星空传媒

Dr. Hamdan’s Lab:

The abundance of protein components of the nodes of Ranvier that were found at the axon initial segment (AIS) strongly suggests that these domains are similar to those that are involved in the maintenance and formation of neuronal structures.

Despite the similarities between the two neuronal domains, the node of Ranvier and the AIS have one major difference. The main difference is that the recruitment of the same proteins to the nodes requires the involvement of myelinating glia, but this does not happen with the AIS. Recent research (in my previous lab, Prof. Rasband at Baylor College of Medicine) has shown that the AIS is an intrinsic part of the neuron, while the node of Ranvier is dependent on the extrinsic factors of the glial environment.

The goal of the Hamdan’s laboratory is to understand the mechanisms by which axon initial segment (AIS) andthe nodes of Ranvier are assembled and maintained in their normal health and during injury or their role in neurodegenerative diseases.

Any therapeutic intervention for the nervous system must involve the proper maintenance and assembly of node of Ranvier and the AIS.

Determine the consequences of nervous system injury/disease (e.g., multiple sclerosis, traumatic brain injury, ischemic brain injury, peripheral nerve injury) on the structure and function of nodes of Ranvier and axon initial segments. 

Investigating novel methods of delivering DNA/RNA into primary hippocampal, cortical neurons and animals (mice and/or rats) using helper dependent virus, adenovirus, BioID and Crispr/Cas9 for genes study, editing and delivery in animal model and/or primary cell culture.

Also, a new research area in Dr. Hamdan’s lab to investigate the gene expression of calcium-linked pathways governing cancer, and developmental neurodegenerative diseases.

Lab Techniques approaches include:  

鈥婱olecular and cellular neurobiology

Microscopy

Viruses (AAV, Adenovirus and Lentivirus) and plasmids genetically construction

CRISPR/CAS9, BioID, TurboID and Gene editing.

Transgenic animals (designing, surgery, in vivo electroporation genotyping and managing).

Autism Spectrum Disorder (ASD) is defined as a neurodevelopmental disorder, highly heterogeneous with no known specific genetic etiology. The diagnosis is based on behavioral patterns varying between ASD individuals, leading to challenges in early diagnosis and delaying early intervention. ASD prevalence is on the rise at a global level and in the UAE, with 1 in 146 births affected at present. ASD poses a social burden and needs significant research contributions to develop molecular diagnostic tools. Understanding the prevalence and characteristics of ASD in the UAE is crucial for developing targeted interventions and specialized healthcare services tailored to the unique needs of this population. Research at the global level identified genes associated with various biological processes relevant to the function of the brain, such as protein synthesis, cellular metabolism, transcriptional control, synapse development, chromatin remodeling, and neurite outgrowth regulation. Disruptions in these mechanisms can impact neuronal stability and contribute to the development of ASD. The study was initiated to understand the molecular etiology of ASD in the UAE.

Whole exome sequencing was performed for the blood DNA obtained from autistic children and their parents from the UAE. Bioinformatic analysis identified seven novel genetic variants never reported to be associated with autism. Most of the genes were known to be involved in neuronal functions, including axon growth, presynaptic maturation, membrane trafficking, and synapse organization. Future investigations on the role of these variants in the pathobiology of autism using CRISPR/Cas9 gene editing technology and proximity binding protein analysis may lead to the development of diagnostic and/or therapeutic tools that can benefit autistic children in UAE for personalized treatment.