23 matching studies

Sponsor Condition of Interest
A New Web Platform to Study Visual Perception
Rockefeller University Visual perception
We will test and validate a video platform tool for visual recognition that can be ultimately used to perform quantitative measurements of perception (psychophysics). We developed a web-based application on a RU platform to present visual stimuli (videos) and to collect detection times from human subjects... expand

We will test and validate a video platform tool for visual recognition that can be ultimately used to perform quantitative measurements of perception (psychophysics). We developed a web-based application on a RU platform to present visual stimuli (videos) and to collect detection times from human subjects with millisecond resolution. These times will be used to calculate perceptual thresholds of visual recognition for each individual. To validate the identification the participants will type a text word describing the identified figures. The goal of this pilot project is to develop a library of videos and to test it in healthy neurotypical adults. We will develop a set of perceptual tasks to test the cognitive ability to perform visual segmentation of a complex visual scene requiring discrimination of relevant stimuli and suppression of irrelevant distractors in naturalistic visual scenes. The novelty of this is study is generating a web-based platform for participants including immersive image aesthetics in the videos creating an engaging experience using more realistic stimuli for psychophysics than the ones typically used by cognitive researchers. Such studies include very controlled subsets of stimuli (dots lines small geometrical shapes) that are not embedded in their natural contexts or visual environment but rather in artificial and unreal scenes. Our goal is to create visual stimuli using figures and objects immersed in naturalistic scenes to mimic the perceptual strategies that individuals use every day to navigate their environment. We created a set of videos that are ready to use in the platform and developed the methodology to create a significant number of them. Their design is motivated by discoveries concerning the nature of visual processing revealed by our research on animal models. Our goal in this pilot project is to test and validate our library of videos and the web-based platform in neurotypical adults to eventually use it as a tool to study visual perception. We will test the sensitivity and resolution to calculate perceptual thresholds for visual recognition by checking whether the number of images in the videos allow participants to discriminate the embedded figures. A valuable outcome of this study will be an estimate of the range of variability of visual recognition thresholds in a population of neurotypical participants. By developing this website application we aim to create an engaging new tool to perform psychophysics in human subjects that can help us understand the fundamental properties that the brain uses to navigate the environment. Integrating the study of behavior and brain function is one of the current challenges of neuroscience. We believe that developing this psychophysics tool can contribute significantly to understand the neurobiological aspects of human cognition. Notably this platform has the potential to be used as a perceptual training tool.

Type: Observational

open study

Identification of post-translation drivers of immune cell misregulation
Rockefeller University Normal immunity
Methods for exerting control over relative quantities and activation states of different immune cell populations have the potential to positively impact autoimmunity cancer neurodegeneration infection and other human diseases. While large-scale transcriptional analyses have been invaluable for enhancing... expand

Methods for exerting control over relative quantities and activation states of different immune cell populations have the potential to positively impact autoimmunity cancer neurodegeneration infection and other human diseases. While large-scale transcriptional analyses have been invaluable for enhancing our understanding of the molecular complexity of immune cell misregulation the extent to which they correlate with changes in protein biochemistry to create a landscape of new opportunities for targeting and selectively manipulating diverse immune cell states with small molecules remains largely unexplored. Furthermore the modifications of proteins following protein biosynthesis (also called post-translational modifications) that are associated with immune pathologies are also frequently poorly understood. This study aims to address this knowledge gap by applying advanced platforms take advantage of chemical modification of proteins isolated from immune cells and further analysis of these modifications using modern mass-spectrometry tools to uncover previously overlooked post-translational drivers of immune pathologies and leverage this knowledge for the development of advanced small molecule modulators of immune protein function that form chemical bonds with the respective protein targets.

Type: Observational

open study

Genome Wide Association Studies in Fibrolamellar Carcinoma
Rockefeller University Fibrolamellar hepatocellular carcinoma (FLC)
Fibrolamellar hepatocellular carcinoma (FLC) is a rare liver cancer that occurs primarily in adolescents and young adults. Unlike the more common liver cancer hepatocellular carcinoma (HCC) the fibrolamellar variant appears in otherwise healthy livers. Surgery when applicable provides patients with the... expand

Fibrolamellar hepatocellular carcinoma (FLC) is a rare liver cancer that occurs primarily in adolescents and young adults. Unlike the more common liver cancer hepatocellular carcinoma (HCC) the fibrolamellar variant appears in otherwise healthy livers. Surgery when applicable provides patients with the only chance for long-term cure; chemotherapy and radiation are currently only supportive treatment options. Our lab had earlier shown that the disease is caused due to a deletion and subsequent specific gene fusion in the DNA found only in the tumor cells. Despite increasing knowledge about the disease it is not known if there are variations in patients' genomes that are associated with how the tumor behaves in the individual patient (e.g. is it highly metastatic or not) and its response to therapeutics. It is also unknown if there are variants in the DNA that are associated with susceptibility to acquiring the mutation in the liver cells and therefore the disease. With this protocol we propose to study the DNA of FLC patients coming from their body's cells without the disease as well as the DNA of healthy people. This could potentially lead to the discovery of DNA that is associated with variations disease progression or sensitivity to different therapeutics as well as variantions that are associated with acquiring the disease.

Type: Observational

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... 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

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

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%-50%. 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... expand

The prevalence of HIV-1 associated neurocognitive disorders (HANDs) is 30%-50%. 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

HBV Vaccination of Healthy Volunteers to Evaluate the Composition of Germinal Centers
Rockefeller University Hepatitis B
Antibodies are the primary mediators of the protection against infection provided by vaccination. Antibodies become most powerful after the B cells that produce them undergo an evolutionary process called affinity maturation, in which antibodies increase their ability to bind... expand

Antibodies are the primary mediators of the protection against infection provided by vaccination. Antibodies become most powerful after the B cells that produce them undergo an evolutionary process called affinity maturation, in which antibodies increase their ability to bind to their targets, and thus neutralize pathogens. Affinity maturation occurs in structures within secondary lymphoid organs (for example lymph nodes or tonsils) known as germinal centers. Germinal centers are well known to be triggered by the first dose of vaccines, generating affinity matured plasma cells (B cells that secrete antibody into serum) and memory B cells, which can be converted into plasma cells by booster doses of vaccine. However, it is not fully understood the extent to which memory B cells can return to germinal centers again upon vaccine boosting. Such return would be very important to allow B cells, for example, to adapt to emerging variants of viruses such as influenza or SARS-CoV-2. This study will involve acquiring samples of B cells from germinal centers that form in response to vaccination with the highly effective hepatitis B vaccine. These cells will be analyzed to determine what fraction of them are memory B cells that returned to germinal centers upon boosting, information that is key to knowledge of how vaccine boosters work. Understanding the "rules" that govern how and when memory B cells choose to return to germinal centers in an effective vaccine such hepatitis B could help efforts to develop effective vaccination against more challenging, rapidly mutating viruses, such as influenza, HIV, and hepatitis C.

Type: Interventional

Start Date: Dec 2022

open study

3BNC117-LS and 10-1074-LS Plus N-803 (bNAb+N-803)
Rockefeller University Human Immunodeficiency Virus
The proposed study is a phase 1, open label, single arm study to evaluate the safety and antiretroviral activity of the combination of two long-acting broadly neutralizing antibodies, 3BNC117-LS dosed once at 30 mg/kg and 10-1074-LS dosed once at 10 mg/kg, both intravenously... expand

The proposed study is a phase 1, open label, single arm study to evaluate the safety and antiretroviral activity of the combination of two long-acting broadly neutralizing antibodies, 3BNC117-LS dosed once at 30 mg/kg and 10-1074-LS dosed once at 10 mg/kg, both intravenously (IV) at week 0, plus an IL-15 superagonist complex, N-803, dosed at 6 mcg/kg, subcutaneously (SC) at week 1 and then every 3 weeks for a total of 8 doses, in ART-treated adults living with HIV during analytical treatment interruption.

Type: Interventional

Start Date: Nov 2022

open study

A Study to Evaluate the Safety and Effects of Repeated Doses of 3BNC117-LS and 10-1074-LS on Persistent...
National Institute of Allergy and Infectious Diseases (NIAID) HIV-1
Background: Antiretroviral therapy (ART) can suppress HIV to undetectable levels in people, but the virus rebounds quickly if the drug treatment is stopped; this is because HIV can remain dormant in a pool of blood cells called the persistent viral reservoir (PVR). Yet lifelong... expand

Background: Antiretroviral therapy (ART) can suppress HIV to undetectable levels in people, but the virus rebounds quickly if the drug treatment is stopped; this is because HIV can remain dormant in a pool of blood cells called the persistent viral reservoir (PVR). Yet lifelong ART is expensive and can lead to serious side effects over the long term. Some drugs may be more effective at reducing the PVR. Objective: To see if 2 study drugs (3BNC117-LS and 10-1074-LS) are safe and if they can lower the number of HIV-infected blood cells in people with HIV who are on ART. Eligibility: People aged 18 to 70 years with HIV who are on ART. Design: Participants will be screened. They will have a physical exam and blood and urine tests. They will undergo leukapheresis. Leukapheresis is a procedure where blood is drawn from a needle in one arm. The blood will pass through a machine that separates out the white blood cells. The remaining blood will be given back through a second needle in the other arm. The study drugs or placebo (normal saline) will be administered 3 times at 20-week intervals. The drugs will be given through a tube attached to a needle inserted into a vein in the arm. This will take 1 hour. Some participants will receive only a saline solution. They will not know if they are getting the drugs or the placebo. Participants will undergo leukapheresis up to 4 more times during the study. Participants will have follow-up visits every 10 weeks until the study ends.

Type: Interventional

Start Date: Feb 2023

open study

Risankizumab Long-term Remission Study
Jaehwan Kim Psoriasis
Although the newly developed biologics (drugs derived from living cells cultured in a laboratory) are highly effective in controlling psoriasis, all the biologics should be continuously injected to suppress recurrence of the disease. In this regard, the observation in the... expand

Although the newly developed biologics (drugs derived from living cells cultured in a laboratory) are highly effective in controlling psoriasis, all the biologics should be continuously injected to suppress recurrence of the disease. In this regard, the observation in the phase II clinical trial conducted by us (Laboratory for Investigative Dermatology at the Rockefeller University) was groundbreaking that just a single dose of anti-IL-23p19 antibody (risankizumab, trade name: Skyrizi, study drug in this clinical trial) administration produced disease clearance up to 66 weeks in 46% (6 of 13) of patients. However, there is a lack of understanding about immune regulation in human skin induced by anti-IL-23p19 antibody injection, and there is a need to conduct a psoriasis clinical trial for single-cell sequencing immune cells in human psoriasis skin before and after anti-IL-23p19 antibody administration, and to correlate regulatory immune cell alterations with clinical disease progression. The overall objective of the clinical trial is to study regulatory immune cell alterations induced by anti-IL-23p19 antibody administration in psoriasis patients who achieve long-term disease clearance off drugs.

Type: Interventional

Start Date: Apr 2021

open study

Entrance into the International Fanconi Anemia Registry (IFAR)
Rockefeller University Fanconi Anemia
The reason for doing this research is to study the nature diagnosis and treatment of individuals affected with the genetic disease Fanconi anemia an inherited disorder that leads to bone marrow failure (aplastic anemia) and cancer development.  In most cases it is a recessive disorder: if both parents... expand

The reason for doing this research is to study the nature diagnosis and treatment of individuals affected with the genetic disease Fanconi anemia an inherited disorder that leads to bone marrow failure (aplastic anemia) and cancer development.  In most cases it is a recessive disorder: if both parents carry a defect (mutation) in the same Fanconi anemia gene each of their children has a 25% chance of inheriting the defective gene from both parents.  When this happens the child will have Fanconi anemia.  Patients may have a variety of birth defects and may eventually develop acute myelogenous leukemia (AML) head and neck gynecological and/or gastrointestinal cancer.  The researchers doing the study will collect information about the medical history genetics clinical course blood test results treatment complications and social issues of Fanconi anemia.  Information about relatives of Fanconi anemia patients will also be collected.  A purpose of this project is to develop a detailed listing or `registry' of people who may have Fanconi anemia and their close family members. Tissue samples are collected in a repository in order to study the genotype of the study subjects for geneotype/phenotype correlation and to understand why bone marrow and cancer develop.  Using patient samples we want to understand the disease so we can develop new preventive and treatment strategies.

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

Racism-based and Biomarkers of Stress
Rockefeller University Racism Stress, Psychological
This feasibility study aims to explore how racism-induced stress impacts the brain and body and how a culturally responsive intervention can reduce the mental and physical effects of this stress among African Americans (AA). We aim to acquire methodological and protocol insights... expand

This feasibility study aims to explore how racism-induced stress impacts the brain and body and how a culturally responsive intervention can reduce the mental and physical effects of this stress among African Americans (AA). We aim to acquire methodological and protocol insights for a subsequent study by assessing 1) the feasibility of recruiting AA for a race-related study and collecting psychological and biomarkers of stress, 2) determining the association between racism-based stress surveys and biomarkers of stress, and 3) explore participants feedback on the impact of racism in their life and their willingness to participate in a 12-week mindfulness intervention with additional assessments, such as fMRI testing.

Type: Observational

Start Date: Oct 2022

open study

The Natural Course and History of Hidradenitis Suppurativa Across the Severity Spectrum in Both Treated...
Rockefeller University Hidradenitis Suppurativa
'The reason for doing this research is to better understand hidradenitis suppurativa also known as HS or acne inversa. HS involves skin folds and causes swelling of the skin and surrounding tissues pain and foul-smelling discharges. These changes normally occur in the armpits groin and under the breasts... expand

'The reason for doing this research is to better understand hidradenitis suppurativa also known as HS or acne inversa. HS involves skin folds and causes swelling of the skin and surrounding tissues pain and foul-smelling discharges. These changes normally occur in the armpits groin and under the breasts however they can occur anywhere.  'Effective treatment options are lacking. Recently clinical trials conducted by researchers from our lab found Brodalumab was an effective drug for this disease. Common treatments for HS include combinations of antibiotics retinoids and the biologic agent Adalimumab/Humira. Yet as these treatments are frequently unsatisfactory many severe patients eventually undergo extensive surgery to remove areas with active skin lesions. Still even after extensive surgery there may be a relapse of the disease in other areas. There is thus a great need to better understand the disease and the drivers of the inflammation in HS that will allow the develop of new therapeutics in the future.  'To do that we will enroll HS patients with different symptoms and severity levels. We will study their disease with one or more of the following assessment tools: blood testing skin biopsies skin tape-strips clinical assessment ultrasound tissue impedance microbiological sampling and clinical photography-before during and after therapy. However we will not be prescribing medication and will not take over patients' medical care.

Type: Observational

open study

Characterizing the interaction between fibrin platelets and Aß using an ex vivo clotting assay.
Rockefeller University Healthy volunteers
The Alzheimer's disease pathological peptide Aß 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 Aß interacts with both fibrin and platelets in human blood. Using this assay... expand

The Alzheimer's disease pathological peptide Aß 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 Aß interacts with both fibrin and platelets in human blood. Using this assay we have already observed that Aß binds to a collagen surface when fibrin is present and that platelets bind to Aß forming clots that are more stable than those formed in the absence of Aß. We will use this clotting assay with real time imaging to explore how different structural forms and known mutants of Aß alter clot formation and structure through their interaction with platelets and fibrin.

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

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

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% in 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% in 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 a4ß1 (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 a4 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

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

HIV-1 RNA Plasma Levels and HIV-1 Integration Sites in HIV-1 Infected Subjects
Rockefeller University Human Immunodeficiency Virus
HIV-1 integrates into host cellular DNA and can persist in a latent state. Antiretroviral therapy (ART) might alter HIV-1 integration site selection. Current antiretroviral regimens are effective in lowering circulating HIV-1 RNA levels to less than 20 copies/ml but in approximately 50% of individuals... expand

HIV-1 integrates into host cellular DNA and can persist in a latent state. Antiretroviral therapy (ART) might alter HIV-1 integration site selection. Current antiretroviral regimens are effective in lowering circulating HIV-1 RNA levels to less than 20 copies/ml but in approximately 50% of individuals persistent low-level viremia can be detected despite years of suppressive ART. Moreover as anti-HIV-1 immune responses develop during the course of infection HIV-1 strains mutate to escape both humoral and cellular immune responses. This study aims at evaluating circulating HIV-1 RNA levels by a single copy assay as well as HIV-1 integration patterns of untreated and ART-treated subjects. We will also evaluate the presence of cell-free HIV-1 DNA in plasma from HIV-1-infected individuals which can serve as a biomarker of HIV-1-induced cell death. Lastly the study also aims at evaluating the sensitivity of viral strains to anti-HIV-1 broadly neutralizing antibodies.

Type: Observational

open study

Healthy Volunteers for the Human Genetics of Infectious Diseases (HGID)
Rockefeller University Healthy volunteers
Our laboratory is working to find mutations in genes that may cause severe infectious diseases. We will draw blood and obtain a skin biopsy sample from healthy volunteers in order to support research studies being conducted in the Casanova Lab of Human Genetics of Infectious Diseases. We will perform... expand

Our laboratory is working to find mutations in genes that may cause severe infectious diseases. We will draw blood and obtain a skin biopsy sample from healthy volunteers in order to support research studies being conducted in the Casanova Lab of Human Genetics of Infectious Diseases. We will perform experiments to test the mutations that we find in patients with severe bacterial viral fungal and other illnesses. The samples collected from healthy volunteers will be compared to those taken from patients with severe infectious diseases. Blood samples will be used as controls for but not limited to the following: for activation production of cytokines molecular expression cellular differentiation of either whole blood or just the white blood cells (leukocytes). A skin biopsy (up to 6mm) will be obtained and will be used to generate fibroblast and keratinocyte cultures. Fibroblasts and keratinocytes may be immortalized and used as controls for but not limited to the following: stimulation of cytokine production protein expression and response to infection with viruses and bacteria. The fibroblasts may also be reprogrammed to become stem cells from which we will derive cells of the central nervous system and the lung for research studies. Some experiments including single-cell RNA sequencing (scRNAseq) require fresh skin tissue. A 6mm biopsy will enable us to conduct multiple techniques in parallel including imaging studies (i.e. hyperion) and scRNAseq on the same individual and the same tissue site. Imaging studies will allow us to characterize the cellular architecture of the tissue and scRNAseq to establish the characteristics of the stratified epithelium (i.e. basal and differentiated keratinocytes) and to define which is the target cell of the pathogen in infected individuals vs. healthy controls. This tissue-based approach enables us to compare the interaction of the cells in the tissue in healthy controls vs. individuals with infectious diseases to better understand the pathophysiology of the disease.

Type: Observational

open study

The Neural Basis of Face Recognition and Social Cognition: A Magnetic Resonance Imaging Study
Rockefeller University Healthy volunteers
We are interested in how we can recognize objects of the social world and react to them. As social animals particular objects of the outside world are of special significance to us. Faces arguably are the most important sources of social information in most if not all primate species. It may thus come... expand

We are interested in how we can recognize objects of the social world and react to them. As social animals particular objects of the outside world are of special significance to us. Faces arguably are the most important sources of social information in most if not all primate species. It may thus come as little surprise that special machinery in our brains is devoted to analyzing faces and making the results of these analyses available for a wide variety of behaviors. Some of these responses are automatic others voluntary but most of them fall into the category of social cognition or thinking about others. Because of this dedicated machinery we are extremely good at recognizing faces yet this is not the case for a fraction of the population estimated to be about one percent that is face blind prosopagnosic. People afflicted by this disorder an estimated one percent of the general population typically detect the presence of a face but cannot tell one individual from another which results in severe social difficulties. (In fact since many prosopagnosics are not aware of the fact of them being face blind we will not use prosopagnosia as an exclusion criterion during subject selection and since testing for prospagnosia takes much effort and time we will also not exhaustively test subjects prior to the experiments.) The goals of this study are to understand the functions of the different components of the face processing network its connectivity and embedding into other brain regions and the way that information about faces is used for behavioral responses. We will study these questions with magnetic resonance imaging (MRI) and behavioral testing. This technique allows us to obtain structural information about a subject's brain its connectivity via diffusion tensor imaging (DTI which measures the molecular diffusion of water along neuronal pathways) and functional specializations via functional MRI (fMRI). Subjects will view pictures and movies of objects faces animals and animated characters while fixating on the screen or performing tasks requiring the detection of a particular stimulus or discrimination of stimuli. By contrasting activity elicited by different stimulus categories we can determine which regions of the brain respond more to stimuli of one category say faces than to those of another say houses. By combining this information across a number of studies we will gain insights into the functional organization of the brain for visual stimuli and in particular socially relevant stimuli. By combining this information with connectivity maps obtained by DTI or resting state connectivity analyses we can learn whether regions specialized for a particular stimulus category are preferentially coupled and form a network - and which other parts of the brain they are coupled to.  

Type: Observational

open study

The human immune response to Staphylococcus aureusSub-study: The human immune response to G(+) bacterium.
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