The overarching goal of Dr. Lu’s research is to combine genetics and pharmacology to develop neural circuit-selective therapies for neuropsychiatric disorders. Trained as a psychiatrist and neuropharmacologist, Dr. Lu completed his postdoctoral training in molecular genetics and was appointed as an Assistant Researcher at Center for Neurobehavioral Genetics of the University of California, Los Angeles (UCLA). Dr. Lu developed the first BAC transgenic Parkinson’s disease (PD) mouse model that recapitulates the cardinal features of PD. His translational study of Huntington’s disease (HD) identified a novel therapeutic strategy (Sci. Transl. Med., 2015; Highlighted in Nat Rev Drug Discov. and was selected as the most influential paper of 2015 by HD insight). Dr. Lu co-invented a single-cell transgenic technology (MORF, Mosaicism with Repeat Frameshift) that received support from the first round of the Brain Initiative award. Funded by a NARSAD Young Investigator Award, Lu lab generated the next-generation mouse model for schizophrenia. Lu lab also has an ongoing collaboration with the National Center for Advancing Translational Sciences (NCATS) to develop small molecule VPAC2 antagonist as a novel antipsychotic agent. Recently, Dr. Lu’s lab invented a robust method for efficient and precise CRISPR/Cas9 mediated genome editing in the adult mammalian brain via intravascular administration of a neurotropic AAV. His team is now actively pursuing therapeutic genome editing for devastating brain disorders, such as Down syndrome and Huntington’s disease.
Genetic Animal Models of Neuropsychiatric Disorders
To dissect pathogenic mechanisms and to identify therapeutic targets for neuropsychiatric disorders (Parkinson’s disease, Huntington’s disease, Schizophrenia, Depression, Stress and Drug Addiction) in genetically-engineered animal models generated using gene targeting/editing (CRISPR/Cas9) and Bacterial Artificial Chromosome (BAC) transgenesis.
Molecular Genetic Tools for Neurocircuit and Single Neuron Manipulation
Employ molecular genetic tools (Designer Receptors Exclusively Activated by Designer Drug (DREADD), optogenetics, DHFR etc) to pinpoint the mechanism of action of pharmacotherapies to genetically defined neuronal population or circuits.
Drug Discovery and Preclinical Trial
In vivo single neuron pharmacology and preclinical trial to study therapeutics for basal ganglia related neuropsychiatric disorders.