|Vikram Khurana, MD, PhD|
A team including Vikram Khurana, MD, PhD, chief of the Division of Movement Disorders, has been awarded $9 million as part of the Aligning Science Across Parkinson’s (ASAP) initiative. ASAP grants focus on underlying Parkinson’s disease (PD) mechanisms, including PD-associated genes and neuro-immune interactions.
Khurana is a co-investigator on a project entitled “Defining the cellular and molecular determinants of variable genetic penetrance in Parkinson’s disease (PD).” The project will use stem-cell models of PD made from genetically diverse patients. They will convert these stem cells into the different types of brain cells implicated in PD — neurons, microglia and astrocytes — allowing them to investigate how genetic risk factors, the aging process and these different cell types interact to trigger disease. AI-based approaches will integrate high-throughput data from stem-cell models with large-scale patient datasets to create coherent network visualization of PD subtypes. This patient-centric approach strives to provide an entirely new level of understanding of how the interplay between genetics, different brain cells and aging shapes individual disease risk — enabling early diagnosis, prediction of therapeutic targets that could halt or reverse the disease, and clustering of PD patients into therapeutically meaningful subgroups.
Khurana’s laboratory integrates stem-cells and genomics to develop precision therapies for diseases like PD that are caused by the abnormal clumping of a protein called alpha-synuclein in the brain. His prior work has advanced therapies targeting alpha-synuclein to clinical trials. In the ASAP project, Khurana and his laboratory will now contribute genome-sequencing data and cutting-edge human stem-cell models for this project. They will lead functional genomic studies that dissect mechanisms through which different combinations of genetic risk factors might trigger PD in individual patients. Other parts of the project will be led by Lorenz Studer MD, of Memorial Sloan Kettering Cancer Center; Gist Croft, PhD, of New York Stem Cell Foundation; Jian Peng, PhD, of University of Illinois at Urbana-Champaign and Joseph Powell, PhD, of Garvan Institute in Australia.
By receiving this grant, the team joins the ASAP Collaborative Research Network, an effort to support international, multidisciplinary, multi-institutional research teams to address key knowledge gaps in the basic disease mechanisms that contribute to PD development and progression. The ASAP Initiative aims to accelerate the pace of discovery in PD research. Its implementation partner The Michael J. Fox Foundation for Parkinson’s Research issued the grant.