The global market for cancer therapeutics is over $40 billion and is anticipated to continue to rise in the future. There remains a significant unmet need for therapeutics for cancers that affect blood, bone marrow, and lymph nodes and the immune system, such as leukemia, multiple myeloma, and lymphoma. The proteasome inhibitor bortezomib, which may prevent degradation of pro-apoptotic factors permitting activation of programmed cell death in neoplastic cells dependent upon suppression of pro-apoptotic pathways, has been a successful mode of treatment for such cancers.

Researchers at NIDDK have developed polyclonal antibodies against the Regulator of G Protein Signalling (RGS) protein, RGS7. RGS7 binds tightly to Gbeta5, a unique and highly specialized G protein that exhibits much less homology than other Gbeta isoforms (~50%). RGS7 is preferentially expressed in brain and neuroendocrine tissue. Like Gbeta5, RGS7 is expressed prominently in the cell membrane, as well as in the cytosol.

Podocytes, cells of the visceral epithelium in the kidneys, are a key component of the glomerular filtration barrier. Podocyte damage and loss contribute to the initiation of glomerular diseases. NIH investigators recently established long-term urinary cell cultures from two patients with focal segmental glomerulosclerosis and two healthy volunteers, via transformation with the thermosensitive SV40 large T antigen (U19tsA58) together with human telomerase (hTERT).

Scientists at NIDDK have developed a fibroblast growth factor receptor 1 (Fgfr1) conditional knock out mouse. Fgfr1 is a member of the Fgfr family of transmembrane protein receptors with intrinsic tyrosine kinase activity. Fgfr1 is important in multiple biological processes, including mesoderm induction and patterning, cell growth and migration, organ formation and bone growth. Fgfr1 is highly expressed in central nervous system tissues and plays a critical role in proliferation, migration, and survival of neurons and glial cells.

Attempts to manage body weight are often unsuccessful or only temporary. This is, in part, due to antiquated dieting methods that attempt to address calorie consumption while ignoring metabolic and physical changes. Personalized and more comprehensive methods to track and manage body weight may be more effective.

Smad4 knockout: Smad4 is essential for epiblast proliferation, egg cylinder formation and mesoderm induction in early embryogenesis.

FGFR4 knockout: Lung alveoli fail to develop normally in double mutant with FGFR4 and FGFR3 knockouts.

mEpoR-/- hEpoR+: The mouse Erythropoietin Receptor knockout that contains a human Erythropoietin Receptor transgene can be used to define the potency of recombinant erythropoietin preparations used to treat anemia associated with chronic kidney disease.

M5 muscarinic receptor knockout: Deficiency of M5Rs reduces drug-seeking behavior.

The five Muscarinic Acetylcholine (ACh) receptors are G-protein coupled receptors (M1R-M5R). M1R, M3R and M5R selectively couple to Gq/G11; M2R and M4R selectively couple to Gi/Go. M5R knockout mice are viable and fertile, and have no major morphological abnormalities.

Selective inactivation of Stat1 in mammary cells indicates that its effect as a tumor suppressor in breast is direct.

STAT1 is considered a tumor suppressor, but it is not known if this effect occurs directly in mammary cells or secondarily by disrupting interferon signaling through the JAK/STAT1 pathway to induce immune responses. ERBB2/neu-induced breast cancer appeared sooner in mice lacking STAT1 only in mammary cells than in wild-type mice, indicating that STAT1 tumor suppression was intrinsic to mammary cells and not secondary to an induced immune response.