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

A promising approach to correct the metabolic dysfunction associated with obesity is to activate brown fat non-shivering thermogenesis (NST). A critical limitation with NST as a therapeutic option, however, is that this beneficial process is silenced under human physiological temperature conditions and the mechanisms of how this occurs is unknown. This study will be the first to identify human NST silencing factors that may be targeted for the treatment of obesity and metabolic disorders.

Type: Interventional

Start Date: Aug 2024

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

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

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