From the first spark of neural development to the challenges of ageing, Dr Lissette Sánchez Aranguren is uncovering how the cell’s powerhouses — mitochondria — hold the key to a healthy brain across the human lifespan.
Her pioneering research at Aston University explores how these microscopic energy generators safeguard the brain’s communication network and how their dysfunction may underlie conditions such as dementia, stroke, and neurodevelopmental disorders.
Mapping the brain’s energy defence system Dr Sánchez Aranguren’s work focuses on the partnership between brain cells and the blood vessels that nourish them — a relationship maintained by the blood–brain barrier. When mitochondria fail, that protective interface can weaken, allowing harmful molecules to penetrate and trigger inflammation or cell loss. Her team’s studies show that mitochondrial malfunction disrupts the dialogue between neurons and vascular cells, an imbalance seen both in the developing and ageing brain.
To counter this, she and her collaborators have engineered a mitochondria-targeted liposome, a nanoscale “bubble” that delivers restorative molecules directly where they are needed most. By re-balancing cellular energy and communication, this innovation could one day reduce brain injury or slow neurodegenerative decline.
From heart cells to the human mind Originally trained in cardiovascular science, Dr Sánchez Aranguren became fascinated by how mitochondria regulate energy and stress in blood-vessel cells — insights that ultimately led her toward neuroscience. View her profile here “Mitochondria do much more than produce energy. They send signals that determine how cells communicate and survive.” That realisation inspired her to trace mitochondrial signalling across the continuum of life — linking early brain development to later-life vulnerability. Her research now bridges traditionally separate fields of developmental biology, vascular physiology, and ageing neuroscience, helping identify shared molecular pathways that influence lifelong brain resilience.
Global collaboration for a healthier brain Her work thrives on multidisciplinary and international partnerships. At Aston, she collaborates with scientists from Coventry University, Queen’s University Belfast, and the University of Lincoln, alongside research partners in the Netherlands, Italy, Malaysia, and China. Together they integrate chemistry, biology, and computational modelling to understand mitochondrial function from molecule to organism — and translate discoveries into practical therapies.
Towards mitochondria-targeted brain therapies The next frontier is refining these mitochondria-targeted nanocarriers to enhance precision and efficacy in preclinical models, while exploring how mitochondrial signals shape the brain’s vascular and neural architecture from infancy through adulthood.
Dr Sánchez Aranguren envisions a future where protecting mitochondrial health becomes central to preventing brain disease, shifting medicine from managing symptoms to preserving the brain’s natural defence and repair systems.
“If we can protect the cell’s own energy engines,” she says, “we can give the brain its best chance to stay healthy for life.”
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Biography
Dr Lissette Sanchez Aranguren joined Aston Medical School in 2020 as Lecturer in Cell Metabolism and Bioenergetics, following a productive Research Fellowship position awarded the 50th Anniversary Aston Prize Fellowship in 2018 at Aston Medical School.
Lissette's research focuses on how blood vessels and the brain work together, specifically looking at the role of mitochondria (the energy producers in cells) in keeping the cells lining blood vessels healthy. Her work aims to understand how problems with these mitochondria might lead to brain diseases from rare genetic disorders, often detected early in life to adverse pathologies like Alzheimer’s or Parkinson’s which often develop later in life.
Her lab has two main goals: first, to figure out how mitochondria problems in blood vessels are connected to brain disorders, and second, to employ small carriers and utilise them to identify new or existing drugs that could improve blood vessel health and, in turn, help treat brain-related conditions.
Areas of Expertise
Cell Bioenergetics
Mitochondrial Function
Nanoformulations
Blood-Brain Barrier
Precision Therapeutics
Accomplishments
Sir Halley Stuart Small Grant Award
2020
BBSRC IAA Award
2023
Education
Universidad de Carabobo
Degree
Biochemistry and Clinical Laboratory Science
2009
Universidad del Valle
PhD
Biomedical Sciences
2017
Aston University
MEd
Education
2023
Affiliations
Higher Education Academy (SFHEA) : Senior Fellow since 2026
Journal of Clinical Bioenergetics (MDPI) : Editorial Board since 2025
Committee Member British Society for Cardiovascular Research, UK
Advancing therapeutics with targeted formulations of hydrogen sulphide donors
European Journal of Pharmaceutical Sciences
2026
Hydrogen sulphide (H2S), is a well described essential physiological molecule that is finely balanced to maintain cellular functions. Considering its important biological roles, H2S has promising therapeutic potential resulting in the development of many H2S donors. Such donors have proved to have therapeutic benefit in cognitive pathways, inflammation, reproduction, and the regulation of blood pressure. However, controlled delivery and targeted administration of this reactive and hazardous gas are necessary yet challenging due to its rapid diffusivity, and toxicity at high doses. Drug delivery systems are vital for the effective administration of many active pharmaceutical excipients, and H2S donors stands to benefit significantly from the tuneable physical, chemical, and pharmacokinetic properties of various formulation systems.
PLGA-Encapsulated Mitochondrial Hydrogen Sulphide Donor, AP39, Resolve Endothelial Inflammation via Mitochondria-Targeted Bioenergetic and Redox Modulation
Clinical Bioenergetics
2026
Vascular inflammation and endothelial dysfunction are key drivers in the development of cardiovascular and neurovascular diseases. Mitochondrial dysfunction and oxidative stress further amplify inflammatory cascades, emphasising the need for targeted strategies that restore endothelial homeostasis at the subcellular level. Hydrogen sulphide (H2S) donors, such as AP39, offer cytoprotective benefits but are limited by short half-life and rapid release of the active compound, H2S. We developed poly(lactic-co-glycolic acid) (PLGA) nanoparticles encapsulating AP39 (PLGA-AP39) to achieve sustained, mitochondria-targeted H2S delivery. Nanoparticles were characterised by size, polydispersity, zeta potential, encapsulation efficiency, and in vitro release kinetics. Human umbilical vein endothelial cells (HUVEC) were exposed to TNF-α to induce inflammation, followed by treatment with free AP39 or PLGA-AP39. Anti-inflammatory effects were assessed by measuring IL-6, IL-8, and TGF-β levels.
Naringenin Loaded Hydrogel Supports Wound Repair in a Cell Model of Diabetic Skin
Pharmaceutical Research
2026
Introduction Diabetic foot ulcers are a major complication of diabetes, driven by inflammation, oxidative stress, and poor vascular function. Naringenin, a citrus flavonoid, addresses these factors but has low solubility and stability. We developed a Na-AMPS hydrogel dressing to enhance its delivery under diabetic-like conditions.
Methods A Na-AMPS hydrogel containing 0.02%(w/w) naringenin was formulated and assessed for rheological and adhesive properties, drug release, and biological activity in HUVEC and HDFa cells. Cytotoxicity (XTT), reactive oxygen species (ROS), mitochondrial membrane potential (TMRM), cytokine levels (IL-6, IL-8, MMP-9, TGF-β), and wound closure (scratch assay) were measured.
Exploring mesoporous silica microparticles in pharmaceutical sciences: Drug delivery and therapeutic insights
International Journal of Pharmaceutics
2025
Nanotechnology has revolutionised pharmaceutical sciences, with mesoporous silica nanoparticles (MSNs) extensively studied as drug carriers. However, their clinical translation is hindered by challenges such as toxicity, tumour accumulation, and uncontrolled endocytosis. Mesoporous silica microparticles (MSMs) have emerged as a safer alternative, offering enhanced drug loading, controlled release, and improved formulation properties. MSMs facilitate protein delivery, solubility enhancement, and bioavailability improvement through pore size modulation, amorphous drug loading, and surface functionalisation. Additionally, they aid in overcoming multi-drug resistance and enable organ-specific targeting using aptamers or magnetic nanoparticles. Beyond drug delivery, MSMs enhance pharmaceutical formulations, with commercial products such as SYLOID®, Aeroperl®, and Neusilin® improving tablet performance and drug stability. Their role in controlled release systems further underscores their pharmaceutical potential. As research advances, MSMs offer promising strategies for precision medicine and optimised drug delivery, reinforcing their potential for future clinical applications.
Novel AP39-Loaded Liposomes Sustain the Release of Hydrogen Sulphide, Enhance Blood-Brain Barrier Permeation, and Abrogate Oxidative Stress-Induced Mitochondrial Dysfunction in Brain Cells
Drug Design, Development and Therapy
2024
Background: Neurodegenerative diseases are often linked to oxidative stress (OS), which worsen neuroinflammation and cause neuronal damage. Managing OS with gasotransmitters such as hydrogen sulphide (H2S) is a promising therapeutic approach to protecting brain cells from oxidative damage. AP39, a mitochondria-targeted H2S donor, has shown neuroprotective potential by reducing OS and improving mitochondrial function. However, its clinical application is limited due to poor stability and rapid release, necessitating a drug delivery system to enhance therapeutic efficacy.
MZe786, a hydrogen sulfide-releasing aspirin prevents preeclampsia in heme oxygenase-1 haplodeficient pregnancy under high soluble flt-1 environment
Redox Biology
2021
Preeclampsia affects one in twelve of the 130 million pregnancies a year. The lack of an effective therapeutic to prevent or treat it is responsible for an annual global cost burden of 100 billion US dollars. Preeclampsia also affects these women later in life as it is a recognised risk factor for cardiovascular disease, stroke and vascular dementia.
Cholesterol and oxysterol sulfates: Pathophysiological roles and analytical challenges
British Journal of Pharmacology
2020
Cholesterol and oxysterol sulfates are important regulators of lipid metabolism, inflammation, cell apoptosis, and cell survival. Among the sulfate-based lipids, cholesterol sulfate (CS) is the most studied lipid both quantitatively and functionally. Despite the importance, very few studies have analysed and linked the actions of oxysterol sulfates to their physiological and pathophysiological roles.
Endothelial dysfunction and preeclampsia: role of oxidative stress
Frontiers in Physiology
2014
Preeclampsia (PE) is an often fatal pathology characterized by hypertension and proteinuria at the 20th week of gestation that affects 5–10% of the pregnancies. The problem is particularly important in developing countries in where the incidence of hypertensive disorders of pregnancy is higher and maternal mortality rates are 20 times higher than those reported in developed countries.
Soluble Fms-Like Tyrosine Kinase-1 Alters Cellular Metabolism and Mitochondrial Bioenergetics in Preeclampsia
Frontiers in Physiology
2018
Preeclampsia is a maternal hypertensive disorder that affects up to 1 out of 12 pregnancies worldwide. It is characterized by proteinuria, endothelial dysfunction, and elevated levels of the soluble form of the vascular endothelial growth factor receptor-1 (VEGFR-1, known as sFlt-1). sFlt-1 effects are mediated in part by decreasing VEGF signaling.
Bioenergetic effects of hydrogen sulfide suppress soluble Flt-1 and soluble endoglin in cystathionine gamma-lyase compromised endothelial cells
Scientific Reports
2020
Endothelial dysfunction is a hallmark of preeclampsia, a life-threatening complication of pregnancy characterised by hypertension and elevated soluble Fms-Like Tyrosine Kinase-1 (sFlt-1). Dysregulation of hydrogen sulfide (H2S) by inhibition of cystathionine γ-lyase (CSE) increases sFlt-1 and soluble endoglin (sEng) release.