Main Menu

The tumor-suppressor p53 protein plays a major role in tumor development. Most human cancers fail to normally activate wild-type p53, which is at least partly responsible for the unregulated growth of cancer cells and their failure to undergo apoptosis. While many chemotherapeutics enhance p53 levels, their non-specific DNA damage (genotoxicity) causes unfavorable side effects.
 

Bone-loss-related diseases, such as periodontitis, are characterized by an imbalance between the formation and activity of osteoblasts and osteoclasts, leading to bone loss. There are several signaling pathways that participate in the osteoclastogenesis process. Finding inhibitors of these pathways and other osteoclastogenesis-related pathways may have an effect on bone-loss diseases.

Human papillomavirus (HPV) has been associated with the cause of several cancer types, including cervical, anal, and head and neck cancers. There has been great success in preventing HPV infections with the development of prophylactic HPV vaccines, Gardasil and Cervarix. However, these vaccines have only been shown to prevent HPV infection and not treat those already infected with HPV. These vaccines elicit antibody responses to late HPV genes, and thus would not be effective in treating established tumors.

Baculoviruses have been used for decades to produce proteins in insect cell hosts. Current systems for generating recombinant baculovirus have several shortcomings which prevent their easy use in high-throughput applications. 

Several Fibroblast Growth Factor Receptor 4 (FGFR4) specific antibodies with binding affinity at the nanomolar range have been successfully developed at the Genetics Branch. These antibodies have been made into different formats of therapeutic including Antibody Drug Conjugate (ADC), Bispecific T cell engager (BiTE) ae well as Chimeric Antigen Receptor (CAR)-T cells.

Proof of principle experiments have shown that when treated with FGFR4 positive tumor cells:  

Tumor necrosis factor receptor type 2 (TNFR2)-expressing regulatory T cells (Tregs), present in the tumor microenvironment, play an important role in tumor immune evasion. TNFR2 plays a crucial role in stimulating the activation and proliferation of Tregs, a major checkpoint of antitumor immune responses. In addition to its expression on Tregs, TNFR2 is also known to be overexpressed on some types of tumors and the survival and growth of these tumor cells is promoted by ligands of TNFR2.

The ability to hold and transport tissue, especially needle biopsies in a pre-defined and controlled environment is critical for the preservation of biopsy samples in downstream analytic applications. Currently, tissue specimens are placed in open containers with variable, poorly controlled solutions applied to them, often in less than sterile conditions.  Evaluation of the tissue by examination through a stereoscope or similar approaches to determine adequacy is limited and requires manipulation of the tissue that can further damage the tissue.

Soluble forms of human CD4 (sCD4) inhibit HIV-1 entry into immune cells.  Different forms of sCD4 and their fusion proteins have been extensively studied in animal models and clinical trials as promising HIV-1 inhibitors. However, they have not been successful in clinical trials due to their transient efficacy.  sCD4 is also known to interact with class II major histocompatibility complex (MHCII) and, at low concentrations, could enhance HIV-1 infectivity. 

The tumor protein p53 is a cell cycle regulator. It responds to DNA damage by triggering the DNA repair pathway and allowing cell division to occur or inducing cell growth arrest, cellular senescence, and/or apoptosis. p53 therefore acts as a tumor suppressor by preventing uncontrolled cell division. However, mutations in p53 that impair its cell cycle regulatory functions can induce uncontrolled cell division leading to cancer.

Medical imaging is an important resource for early diagnostic, detection, and effective treatment of cancers. However, the screening and review processes for radiologists have been shown to overlook a certain percentage of potentially cancerous image features. Such review errors may result in misdiagnosis and failure to identify tumors. These errors result from human fallibility, fatigue, and from the complexity of visual search required.