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The Transforming Growth Factor Beta (TGF-ß) ligands (i.e., TGF-ß1, -ß2, -ß3) are key regulatory proteins in animal physiology. Disruption of normal TGF-ß signaling is associated with many diseases from cancer to fibrosis. In mice and humans, TGF-ß activates TGF-ß receptors (e.g., TGFBR1), which activates SMAD proteins that alter gene expression and contribute to tumorigenesis.  Reliable animal models are essential for the study of TGF-ß signaling.

Studies have shown that Tissue Inhibitor of Metalloproteinases 2 (TIMP-2) suppresses tumor growth and tumor-associated angiogenesis. Currently, the main obstacle in using TIMP-2 as a biologic therapeutic has been the inability to produce sufficient quantities of the protein for testing and development. 

Cancer stem cells are a minority population of cells in tumors that initiate and sustain the cancer and which are resistant to therapy; they may cause tumors to recur after curative treatment.  Current therapies generally do not target cancer stem cells.

Scientists at NIAID have developed two immortalized stable B cell lines from rhesus macaques that can have value as research tools for the discovery of neutralizing antibodies of simian origin against HIV and that may have value in the development of an HIV vaccine. These B cell lines encode human Bcl-6 and Bcl-xL proteins, which are major regulators of apoptosis. These B cell lines are derived from the lymph node of a rhesus macaque (RM) that was infected with SHIV.CH505.

Gene therapy research has yielded FDA-approved treatments for an array of diseases. However, challenges facing nucleic-acid based therapeutics include non-specific delivery and degradation of the nanoparticles. NCI investigators have developed a solution to address these challenges in their novel nucleic-based therapy based on the conditional activation strategy. 

Researchers at the National Cancer Institute (NCI) have developed a method of stimulating an immune response in humans at risk for infection by, or already infected with, an Human Immunodeficiency Virus (HIV)-1 retrovirus. This method utilizes deoxyribonucleic acid (DNA) vaccines to stimulate CD8+ T cell immune responses. The DNA vaccine encodes antigens known to be effective against retroviruses, such as HIV-1gag, gp120, nefCTL, and proCTL. The same antigens are also expressed by the pox virus vaccine, which elicits an increased immune response when combined with the DNA vaccine.

Lung metastases are a sign of widespread cancer with poor survival rate. Lung malignancies can originate from almost any cancer type spread via the blood stream. Most common lung metastases are from melanoma, breast cancer, bladder cancer, colon cancer, prostate cancer, neuroblastoma, and sarcoma. Living more than 5 years with lung metastases is uncommon, and surgical procedures are only effective with localized lung metastases. Lung metastasis are extremely frequent and resistant to regular treatment due to immunosuppressive regulatory sulfatide-reactive type II NKT cells.

Human immunodeficiency virus (HIV) remains a major global health challenge despite the advancement made in development of effective antiretrovirals (ARVs). ARVs are effective at limiting replication and spread of the virus, and progression to acquired immuno-deficiency syndrome (AIDS). However, ARVs often lead to emergence of drug-resistant virus strains insensitive to treatment and with toxic effects following long-term usage.

Researchers at the National Cancer Institute (NCI) have developed a new method of improving the efficacy of vaccines in patients with human immunodeficiency virus (HIV) by activating Ras. This method can be used to develop more efficacious vaccine compositions by activating Ras before, during, or after vaccination. Additionally, the researchers discovered that modulation of the Ras pathways could be a predictive biomarker of protection against HIV.

This technology includes a method for performing cardiac imaging without the need for the patient to hold their breath. Free breathing pixel-wise myocardial T1 parameter mapping includes performing a free-breathing scan of a cardiac region at a plurality of varying saturation recovery times to acquire a k-space dataset; generating an image dataset based on the k-space dataset; and performing a respiratory motion correction process on the image dataset.