Julie Reisz Haines

Julie Reisz Haines
University of Colorado | UCD

Ph.D.

About

180
Publications
24,055
Reads
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4,657
Citations
Citations since 2016
161 Research Items
4351 Citations
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201620172018201920202021202202004006008001,0001,200
201620172018201920202021202202004006008001,0001,200
Additional affiliations
January 2017 - January 2017
University of Colorado
Position
  • Research Assistant Professor | Biological Mass Spectrometry Core
July 2015 - present
University of Colorado
Position
  • Research Associate | Biological Mass Spectrometry Core
August 2014 - June 2015
Wake Forest University
Position
  • Research Assistant Professor

Publications

Publications (180)
Article
Full-text available
Glioblastoma (GBM) is the most common and aggressive primary brain tumor, but the mechanisms underlying tumor growth and progression remain unclear. The protein arginine methyltransferases (PRMTs) regulate a variety of biological processes, however, their roles in GBM growth and progression are not fully understood. In this study, our functional an...
Article
Mitochondrial Ca²⁺ uptake, mediated by the mitochondrial Ca²⁺ uniporter, regulates oxidative phosphorylation, apoptosis, and intracellular Ca²⁺ signaling. Previous studies suggest that non-neuronal uniporters are exclusively regulated by a MICU1-MICU2 heterodimer. Here, we show that skeletal-muscle and kidney uniporters also complex with a MICU1-MI...
Article
Full-text available
Pulmonary arterial hypertension is an incurable disease marked by dysregulated metabolism, both at the cellular level in the pulmonary vasculature, and at the whole-body level characterized by impaired exercise oxygen consumption. Though both altered pulmonary vascular metabolism and abnormal exercise physiology are key markers of disease severity...
Article
Acute myeloid leukemia (AML) is a hematologic malignancy metabolically dependent on oxidative phosphorylation and mitochondrial electron transport chain (ETC) activity. AML cells are distinct from their normal hematopoietic counterparts by this metabolic reprogramming, which presents targets for new selective therapies. Here, metabolic changes in A...
Article
Full-text available
The non-psychoactive cannabinoid, cannabidiol (CBD), is FDA-approved for treatment of two drug-resistant epileptic disorders, and is seeing increased use among the general public, yet the mechanisms that underlie its therapeutic effects and side-effect profiles remain unclear. Here, we report a systems-level analysis of CBD action in human cell lin...
Article
Background: We compared plasma metabolites of amino acid oxidation and the tricarboxylic acid (TCA) cycle in youth with and without type 1 diabetes mellitus (T1DM) and related the metabolites to glomerular filtration rate (GFR), renal plasma flow (RPF), and albuminuria. Metabolites associated with impaired kidney function may warrant future study...
Article
Background: Age-related declines in cardiorespiratory fitness (CRF) and exercise tolerance are major independent risk factors for cardiovascular diseases and mortality in midlife/older adults (ML/O; ≥50 years). Aerobic exercise is a well-established strategy to improve CRF and exercise tolerance; however, adherence to time-intensive physical activ...
Article
BACKGROUND Acute myeloid leukemia (AML) is a hematopoietic malignancy that results from the accumulation of undifferentiated myeloid cells in the peripheral blood and bone marrow. Limited therapeutics contribute to unfavourable patient outcomes, highlighting the need for novel therapeutics to improve prognosis. We previously demonstrated that shiko...
Article
Additive solutions are used to limit changes that red blood cells (RBCs) undergo during storage. Several studies have shown better preservation of glucose and redox metabolism using the alkaline additive solution PAGGGM (phosphate-adenine-glucose-guanosine-gluconate-mannitol). In this randomized open label intervention trial in 20 healthy volunteer...
Article
Full-text available
Significance The interferon (IFN) family of proteins plays key roles in the immune response against viruses and other pathogens. In the context of COVID-19, IFNs have been shown to be key for restraining SARS-CoV-2 infection but have also been described as drivers of severe symptoms. However, it is not fully understood how each member of the IFN fa...
Article
Full-text available
Phagocytosis of apoptotic cells, termed efferocytosis, is critical for tissue homeostasis and drives anti-inflammatory programming in engulfing macrophages. Here, we assess metabolites in naive and inflammatory macrophages following engulfment of multiple cellular and non-cellular targets. Efferocytosis leads to increases in the arginine-derived po...
Article
Full-text available
Aging and obesity independently contribute toward an endothelial dysfunction that results in an imbalanced VWF to ADAMTS13 ratio. In addition, plasma thrombin and plasmin generation are elevated and reduced, respectively, with increasing age and also with increasing body mass index (BMI). The severity risk of Corona Virus Disease 2019 (COVID-19) in...
Article
Introduction: 15-Lipoxygenase (15-LO) is a non-heme iron-containing dioxygenase that has both pro- and anti-inflammatory roles in many tissues and disease states. 15-LO is thought to influence macrophage phenotype; and silencing 15-LO reduces fibrosis after acute inflammatory triggers. The goal of this study was to determine if altering 15-LO expr...
Article
Dendritic cell (DC) activation is characterized by sustained commitment to glycolysis that is a requirement for survival in DC subsets that express inducible NO synthase (Nos2) due to NO-mediated inhibition of mitochondrial respiration. This phenomenon primarily has been studied in DCs from the classic laboratory inbred mouse strain C57BL/6J (B6) m...
Article
Acute myeloid leukemia (AML) is a hematological malignancy, characterized by an increased reliance on mitochondria-related energetic pathways including oxidative phosphorylation (OXPHOS). Consistent with this, the electron transport chain (ETC), a component of OXPHOS has been demonstrated to be a suitable anti-leukemia target, with ETC complex I in...
Article
Bone marrow resident and rarely dividing hematopoietic stem cells (HSC) harbor an extensive self-renewal capacity to sustain life-long blood formation, albeit their function declines during ageing. Various molecular mechanisms confer stem cell identity, ensure long-term maintenance and are known to be deregulated in aged stem cells. How these progr...
Article
Acute myeloid leukemia (AML) in adults has a 5-year survival of approximately 30% and a high rate of disease recurrence in part due to our inability to eliminate the disease-initiating leukemic stem cells (LSCs) (Shlush et al. Nature, 2017). Previous studies have shown that LSCs uniquely rely on oxidative phosphorylation (OXPHOS) for survival (Laga...
Article
Full-text available
Glycolysis controls cellular energy, redox balance, and biosynthesis. Antiglycolytic therapies are under investigation for treatment of obesity, cancer, aging, autoimmunity, and microbial diseases. Interrupting glycolysis is highly valued as a therapeutic strategy, because glycolytic disruption is generally tolerated in mammals. Unfortunately, anem...
Article
Full-text available
The Corona Virus Disease 2019 (COVID-19) pandemic represents an ongoing worldwide challenge. The present large study sought to understand independent and overlapping metabolic features of samples from acutely ill patients (n = 831) that tested positive (n = 543) or negative (n = 288) for COVID-19. High-throughput metabolomics analyses were compleme...
Preprint
Full-text available
Bone marrow resident and rarely dividing haematopoietic stem cells (HSC) harbour an extensive self-renewal capacity to sustain life-long blood formation; albeit their function declines during ageing. Various molecular mechanisms confer stem cell identity, ensure long-term maintenance and are known to be deregulated in aged stem cells. How these pro...
Preprint
Full-text available
The impacts of IFN signaling on COVID19 pathology are multiple, with protective and harmful effects being documented. We report here a multi-omics investigation of IFN signaling in hospitalized COVID19 patients, defining the biosignatures associated with varying levels of 12 different IFN ligands. Previously we showed that seroconversion associates...
Conference Paper
Standard of care for AML includes chemotherapy and stem cell transplant, with 5-year survival rates <30%. We sought to identify genes critical to AML cells, irrespective of mutational status, and performed an shRNA screen targeting 1,287 genes on 12 AML patient samples. This screen identified Sirtuin 5 (SIRT5) as a top candidate. SIRT5 is the only...
Article
Background & aims: Chronically administered parenteral nutrition (PN) in patients with intestinal failure carries the risk for developing PN associated cholestasis (PNAC). We have demonstrated that FXR and LXR, proinflammatory IL-1β and infused phytosterols are important in murine PNAC pathogenesis. In this study we examined the role of nuclear re...
Article
Full-text available
Background High‐resistance inspiratory muscle strength training (IMST) is a novel, time‐efficient physical training modality. Methods and Results We performed a double‐blind, randomized, sham‐controlled trial to investigate whether 6 weeks of IMST (30 breaths/day, 6 days/week) improves blood pressure, endothelial function, and arterial stiffness i...
Article
Full-text available
Hypoxia drives aging and promotes age-related cognition and hearing functional decline. Despite the role of erythrocytes in oxygen (O 2 ) transport, their role in the onset of aging and age-related cognitive decline and hearing loss (HL) remains undetermined. Recent studies revealed that signaling through the erythrocyte adenosine A2B receptor (ADO...
Article
Full-text available
Human peroxiredoxins (Prx) are a family of antioxidant enzymes involved in a myriad of cellular functions and diseases. During the reaction with peroxides (e.g., H2O2), the typical 2-Cys Prxs change oligomeric structure between higher order (do)decamers and disulfide-linked dimers, with the hyperoxidized inactive state (-SO2H) favoring the multimer...
Article
Down syndrome (DS) is the most common genetic cause of intellectual disability. Mechanistically, oxidative stress and mitochondrial dysfunction are reported to be etiological factors for many of the DS-related comorbidities and have previously been reported in a number of in vitro and in vivo models of DS. The purpose of this study was to test for...
Article
Cancer is one of the most common age-related diseases, and over one-third of cancer patients will receive chemotherapy. One frequently reported side effect of chemotherapeutic agents like doxorubicin (Doxo) is impaired cognitive function, commonly known as “chemotherapy-induced cognitive impairment (CICI)”, which may mimic accelerated brain aging....
Article
Our study details the stepwise evolution of gilteritinib resistance in FLT3-mutated acute myeloid leukemia (AML). Early resistance is mediated by the bone marrow microenvironment, which protects residual leukemia cells. Over time, leukemia cells evolve intrinsic mechanisms of resistance, or late resistance. We mechanistically define both early and...
Article
Acute kidney injury (AKI) is a complex disease associated with increased mortality that may be due to deleterious distant organ effects. AKI associated with respiratory complications, in particular, has a poor outcome. In murine models, AKI is characterized by increased circulating cytokines, lung chemokine upregulation, and neutrophilic infiltrati...
Article
Glycolysis is a well‐known process by which metabolically active cells, such as tumor or immune cells meet their high metabolic demands. Previously, our laboratory has demonstrated that in airway epithelial cells, the pleiotropic cytokine, interleukin‐1 beta (IL1B) induces glycolysis and that this contributes to allergic airway inflammation and rem...
Preprint
Full-text available
The Corona Virus Disease 2019 (COVID-19) pandemic represents an ongoing worldwide challenge. Exploratory studies evaluating the impact of COVID-19 infection on the plasma metabolome have been performed, often with small numbers of patients, and with or without relevant control data; however, determining the impact of biological and clinical variabl...
Article
We discovered that the survival and growth of many primary acute myeloid leukemia (AML) samples and cell lines, but not normal CD34⁺ cells, are dependent on SIRT5, a lysine deacylase implicated in regulating multiple metabolic pathways. Dependence on SIRT5 is genotype agnostic and extends to RAS- and p53-mutated AML. Results were comparable between...
Article
Background During storage, red blood cells (RBCs) undergo significant biochemical and morphologic changes, referred to collectively as the “storage lesion”. It was hypothesized that these defects may arise from disrupted oxygen‐based regulation of RBC energy metabolism, with resultant depowering of intrinsic antioxidant systems. Study Design and M...
Article
Full-text available
The recruitment and subsequent polarization of inflammatory monocytes/macrophages in the perivascular regions of pulmonary arteries is a key feature of pulmonary hypertension (PH). However, the mechanisms driving macrophage polarization within the adventitial microenvironment during PH progression remain unclear. We previously established that reci...
Article
Full-text available
Pancreatic cancer is the seventh leading cause of cancer-related death worldwide, with a 5 year survival rate as low as 9%. One factor complicating the management of pancreatic cancer is the lack of reliable tools for early diagnosis. While up to 50% of the adult population has been shown to develop precancerous pancreatic cysts, limited and insuff...
Preprint
Full-text available
COVID-19 pathology involves dysregulation of diverse molecular, cellular, and physiological processes. In order to expedite integrated and collaborative COVID-19 research, we completed multi-omics analysis of hospitalized COVID-19 patients including matched analysis of the whole blood transcriptome, plasma proteomics with two complementary platform...
Article
Full-text available
The activation of mostly quiescent haematopoietic stem cells (HSCs) is a prerequisite for life-long production of blood cells¹. This process requires major molecular adaptations to allow HSCs to meet the regulatory and metabolic requirements for cell division2–4. The mechanisms that govern cellular reprograming upon stem-cell activation, and the su...
Article
To determine the efficacy of inorganic nitrite supplementation on endothelial function in humans and mechanisms of action, we performed (1) a randomized, placebo-controlled, parallel-group clinical trial with sodium nitrite (80 mg/day, 12 weeks) in older adults (N=49, 68±1 year) and (2) reverse-translation experiments in young (6 months) and old (2...
Article
Full-text available
Intestinal microbial dysbiosis, intestinal inflammation, and Th17 immunity are all linked to the pathophysiology of spondyloarthritis (SpA); however, the mechanisms linking them remain unknown. One potential hypothesis suggests that the dysbiotic gut microbiome as a whole produces metabolites that influence human immune cells. To identify potential...
Article
In acute myeloid leukemia (AML), activating mutations in FLT3 are the most common genetic abnormality. Multiple FLT3 inhibitors have been developed, including the FDA-approved inhibitor gilteritinib. However, AML patients only respond to gilteritinib for approximately 6 months due to the emergence of drug resistance. While gilteritinib eliminates b...
Article
Full-text available
The lipogenic enzyme stearoyl CoA desaturase (SCD) plays a key role in tumor lipid metabolism and membrane architecture. SCD is often up-regulated and a therapeutic target in cancer. Here, we report the unexpected finding that median expression of SCD is low in glioblastoma relative to normal brain due to hypermethylation and unintentional monoalle...
Article
Full-text available
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a powerful platform for biomedical research. However, they are immature, which is a barrier to modeling adult-onset cardiovascular disease. Here, we sought to develop a simple method that could drive cultured hiPSC-CMs toward maturity across a number of phenotypes, with the...
Article
Full-text available
Omega 3 polyunsaturated fatty acids (PUFAs) influence metabolism and thermogenesis in non-hibernators. How omega 3 PUFAs influence Arctic Ground Squirrels (AGS) during hibernation is unknown. Prior to hibernation we fed AGS chow composed of an omega 6:3 ratio approximately 1:1 (high in omega 3 PUFA, termed Balanced Diet), or an omega 6:3 ratio of 5...
Article
The dithiocarbamate fungicide maneb (MB) has attracted interest due to increasing concern of the negative health effects of pesticides, as well as its association with Parkinson's disease (PD). Our laboratory has previously reported distinct phenotypic changes of neuroblastoma cells exposed to acute, sub-toxic levels of MB, including decreased mito...
Article
Severe congenital neutropenia type 4 (SCN-4) is an autosomal recessive condition in which mutations in the G6PC3 gene encoding for the catalytic 3 subunit of glucose-6-phosphatase-β result in neutropenia, neutrophil dysfunction, and other syndromic features. We report a child with SCN-4 caused by compound heterozygous mutations in G6PC3, a previous...
Article
Full-text available
BACKGROUND Diffuse intrinsic pontine glioma (DIPG) and diffuse midline glioma (DMG) are metastatic diseases, as demonstrated by early convection-enhanced delivery (CED) clinical trials in which prolonged local tumor control can sometimes be achieved, but fatal disseminated disease then develops. We hypothesize that improvements in treatment of both...
Article
Full-text available
Hibernation is a state of extraordinary metabolic plasticity. The pathways of amino acid metabolism as they relate to nitrogen homeostasis in hibernating mammals in vivo are unknown. Here we show, using pulse isotopic tracing, evidence of increased myofibrillar (skeletal muscle) protein breakdown and suppressed whole-body production of metabolites...
Article
Objectives: Identify the metabolites that are increased in the plasma of severely injured patients that developed ARDS versus severely injured patients that did not, and assay if these increased metabolites prime PMNs and induce pulmonary sequestration in an animal model of ARDS. We hypothesize that metabolic derangement due to advanced shock in c...
Article
Fatty acid desaturation is an enzymatic reaction in which a double bond is introduced into an acyl chain. Of the four functionally distinct desaturase subfamilies, the First Desaturase Family of enzymes introduce the first double bond into a saturated fatty acid, resulting in the synthesis of monounsaturated fatty acids (MUFA). MUFA are essential c...
Article
Activating mutations in the tyrosine kinase receptor FLT3 are observed in ~35% of all acute myeloid leukemia (AML) cases. Multiple FLT3 inhibitors are currently in clinical development and while most patients initially respond well to FLT3 inhibition, resistance inevitably develops in a period of months. During the initial response to FLT3 inhibito...
Preprint
Pancreatic cancer is the seventh leading cause of cancer-related death worldwide, with a 5-year survival rate as low as 9%. One factor complicating the management of pancreatic cancer is the lack of reliable tools for early diagnosis. While up to 50% of the adult population has been shown to develop precancerous pancreatic cysts, limited and insuff...
Preprint
Full-text available
Glycolysis controls cellular energy, redox balance, and biosynthesis. Antiglycolytic therapies are being investigated for obesity, cancer, aging, autoimmunity, and microbial diseases. Interrupting glycolysis is highly valued as a therapeutic strategy, because glycolytic disruption is generally tolerated in mammals. Unfortunately, anemia is a key do...
Article
Full-text available
Background and aims: As the incidence of nonalcoholic steatohepatitis (NASH) continues to rise, understanding how normal liver functions are affected during disease is required before developing novel therapeutics which could reduce morbidity and mortality. However, very little is understood about how the transport of proteins and cells from the l...
Article
Full-text available
Background Doxorubicin (DOXO) chemotherapy increases risk for cardiovascular disease in part by inducing endothelial dysfunction in conduit arteries. However, the mechanisms mediating DOXO-associated endothelial dysfunction in (intact) arteries and treatment strategies are not established. Objectives We tested the hypothesis that DOXO impairs endo...
Article
We previously demonstrated that leukemia stem cells (LSCs) in de novo acute myeloid leukemia (AML) patients are selectively reliant on amino acid metabolism and that treatment with the combination of venetoclax and azacitidine (ven/aza) inhibits amino acid metabolism, leading to cell death. In contrast, ven/aza fails to eradicate LSCs in relapsed/r...
Article
BACKGROUND Reprogramming of host metabolism supports viral pathogenesis by fueling viral proliferation, by providing, for example, free amino acids and fatty acids as building blocks.METHODS To investigate metabolic effects of SARS-CoV-2 infection, we evaluated serum metabolites of patients with COVID-19 (n = 33; diagnosed by nucleic acid testing),...
Article
Full-text available
Epidemiological studies suggest that individuals in the Mediterranean region with a loss-of-function, nonsynonymous single nucleotide polymorphism (S188F), in glucose-6-pho