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Jimmy Holder, MD, PHO

Profile written by J. Nicholas Brenton, MD

Jimmy Holder, MD

Jimmy Holder MD, PhD has the distinct honor of recognition with this year’s Philip R. Dodge Young Investigator Award. This well-deserving scientist began his training at the Johns Hopkins University, where he obtained his bachelor’s degree in biologic studies. Here, Dr. Holder first became exposed to and enthralled by the scientific aspects of molecular biology. Dr. Holder was consistently on the Dean’s list throughout all four years of undergraduate study and Hopkins, and he was awarded the Provost’s Award for Research and excellence midway through his undergraduate course.

Aller graduating from Hopkins, he was accepted into the University of Texas Southwestern’s MD/ PhD graduate program. Under the guidance of scientific mentor, Dr. Andrew Zinn, Dr. Holder honed his skills in molecular biology and cell culture and was introduced to the techniques of mouse modeling in human disease. During his time as a graduate student, he identified a novel obesity gene, SIM 1, in a child that had early-onset, profound obesity. By utilizing a mouse model, he was able to demonstrate that over-expression of SIMl protects against diet-induced obesity via gene-regulated actions upon the central melanocortin system. The initial results of his findings were published in Human Molecular Genetics with his co-author and mentor, Dr. Zinn.

Following graduation from UT Southwestern, Dr. Holder pursued a post-doctoral fellowship in neurogenetics at the University of California, San Francisco. Under the mentorship of Dr. Louis Ptacek, Dr. Holder enhanced his knowledge analyzing rodent behaviors to model human neurologic diseases. He accomplished this by performing research relating to the role of a putative circadian rhythm gene in sleep homeostatsis within the mouse model. The results of his study yielded a publication in Science in 2009. Dr. Holder successfully completed his post-doctoral training in 2007; yet, this training al UCSF left him with a recognized need for hands-on clinical training in attempts to inform and guide his future research endeavors.

From 2007 to 2012, Dr. Holder trained as a child neurology resident at the Baylor College of Medicine in Houston, Texas. With this training, Dr. Holder gained a deeper appreciation and understanding for the breadth of neurologic disease in children. His ABPN Certification in Neurology/Child Neurology was conferred in 2013. During his time in residency training, Dr. Holder first encountered a child with an autism spectrum disorder, known as Phelan McDermid syndrome. Caused by a loss of function mutation in the SHANK3 gene, this clinical entity enthralled Dr. Holder, leading him to question the underlying neuronal and circuitry mechanisms of neurodevelopmental disorders through the detailed study of the SHANK3 gene. As a result of this interesting case and his deeper interest in the underlying genetics, Dr. Holder began to work under the guidance of mentor, Dr. Huda Zoghbi, to determine if overexpression of SHANK3 could result in neurodevelopmental abnormalities. Sure enough, Dr. llolder discovered that mice that over express SHANK3 have behavioral abnormalities in addition to epilepsy, the results of which were published in Nature in 2013.

Given his contributions to the understanding of Phelan-McDermind Syndrome, Dr. Holder has been invited to give both lectures and platform presentations on the topic at various venues, including the annual meetings of the Child Neurology Society and the American Academy of Neurology.

Given his exciting new collaborations with Dr. Zoghbi, Dr. Holder returned to the world of translational research at the Jan and Dan Duncan Neurological Research Institute upon finishing his residency training. It is here that he currently holds the title of Assistant Professor in the Departments of Pediatrics at Baylor College of Medicine. As faculty at Baylor, Dr. Holder has established a SHANKopathy clinic in order to provide care for children demonstrating both loss and gain of function mutations within this gene. In addition, he has been successfully funded by the Thrasher Research Fund Early Career Award as a primary investigator to study and characterize the phenotypes of individuals with SHANK3 duplications. As one already notes, Dr. Holder has made significant, early-career contributions to the field of neurodevelopmental disorders exhibiting a genetic basis. His future work seems certain to yield similar, if not greater, advancements in the growing field of neurogenetics.