Browsing by Author "Nohe, Anja"
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Item Development of Physiologically Based Pharmacokinetic Model (PBPK) of BMP2 in Mice(OMICS Group, 2013) Utturkar, A.; Paul, B.; Akkiraju, H.; Bonor, J.; Dhurjati, Prasad; Nohe, Anja; Utturkar A, Paul B, Akkiraju H, Bonor J, Dhurjati P, Nohe A; Utturkar, A.; Paul, B.; Akkiraju, H.; Bonor, J.; Dhurjati, Prasad; Nohe, AnjaBone Morphogenetic protein 2 holds great promise for potential applications in the clinic. It is a potent growth factor for the use in the cervical spine surgery (FDA approved 2002) and has been marketed as “Infuse” for treating open tibial shaft fractures (FDA approved 2004). However, its use is limited by several significant side effects that maybe due to its potency and effect on different stem cell populations in the spine. BMP2 is expressed throughout the human body in several tissues and at a very high concentration in the blood. BMP receptors, especially BMP receptor type Ia, is ubiquitously expressed in most tissues. Currently, it is difficult to determine how BMP2 is physiologically distributed in mice or humans and no quantitative models are available. A Physiologically-Based Pharmaco-Kinetic (PBPK) model has been developed to determine steady-state distribution of BMP2 in mice. The multi-compartmental PBPK model represents relevant organ/tissues with physiological accuracy. The organs/tissue compartments chosen were brain, lung, heart, liver, pancreas, kidney, uterus, bone and fat. A blood compartment maintained connectivity among the various organs. Four processes characterized the change in the concentration of the protein in every compartment: blood flow in, blood flow out, protein turnover and receptor binding in the organ. The unique aspects of the model are the determination of elimination using receptor kinetics and generation using protein turnover. The model also predicts steady state concentrations of BMP2 in tissues in mice and may be used for possible scale-up of dosage regimens in humans.Item The Role of Protein Kinase CK2 in Development and Disease Progression: A Critical Review(Journal of Developmental Biology, 2022-07-27) Halloran, Daniel; Pandit, Venu; Nohe, AnjaProtein kinase CK2 (CK2) is a ubiquitous holoenzyme involved in a wide array of developmental processes. The involvement of CK2 in events such as neurogenesis, cardiogenesis, skeletogenesis, and spermatogenesis is essential for the viability of almost all organisms, and its role has been conserved throughout evolution. Further into adulthood, CK2 continues to function as a key regulator of pathways affecting crucial processes such as osteogenesis, adipogenesis, chondrogenesis, neuron differentiation, and the immune response. Due to its vast role in a multitude of pathways, aberrant functioning of this kinase leads to embryonic lethality and numerous diseases and disorders, including cancer and neurological disorders. As a result, CK2 is a popular target for interventions aiming to treat the aforementioned diseases. Specifically, two CK2 inhibitors, namely CX-4945 and CIBG-300, are in the early stages of clinical testing and exhibit promise for treating cancer and other disorders. Further, other researchers around the world are focusing on CK2 to treat bone disorders. This review summarizes the current understanding of CK2 in development, the structure of CK2, the targets and signaling pathways of CK2, the implication of CK2 in disease progression, and the recent therapeutics developed to inhibit the dysregulation of CK2 function in various diseases.