Safadi Pilot Grant Recipients 2019

Ten applications were received by the designated deadline, reviewed and scored by three senior neuroscientists.

Bakhtiar Yamini, MD earned the best composite score among a strong class of applicants, while Hemraj B. Dodiya, PhD and Dongdong Zhang, MD tied for second. Scoring was reflected through the summed grades on: (1) innovation; (2) scientific rigor, (3) uniqueness of opportunity, infrastructure, milieu; (4) multidisciplinary perspective, broadening neuroscience; (5) translational potential, clinical and disease relevance; and (6) future direction, impact potential. 

We are very excited about the breadth and potential integrational and translational impact of these projectsCongratulations to our awardees!

Bakhtiar Yamini, MD

Bakhtiar Yamini, MD, specializes in neuro-oncology, vascular neurosurgery, and spine surgery, working in conjuction with the Neurology Department, the Institute for Molecular Engineering, and The Digestive Disease Research Center Core (DDRCC).

"NF-κB and the Microbiome in Neurodegeneration"

Inflammation is one of the most important factors underlying the development of neurodegenerative disease. Although the gut microbiome plays a central role in promoting tissue inflammation, the mechanism by which the microbiome modulates inflammatory signaling is unknown. One of the critical regulators of inflammation is the molecule NF-κB, a factor that increases in human tissue with advancing age. In this study, we propose to examine whether changes in the gut microbiome alter the NF-κB response in the brain leading to cellular senescence. Successful completion of this project will provide useful information on the mechanism by which the gut alters signaling in distant organs, data that will ultimately improve our understanding of the mechanism underlying aging and the development of neurodegenerative disease.

Hemraj B. Dodiya, PhD 

Postdoctoral Scholar, working in the Sisodia Lab in Neurobiology, in collaboration with the Section of Neurosurgery, and the Center for Digestive Diseases Research.

 

"Role of Intestinal Hyperpermeability “leaky gut” in Alzheimer’s Disease Pathogenesis"

Alzheimer’s disease (AD) is a progressive neurodegenerative disease and the most prevalent form of dementia. The pathogenic role of neuroinflammation is well recognized in the field of neurodegenerative diseases, including AD. However, the biological source(s) that drive neuroinflammation and underlying mechanisms have not been elucidated. Dr. Dodiya proposes that intestinal hyperpermeability, also known as “leaky gut” could be that biological source. Leaky gut is defined as translocation of microbes and/or their metabolites into periphery, which in turn can trigger inflammation at the distal site such as brain. Under Drs. Sangram S. Sisodia and Le Shen’s mentorship, Dr. Dodiya will perform pilot studies to investigate the exact role of leaky gut in AD pathogenesis. These research studies promise to uncover a new mechanism targeting the gut-brain axis in AD pathogenesis. The research establishes novel collaborations between neurobiology, neurosurgery, and digestive diseases research labs.

Dongdong Zhang, MD

Postdoctoral fellow, working in the Section of Neurosurgery, in collaboration with Rheumatology, Pathology, Proteomics Core and Center for Research Informatics

 

"The Antigen Recognition Study in Cerebral Cavernous Malformation Disease"

Cerebral cavernous malformations (CCMs), present in 1,000,000 Americans, can trigger brain bleeding, seizures, headaches, limb weakness, etc. A role was shown for immune cell involvement in CCM disease from our previous studies revealing robust immune cell, antibody presence and specific B-immune cell clonal expansion in CCMs, and reduction of CCM maturation in B-cell depleted mouse models of CCMs. Dr. Zhang will investigate the identity and localization of specific substances (antigens) that trigger the immune response in CCMs. For this project, he will use artificial antibodies generated from the variable genetic sequences of antibodies from immune (plasma) cells isolated from surgically resected CCMs from patients.  He labeled these antibodies to visualize the presence in other human CCMs. 

To localize the antigen, Dr. Zhang will double label additional CCMs and normal brain tissue with the artificial antibodies and markers of blood vessels, nerve cells, and structures outside of the cells. Using artificial antibodies, he will separate antigens from ground-up human CCMs. He will digest the antigens into protein fragments and determine the molecular weight of these fragments by mass spectrometry to characterize this antigen. This may open novel therapeutic venues in CCM disease.