Research

San Diego boasts a multitude of high-profile scientists in neuroscience, genetic, behavioral, clinical and imaging studies of neuro-developmental disorders. The newly formed Center for Neurodevelopmental Disorders consolidates the programs of these scientists into a collaborative group to create an outstanding research program with an important focus on translation of basic research to treatment.

The Center provides a forum for multi-disciplinary collaborations among basic and clinical research scientists, and provides mechanisms for training of graduate and medical students.

Neurosciences Professor and Child Neurologist Doris Trauner heads a large team of investigators whose multi-disciplinary study of neurodevelopmental disorders has been supported by NIH funding for more than two decades.

Ongoing research investigates the brain bases of language and cognition in typically developing children and in clinical populations with developmental disorders including autism, Williams syndrome, language impairment and pre- or peri-natal stroke. The project examines the developmental influence of atypical sensory and attention processing on higher cognitive function including language and social communication.

Also see our Neurodevelopmental Interest Group and UCSD's Autism Center.

Jonathan Bui is conducting research on stroke using NMR microscopy at high fields utilizing 600MHz (14.1 Tesla) and 750MHz (17.6 Tesla) magnets to probe cellular and tissue origins of the MR signal. He has applied non-monoexponential diffusion measurements to elucidate the mechanisms underlying diffusion weighted imaging (DWI) changes during acute ischemic stroke.

Jennifer Friedman and colleagues are enrolling patients in a study funded by the Tourette Syndrome Association to examine the brain mechanisms underlying the success of a specific behavioral therapy for tics – CBIT (Cognitive Behavioral Intervention for Tics)/Habit Reversal Therapy.

This study, conducted in collaboration with Drs. Yu-Chin Chiu and Adam Aron in the UCSD psychology department, involves training in CBIT as well as fMRI imaging to determine what brain regions are active during the performance of CBIT.

In 1996, Richard Haas collaborated with Dr. Richard Naviaux to help establish the UCSD Mitochondrial and Metabolic Disease Center (MMDC).

The MMDC is an international leader in the diagnosis, treatment and research (including clinical trials) of metabolic disorders.

In 1999 Dr. Haas worked Dr. Naviaux again to identify mitochondrial DNA polymerase mutations as the cause of the first reported mitochondrial disease, Alper’s syndrome. Mitochondrial DNA depletion syndromes, polymerase defects and abnormalities of the mitochondrial replisome are now known to be common causes of mitochondrial disease in children and adults. He remains actively involved in research in this area to this day.

Recent research out of the MMDC has identified a subset of children with Autism who also have mitochondrial dysfunction. In a recent project, Dr. Haas was UCSD principal investigator in a study looking mitochondrial dysfunction in children with autism.

Current research in collaboration with researchers at the Sanford-Burnham Institute focuses on creating stem cells from mitochondrial disease cell lines. The aim is to create neurons and muscle cells carrying mitochondrial disease mutations as model systems for drug development.

Dr. Haas recently completed a phase I/II pharmacokinetic study of a new anticonvulsant drug, levetiracetam, in the treatment of neonatal seizures. Results of data from this study should improve the care of neonates with seizures. The development of EEG remote video monitoring was an important part of this project. benefiting babies in the major neonatal units throughout San Diego.

Key papers:

A seven-day study of the pharmacokinetics of intravenous levetiracetam in neonates: marked changes in pharmacokinetics occur during the first week of life.
Sharpe CM, Capparelli EV, Mower A, Farrell MJ, Soldin SJ, Haas RH.
Pediatric Research. 2012 Apr 11. doi: 10.1038/pr.2012.51.

Autism and mitochondrial disease.
Haas RH.
Developmental Disabilities Research Reviews. 2010 Jun;16(2):144-53. Review.

Mitochondrial disease: a practical approach for primary care physicians.
Haas RH, Parikh S, Falk MJ, Saneto RP, Wolf NI, Darin N, Cohen BH.
Pediatrics. 2007 Dec;120(6):1326-33. Review.

John Crawford’s research focuses on the neurobiology of pediatric brain tumors. More specifically, he is interested in both neuroimmunological and neurovirological mechanisms of tumor development, progression, and potential treatment.

He studies the interplay between neuro-tropic viruses (Human Herpesvirus and Human Cytomegalovirus in particular) and brain tumors. These neurotropic viruses have been detected in a variety of pediatric and adult brain tumors and he has previously shown the glial-tropic features of HHV-6 in pediatric brain tumors and am interested in studying the biological effects of viral infection on glial cells and glial tumor development.

In addition to known genetic predisposing features that govern neuro-oncogenesis, neurotropic viruses may play an important epigenenic regulatory phenomenon that may both influence protein expression as well as modulation of brain tumor growth and metastasis. Dr. Crawford is interested in both direct neurovirulent effects on brain tumor growth, as well as the immune dysregulation that allows neurotropic viruses to propogate in both children and adults with CNS tumors.

Joseph Gleeson’s current research looks at the cellular, molecular and genetic causes of pediatric developmental brain abnormalities. His laboratory seeks to identify the chromosomal location of each condition, identify the gene that is mutated in each chromosomal locus, and finally characterize the function of the critical gene in normal brain development.

Specifically, the laboratory is looking at both lissencephaly (a severe disorder of neocortical development) and Joubert Syndrome (the most common inherited congenital ataxia syndrome).

Resulting publications from his recent research efforts have appeared in top journals, including Neuron and Nature Neurosciences.

The Gleeson laboratory is also expanding their human genetics program to encompass other pediatric brain diseases (approximately 20 other diseases) and to develop collaborative research efforts. The result of recruitment efforts has yielded over 500 Middle Eastern families (who provide optimized genetic mapping strategies) for analysis, with approximately 20% of such families identified as appropriate for gene identification projects.

The goal is to perform genome-wide linkage scans to identify the diseased chromosomal interval, and then identify the gene that is mutated in the particular family.

Watch a video about Dr. Gleeson's research. 

Also see the Neurogenetics Interest Group.