Our Team

Research team group

William Mobley, MD, PhD, Executive Director

Dr. Mobley’s research focuses on the neurobiology of neurotrophic factor actions (a family of proteins responsible for the growth and survival of developing neurons and the maintenance of mature neurons) and signaling and their link to neuronal dysfunction in developmental and age-related disorders of the nervous system.

His emphasis on the neurobiology of Down syndrome has brought new insights into the disease, including possible treatments. He has also done pioneering work on the neurobiology of Alzheimer’s disease.

Pavel Belichenko, MD, PhD, Director for Circuit Structure

Dr. Belichenko produces morphological and behavioral data in developing treatment to improve cognition and learning in people with Down syndrome.

He identifies and investigates treatments for synaptic structure of the hippocampus of Down syndrome mice models that may contribute to diminished synaptic plasticity (neurochemical foundations of learning and memory) in DS.

Ricardo Capone, PhD, Scientist

Dr. Capone's studies currently focus on γ-secretase activity assays and modulation of its proteolytic activity. The enzyme γ-secretase is responsible for the last proteolytic step that generates amyloid β peptides, eventually forming β-amyloid plaques. Amyloid plaques are found in several neurodegenerative diseases, such as in older persons with Down syndrome, in Alzheimer’s disease and other age-related dementias.

The ultimate goal of this research is to find ways reduce the excess production of Aβ so that the normal cellular mechanisms of protein clearance can maintain the normal required levels of Aβ peptides.

Geoffrey Chang, PhD, Director, Structural Biology

Dr. Chang’s research focuses on the x-ray structure determination of transporters and other membrane proteins involved in several human diseases.

His research has an emphasis on understanding the molecular structures of those proteins and membrane protein complexes involved in Down syndrome.

Alexander Kleschevnikov,  PhD, Director for Circuit Function

The focus of Dr. Kleschevnikov's research is on synaptic plasticity, learning and memory in Down syndrome. In these studies he used several mouse genetic models of Down syndrome to find the cellular mechanisms underlying memory deficits, which may lead to specific treatments to improve learning and memory in Down syndrome and related disorders.

Dr. Kleschevnikov plans to expand this research to include studies of the pH regulatory system in Down syndrome. Preliminary data show that pH regulation is altered in the brain of subjects with Down syndrome, and that this change may contribute to abnormal synaptic plasticity.

He also plans to examine the status of the inflammatory system in Down syndrome and interaction between the inflammatory system and long-term synaptic plasticity.

Michael Rafii, MD, PhD, Director of Clinical Trials

Dr. Rafii is clinical director of the new Adult Down Syndrome Center at UCSD and serves as co-director of the UCSD Memory Disorders Clinic. He is also associate medical director of the Alzheimer's Disease Cooperative Study. He specializes in cognitive disorders, including dementias such as Alzheimer's disease.

Nishant Singhal, PhD, Scientist

Dr. Singhal will focus on utilizing human induced pluripotent cells to model Down syndrome. Human induced pluripotent cells based in an in-vitro model will help us understand the underlying causes of cognition deficit as well as progression of Alzheimer’s disease in individuals with Down syndrome.

Further, molecular biomarkers identified during these studies will be used to generate reporter cell lines. These reporter cells lines will be useful in identifying newer drugs to improve cognition and treat Alzheimer’s disease.

Steve L. Wagner, PhD, Director of Neurodegenerative Research

Dr. Wagner's research focuses on the discovery, design and preclinical development of therapeutic small molecules known as gamma-secretase modulators (GSMs). 

These drug-like small molecules are aimed at preventing and/or delaying the buildup of specific neuropathological lesions known as neuritic plaques that are invariably abundant in the brains of both patients with Down syndrome  and Alzheimer's disease.

Chengbiao Wu, PhD, Director for Cellular and Molecular Biology

Dr. Wu focuses on understanding the molecular and cellular mechanisms(s) of neurotrophin signaling in health and disease.

Neurotrophic factors (NTFs) are small proteins that support the survival and maintenance of nerve cells. Many types of neurodegenerative diseases such as Down syndrome, Alzheimer’s disease and Huntington disease are linked to insufficient supply of NTFs. He is discovering how neurotrophin signals are generated and transduced in nerve cells and how defective neurotrophin signaling pathways lead to neurodegenerative diseases.