The Rockefeller University

Hypertensive disorders of pregnancy (including preeclampsia) are among the leading causes of pregnancy complications and maternal deaths worldwide. They also increase the risks to the babies. Numerous interventions have been suggested in order to reduce the rate of preeclampsia. Low-dose aspirin is the most beneficial prophylactic approach in this regard. Nevertheless, aspirin failure is not uncommon. The genetic, laboratory, and clinical factors associated with low-dose aspirin failure in the prevention of preeclampsia are largely unknown. The presence of a genetic variant in PAR4 receptor expressed on platelets, is associated with increased platelet function and possibly with aspirin failure.

Type: Interventional

Start Date: Apr 2023

open study

data-pm-slice=0 0 []>Fibrolamellar carcinoma (FLC) is a rare liver cancer that primarily affects adolescents and young adults with no prior liver disease. It is defined by a unique genetic fusion and patients often present with vague symptoms which can delay diagnosis and limit treatment options. Currently there are no reliable blood tests or biomarkers to detect or monitor FLC making it difficult to track disease progression or response to therapy.Neutrophils are a type of white blood cell that help defend against infection. When activated neutrophils can release web-like structures called neutrophil extracellular traps (NETs). While NETs play a role in fighting infections research in other cancers suggests they may also promote tumor growth spread and resistance to therapy. However the role of NETs in FLC remains unknown.This study will specifically examine whether neutrophils from FLC patients are capable of forming NETs in the laboratory (in vitro). Patients with FLC will provide a blood sample and neutrophils will be isolated and tested under controlled conditions to measure NET release using imaging and biochemical methods. To provide a comparison a group of healthy volunteers will also donate blood samples so that differences in NET formation between FLC patients and healthy controls can be evaluated.The knowledge gained from this project may provide important insight into how the immune system interacts with FLC and may eventually guide the development of new biomarkers or therapeutic approaches for this rare cancer.

Type: Observational

open study

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

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

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

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

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 production of alternatively spliced protein isoforms(changes in RNA splicing) or additional changes 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 that 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 alternative splicing or 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

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

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. style=>This study aims at evaluating circulating HIV-1 RNA levels by a single copy assay as well as characterize the HIV latent reservoir including quantification of infected cells and analyzing HIV-1 integration patterns of untreated and ART-treated participants. We will also evaluate the presence of cell-free HIV-1 DNA in plasma from people living with HIV 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

Human Pegivirus (HPgV) is an RNA virus that infects humans and typically causes no symptoms. Some studies suggest that the virus may regulate immune function in beneficial ways-for example it has been associated with slower disease progression in HIV and improved survival in Ebola infection. HPgV can persist in the blood for long periods. Recent data suggest it may also be detectable in the central nervous system.This study aims to discover how HPgV infection affects the immune system. We will first develop a digital PCR test to detect viral RNA in blood plasma. We will screen healthy adults and a small group of adults with Parkinson's disease because HPgV has recently been detected in the brains of individuals with Parkinson's disease. Qualifying study participants will be invited to participate in a follow-up phase lasting about 6 months.Participants will donate blood about every 4 weeks. We will measure two things: (1) whether the virus is detectable and how much of it is present in different blood components and (2) how the virus changes the activity of the immune system. We will sequence RNA in blood cells and circulating RNA fragments to understand which genes change in response to virus presence. We will also monitor standard immune laboratory markers.This research may clarify how HPgV influences immunity and whether it alters inflammatory pathways. The results could eventually guide the development of virus-inspired therapies for inflammatory or immune-mediated diseases.

Type: Observational

open study

This is a first-in-human, placebo-controlled, single dose, dose-escalation phase 1 study to evaluate the safety, pharmacokinetics and antiviral activity of a highly potent neutralizing anti-HBV monoclonal antibody (mAb), HepB mAb19, which targets the S-protein in individuals with chronic hepatitis B (CHB) on nucleos(t)ide analog therapy (NRTI).

Type: Interventional

Start Date: Aug 2023

open study

TMB-365 is a monoclonal antibody that binds to the CD4 receptor. TMB-380, aka VRC07-523LS is a monoclonal antibody that binds to HIV. Both interfere with HIV entry. This study is designed to test the combination of the antibodies as maintenance therapy in HIV infected suppressed individuals discontinuing oral cART for 48 weeks. Researchers will compare TMB-365/TMB-380 given IV every 8 weeks to continuation of daily oral cART to see if TMB-365/TMB-380 can also maintain viral suppression. Participants will: 1. Receive TMB-365/TMB-380 infusion or take oral cART as scheduled for 48 weeks 2. Visit the clinic as schedule for checkups and tests

Type: Interventional

Start Date: Dec 2025

open study

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