Current Kronos Science research includes, but is not limited to the following projects:
Project Name
Development of High-sensitivity LC/MS/MS Methods for Determination of Hormones in Serum
Funding Source
Kronos Science
PI
Yali Su, PhD; KS
Status
In Process
Estrogens and/or their metabolites play an important role in carcinogenesis, reproduction process, and neuroprotective processes. Quantitative profiling of estrogens and their metabolites in biological fluids can provide valuable information in the fields of early diagnosis of carcinogens and other endocrine related diseases. Estrone, Estradiol, Estradiol-sulfate, Progesterone, DHEA, DHEA-sulfate, 27-hydroxy-cholesterol, Dihydrotesterone, and Testosterone will be developed in human serum by LC/MS/MS methodology for precise measurement in research.
Project Name
Fast Immune, Lymphocyte subsets, and CD28 aging marker on Flow: Investigation of Function of Immune Systems
Funding Source
Kronos Science
PI
Yali Su, PhD; KS
Status
Ongoing
Aging is accompanied by a decline in the function of the immune system leading to increased susceptibility to infections, neoplastic and autoimmune diseases. The loss of effective immune activity is largely due to a progressive decrease of circulating lymphocytes as a direct consequence of thymic involution. The Lymphocyte Subset and Fast Immune were developed to identify certain immune parameters that may offer predictive clinical value.
Project Name
Oxidative Stress Biomarkers in CSF for AD
Funding Source
Kronos Science
PI
Yali Su, PhD; KS
Status
In Process
Cerebrospinal fluid (CSF) is considered to be the most promising matrix for detecting the onset of AD early in the process. LC/MS/MS methodology will be utilized to measure oxidative stress biomarkers in CSF of both AD subjects and controls. These markers include isoprostanes, nitrotyrosine, dityrosine, chlorotyrosine, 8-hydroxy guanosine and 8-hydroxy-2-deoxy guanosine.
Project Name
Genetic (SNP-based) Test for Risk of Alzheimer’s Disease
Funding Source
Kronos Science, TGEN, Banner Health
PI
Christopher B. Heward, PhD; KS, (deceased)
Dennis Peffley, PhD, JD, KS
Eric Reiman, MD, BH
Status
Sequencing complete; AD risk screening test development underway
The project is being performed in collaboration with the Translational Genomic Research Institute (TGen). The goal of this project is to identify new genetic determinants (SNPs) of AD, the most common cognitive function problem in older persons. If such SNPs can be identified, they may be used in combination with APOE genotyping to develop new diagnostic tests and therapeutic strategies for AD. Over 570,000 SNPs have been surveyed in the DNA of 1,000 persons confirmed to have Alzheimer's disease at autopsy and 1,000 controls. Data analysis for this project is unprecedented in scope because of the number of SNPs being surveyed, more than ever before in a single research project of this nature. From this research, a paper has been published on the GAB2 SNP in Neuron. An additional Five (5) SNP set has also been identified. Additional papers will be submitted on this finding to a peer-reviewed journal for publication shortly. A patent application for these discoveries have been filed as well.
Both SNP assays hold promise as diagnostic tests for AD, for use in clinical trials, and potentially as predictive tests. For more information on these Alzheimer’s Disease assays, click here.
Project Name
Kronos Early Estrogen Prevention Study (KEEPS)
Funding Source
Kronos Longevity Research Institute
PI
S. Mitchell Harman, MD, PhD; KLRI
Status
Ongoing
KEEPS is a randomized, controlled, double-blind trial of 720 women, designed to provide prospective data on the risks and benefits of MHT in recently menopausal women. KEEPS is designed to explore issues raised by the WHI, specifically age of participants, method of delivery and dose of hormones. Outcomes to be monitored will include imaging of key arteries and various laboratory biomarkers of CVD risk. Kronos Science Laboratory serves as the core laboratory for this study.
Project Name
Oxidative Stress and Aging: Laboratory Method Analysis
Funding Source
Kronos Longevity Research Institute
PIs
S. Mitchell Harman, MD, PhD; KLRI, Christopher B. Heward, PhD (deceased); KS, Yali Su, PhD; KS
Status
Ongoing
The goal of this project is to characterize and validate laboratory methods for assessing oxidative stress in healthy mammals, including humans. A major part of the human aspect of this effort is to determine normal ranges for several markers of study oxidative stress as a function age. This is an ongoing study as the panel of oxidative stress tests at Kronos Science Laboratory continues to expand.
Project Name
Quantification of Retinol Binding Protein 4 (RBP4) in Human Serum by Western Blot
Funding Source
National Institute of Health
PIs
Rachel Wildman, PhD; Albert Einstein College of Medicine
Dennis Peffley, PhD, JD; KS Yali Su, PhD; KS
Status
In Process
In humans, circulating RBP4 levels have been shown to be highly correlated with levels of insulin sensitivity, and to be increased with obesity and type 2 diabetes, as well as with an adverse CVD risk factor profile or metabolic syndrome. However, conflicting data have also been reported. Discrepancies in published RBP4 data may relate to complications of the RBP4 assay methodology. Complications were reported with the ELISA methodology for RBP4 among insulin resistant individuals when they compared ELISA kits to quantitative western blotting standardized to full-length RBP4 protein.Overall, ELISA method underestimates the concentration of RBP4 in insulin resistance patients compare to western blot. In order to accurately measure RBP4, quantitative western blot method is needed. The validated western blot method will be used to measure RBP4 in human serum.
Project Name
Isoprostane Correlation Study
Funding Source
Kronos Science
PIs
Yali Su, PhD; KS
Status
In Process
The isoprostanes (iP) are prostaglandin (PG) isomers that are produced by free radical attack on arachidonic acid in situ in membrane phospholipids. They offer advantages over other indices of lipid peroxidation. Of the many different prostaglandin oxidation products that can be measured, 8-iso-prostaglandin F2α (iPF2α–III), iPF2α-VI, 8,12-iPF2α -VI, and 2,3-dinor-8-iso-prostaglandin F2α (2,3-dinor-iPF2α–III), in serum and urine are particularly useful because it has been demonstrated that they are valuable markers to assess the total endogenous formation of iPF2α in vivo. At Kronos Science, LC/MS/MS technique is used to assay serum and urinary iPF2α-III, iPF2α–VI, 8,12-iPF2α–VI, and 2,3-dinor- iPF2α–III. Various methods have been used in the literature for determination of isoprostanes, including ELISA, GCMS, and LC/MS/MS. We propose to measure 42 samples with all possible isoprostanes available in serum. The samples will be measured and will compare the results of iPF2a-III in two labs.
Project Name
KLAS project, Kronos Longitudinal Aging Study
Funding Source
Kronos Science and Participants
PIs
Susan Kaib, MD and Dennis Peffley, PhD, JD
Status
In progress
Kronos Science has assembled patient data derived from Kronos’ physician wellness history and physical exams of over 4000 individuals. This health-related program is designated as the Kronos Longitudinal Aging Study (KLAS) and is designed to measure key biomarkers of health and disease over time. The overall goal is to track an extensive panel of biomarkers over a patient’s lifetime and identify biomarkers that track aging and disease.
Project Name
HSCAN Reproducibility Study
Funding Source
Kronos Science
PIs
Susan Kaib, MD, Rolf Martin, PhD
Status
In progress
The need for validated biomarkers of aging that can be investigated as response variables for intervention programs is a major issue in gerontology. The H-SCAN (Hochschild Scan) is a set of 12 different physiological tests administered with a commercially available computerized instrument. We will evaluate the reproducibility of the test