Nagi G. Ayad, Ph.D.
Associate Professor, Department of Neurological Surgery
Co-Director, University of Miami Brain Tumor Initiative
The Miami Project to Cure Paralysis
1095 NW 14th Terrace (R-48)
Miami, FL 33136
Areas Of Research
Nagi G. Ayad, Ph.D. is an Associate Professor in the Department of Neurological Surgery, Co-director of the University of Miami Brain Tumor Initiative, a member of the Center for Therapeutic Innovation, The Miami Project to Cure Paralysis, and the Sylvester Comprehensive Cancer Center. Dr. Ayad received his undergraduate degree from Rutgers University in 1992, worked for Merck & Co., Inc. as a biochemist and then pursued graduate studies with Dr. Ira Mellman at Yale University. Dr. Ayad completed his Ph.D. in Cell Biology in 1998 and moved to Harvard Medical School in 1999 to perform a postdoctoral fellowship with Dr. Marc Kirschner. Dr. Ayad then joined The Scripps Research Institute in Jupiter, Florida as an Assistant Professor in 2005 and moved to the University of Miami as an Associate Professor in 2011. Dr. Ayad’s research has focused on elucidating novel cell cycle pathways. His graduate studies identified a novel means through which endocytosis is inhibited during mitosis, while his postdoctoral studies identified two novel cell cycle regulators, Tome-1 and sororin. His work in his own laboratory has utilized high-throughput screens to identify regulators of cell cycle transitions, cancer, and neurite outgrowth. These regulators include Wee1, Casein Kinase 1, the Anaphase Promoting Complex (APC/C), and BRD4.
The main research objective of the Ayad laboratory is to identify therapeutic combinations for nervous system disorders. These include brain cancers such as glioblastoma and medulloblastoma, as well as spinal cord injury and traumatic brain injury. We are working closely with chemists to generate novel brain/spinal cord penetrant epigenetic enzyme and kinase inhibitors. We are also working with the LINCS consortium to identify small molecules that target epigenetic and kinase pathways simultaneously. We collaborate with a large group of basic scientists and clinicians to move our small molecules into clinical trials. These include Dr. Ricardo Komotar, Dr. Michael Ivan, Dr. Macarena de la Fuente, Dr. Nori Kasahara, Dr. Claes Wahlestedt, Dr. Stephan Schürer, Dr. Mary E. Hatten, Dr. Martine Roussel, and Dr. Jann Sarkaria for the brain tumor work, and Drs. Jae Lee, Vance Lemmon, and John Bixby for the spinal cord injury studies. Interestingly, we find that the same small epigenetic/kinase molecule inhibitors we are developing for brain cancer are effective in spinal cord injury as they reduce inflammation.
Identifying therapeutic combinations in brain cancer and spinal cord injury
- We are using cerebellar granule cell progenitors (GCPS) to model cell cycle exit in the nervous system. Our time series models of GCP cell cycle exit have identified targets in medulloblastoma and neurite outgrowth.
- We are utilizing The Cancer Genome Atlas (TCGA) data and information from the Library of Integrated Cell Signatures (LINCS) consortium to identify therapeutic combinations in glioblastoma.
- In collaboration with laboratories at The Miami Project to Cure Paralysis we are determining whether epigenetic enzymes play a role in inflammation after spinal cord injury
a. A Disease Signature is calculated by identifying the Differentially Expressed Genes between tumor samples and same-tissue controls.b. Transcriptional Consensus Signatures (TCS) are calculated for a reference small molecule and the LINCS L1000 Small Molecules.c. The overlap between the Reference TCS and the disease signature is calculated.d.The LINCS L1000 Small Molecules are ranked as to maximize the reversal of the Disease Signature.e. The LINCS L1000 Small Molecules are plotted based on their similarity against the Reference small molecule and the reversal of the Disease Signature.From Stathias, Jermakowicz, et al., Nature Communications, 2018.
PROFESSIONAL AFFILIATIONS / MEMBERSHIPS
- American Association for Cancer Research
- Society for Neuro-Oncology