23 matching studies

Sponsor Condition of Interest
3BNC117-LS and 10-1074-LS in Viremic HIV-infected Individuals
Rockefeller University Human Immunodeficiency Virus
The proposed study is a phase 1, open label, single arm study to evaluate the safety, pharmacokinetics and antiviral activity of single intravenous infusions of 3BNC117-LS and 10-1074-LS, each monoclonal antibody (mAb) dosed at 30 mg/kg in viremic human immunodeficiency virus... expand

The proposed study is a phase 1, open label, single arm study to evaluate the safety, pharmacokinetics and antiviral activity of single intravenous infusions of 3BNC117-LS and 10-1074-LS, each monoclonal antibody (mAb) dosed at 30 mg/kg in viremic human immunodeficiency virus (HIV)-infected individuals.

Type: Interventional

Start Date: Aug 2020

open study

The Genetics and Functional Basis of Inherited Platelet, White Blood Cell, Red Blood Cell, and Blood...
Rockefeller University Glanzmann Thrombasthenia
Blood contains red blood cells, white blood cells, and platelets, as well as a fluid portion termed plasma. We primarily study blood platelets, but sometimes we also analyze the blood of patients with red blood cell disorders (such as sickle cell disease), white blood cell disorders,... expand

Blood contains red blood cells, white blood cells, and platelets, as well as a fluid portion termed plasma. We primarily study blood platelets, but sometimes we also analyze the blood of patients with red blood cell disorders (such as sickle cell disease), white blood cell disorders, and disorders of the blood clotting factors found in plasma. Blood platelets are small cell fragments that help people stop bleeding after blood vessels are damaged. Some individuals have abnormalities in their blood platelets that result in them not functioning properly. One such disorder is Glanzmann thrombasthenia. Most such patients have a bleeding disorder characterized by nosebleeds, gum bleeding, easy bruising (black and blue marks), heavy menstrual periods in women, and excessive bleeding after surgery or trauma. Our laboratory performs advanced tests of platelet function and platelet biochemistry. If we find evidence that a genetic disorder may be responsible, we analyze the genetic material (DNA and RNA) from the volunteer, and when possible, close family members to identify the precise defect.

Type: Observational

Start Date: Sep 2005

open study

A Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Orally Inhaled Aerosolized Hydroxychloroquine...
Pulmoquine Therapeutics, Inc Severe Acute Respiratory Syndrome Coronavirus 2
This study is 'A Randomized Phase 1 Double Blind Placebo Controlled, Single-Dose, Dose-Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Orally Inhaled Aerosolized Hydroxychloroquine Sulfate in Healthy Adult Volunteers.' The primary objectives are... expand

This study is 'A Randomized Phase 1 Double Blind Placebo Controlled, Single-Dose, Dose-Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Orally Inhaled Aerosolized Hydroxychloroquine Sulfate in Healthy Adult Volunteers.' The primary objectives are as follows: - To assess the safety and tolerability of AHCQ administered as a single dose by oral inhalation in healthy individuals at escalating doses until either the maximum tolerated dose (MTD) is identified or 1 mL of a 50 mg/mL solution is administered. - To determine the recommended Phase 2a dose (RP2D). Secondary objectives: • To characterize pharmacokinetics (PK) of single dose AHCQ in healthy individuals.

Type: Interventional

Start Date: Jun 2020

open study

When the Kidney Reacts to Nutritional Changes
Rockefeller University Prehypertension
Hypertension is one of the leading causes of morbidity and mortality in the industrialized world, attributed mostly to modifiable lifestyle factors. Aspects that are controlled by patients include physical activity, smoking, alcohol consumption, and nutrition. The DASH (Dietary... expand

Hypertension is one of the leading causes of morbidity and mortality in the industrialized world, attributed mostly to modifiable lifestyle factors. Aspects that are controlled by patients include physical activity, smoking, alcohol consumption, and nutrition. The DASH (Dietary Approach to Stop Hypertension) diet is a proven effective intervention in lowering blood pressure in multiple populations. In this proof of concept study, volunteers with untreated stage 1 hypertension, defined as mild high blood pressure with numbers in the range of 130 - 139 over 80 - 89, will receive a DASH-based menu during 5 days of hospitalization, during a weekend at home where they will continue the menu, another 5 days as inpatients, followed by a weekend at home on the same menu, and the return to the inpatient unit for an additional day for final testing. Throughout the intervention period, participants will be followed clinically and undergo repeated laboratory testing. The aim of this project is to characterize changes in urine electrolytes and exosome protein abundance pattern during nutritional changes, shifting from a "westernized diet" to a DASH diet.

Type: Interventional

Start Date: Feb 2020

open study

3BNC117 and 10-1074 in ART-treated Individuals
Rockefeller University Human Immunodeficiency Virus
The proposed study is a phase 1, open label, randomized study to evaluate the safety and antiretroviral activity of seven infusions of 3BNC117 and 10-1074, administered intravenously at 30 mg/kg dose level, in human immunodeficiency virus (HIV)-infected individuals on combination... expand

The proposed study is a phase 1, open label, randomized study to evaluate the safety and antiretroviral activity of seven infusions of 3BNC117 and 10-1074, administered intravenously at 30 mg/kg dose level, in human immunodeficiency virus (HIV)-infected individuals on combination antiretroviral therapy (ART) and during an analytical interruption of ART.

Type: Interventional

Start Date: Jun 2018

open study

A Study Investigating the Safety and Tolerability of an Immune Treatment in Cancer Patients With Lesions...
Rockefeller University Cancer Solid Tumor Cancer of Skin
The purpose of this study is to test the safety and tolerability of 2141-V11 in people who have cancer that does not respond to standard treatment and who have skin lesions (skin tumors) associated with their cancer. The study will also test how the body processes and responds... expand

The purpose of this study is to test the safety and tolerability of 2141-V11 in people who have cancer that does not respond to standard treatment and who have skin lesions (skin tumors) associated with their cancer. The study will also test how the body processes and responds to 2141-V11, and if the study drug has cancer fighting activity in people. The study drug activates a naturally occurring protein called CD40. By activating CD40, cells of the immune system are better able to identify and kill cancer cells. We are testing if injection of 2141-V11 into metastasis to the skin will be safe and well tolerated, and may result in immune activation in patients with solid tumors that have metastasis to the skin.

Type: Interventional

Start Date: Jan 2020

open study

Safety and Pharmacokinetics of the Combination Broadly Neutralizing Antibodies, 3BNC117-LS-J and 10-1074-LS-J,...
International AIDS Vaccine Initiative HIV-1-infection
This is a Phase 1/2 study to evaluate the safety, tolerability, and pharmacokinetics of two broadly neutralizing monoclonal human antibodies (bNAbs), 3BNC117-LS-J, which targets the CD4 binding site on HIV-1 envelope protein, and 10-1074-LS-J which targets the V3 loop of HIV-1... expand

This is a Phase 1/2 study to evaluate the safety, tolerability, and pharmacokinetics of two broadly neutralizing monoclonal human antibodies (bNAbs), 3BNC117-LS-J, which targets the CD4 binding site on HIV-1 envelope protein, and 10-1074-LS-J which targets the V3 loop of HIV-1 envelope protein. The hypothesis is that the two antibodies will be safe for healthy HIV-1 uninfected adults when co-administered subcutaneously or intravenously and, after subcutaneous administration in the optimal ratio, each antibody will maintain serum levels >10 µg/ml for at least 3 months in HIV-uninfected participants.

Type: Interventional

Start Date: Jan 2019

open study

Human Genetic Correlates of the Addictive Diseases
Rockefeller University Addictive diseases
Studies of genetic epidemiology have demonstrated that there exists a heritable contribution to individual variability in vulnerability to specific addictions. The overall goal of this project is to determine which variants of specific genes affect vulnerability to specific addictions. Our primary focus... expand

Studies of genetic epidemiology have demonstrated that there exists a heritable contribution to individual variability in vulnerability to specific addictions. The overall goal of this project is to determine which variants of specific genes affect vulnerability to specific addictions. Our primary focus is on opiate addiction but addiction to other drugs and alcohol is also under study. Study subjects are thoroughly characterized using several structured and semi-structured instruments. We use both case-control and family-genetic approaches. Hypothesis driven selection of genes for study is used as well as positional methods using a variety of genetic markers to identify additional genes and gene variants contributing to addiction vulnerability.

Type: Observational

open study

Characterizing the interaction between fibrin platelets and Aβ using an ex vivo clotting assay.
Rockefeller University Healthy volunteers
The Alzheimer's disease pathological peptide Aβ can affect blood clotting but a mechanism for this action is not fully understood. To investigate this effect further we will use an test tube assay for clotting to determine how Aβ interacts with both fibrin and platelets in human blood. Using this assay... expand

The Alzheimer's disease pathological peptide Aβ can affect blood clotting but a mechanism for this action is not fully understood. To investigate this effect further we will use an test tube assay for clotting to determine how Aβ interacts with both fibrin and platelets in human blood. Using this assay we have already observed that Aβ binds to a collagen surface when fibrin is present and that platelets bind to Aβ forming clots that are more stable than those formed in the absence of Aβ. We will use this clotting assay with real time imaging to explore how different structural forms and known mutants of Aβ alter clot formation and structure through their interaction with platelets and fibrin.

Type: Observational

open study

Discovering novel therapeutic options for HIV-Associated Neurocognitive Disorders (HAND) by exploiting...
Rockefeller University Human Immunodeficiency Virus
HIV-Associated Neurocognitive Disorders (HAND) are an important clinical complication of HIV infection and can result in an array of cognitive behavioral and motor deficits. With an estimated prevalence of 30-45 0n the combination antiretroviral therapy (cART) era HANDs are pervasive with significant... expand

HIV-Associated Neurocognitive Disorders (HAND) are an important clinical complication of HIV infection and can result in an array of cognitive behavioral and motor deficits. With an estimated prevalence of 30-45 0n the combination antiretroviral therapy (cART) era HANDs are pervasive with significant potential to adversely affect quality of life morbidity and mortality. At present no adjunctive therapies for HAND exist making the need for their development of paramount clinical importance. HIV is postulated to cross the blood-brain barrier (BBB) via the infiltration of infected monocytes CD4+ T lymphocytes or as cell-free virus. The integrin α4β1 (VLA-4) is an integrin dimer often referred to as a marker of CNS homing. VLA-4 is widely expressed on leukocyte plasma membranes and binds the integrin receptor vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells. Antibodies against the α4 subunit of VLA-4 have been shown to block monocyte/macrophage and SIV virus traffic to the brain and stabilize CNS injury in a rhesus macaque model of HIV infection. We hypothesize that VLA-4 expressing leukocytes are enriched for cells trafficking to the CNS and the transcriptional profiling of these cells in the periphery of HAND patients can identify genes signaling pathways and ultimately small molecule candidates for therapeutic development in HAND. To explore this hypothesis we performed preliminary experiments employing transcriptome sequencing (RNA-seq) of purified VLA-4 expressing CD14+ monocytes and CD4+ T cells from the PBMC of chronically infected HIV positive subjects on suppressive cART. We identified a number of highly differentially expressed genes between individuals with HAND (n=6) and those with normal neurocognitive function (NCN) (n=6) including some (e.g. CCL2) also referred to as monocyte chemoattractant protein 1 (MCP-1) that have been long implicated in HAND pathogenesis. This led to a preliminary "HAND gene-expression signature". These exciting results will be expanded upon in this 3-year proposal. Here we will seek to: AIM 1) Enroll and immunologically phenotype a larger cohort of HIV-positive individuals. We will perform neuropsychological testing (NPT) to identify 15 individuals with HAND and 15 individuals with NCN. Novel flow cytometry experiments will determine the distribution of VLA-4 expression on leukocytes from paired cerebrospinal fluid (CSF) and blood in treated suppressed HIV. A third control group of 15 HIV-negative individuals will be similarly characterized. Potential relationships between levels of VLA-4 expression and NPT performance will be examined through multivariate modeling; and AIM 2) Validate our preliminary HAND gene-expression signature. We will perform RNA-seq analysis on RNA from VLA-4 expressing CD14+ monocytes and CD4+ T cells from peripheral blood obtained from all participants enrolled in AIM 1 apply GSEA pathway analysis and confirm candidate genes using q-PCR. In this way we expect to identify robust candidate disease biomarkers and exploitable molecular targets for therapy. Additionally using the Broad Institute Connectivity map we will identify therapeutic candidate molecules for reversal of the HAND signature in future studies. In summary we propose a rational integrated clinical systems biology molecular approach that has the potential to transform the treatment landscape for an important HIV co-morbidity.

Type: Observational

open study

Peripheral Blood of Coronavirus Survivors to Identify Virus-Neutralizing Antibodies
Rockefeller University Coronavirus
The diversity of the antibody repertoire is generated by somatic recombination of immunoglobulin gene segments during early B cell development in the bone marrow. This random rearrangement process and the following antibody-maturation process generate a diverse repertoire of antibodies including antibodies... expand

The diversity of the antibody repertoire is generated by somatic recombination of immunoglobulin gene segments during early B cell development in the bone marrow. This random rearrangement process and the following antibody-maturation process generate a diverse repertoire of antibodies including antibodies that recognize pathogens (e.g. Coronaviruses in Coronavirus-infected individuals). In order to study the B cell repertoire of individuals who have been exposed to the Coronaviruses (a group of pathogenic viruses that includes Wuhan Coronavirus (nCoV-2019 recently renamed SARS-CoV-2 responsible for COVID-19 severe acute respiratory syndrome [SARS] and Middle East respiratory syndrome [MERS]) we developed a method to clone and express antibodies from single human B cells at different stages of development or B cells that are specific for defined antigens (e.g. Coronavirus-spike proteins). Our goal with this study is to identify antibodies that target and potentially neutralize the Coronaviruses in individuals that have been exposed to the virus and have cleared the infection. We have previously shown that antibodies with potent neutralizing activity can be identified in HIV-infected and ZIKA-convalescent subjects. These antibodies can protect non-human primates from infection and are therefore highly valuable for HIV and ZIKA-vaccine design. Moreover we have shown that broadly neutralizing anti-HIV antibodies are able to suppress viral replication in HIV-infected humanized mice and non-human primates. As a result of these findings some of these antibodies are currently tested in clinical trials. Therefore we have a broad knowledge about anti-viral neutralizing antibodies. We want to apply this knowledge to identify Coronavirus-neutralizing antibodies that might be of potential benefit to protect and treat Coronavirus infection. In order to identify antigen-specific B lymphocytes single B cells will be isolated by fluorescence activated single cell sorting (FACS). Immunoglobulin heavy and light chain rearrangements will be cloned from purified individual cells and expressed in vitro to produce recombinant antibodies for further reactivity testing. Identified Coronavirus reactive antibodies will be further tested for Coronavirus-neutralization using in vitro assays and in vivo models but this will be performed by virologists elsewhere. This work will provide a valuable insight into specific B cell response against Coronavirus-infection. B cells and other cells of the immune system that will be analyzed will be obtained from a leukapheresis procedure or from a regular blood draw.

Type: Observational

open study

Neuroendocrine Function in Healthy Volunteers and Volunteers with Cannabis Use Disorders
Rockefeller University Cannabis use disorder
How does the hypothalamic-pituitary-adrenal axis (HPA) system contribute to the use of cannabis the development of a cannabis use disorder and the relapse to cannabis use? The HPA axis is an important hormonal response system to stress. The actions of this hormone system normally are regulated to ensure... expand

How does the hypothalamic-pituitary-adrenal axis (HPA) system contribute to the use of cannabis the development of a cannabis use disorder and the relapse to cannabis use? The HPA axis is an important hormonal response system to stress. The actions of this hormone system normally are regulated to ensure that the body can respond quickly to stressful events and return to a normal state. The main determinants of HPA axis activity are genetic background early-life environment and current life stress. According to the National Institute on Drug Abuse (NIDA) marijuana use among high schoolers is at an all-time high. In 2018 43.60f 12th graders reported that they have tried marijuana. This percentage appears to be increasing; however the number of young people who believe regular marijuana use is risky is decreasing. As of October 2019 a total of 33 states District of Columbia Guam Puerto Rico and U.S. Virgin Islands have approved a comprehensive publicly available medical marijuana programs. However only 2.50f the population uses medical marijuana. Cannabis is widely available in the United States and use is becoming culturally acceptable (123). Additionally THC concentration has increased dramatically over the last 10 years from 8.9 0n 2008 to 17.1 0n 2017 (4). The mean THC:CBD ratio also rose substantially from 23 in 2008 to 104 in 2017.Therefore it is more relevant now than ever before to determine the effects of marijuana on the brain.

Type: Observational

open study

Developing Directly Reprogrammed Human Neurons to Investigate the Molecular Basis of Neurodegeneration...
Rockefeller University Human Immunodeficiency Virus
The prevalence of HIV-1 associated neurocognitive disorders (HANDs) is 30% . Advancing age is strongly associated with increased HAND prevalence and investigating the molecular basis of synaptodendritic injury and neurocognitive decline in this context... expand

The prevalence of HIV-1 associated neurocognitive disorders (HANDs) is 30% . Advancing age is strongly associated with increased HAND prevalence and investigating the molecular basis of synaptodendritic injury and neurocognitive decline in this context is paramount. Recently the ability to generate directly induced neurons (iNs) from patient-derived fibroblasts has been demonstrated. Unlike the immature neuronal populations generated from induced pluripotent stem cells (iPSCs) iNs reportedly retain aging-associated characteristics of the donor. In this proposal we aim to develop directly induced neurons (iNs) from HIVnegative individuals that retain age-associated transcriptional signatures. We will then determine if directly induced neurons (iNs) derived from HIV-positive individuals reveal age- and additional HIV disease-associated transcriptional signatures.

Type: Observational

open study

The Genetics of Developmental Face Blindness Prosopagnosia - a Clinical Pilot Project
Rockefeller University Prosopagnosia
Developmental face blindness also referred to as developmental Prosopagnosia is estimated to affect up to 2.5 percent of the general population causing severe consequences for the quality of lives of those affected. The condition is thought to result from genetic alterations which are currently unknown.... expand

Developmental face blindness also referred to as developmental Prosopagnosia is estimated to affect up to 2.5 percent of the general population causing severe consequences for the quality of lives of those affected. The condition is thought to result from genetic alterations which are currently unknown. To better understand the genesis of the condition and to evaluate potential strategies for treatment the current project aims to determine the genetic underpinnings of developmental prosopagnosia through genetic testing to identify causal mutations. This study will combine genetic testing with psychophysical testing of face recognition abilities. We will recruit individuals through the following major routes. (For the first route) We have created a recruitment flyer which we will distribute in the community. This flyer contains a summary regarding the study as well as the contact information of RU"s recruitment office. Additionally to this recruitment path we will utilize a preexisting online database (https://www.faceblind.org/contactus/index.html) established by Ken Nakayama and Bradley Duchaine one of our collaborators. Potential participants will be recruited from faceblind.org where they will have expressed their willingness to participate in research beforehand. Bradley Duchaine will distribute the study flyer to the individuals who expressed interest. By applying these two strategies we hope to reach a large number of individuals from diverse communities. Through the distribution of the same flyer to all potential participants we make sure that all individuals are instructed to contact the recruitment office and undergo the same enrollment processes. The RU recruitment team will screen individuals for eligibility record demographic information and their contact information and provided the participants with their unique code for identification and provide the test link leading to the online behavioral testing. style="margin-left:29.65pt">

Type: Observational

open study

Isolation of human antibodies against Powassan virus for potential therapy vaccine and diagnostic purposes.
Rockefeller University Powassan virus
Powassan virus (POWV) is a virus spread by the same tick that spreads Lyme disease. When humans are bitten by an infected tick they can develop severe disease including encephalitis and POWV infection can be fatal. There is currently no specific treatment available. Ticks carrying the virus are found... expand

Powassan virus (POWV) is a virus spread by the same tick that spreads Lyme disease. When humans are bitten by an infected tick they can develop severe disease including encephalitis and POWV infection can be fatal. There is currently no specific treatment available. Ticks carrying the virus are found in several regions of the United States including the upper Midwest and the Northeast. There is concern that cases are increasing and POWV is emerging as a significant public health threat. Upon infection with germs such as bacteria and viruses the human body mounts a protective response including the production of special proteins called antibodies that block the germs and protect against similar infections in the future. Antibodies are made by special cells in the blood called B cells which have been shown to play important roles in protection from a number of viruses. B cells can be isolated from blood and analyzed to identify those that make the protective antibody for a specific virus. The genes that code for the protective antibody can be cloned and antibodies can be made outside the body. After they are purified the antibodies are further tested for their ability to bind to and block the virus's ability to infect cells. This has been a successful strategy to obtain HIV blocking antibodies which are being tested in clinical trials and have been found to be safe and to have significant activity against HIV. We propose to take a similar approach to isolate B cells and make antibodies that can block POWV. The antibodies could be useful for POWV treatment or the development of tests to aid diagnosis and may inform the design of vaccines against this emerging virus.

Type: Observational

open study

Bactericidal Assays to Determine Antibody Effiicacy
Rockefeller University Healthy volunteers
Our laboratory develops methods to control infections by gram-positive bacteria. In the process we need to test what we have developed (vaccine-induced antibodies recombinant antibodies chimeric antibodies) in a human system. One of the best systems is human blood which contains white blood cells that... expand

Our laboratory develops methods to control infections by gram-positive bacteria. In the process we need to test what we have developed (vaccine-induced antibodies recombinant antibodies chimeric antibodies) in a human system. One of the best systems is human blood which contains white blood cells that phagocytize disease bacteria. Therefore to test the products we have developed we need to take blood from volunteers and use the white blood cells in that blood to test our products to determine if they enhance the ability of the white cells to kill the bacteria and also evaluate the immune response by these WBC to the bacteria. In some cases we will compare the activity of the product following previous activation of the WBC with the person"s own bacteria to that with no previous encounter with the bacteria. To this end the donor will be swabbed. The swabbed bacteria from the skin (forearm) and the nares will be grown and used with the above assay.

Type: Observational

open study

Development of ELISA for cleaved High Molecular Weight Kininogen as a diagnostic tool for Alzheimer's...
Rockefeller University Alzheimer's disease
The contact system is activated in the plasma of many Alzheimer"s disease (AD) patients. This system launches a pro-inflammatory pathway which could contribute to neuronal dysfunction. High molecular weight kininogen HK(intact) (HKi) is part of this pathway and is cleaved to HK(cleaved) (HKc) when the... expand

The contact system is activated in the plasma of many Alzheimer"s disease (AD) patients. This system launches a pro-inflammatory pathway which could contribute to neuronal dysfunction. High molecular weight kininogen HK(intact) (HKi) is part of this pathway and is cleaved to HK(cleaved) (HKc) when the contact system is activated. We have validated activation of the contact system in AD patients using Western blots which is not clinically practical. ELISAs are preferable but there are no commercially available antibodies that differentiate between HKi and HKc. We therefore developed HKi- and HKc-specific antibodies which will be used to develop a sandwich ELISA that can quantitate HK cleavage in human plasma. We will validate this assay by comparing the results with Western blot analyses of the same human plasma samples. We will then analyze non-demented and AD patient cohorts to determine the utility of the assay.

Type: Observational

open study

Genetic Predisposition to Appendicitis: A Pilot Study
Rockefeller University Appendicitis
7.5% of the American population develop acute appendicitis making it the most common source of acute abdominal pain requiring surgery in the United States. By the end of the nineteenth century scientists and clinicians had already characterized the disease and recommended appendectomy as treatment [12].... expand

7.5% of the American population develop acute appendicitis making it the most common source of acute abdominal pain requiring surgery in the United States. By the end of the nineteenth century scientists and clinicians had already characterized the disease and recommended appendectomy as treatment [12]. More than a century later this major surgical intervention remains the standard treatment for acute appendicitis with more than 300000 appendectomies performed annually in the United States alone [3]. The causes of the disease remain however largely unknown [8]. Recently clinical trials have demonstrated than in the majority of the cases appendectomy is actually not required and that antibiotics are an appropriate initial treatment for uncomplicated acute appendicitis [910]. This is a change of paradigm for the treatment of the disease but it also improves our understanding of the causes of acute appendicitis as it proves that infectious agents are involved which had been previously hypothesized by researchers [11]. Furthermore there is evidence in the medical literature of familial cases of appendicitis reported since 1937 [12]. Life habits and environmental factors cannot fully explain this pattern of familial aggregation and statistical models have estimated than between 25 to 50% of the heritability of the disease is due to genetic transmission [13-15]. The infectious and genetic nature of acute appendicitis leads us to the hypothesis that genetic variations of the immune system are involved in its causes. Scientists have previously addressed appendicitis from a genetic prospective [[16]. These authors found a large region of the human genome involved in the heritability of the disease. However there are no published studies using modern high-throughput sequencing methods which would help us look at genetic content at a finer resolution and find specific candidate genes involved in the transmission of the disease. In this study we plan to use whole exome sequencing in patients of interest. Whole exome sequencing has proven to be a reliable tool to extract genomic variations in the coding regions of the human genome [1718]. We will use this technique to highlight any candidate genes or events in the subjects" genome that may be involved in predisposition to appendicitis. Finding the genetic factors involved in the etiology of acute appendicitis will help us improve our understanding of the disease but due to the infectious nature of appendicitis it will also improve our understanding of the whole human immune system.

Type: Observational

open study

Derivation and Characterization of Keratinocytes in Healthy Volunteers
Rockefeller University Fanconi anemia
Fanconi anemia is an inherited genetic disorder which results in a decrease in the body"s ability to repair damage to DNA. The main features of the disorder are bone marrow dysfunction and cancer predisposition. Squamous cell carcinomas of the head and neck are the most commonly diagnosed solid tumors... expand

Fanconi anemia is an inherited genetic disorder which results in a decrease in the body"s ability to repair damage to DNA. The main features of the disorder are bone marrow dysfunction and cancer predisposition. Squamous cell carcinomas of the head and neck are the most commonly diagnosed solid tumors in patients with Fanconi anemia. These tumors originate from skin cells called keratinocytes. In patients with Fanconi anemia the tumors are more aggressive and develop at an earlier age than in persons without the disorder. The tumors are also more difficult to treat in patients with Fanconi anemia since they experience extreme toxicity from standard therapies such as chemotherapy and radiation. Prevention of this type of cancer is therefore critically important. Understanding the steps in the development of squamous cell carcinomas and the reasons why the cells involved become cancerous can help us to develop ways to prevent this process from occurring. Our current study aims to grow and characterize keratinocyte cells from healthy individuals. Eventually we will also study these cells from patients with Fanconi anemia. By doing this we hope to learn why these cells are particularly susceptible to developing tumors in the context of the genetic changes seen in Fanconi anemia. Since the DNA damage repair pathways that are dysfunctional in Fanconi anemia are present in all humans the information we gain will also help us to understand more about cancer susceptibility in the general population.

Type: Observational

open study

The human immune response to Staphylococcus aureus
Rockefeller University Staphylococcus aureus
Staphylococcus aureus (SA) is a leading cause of morbidity mortality and as a result it is responsible for a marked economic burden on today"s health care system. Infections with SA that are resistant to Methicillin antibiotic (MRSA) are very common and are a major part of this burden. 30% of the population... expand

Staphylococcus aureus (SA) is a leading cause of morbidity mortality and as a result it is responsible for a marked economic burden on today"s health care system. Infections with SA that are resistant to Methicillin antibiotic (MRSA) are very common and are a major part of this burden. 30% of the population are colonized with S. aureus so at least theoretically their immune system is constantly exposed to the bacteria and expected to induce protective immunity. However at the same time 30% of the population experiencing an infection with S. aureus will be afflicted with recurrent infections with this bacterium and despite previous exposure. Developing a vaccine would be an ideal solution for prevention of these infections. However despite intensive study in the last 3 decades a successful vaccine against S.aureus is still unavailable. For developing and designing an efficient vaccine a better understanding of the immune response to S. aureus is needed..For many yearsthe concept was that B cell responses and antibody production are enough for protection against S.aureus. In recent years direct evidence from KO mice as well as evidence from humans with primary immune deficiency demonstrates that CD4 Th1 and Th17 immune responses are necessary for protection from S. aureus. Nevertheless our recent results demonstrate that the Th1 and Th17 response to the various S. aureus strains varied extensively in response to in-vitro stimulation. Further wide variability was also inspected in IgG expression by proliferating B cells in response to the different strains. We could show that mobile genetic elements carried by phages are responsible for a significant portion of this immune response variability. These findings are bringing up the possibility that the strain specificity is a new factor that might need to be taken into account when we are evaluating protection. At this time point what is not known/understood and what we want to clarify in the current study is: (i) Whether previous exposure to various strains results in different level of protective memory. (ii) How immune memory induced by exposure to one strain affect the ability to respond to other strains of S. aureus.

Type: Observational

open study

Biomarker assay development and quality control assays for studies of exRNA/extracellular nucleic acids.
Rockefeller University Healthy volunteers
Ribonucleic acid (RNA) is a biomolecule with a variety of function within living cells. It is biochemically very similar to deoxyribonucleic acid (DNA) the biomolecule encoding the genetic information. In contrast to DNA however RNA is less stable and easily degraded by ubiquitiously present enzymes... expand

Ribonucleic acid (RNA) is a biomolecule with a variety of function within living cells. It is biochemically very similar to deoxyribonucleic acid (DNA) the biomolecule encoding the genetic information. In contrast to DNA however RNA is less stable and easily degraded by ubiquitiously present enzymes (RNases or more generally nucleases). There is a high nuclease activity in extracellular fluids (biofluids) so that extracellular RNA are commonly viewed as being rapidly degraded and useless for diagnostic applications. But recent research inlcuding in our laboratory showed that at least certain RNA classes are to a certain degree protected from degradation. This is particularly true for miRNAs. We and others have shown that they can be reliably measured in the blood circulation and that a characteristic and robust miRNA signature exists for selected diseases or in pregnancy. However there is very limited data on the biogenesis or the clearance of RNA containing complexes circulating micro RNAs (miRNAs) and almost no data about confounding factors during the sample preparation. Our data on archived clinical samples and publications by other groups indicate that the extracellular RNA content is strongly influenced by blood cell damage variables during samples procurement sample handling as well as by different RNA isolation methods. The use of assays based on distinct technologies and the lack of standardization and precise quantification additionally makes it very hard to compare available results. In this study which follows our pilot study on exRNA isolation for biomarker discovery (IRB KAK-839) we want to identify confounders in sample handling and quantification that can critically influence the circulating RNA profile. In addition we aim to explore techniques for enrichment or concentration of certain RNA classes including but not limited to messenger RNAs (mRNAs) that can be linked to physiological and pathophysiological states. While our focus of this study is on RNA retrieval an characterization a second goal is to direct method development towards optionally extracting extracellular DNA from the same sample after extraction of the RNA an opportinity that discovered unexpectedly when developing our own RNA extraction method. To ensure proper blood collection we will use blood from a cohort of healthy volunteers prepared with different types of anticoagulant and treated with different enzymes and additives after collection. Blood from this cohort will be used for method development in this study and and for quality control purposes in this study and in other studies of extracellular RNA and DNA conducted in this group.

Type: Observational

open study

Identifying the Initial Triggers of Multiple Sclerosis (MS)
Rockefeller University Multiple Sclerosis
Multiple sclerosis (MS) is a disease of the brain in which blood vessels and the fatty tissue that insulates nerve cells myelin are damaged. How the brain tissues are damaged remains unknown. We have identified a toxin that is produced by the intestinal bacterium Clostridium perfringens as a possible... expand

Multiple sclerosis (MS) is a disease of the brain in which blood vessels and the fatty tissue that insulates nerve cells myelin are damaged. How the brain tissues are damaged remains unknown. We have identified a toxin that is produced by the intestinal bacterium Clostridium perfringens as a possible cause of MS. This bacterial toxin named epsilon toxin specifically damages brain blood vessels and brain myelin. Additionally we have found that epsilon toxin damages immune cells in the blood called T cells. In this study we wish to collect blood from MS patients who are currently experiencing symptoms. We will test these blood samples for the presence of epsilon toxin. Damage to T cells by epsilon toxin also causes indirect damage to neighboring red blood cells the cells that carry oxygen in the blood. We have found that copper and iron released from toxin exposed T cells causes red blood cells to swell and breakdown more easily than normal. For these reasons we also wish to determine the mechanism by which copper and iron release is triggered by T cell toxin exposure.

Type: Observational

open study

Investigating the Impact of Race on Gene-Expression Profiles in HIV Associated Neurocognitive Disorders
Rockefeller University Human Immunodeficiency Virus
HIV-Associated Neurocognitive Disorders (HANDs) are a pervasive and debilitating complication of HIV infection with an estimated prevalence of 30-45%. The identification of robust validated specific and sensitive biomarkers for HAND that do not require invasive CSF sampling has been elusive and is of... expand

HIV-Associated Neurocognitive Disorders (HANDs) are a pervasive and debilitating complication of HIV infection with an estimated prevalence of 30-45%. The identification of robust validated specific and sensitive biomarkers for HAND that do not require invasive CSF sampling has been elusive and is of paramount importance. However unrecognized racial differences in gene expression could significantly impact the predictive value of biomarkers of HAND if applied to populations in which they have not been developed or validated. We hypothesize that significant racial differences will be identified in the peripheral blood single-cell based gene-expression profiles of HAND. We further hypothesize that these differences may be largely attributed to delays in viral suppression and delayed/decreased access to care. To test these hypotheses we will use multivariate modeling to determine the relative influence of clinical and sociodemographic variables and social determinants of health on unbiased single-cell based gene transcriptional profiles in the peripheral blood of HIV-positive virally suppressed African American and Caucasian cohorts with and without HAND.

Type: Observational

open study