Reflections and Roadmaps: Career Development beyond the FDA-AACR Oncology Educational Fellowship.

In 2020, the FDA's Oncology Center of Excellence, in collaboration with the American Association for Cancer Research, launched a novel educational partnership known as the FDA-AACR Oncology Educational Fellowship. This year-long program is aimed for hematology/oncology fellows, scientists, and early-career investigators, offering an in-depth exploration of the regulatory review process by blending didactic learning with practical cases discussing oncology drug approvals. The fellowship has been met with enthusiastic feedback, with participants lauding its role in demystifying the regulatory landscape and enhancing their professional careers.

Regulation of EGFR signalling by palmitoylation and its role in tumorigenesis.

The epidermal growth factor receptor (EGFR) is an essential driver of oncogenic signalling, and EGFR inhibitors are some of the earliest examples of successful targeted therapies in multiple types of cancer. The tractability of EGFR as a therapeutic target is overshadowed by the inevitable drug resistance that develops. Overcoming resistance mechanisms requires a deeper understanding of EGFR regulation in cancer cells.

Differences in self-association between kindlin-2 and kindlin-3 are associated with differential integrin binding.

The integrin family of transmembrane adhesion receptors coordinates complex signaling networks that control the ability of cells to sense and communicate with the extracellular environment. Kindlin proteins are a central cytoplasmic component of these networks, directly binding integrin cytoplasmic domains and mediating interactions with cytoskeletal and signaling proteins. The physiological importance of kindlins is well established, but how the scaffolding functions of kindlins are regulated at the molecular level is still unclear.

Chapter 22: Structural and signaling functions of integrins.

The integrin family of transmembrane adhesion receptors is essential for sensing and adhering to the extracellular environment. Integrins are heterodimers composed of non-covalently associated α and β subunits that engage extracellular matrix proteins and couple to intracellular signaling and cytoskeletal complexes. Humans have 24 different integrin heterodimers with differing ligand binding specificities and non-redundant functions.

Kindlin-2 interacts with a highly conserved surface of ILK to regulate focal adhesion localization and cell spreading.

The integrin-associated adaptor proteins integrin-linked kinase (ILK) and kindlin-2 play central roles in integrin signaling and control of cell morphology. A direct ILK-kindlin-2 interaction is conserved across species and involves the F2PH subdomain of kindlin-2 and the pseudokinase domain (pKD) of ILK. However, complete understanding of the ILK-kindlin-2 interaction and its role in integrin-mediated signaling has been impeded by difficulties identifying the binding site for kindlin-2 on ILK.

Structural and chemical properties of the nitrogen-rich energetic material triaminoguanidinium 1-methyl-5-nitriminotetrazolate under pressure.

The structural and chemical properties of the bi-molecular, hydrogen-bonded, nitrogen-rich energetic material triaminoguanidinium 1-methyl-5-nitriminotetrazolate C(3)H(12)N(12)O(2) (TAG-MNT) have been investigated at room pressure and under high pressure isothermal compression using powder x-ray diffraction and Raman and infrared spectroscopy. A stiffening of the equation of state and concomitant structural relaxation between 6 and 14 GPa are found to correlate with Raman mode disappearances, frequency discontinuities, and changes in the pressure dependence of modes. These observations manifest the occurrence of a reversible martensitic structural transformation to a new crystalline phase.