About

Pedro Cabrales, Ph.D, is a Professor of Bioengineering and the Principal Investigator of the Cabrales Lab. His research focuses on various aspects of biological and biomedical engineering, including atmospheric ligands in biology, blood substitutes, cardiovascular function, microvascular hydrodynamics, and related fields. The lab's work involves exploring complex biological systems and developing innovative solutions in biomedical engineering, with a particular emphasis on understanding microvascular dynamics and blood-related therapies. Dr. Cabrales's expertise and leadership drive the lab's contributions to advancing knowledge in these areas, fostering collaborations with visiting scholars, postdoctoral researchers, graduate students, and undergraduate students.

Research topics

• Medicine
• Chemistry
• Biology
• Pharmacology
• Biomedical engineering
• Cancer research
• Computational biology
• Biochemistry
• Cell biology

Selected publications

• Sex determines cardiac and renal Vulnerability to chronic hemoglobin toxicity

  Biomedicine & Pharmacotherapy · 2026-04-27

  articleOpen accessSenior author

  Hemolytic anemias are characterized by chronic intravascular hemolysis, leading to sustained release of acellular hemoglobin (Hb). Circulating Hb scavenges nitric oxide, releases redox-active heme, and promotes oxidative and inflammatory injury, contributing to progressive cardiac and renal dysfunction. Despite the known cardiopulmonary and renal complications in hemolytic disorders, the direct mechanisms of Hb-mediated injury and the influence of sex as a biological variable remain partially understood. In this study, we investigated the effects of chronic Hb exposure on cardiac and renal function in male and female mice. Animals received daily intraperitoneal injections of acellular Hb (320 mg/kg) for six weeks. Cardiac function was evaluated by echocardiography, renal function by transdermal glomerular filtration rate, and tissue injury biomarkers were quantified by ELISA. Mitochondrial respiratory function was also assessed in cardiac and renal tissues. Chronic Hb exposure induced significant cardiac dysfunction and renal impairment in male mice, evidenced by reduced ejection fraction, decreased stroke volume, diminished glomerular filtration rate, and elevated injury biomarkers. In contrast, female mice showed less impairment of cardiac and renal function and exhibited lower levels of biomarkers. Mitochondrial respiration revealed marked reductions in bioenergetics in males, whereas females maintained superior mitochondrial bioenergetics in both organs. These findings identify mitochondrial dysfunction as a mechanistic link between chronic Hb exposure and multi-organ injury and demonstrate sex-dependent bioenergetic adaptability as a key determinant of disease severity. Collectively, this work underscores the importance of incorporating sex as a biological variable and supports the development of Hb-neutralizing therapeutic strategies to mitigate Hb-induced organ damage.

  PublisherDOI

• Intermittent Hypoxia Associated with Sleep Apnea Disrupts Microvascular Hemodynamics and Oxygen Delivery

  Communications Biology · 2026-04-11

  articleOpen accessSenior authorCorresponding

  Obstructive sleep apnea (OSA) is characterized by recurrent episodes of intermittent hypoxia (IH). In this study, we investigated how cyclic IH (21%/10% O₂) acutely alters systemic hemodynamics and microvascular vascular tone, hemodynamics, and oxygen transport compared to the control (21%/21% O₂). Using a dorsal window chamber model on unanesthetized Golden Syrian hamsters, we applied 30-second oxygen cycling for 60 minutes. Microvascular oxygen saturation was continuously monitored using hyperspectral imaging (HSI), and vessel diameter, red blood cell velocity, functional capillary density (FCD), and vascular resistance were quantified through intravital microscopy. Animals exposed to IH exhibited significant reductions in mean arterial pressure and arterial oxygen saturation, along with increased heart rate and blood lactate. Microvascular SO₂ declined rapidly in the microcirculation and stabilized after 8 mins. Arteriolar blood flow decreased, and FCD was significantly reduced relative to both baseline and control. Despite a decrease in vascular resistance, vasodilatory compensation was insufficient and resulted in decreased oxygen delivery (DO₂) and oxygen extraction (VO₂) to tissues. The oxygen extraction ratio increased, suggesting a limited capacity to offset hypoxic stress. These findings demonstrate that cyclic IH significantly disrupts peripheral microcirculatory flow and oxygenation, highlighting the relevance of IH models in assessing oxygen transport during OSA.

  PublisherOA PDFDOI

• Tunable Regional Targeting of Self‐Assembling Peptide Nanomaterials in Acute Myocardial Infarction

  Advanced NanoBiomed Research · 2026-04-28

  articleOpen access

  Acute myocardial infarction (AMI) causes cardiac tissue damage and creates a transient leaky vasculature, which is an attractive target for intravascular therapeutics. Nanomaterials have the potential to deliver therapeutics to the injured heart, yet the influence of particle size, shape, and surface decoration on infarct localization has not been systematically examined. Here, we evaluated a self‐assembling peptide platform that can be tuned to form high aspect ratio nanofibers or globular nanoparticles by modifying the β sheet forming domain. This platform has tunable nanofiber length distribution via sonication and aging as well as surface decoration via targeting peptides. In a rat model of AMI, the incorporation of a type IV collagen targeting peptides significantly increased localization of the nanofibers to the injured leaky vasculature while globular peptides diffuse through and targeted the infarcted myocardium. These results demonstrate that this modular peptide nanomaterial can be tuned via geometry and surface moieties to either target to the compromised vasculature components or infiltrate the infarct. This study establishes size, shape, and surface decoration as critical features for effective intravascular nanomaterial delivery after AMI.

  PublisherDOI

• Hemoglobin binders reduce inflammation and tissue injury from hemolysis in venovenous extracorporeal circulation

  Blood Advances · 2026-01-23

  articleOpen accessSenior author

  ABSTRACT: This study investigated the pathophysiological effects of cell-free hemoglobin (Hb) generated by mechanical hemolysis during venovenous extracorporeal circulation (VVECC). We hypothesized that Hb scavenger protein constructs that bind Hb, heme, and iron could attenuate end-organ injury caused by intravascular hemolysis during VVECC. Scavenger constructs consisted of an apohemoglobin-haptoglobin (apoHb-Hp) complex designed to bind Hb and heme, as well as a separate preparation of haptoglobin, albumin, hemopexin, and transferrin, termed the protein cocktail. To test the hypothesis, Golden Syrian hamsters were instrumented with dorsal window chambers and catheters, and VVECC was maintained for a total of 2 hours, with a maximum flow rate equivalent to 50% of the animal's cardiac output. VVECC circuits were primed with either 2 binding materials, apoHb-Hp and the protein cocktail, or a control solution of 5% human serum albumin (HSA). Microvascular Hb oxygen saturation in arterioles (saO2) and venules (svO2) were studied. All groups displayed a significant decrease in saO2 and svO2 at maximum VVECC when compared with baseline, whereas statistically significant changes between treatment groups showed no consistent trend. The protein cocktail bound 24% of cell-free Hb, whereas the apoHb-Hp bound 66% of cell-free Hb. In addition, markers of renal damage and inflammation, such as plasma creatinine, urinary NGAL (neutrophil gelatinase-associated lipocalin), 4-HNE (4-hydroxynonenal), and KIM-1 (kidney injury molecule 1), were significantly reduced in both Hb scavenger groups compared with those in the HSA control group. Results from this study suggest that Hb, heme, and iron scavenging solutions used to prime VVECC circuits support organ function.

  PublisherDOI

• Apohemoglobin-haptoglobin complex is a therapeutic against vaso-occlusive crisis: scavenging of hemoglobin and heme

  Blood Advances · 2026-01-21

  articleOpen accessSenior author

  ABSTRACT: Sickle cell disease (SCD) leads to vaso-occlusive episodes (VOEs) releasing cell-free hemoglobin (Hb) and heme that drive oxidative stress, inflammation, and microvascular dysfunction. Current treatments for VOEs remain limited with no targeted therapies addressing these hemolytic byproducts. This study investigated the potential of an apohemoglobin-haptoglobin (ApoHb-Hp) complex (protein scavenger of both Hb and heme) vs Hp (scavenger of only Hb), in transgenic SCD mice exposed to hypoxia-reoxygenation. Briefly, HbSS-Townes mice instrumented with a dorsal skinfold window chamber received ApoHb-Hp (150 mg/kg), Hp alone (150 mg/kg), or an equal volume of saline vehicle, and groups were compared with HbAA controls. At the same dose, ApoHb-Hp had reduced Hb-binding capacity compared with Hp alone, but it possessed heme-binding capacity from the associated ApoHb moiety. Despite the reduced Hb-binding capacity, ApoHb-Hp produced significantly greater protective effects than Hp alone. During hypoxia, ApoHb-Hp preserved >90% of baseline arteriolar and venular flow, whereas untreated and Hp-treated mice exhibited >50% reductions. Functional capillary density at 72 hours post-hypoxia declined by 80% in untreated mice and 44% in Hp-treated mice, but only 27% in ApoHb-Hp-treated mice. Pulmonary inflammation was significantly lower in ApoHb-Hp-treated mice compared with Hp-treated mice, with reduced numbers of macrophages (15 ± 2 vs 18 ± 3), neutrophils (5 ± 1 vs 7 ± 1), and lymphocytes (18 ± 4 vs 20 ± 3). The increased effectiveness of ApoHb-Hp is due to its unique dual-scavenging mechanism. This addresses both Hb and heme toxicity, which each contribute to the pathophysiology of SCD. These findings indicate that the ApoHb-Hp complex is a promising therapeutic option for SCD.

  PublisherDOI

• Tonicity and colloid osmotic pressure drive microvascular recovery from low volume hypotensive resuscitation from hemorrhagic shock

  Resuscitation Plus · 2026-01-06

  articleOpen accessSenior authorCorresponding

  Hypertonic saline solution containing 7.5% sodium chloride provides rapid intravascular volume expansion during severe hypovolemic shock, reducing the total fluid required to restore perfusion. Unlike traditional large-volume crystalloid resuscitation, which dilutes circulating blood components, Hypertonic saline mobilizes intracellular and interstitial fluids into the vascular space, improving perfusion with minimal infusion volume. This strategy is particularly valuable in military and emergency settings where rapid stabilization and limited fluid availability are critical. In this study, we integrated ex vivo rheological analyses and in vivo microvascular measurements to elucidate the mechanisms underlying low-volume resuscitation with hypertonic saline. In a rheological perspective, using controlled shear flow conditions ranging from 1 to 10,000 s - 1, oscillatory amplitude sweeps (0.002–2.0 pascals at 0.5 hertz), and low-shear aggregation assays, we characterized the interaction of hypertonic saline with common resuscitation fluids, lactated Ringer’s and 5% human serum albumin. Following ex vivo investigation, severe hemorrhagic shock was induced in Golden Syrian hamsters, instrumented with dorsal window chamber to quantify the microhemodynamics, by controlled withdrawal of 50% blood volume, followed by 30 minutes of hypovolemic shock. At the conclusion of the hypovolemia period resuscitation consisted of an initial infusion of hypertonic saline equal to 3.5% of blood volume, followed by either Lactated Ringer’s solution or 5% human serum albumin at 10% of animal’s blood volume. Microhemodynamics were assessed over 60 minutes following resuscitation. Resuscitation with hypertonic saline followed by human serum albumin produced the most favorable microcirculatory outcomes, enhancing arteriolar blood flow and functional capillary density compared to Lactated Ringer’s solution. This combination increased reversible red blood cell aggregation and blood rheological changes which may promote plasma skimming in small arterioles and improved red cell flux in the microcirculation. Although systemic recovery of mean arterial pressure and heart rate was incomplete, blood gas parameters significantly improved, indicating the benefits of effective microvascular reperfusion from severe hypovolemic conditions.

  PublisherDOI

• Acellular Hemoglobin Impairs Cardiomyocyte Excitation-Contraction Coupling

  ASAIO Journal · 2026-03-04

  articleSenior authorCorresponding

  Heart failure is a significant complication of chronic intravascular hemolysis, a condition characterized by red blood cells (RBCs) breakdown, leading to the release of acellular hemoglobin (Hb) and its oxidized form, methemoglobin (MetHb), into the bloodstream. Acellular Hb promotes nitric oxide (NO) scavenging, oxidative stress, inflammation, iron overload, and functional tissue impairment. This study investigates the direct impact of Hb and MetHb on cardiomyocyte function by assessing calcium transients, fractional shortening, and reactive oxygen species (ROS) formation. The study also evaluated the effects of polymerized Hb, NO scavenging, and antioxidant therapy using N-acetylcysteine (NAC) on cardiomyocyte contractility. Our results show that acellular Hb and MetHb impair cardiomyocyte function by prolonging calcium transient half-life, reducing contractility, and increasing ROS production. Polymerization of Hb and antioxidant supplementation offered partial protection but did not fully mitigate these effects. Inhibiting NO synthase did not increase Hb toxicity, indicating that NO scavenging is not the sole toxicity pathway. These findings demonstrate that Hb-induced cardiomyocyte dysfunction involves a multifactorial mechanism, including NO scavenging, oxidative stress, and disrupted calcium dynamics. Although Hb polymerization and antioxidants offer limited protection, novel multi-target strategies are essential to address Hb toxicity in hemolytic disorders and the use of Hb-based oxygen carriers.

  PublisherDOI

• Modulatory effects of exogenous estradiol during endotoxemia

  The International Journal of Biochemistry & Cell Biology · 2026-02-20

  articleSenior author
  PublisherDOI

• Transferrin Purification, Biophysical Characterization, and Lung Biodistribution in Sickle Cell Disease Mice

  Biotechnology and Bioengineering · 2025-06-30 · 3 citations

  articleOpen access

  Plasma transferrin (Tf) is the transport protein central to the process of iron recycling and metabolism. Holo-Tf serves as the body's pool of ferric iron, facilitating transport from tissues such as the intestine, liver, spleen, and finally bone marrow, where iron is incorporated into erythropoiesis. In sickle cell disease (SCD), iron overload is primarily caused by chronic blood transfusions in patients at risk of stroke or frequent acute pain crisis. However, we have identified that pulmonary vascular iron accumulation, independent of transfusion, is a driver of pulmonary hypertension in SCD patients and murine models. Therefore, we hypothesize that intra-pulmonary administration of apo-Tf localizes the protein to sites of iron accumulation within the lung, where reactive iron-driven pathology develops. This approach to therapeutic development focuses on optimizing administration using aerosol drug delivery, which can increase clinical compliance compared to subcutaneous or intravenous administration. The goal of this study was to purify apo-Tf using a novel process, perform biochemical characterization on the material, and test the proof of concept that apo-Tf protein can be delivered to lung regions where iron accumulation occurs in SCD pulmonary hypertension. We conclude that apo-Tf can be isolated from plasma Cohn fraction IV paste using a simple process and that characterization of the material identified a high-purity apo-Tf product with functional iron binding properties. Further, this material was administered to SCD mice to target pulmonary anatomical regions where pathology occurs. This data suggests an intriguing approach to iron chelation applicable to a relevant clinical population.

  PublisherOA PDFDOI

• Biophysical and Biochemical Characterization of High Molecular Weight Co-Polymerized Human Hemoglobin and Albumin as a Potential Hemoglobin-Based Oxygen Carrier

  ACS Biomaterials Science & Engineering · 2025-12-02 · 1 citations

  article

  Human hemoglobin (hHb) in the tense (T) quaternary state was copolymerized with human serum albumin (HSA) at various hHb:HSA mass fractions to form polymerized hHb-HSA Poly(hHb:HSA) conjugates as a potential next-generation hemoglobin-based oxygen carrier (HBOC). These conjugates were evaluated for molecular weight (MW), hydrodynamic size, oxygen transport characteristics, heme and oxidative stability, as well as hemorheological and colloid osmotic pressure (COP) properties. Among the variants, Poly(hHb75:HSA25) achieved a high MW (2024 ± 262 kDa), hydrodynamic diameter (29.6 ± 2.3 nm), yield (39 ± 1%), and batch mass (11.8 ± 0.2 g), closely matching PolyhHb100. In comparison, Poly(hHb50:HSA50) exhibited a lower MW (875 ± 84 kDa) and diameter (21.5 ± 1.9 nm), with a reduced yield (26 ± 4%) and batch mass (7.7 ± 1.3 g). Both formulations demonstrated rapid oxygen offloading (63.1 ± 0.5 and 59.0 ± 1.4 s–1) and low oxygen affinity (P50 = 49.04 ± 0.95 and 41.79 ± 0.81 mmHg), indicating effective oxygen delivery under moderate oxygen tensions. Although polymerization modestly elevated the auto-oxidation rate compared to the precursor hHb, the oxidative stability remained comparable between Poly(hHb75:HSA25) and Poly(hHb50:HSA50), suggesting that HSA incorporation does not significantly impact the rate of auto-oxidation. Both Poly(hHb75:HSA25) and Poly(hHb50:HSA50) reduced haptoglobin binding (0.005 and 0.004 μM–1 s–1) and heme release rates, reflecting enhanced heme retention and reduced oxidative risk. Both Poly(hHb75:HSA25) and Poly(hHb50:HSA50) exhibited similar zeta potentials (−23.2 ± 1.3 mV and −27.0 ± 1.7 mV respectively). Structural analyses confirmed the preserved α-helical content, thermal stability (69.5–70.9 °C), and retained intrinsic catalase activity of the two variants. Hemorheological and COP analyses further revealed that both Poly(hHb75:HSA25) and Poly(hHb50:HSA50) exhibited low COP, were hyperviscous solutions with shear-thinning behavior, and exhibited reversible red blood cell (RBC) aggregation at low shear rates. Therefore, both T-state Poly(hHb75:HSA25) and Poly(hHb50:HSA50) offer an optimal balance of oxygen delivery, oxidative resilience, manufacturability, shear-thinning behavior, making them strong candidates for further HBOC development.

  PublisherDOI

Recent grants

• PEGylated megahemoglobin for use as a red blood cell substitute

  NIH · $2.9M · 2017–2023

• NIH Grant R56HL123015

  NIH · $400k · 2017

• Bioengineering a Dual Function Protein Construct to Detoxify Heme and Hemoglobin

  NIH · $2.6M · 2021–2026

• Attenuating the Oxidative and Myocardial Side-Effects of Acellular Hemoglobin

  NIH · $1.7M · 2016–2021

• NIH Grant R01HL052684

  NIH · $4.5M · 2014

Frequent coauthors

• Marcos Intaglietta

  University of California, San Diego

  221 shared

• Amy G. Tsai

  205 shared

• Cynthia R. Muller

  99 shared

• Andre F. Palmer

  The Ohio State University

  99 shared

• Carlos Muñoz

  University of California, San Diego

  82 shared

• Alexander T. Williams

  University of California, San Diego

  78 shared

• Bryan Oronsky

  64 shared

• Krianthan Govender

  University of California, San Diego

  51 shared

Labs

• Cabrales LabPI