David W Killilea

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Verified

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• PhD
• Manager at University of California, San Francisco

Urolithiasis affects around 10% of the US population with an increasing rate of prevalence, recurrence and penetrance. The causes for the formation of most urinary calculi remain poorly understood, but obtaining the chemical composition of these stones might help identify key aspects of this process and new targets for treatment. The majority of ur...

Background: Plasma or serum zinc concentration (PZC or SZC) is the primary measure of zinc status, but accurate sampling requires controlling for hemolysis to prevent leakage of zinc from erythrocytes. It is not established how much hemolysis can occur without changing PZC/SZC concentrations. Objective: This study determines a guideline for the lev...

When consumed as whole grain, wheat has a high nutrient density that contributes to a healthy diet. Yet, products labeled as whole wheat can still contain a substantial amount of refined grain leading to the confusion for consumers, so a method was designed to determine the whole grain status within wheat‐based foods. Wheat germ agglutinin (WGA), a...

Professor Bruce Ames demonstrated that nutritional recommendations should be adjusted in order to ‘tune-up’ metabolism and reduce mitochondria decay, a hallmark of aging and many disease processes. A major subset of tunable nutrients are the minerals, which despite being integral to every aspect of metabolism are often deficient in the typical West...

Zinc deficiency continues to be a major concern for global public health. The zinc status of a target population is typically estimated by measuring circulating zinc levels, but the sampling procedures are not standardized and thus may result in analytical discrepancies. To examine this, we designed a study that controlled most of the technical par...

Objective To determine the urolith trace elemental profile and the association of these elements with urolith type and animal variables. Methods This was a cross-sectional study of 165 goat and 50 pig uroliths collected from urinary bladders from January 1, 1982, through December 31, 2020. Urolith mineral composition was determined using polarized...

Copper is an essential nutrient for sustaining vital cellular processes spanning respiration, metabolism, and proliferation. However, loss of copper homeostasis, particularly misregulation of loosely bound copper ions which are defined as the labile copper pool, occurs in major diseases such as cancer, where tumor growth and metastasis have a heigh...

Circulating mineral concentrations are used to assess nutritional status or as markers for clinical conditions, but the quality of these measurements depends on the methods used for blood processing. Since the procedures for measuring mineral levels in blood are not standardized, discrepancies in sampling may influence the analytical results. We pr...

This study evaluates the effectiveness of the UCSF Summer Student Research Program (SSRP) in enhancing research-related skills, academic outcomes, and post-baccalaureate aspirations of underrepresented minority (URM) and non-URM undergraduate students in biomedical sciences and STEM fields. The SSRP, spanning 9 weeks, provides immersive research ex...

Tissue iron overload is a frequent pathologic finding in multiple disease states including non-alcoholic fatty liver disease (NAFLD), neurodegenerative disorders, cardiomyopathy, diabetes, and some forms of cancer. The role of iron, as a cause or consequence of disease progression and observed phenotypic manifestations, remains controversial. In ad...

Background/aims: Cells adapt to chronic extracellular hypotonicity by altering metabolism. Corresponding effects of sustained hypotonic exposure at the whole-person level remain to be confirmed and characterized in clinical and population-based studies. This analysis aimed to 1) describe changes in urine and serum metabolomic profiles associated w...

Zinc deficiency continues to be a major concern for global public health. The zinc status of a target population is typically estimated by measuring circulating zinc levels, but the sampling procedures are not standardized and thus may result in analytical discrepancies. To examine this, we designed a study that controlled most of the technical par...

Zinc could play a causal role in the etiology of anemia because of its many required functions in iron metabolism and immune health. Zinc deficiency and anemia often coexist, especially in low-income settings, where there are low intakes of iron and zinc, high intakes of phytates, and increased risk of inflammation. Although it is unknown to what d...

Anemia is a continuing global public health concern and a priority for international action. The prevalence of anemia is estimated from the hemoglobin (Hb) levels within target populations, yet the procedures for measuring Hb are not standardized and different approaches may result in discrepancies. Several analytical variables have been proposed t...

Purpose: As patients with transfusion-dependent thalassemia (TDT) are living longer, novel morbidities are being recognized. The purpose of this review is to summarize the current knowledge regarding the prevalence and risk factors of nephrolithiasis in patients with TDT. Methods: A non-systematic, narrative review of the current literature publish...

Anemia is a continuing global public health concern and a priority for international action. The prevalence of anemia is estimated from the hemoglobin (Hb) levels within target populations, yet the procedures for measuring Hb are not standardized and different approaches may result in discrepancies. Several analytical variables have been proposed t...

In 2020, STEM training programs across the country were challenged to provide support to students during a nationwide shutdown of research institutions in response to the COVID-19 pandemic. Five U.S. high school science internship programs funded by the Doris Duke Charitable Foundation, with a history of collaboration, developed innovative strategi...

In the original article, errors were noted and have been listed in this corrigendum. These details have been corrected only in this corrigendum to preserve the published version of record. In the Methods section, for the “Calculations for hemolysis estimates” subsection, the formula G ÷ [(A x B)÷(C x D)] = H has an incorrect operator. The formula...

Background Nutritional deficiencies in children with cancer at time of diagnosis and during treatment may negatively affect disease outcome and increase treatment-related toxicity. Yet zinc, an essential nutrient important for supporting immune function and known for reducing diarrheal episodes, is rarely assessed in these children. Procedures Fif...

Micronutrient deficiencies are a significant public health problem affecting a large portion of the world’s population. Disproportionately affected populations—infants, young children, adolescents and women of reproductive age including pregnant women — are especially susceptible to the health consequences of insufficient micronutrient intakes. How...

Plasma zinc concentrations (PZC) have been shown to significantly increase during zinc supplementation. This study investigated the effects of daily preventive zinc supplementation on hair and nail zinc concentrations compared with a control group. In a randomized controlled trial, 6- to 23-month-old children (n = 3407) in Lao PDR were randomly ass...

In this post, we are highlighting Dr. David Killilea and Dr. Ellen Fung’s experience with transitioning the CHORI Summer Student Research Program amidst the pandemic. The CHORI program is a three month immersive research experience for high school and undergraduate students from diverse backgrounds. In the Zoom interview below, watch both of them r...

Objective: Micronutrient deficiencies are a significant public health. Vulnerable populations —infants, children, adolescents, pregnant and reproductive aged women—are especially susceptible to the health consequences of inadequate nutrition. However, direct assessment of micronutrient deficiencies is not routinely included in population surveys. T...

Pelizaeus-Merzbacher disease (PMD) is an X-linked leukodystrophy caused by mutations in Proteolipid Protein 1 (PLP1), encoding a major myelin protein, resulting in profound developmental delay and early lethality. Previous work showed involvement of unfolded protein response (UPR) and endoplasmic reticulum (ER) stress pathways, but poor PLP1 genoty...

Elevated uric acid (UA) is a key risk factor for many disorders, including metabolic syndrome, gout and kidney stones. Despite frequent occurrence of these disorders, the genetic pathways influencing UA metabolism and the association with disease remain poorly understood. In humans, elevated UA levels resulted from the loss of the of the urate oxid...

Pelizaeus-Merzbacher disease (PMD) is a X-linked leukodystrophy caused by mutations in Proteolipid Protein 1 (PLP1), encoding a major myelin protein, resulting in profound developmental delay and early lethality. Previous work showed involvement of unfolded protein response (UPR) and endoplasmic reticulum (ER) stress pathways, but poor PLP1 genotyp...

Background: Since 2011 Cameroon has mandated the fortification of refined vegetable oil with vitamin A and wheat flour with iron, zinc, folic acid, and vitamin B-12. In 2012, measured fortification levels for flour, and particularly oil, were below target. Objectives: We assessed Cameroon's food fortification program using a program impact pathw...

In the United States, western Washington and the Alaska Interior are two regions where maritime and continental climates, high latitude, and cropping systems necessitate early maturing spring wheat (Triticum aestivum L.). Both regions aim to increase production of hard spring bread wheat for human consumption to support regional agriculture and foo...

Lysosome function is compromised during aging and in many disease states. Interventions that promote lysosomal activity and acidification are thus of prime interest as treatments for longevity and health. Intracellular pH can be controlled by the exchange of protons for inorganic ions, and in cells from microbes to man, when potassium is restricted...

Large‐scale food fortification is being scaled up globally, but little information is available on program effectiveness. We evaluated the impact of wheat flour fortification with iron, zinc, folic acid, and vitamin B12 on micronutrient (MN) status among women and young children in urban Cameroon. We conducted representative cluster surveys (30 clu...

Objective To measure biomarkers of lipid metabolism in response to a marginal zinc depletion, repletion, and supplementation in healthy male subjects. Methods Eighteen male subjects between ages of 18–45 consumed a controlled diet (80% carbohydrate, 10% fat, 10% protein) with two levels of dietary zinc. Phase I: Low zinc: 6 mg/day with 1.5 mg of p...

Objective To determine the effects of marginal zinc deficiency and repletion on essential fatty acid, sphingolipid, and lipoprotein metabolism. Methods Sixteen apparently healthy male subjects between ages of 18–45 were subjected to three sequential phases of dietary zinc intake modulation: Phase 1: Low Zinc intake: 6 mg/day with 1.5 g of phytate...

Metals such as copper, iron, manganese, and zinc are clearly required for proper metabolism and development, while imbalances can lead to systemic dysfunction and disease. As a result, organisms have evolved complex genetic systems for the regulation of metal levels, including import, export, and sequestration of metals within cells and sub-cellula...

Nutritional deficits are common in thalassemia. One hypothesized etiology behind these deficiencies is chelation; we have taken transformed hepatocytes, induced an iron overload similar to that found in the liver of a patient with thalassemia, and used clinically used iron chelators to assess secondary mineral (non-iron) removal.

Elevated uric acid (UA) is a key factor for disorders, including gout or kidney stones and result from abrogated expression of Urate Oxidase (Uro) and diet. To understand the genetic pathways influencing UA metabolism we established a Drosophila melanogaster model with elevated UA using Uro knockdown. Reduced Uro expression resulted in the accumula...

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Breaducation, Part 1: What makes flour "whole" and why does that matter for our health? Kiko talks with Heinz Thomet, a Maryland farmer who grows and mills wheat, rye and other grains. We also hear from David Killilea, PhD about the research he's leading in Oakland on the nutritional content of flour sold at supermarkets. http://lunchagenda.fullse...

Excess urinary cystine can lead to painful stone formation. There is no current effective treatment, but here Pankaj Kapahi, Marshall Stoller and colleagues have found that α-lipoic acid can prevent or even reverse formation of these stones in a mouse model.

This secondary data analysis addressed gaps in knowledge about effects of chronic water intake. Longitudinal data from the Adapt Study were used to describe effects of prescribing a sustained increase in water intake relative to baseline, for 4 weeks, on multiple indices of total body water (TBW) flux, regulation, distribution, and volume in five h...

Background: Few data are available on the effectiveness of large-scale food fortification programs. Objective: We assessed the impact of mandatory wheat flour fortification on micronutrient status in Yaoundé and Douala, Cameroon. Methods: We conducted representative surveys 2 y before and 1 y after the introduction of fortified wheat flour. In each...

Making bread more nutritious: In our Real Food series, we're looking at new ways food is being grown and prepared. As low-carb diet trends have led people away from eating bread, one baker is on a mission to make delicious bread that is also packed with important nutrients. John Blackstone reports. https://www.cbsnews.com/video/baker-aims-to-make-...

Prolonged exposure to the flame retardants found in many household products and building materials is associated with adverse developmental, reproductive, and carcinogenic consequences. While these compounds have been studied in numerous epidemiological and animal models, less is known about the effects of flame retardant exposure on cell function....

Historically, physicochemical analyses of calcium based stones has embraced the assumption that individual stones can be segregated into meaningful categories based on routine stone analysis to describe stone composition. Routine stone analytics reports predominant crystalline components, but up to 30% of stone volume is non crystalline. Advances i...

Calcium-based renal calculi demonstrated significant heterogeneity in the structure, density, mineral composition, and material hardness not elucidated by routine clinical testing. Mineral density distributions within calcium oxalate stones revealed differential areas of low (590±80 mg/cc), medium (840±140 mg/cc), and high (1100±200 mg/cc) densitie...

INTRODUCTION AND OBJECTIVES: Cystinuria is a disorder characterized chronic kidney stone formation and caused by genetic mutations in the heterodimeric cystine transporter (SLC3A1 and SLC7A9) that is responsible for cystine reabsorption. Individuals afflic- ted with cystinuria are often treated by hyper-hydration, urine alkaliza- tion, and/or pharm...

Calcium-based renal calculi demonstrated significant heterogeneity in the structure, density, mineral composition, and material hardness not elucidated by routine clinical testing. Mineral density distributions within calcium oxalate stones revealed differential areas of low (590680 mg/cc), medium (8406140 mg/cc), and high (11006200 mg/cc) densitie...

Objective To determine the effects of marginal zinc deficiency and repletion on essential fatty acid, sphingolipid, and lipoprotein metabolism. Methods Sixteen apparently healthy male subjects between ages of 18–45 were subjected to three sequential phases of dietary zinc intake modulation: Phase 1: Low Zinc intake: 6 mg/day with 1.5 g of phytate...

Objective To measure biomarkers of lipid metabolism in response to a marginal zinc depletion, repletion, and supplementation in healthy male subjects. Methods Eighteen male subjects between ages of 18–45 consumed a controlled diet (80% carbohydrate, 10% fat, 10% protein) with two levels of dietary zinc. Phase I: Low zinc: 6 mg/day with 1.5 mg of p...

Cystinuria is an incompletely dominant disorder characterized by defective urinary cystine reabsorption that results in the formation of cystine-based urinary stones. Current treatment options are limited in their effectiveness at preventing stone recurrence and are often poorly tolerated. We report that the nutritional supplement α-lipoic acid inh...

Background: Food fortification has been recommended to improve a population’s micronutrient status. Biofortification techniques modestly elevate the zinc content of cereals, but few studies have reported a positive impact on functional indicators of zinc status. Objective: We determined the impact of a modest increase in dietary zinc that was simil...

Molecular pathways involved in dauer formation, an alternate larval stage that allows Caenorhabditis elegans to survive adverse environmental conditions during development, also modulate longevity and metabolism. The decision to proceed with reproductive development or undergo diapause depends on food abundance, population density, and temperature....

Introduction:Patients with transfusion dependent thalassemia (TDT) have a genetic anemia that causes incomplete erythropoiesis and iron overload. Plasma zinc deficiency is also seen in roughly 25% of patients with TDT. Iron overload is thought to be related to a number of secondary complications in TDT including cardiomyopathy and diabetes. However...

Purpose: To determine the association between dietary zinc intake and incident calcium kidney stones and examine the relationship between dietary zinc intake and urinary zinc excretion among adolescents. Material and methods: This study was a nested case-control study conducted within a large pediatric healthcare system. Three 24-hour dietary re...

Thalassemia (THAL) patients have a genetic anemia causing incomplete erythropoiesis and iron overload, possibly leading to cardiomyopathy and diabetes. Plasma zinc (Zn) and Copper (Cu) deficiency are also observed in some patients with THAL, however, these effects are not as well characterized. It has been suggested that oxidative stress can be cau...

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Background: β-Thalassemia (Thal) is a genetic anemia of incomplete erythropoiesis causing iron overload and roughly 25% of patients to be marginally zinc (Zn) deficient. Nearly 30% of adult subjects with Thal will develop diabetes, thought to be related to transfusional iron overload, but the diabetogenic effects of altered Zn status are not well k...

Zinc is an essential trace metal that has integral roles in numerous biological processes, including enzymatic function, protein structure, and cell signaling pathways. Both excess and deficiency of zinc can lead to detrimental effects on development and metabolism, resulting in abnormalities and disease. We altered the zinc balance within Caenorha...

INTRODUCTION AND OBJECTIVES: An association between high dietary zinc intake and an increased risk of nephrolithiasis has been observed in adults and animal models, but knowledge of the relationship between dietary zinc and kidney stone disease that begins during childhood is limited. We sought to determine the association between dietary zinc cont...

INTRODUCTION AND OBJECTIVES: Nephrolithiasis is a systemic disease and falls within the spectrum of pathologic biominer- alization processes occurring throughout the body. Biomineralization has been described in all organ systems. An understanding of these processes may provide insights into how and why kidney stones form. We evaluated heterogenous...

Research Updates section of Children's Handprints Spring 2016

Research Updates section of Children's Handprints Spring 2015

Research Updates section of Children's Handprints 2014

The link between hair loss and iron deficiency has been established in many studies. Androgenetic alopecia (AA), one of the most common causes of hair loss in women is associated with decreased serum ferritin levels. We previously generated knockout mice that lack Hephaesetin (Heph), a ferroxidase involved in intestinal iron efflux. Heph null mice...

Disability or death due to intracerebral hemorrhage (ICH) is attributed to blood lysis, liberation of iron, and conse- quent oxidative stress. Iron chelators bind to free iron and prevent neuronal death induced by oxidative stress and disability due to ICH, but the mechanisms for this effect remain unclear. We show that the hypoxia-inducible factor...

Introduction: β-thalassemia major requires a lifetime of transfusion and chelation therapy and despite improved chelation therapies, patients endure organ iron overload and increased hemolysis leading to organ injury and release of damage associated bio-markers. The structure of these markers are recognized by pattern recognition receptors (PRR) of...

A coordinated network of zinc transporters and binding proteins tightly regulate cellular zinc levels. Canonical responses to zinc availability are thought to be mediated by changes in gene expression of key zinc transporters. We investigated the temporal relationships of actual zinc uptake with patterns of gene expression in membrane-bound zinc tr...

Patients with cystic fibrosis (CF) may be at risk for micronutrient depletion, particularly during periods of illness and infection. The purpose of this study was to investigate serum micronutrient status over time in adults with CF initially hospitalized with a pulmonary exacerbation. This was an ancillary study of a multicenter trial investigatin...

One of the most common types of urinary stones formed in humans and some other mammals is composed of calcium oxalate in ordered hydrated crystals. Many studies have reported a range of metals other than calcium in human stones, but few have looked at stones from animal models such as the dog. Therefore, we determined the elemental profile of canin...

Ectopic calcification is a driving force for a variety of diseases, including kidney stones and atherosclerosis, but initiating factors remain largely unknown. Given its importance in seemingly divergent disease processes, identifying fundamental principal actors for ectopic calcification may have broad translational significance. Here we establish...

Background: Magnesium (Mg) is an essential intracellular element thought to play a role in asthma. It has bronchodilator capacity as a smooth muscle relaxant, which is the basis of its use in acute asthma. Conversely, calcium (Ca) promotes smooth muscle contraction, and is implicated in the inflammatory and bronchospastic processes that drive asthm...

INTRODUCTION AND OBJECTIVES: Heterogeneous nucle- ation is the process whereby calcium hydroxyapatite is thought to serve as a nidus for nephrolithiasis formation. This nucleation process is not traditionally held to be important for most non-calcium stones. Xanthine stones have been described as being composed entirely of xanthine. We applied a Dr...

Introduction and Objectives: Nucleation and growth of cystine crystals in urine are dependent upon the concentration of urinary cysteine and pH. Cystine crystals include two primary components: microcrystallites formed of cystine, a sulfur bonded cysteine dimer, and proteins. Recent human and mouse studies have identified selenium (Se) in cystine s...

thalassemia major (TM) patients experience iron overload and hemolysis resulting in oxidative stress, chronic inflammation and an increased risk for infection. Monocytes of the innate immune system rely on pattern recognition receptors (PRR; e.g., toll-like receptor 4 [TLR4]) to provide defense against pathogens. Recently, PRR ligands have been fou...

Many late-onset proteotoxic diseases are accompanied by a disruption in homeostasis of metals (metallostasis) including iron, copper and zinc. Although aging is the most prominent risk factor for these disorders, the impact of aging on metallostasis and its role in proteotoxic disease remain poorly understood. Moreover, it is not clear whether a lo...

Preliminary data has suggested that ~25% of patients with β-thalassemia major (Thal) are marginally zinc deficient. Additionally ~10-15% of adult patients with Thal will develop diabetes secondary to pancreatic damage from transfusional iron overload. The diabetogenic effects of altered zinc status are well known outside iron overload disorders. It...

Parkinson's disease (PD) is a debilitating motor and cognitive neurodegenerative disorder for which there is no cure. While aging is the major risk factor for developing PD, clear environmental risks have also been identified. Environmental exposure to the manganese (Mn) metal is a prominent risk factor for developing PD and occupational exposure t...

Background The Cystic Fibrosis Transmembrane conductance Regulator (CFTR) is a chloride channel that primarily resides in airway epithelial cells. Decreased CFTR expression and/or function lead to impaired airway surface liquid (ASL) volume homeostasis, resulting in accumulation of mucus, reduced clearance of bacteria, and chronic infection and inf...

Ectopic calcification is a driving force for a variety of diseases, including kidney stones and atherosclerosis, but initiating factors remain largely unknown. Given its importance in seemingly divergent disease processes, identifying fundamental principal actors for ectopic calcification may have broad translational significance. Here we establish...

Zinc deficiency continues to be a major concern of international nutrition, yet there are still few sensitive and reliable biomarkers for identifying moderate zinc deficiency or monitoring changes in zinc status. Plasma zinc content is used most frequently, but it is influenced by conditions other than zinc intake and, therefore, is not reliable ex...

Iron is an essential element that is required for many cellular functions. Multiple symptoms of iron deficiency have been reported in humans, including anemia, hair loss, stunted growth, and reduced oxygen transport. Mammalian iron intake is mediated in two different ways, across the placenta during fetal growth, and through the intestine during po...

Before initiating a mass zinc fortification program, this study assessed the prevalence of and risk factors for low zinc status among Cameroonian women and children. In a nationally representative survey, we randomly selected 30 clusters in each of 3 strata (North, South, and Yaoundé/Douala) and 10 households per cluster, each with a woman aged 15-...

The loss of NPC1 protein function is the predominant cause of Niemann-Pick type C1 disease (NP-C1), a systemic and neurodegenerative disorder characterized by late-endosomal/lysosomal accumulation of cholesterol and other lipids. Limited evidence from post-mortem human tissues, an Npc1(-/-) mouse model, and cell culture studies also suggest failure...

Introduction The thalassemias are inherited anemias sometimes characterized by severe transfusion dependence that can lead to extra-hepatic cardiac iron overload, causing cardiomyopathy. Despite improved chelation therapies, patients with transfusion-dependent thalassemia still endure cardiomyopathy and chronic inflammation. The innate immune syste...

Zinc (Zn) deficiency and obesity are global public health problems. Zn deficiency is associated with obesity and comorbid conditions that include insulin resistance and type 2 diabetes. However, the function of Zn in obesity remains unclear. Using a mouse model of combined high-fat and low-Zn intake (0.5-1.5 mg/kg), we investigated whether Zn defic...

Despite improved chelation therapies in thalassemia there is risk for iron overload, organ failure, infection, oxidative stress and chronic inflammation, resulting in elevated levels of pro- and anti-inflammatory proteins such as CRP and IL10 (Walter et al, 2008). Infection is the second most common cause of death in thalassemia (thal). The innate...

Iron deficiency is one of the most common nutrition concerns in the world, with an estimated 4−5 billion affected persons. Debilitating fatigue, altered immune function, decreased work capacity and anemia are among the deleterious consequences of this pervasive disorder. Recent findings have shown that obesity is often associated with iron deficien...

Activation of the transcription factor NF-κB is essential for innate immune function and requires strict regulation. The micronutrient zinc modulates proper host defense, and zinc deficiency is associated with elevated inflammation and worse outcomes in response to bacterial infection and sepsis. Previous studies suggest that zinc may regulate NF-κ...