The Rockefeller University

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

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

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

Multiple sclerosis (MS) is a disease of the brain in which brain blood vessels and the fatty tissue that insulates nerve cells myelin are damaged. How these brain tissues are damaged remains unknown. We have identified a toxin that is produced by the intestinal bacterium Clostridium perfringens as a possible trigger for MS. This bacterial toxin named epsilon toxin specifically damages brain blood vessels and brain myelin. To attack the brain the toxin must travel from the intestine and into the bloodstream. Momentary presence of the toxin in the blood circulation may give us an opportunity to validate the epsilon toxin-MS hypothesis if we can identify epsilon toxin in blood samples harvested from MS patients during periods of active disease. Accurately determining the percentage of MS patients that actively carry Clostridium perfringens bacteria in their intestines may also provide important supporting evidence for the hypothesis. In this study we wish to collect blood and stool samples from MS patients in an effort to detect blood-borne epsilon toxin and fecal carriage of Clostridium perfringens bacteria. 

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