Engineering topics

Alraawi, Zeina

Publications and source records attributed to Alraawi, Zeina.

3 records

DOE OSTI2024

Decoding FGF/FGFR Signaling: Insights into Biological Functions and Disease Relevance

Fibroblast Growth Factors (FGFs) and their cognate receptors, FGFRs, play pivotal roles in a plethora of biological processes, including cell proliferation, differentiation, tissue repair, and metabolic homeostasis. This review provides a comprehensive overview of FGF-FGFR signaling pathways while highlighting their complex regulatory mechanisms and interconnections with other signaling networks. Further, we briefly discuss the FGFs involvement in developmental, metabolic, and housekeeping functions. By complementing current knowledge and emerging research, this review aims to enhance the understanding of FGF-FGFR-mediated signaling and its implications for health and disease, which will be crucial for therapeutic development against FGF-related pathological conditions.

Edirisinghe, Oshadi↗

DOE OSTI2022

Amyloidogenesis: What Do We Know So Far?

The study of protein aggregation, and amyloidosis in particular, has gained considerable interest in recent times. Several neurodegenerative diseases, such as Alzheimer’s (AD) and Parkinson’s (PD) show a characteristic buildup of proteinaceous aggregates in several organs, especially the brain. Despite the enormous upsurge in research articles in this arena, it would not be incorrect to say that we still lack a crystal-clear idea surrounding these notorious aggregates. In this review, we attempt to present a holistic picture on protein aggregation and amyloids in particular. Using a chronological order of discoveries, we present the case of amyloids right from the onset of their discovery, various biophysical techniques, including analysis of the structure, the mechanisms and kinetics of the formation of amyloids. We have discussed important questions on whether aggregation and amyloidosis are restricted to a subset of specific proteins or more broadly influenced by the biophysiochemical and cellular environment. The therapeutic strategies and the significant failure rate of drugs in clinical trials pertaining to these neurodegenerative diseases have been also discussed at length. At a time when the COVID-19 pandemic has hit the globe hard, the review also discusses the plausibility of the far-reaching consequences posed by the virus, such as triggering early onset of amyloidosis. Finally, the application(s) of amyloids as useful biomaterials has also been discussed briefly in this review.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

DOE OSTI2021

The Saga of Endocrine FGFs

Fibroblast growth factors (FGFs) are cell-signaling proteins with diverse functions in cell development, repair, and metabolism. The human FGF family consists of 22 structurally related members, which can be classified into three separate groups based on their action of mechanisms, namely: intracrine, paracrine/autocrine, and endocrine FGF subfamilies. FGF19, FGF21, and FGF23 belong to the hormone-like/endocrine FGF subfamily. These endocrine FGFs are mainly associated with the regulation of cell metabolic activities such as homeostasis of lipids, glucose, energy, bile acids, and minerals (phosphate/active vitamin D). Endocrine FGFs function through a unique protein family called klotho. Two members of this family, α-klotho, or β-klotho, act as main cofactors which can scaffold to tether FGF19/21/23 to their receptor(s) (FGFRs) to form an active complex. There are ongoing studies pertaining to the structure and mechanism of these individual ternary complexes. These studies aim to provide potential insights into the physiological and pathophysiological roles and therapeutic strategies for metabolic diseases. Herein, we provide a comprehensive review of the history, structure–function relationship(s), downstream signaling, physiological roles, and future perspectives on endocrine FGFs.

59 BASIC BIOLOGICAL SCIENCES↗