas prodrug that traffics elsewhere has a higher chance of being cleared from the body before cleavage. In this manner, we can achieve targeted immunosuppression and sustained release, rendering corticosteroids, and potentially other small molecules, safer for longer term use in treating patients with UC.

  PublisherDOI

• Feedback-responsive cell factories for dynamic modulation of the unfolded protein response

  Nature Communications · 2025-05-02 · 9 citations

  articleOpen accessSenior author

  Engineering cell factories that support the production of large quantities of protein therapeutics remains a significant biomanufacturing challenge. The overexpression of secretory proteins causes proteotoxic stress, affecting cell viability and protein productivity. Proteotoxic stress leads to the activation of the Unfolded Protein Response (UPR), a series of signal transduction pathways regulating protein quality control mechanisms aimed at restoring homeostasis. Sustained UPR activation culminates with the induction of apoptosis. Current strategies for enhancing the production of therapeutic proteins have focused on the deregulated modulation of key components of the UPR. These strategies have resulted in limited and often protein-specific improvements as they may lead to adaptation and cell toxicity and do not account for natural population heterogeneities. We report here feedback-responsive cell factories that sense proteotoxic stress and, in response, modulate the UPR to enhance stress attenuation and delay cell death, addressing the limitations of current strategies. We demonstrate that our cell engineering approach enables dynamic UPR modulation upon proteotoxic stress. The sense-and-respond systems that mediate dynamic UPR modulation enhance the production of the therapeutic enzyme tissue plasminogen activator and the bispecific antibody blinatumomab. Our feedback-responsive cell factories provide an innovative strategy for dynamically adjusting the innate cellular stress response and enhancing therapeutic protein manufacturing. Engineering cell factories that support the production of large quantities of protein therapeutics remains a significant biomanufacturing challenge. Here the authors engineered cells to sense an early marker of the Unfolded Protein Response (UPR) and, in response, modulate specific UPR signaling pathways mediating stress attenuation and/or apoptosis.

  PublisherOA PDFDOI

• Pyroglutamate PTMs as Bioorthogonal Reactive Handles: Ru/Ni Photoredox Coupling

  Angewandte Chemie · 2025-12-18

  article

  Abstract Post‐translational modifications (PTMs) play essential roles in living systems. However, the biological roles of some PTMs, such as N‐terminal pyroglutamate, are poorly understood due to a dearth of chemical and/or biological tools to label, quantify, or identify pyroglutamate residues. In this report, we describe a photoredox catalysis process that enables direct pyroglutamate N–H arylation in peptides and proteins, using (hetero)aryl bromide reagents. The reactivity demonstrates the potential for multi‐point binding to recognize peptide backbone structures for exquisitely chemoselective modifications in complex polyfunctional environments. The results provide the first chemical tool to modify pyroglutamate residues within complex polypeptides in biocompatible aqueous environments.

  PublisherDOI

• Pyroglutamate PTMs as Bioorthogonal Reactive Handles: Ru/Ni Photoredox Coupling

  Angewandte Chemie International Edition · 2025-12-18

  articleOpen access

  Post-translational modifications (PTMs) play essential roles in living systems. However, the biological roles of some PTMs, such as N-terminal pyroglutamate, are poorly understood due to a dearth of chemical and/or biological tools to label, quantify, or identify pyroglutamate residues. In this report, we describe a photoredox catalysis process that enables direct pyroglutamate N-H arylation in peptides and proteins, using (hetero)aryl bromide reagents. The reactivity demonstrates the potential for multi-point binding to recognize peptide backbone structures for exquisitely chemoselective modifications in complex polyfunctional environments. The results provide the first chemical tool to modify pyroglutamate residues within complex polypeptides in biocompatible aqueous environments.

  PublisherOA PDFDOI

• Generating Tolerance Through in Situ Recruitment of Regulatory T Cells for Allogeneic Cell Transplantation in a Bioengineered Lymphoid Platform

  SSRN Electronic Journal · 2025-01-01 · 1 citations

  preprintOpen access
  PublisherDOI

• Establishing an RNA sensor with high sensitivity and dynamic range utilizing a signal amplifier platform

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-17

  preprintOpen accessSenior author

  Precise control of gene expression in a cell-state-specific manner is essential for effective therapeutic interventions in complex and dynamic disease microenvironments. Traditional targeting strategies that rely on surface markers or cell type-specific promoters often assume static cellular identities, limiting effectiveness in contexts such as cancer and inflammation, where cell states are highly heterogeneous and dynamic. RNA sensors, such as RADAR (RNA sensing using Adenosine Deaminases Acting on RNA), provide a modular, programmable, and non-integrating platform for classifying cell states. However, it is also characterized by low sensitivity and dynamic range, which limits its applications in detecting low-abundance transcripts. In this work, we integrate RADAR sensors with a signal amplification circuit to enhance sensitivity and dynamic range. We demonstrate that this combined RADAR-amplifier platform enables real-time monitoring of subtle changes in the abundance of endogenous transcripts under physiological conditions. Our results demonstrate the utility of this platform for fundamental biological studies and the development of precision therapeutic strategies.

  PublisherOA PDFDOI

• A Computational Modeling Approach for the Design of Genetic Control Systems that Respond to Transcriptional Activity

  Methods in molecular biology · 2024-01-01

  articleSenior authorCorresponding
  PublisherDOI

Recent grants

• A platform for targeted, post-translational control of protein levels in mammalian cells

  NSF · $773k · 2016–2020

• EAGER: Engineering Molecular Sensors Of Endoplasmic Reticulum-Associated Degradation (ERAD)

  NSF · $100k · 2011–2013

• CAREER: Engineering cellular clearance pathways using nanoparticles

  NSF · $400k · 2013–2018

• Engineering nanoparticles and nanostructures with precise and tunable modalities of interaction with the autophagy-lysosome system

  NSF · $342k · 2018–2022

• Understanding the impact of engineered nanoparticles on the lysosome-autophagy system

  NSF · $305k · 2013–2017

Frequent coauthors

• Marco Sardiello

  12 shared

• Renaud Legouis

  Université Paris-Saclay

  9 shared

• William K.K. Wu

  9 shared

• Matias Simons

  Heidelberg University

  9 shared

• Frank Lafont

  9 shared

• Parisa Lotfi

  Danbury Hospital

  9 shared

• Baharia Mograbi

  9 shared

• Hervé Le Stunff

  Centre National de la Recherche Scientifique

  9 shared

Labs

• Segatori LabPI

Education

• Postdoc

  Scripps Research Institute

  2007

• PhD, Chemical Engineering

  University of Texas at Austin

  2005

Awards & honors

• Hamill Innovation Awards (2009, 2011, 2013, 2014, 2015, 2017…
• NSF CAREER Award (2013)
• Medical Innovation Award (2010) from Rice’s Institute of Bio…