Sreeganga S Chandra, PhD

Associate Professor of Neurology and of Molecular, Cellular, and Developmental Biology

Research Organizations

Interdepartmental Neuroscience Program

National Gaucher Disease Treatment Center

Neurology: Chandra Lab

Program in Cellular Neuroscience, Neurodegeneration and Repair

Stem Cell Center, Yale

Research Summary

My lab explores two related themes, those of synapse loss and neurodegeneration. Synapse loss is an early, defining event in neurodegenerative diseases, such as Parkinson's disease. In these prolonged diseases, decreases in synapse density are the best correlates of disease progression.Yet, little is known about the pathways that maintain synapses and their roles in aging and neurodegeneration. We are characterizing a novel presynaptic mechanism for the prevention of synapse loss and neurodegeneration involving the co-chaperone Cysteine String Protein alpha. This gene is also mutated in adult-onset neuronal ceroid lipofuscinosis, a neurodegenerative disorder with lysosomal pathology. We are also screening for new synapse maintenance genes using a dissociated neuronal culture system.

Parkinson's disease (PD) is a prevalent, neurodegenerative disease with a strong genetic underpinnings. The first PD gene to be identified was the alpha-synuclein gene. Three point mutations and gene multiplications link alpha-synuclein to familial PD. In addition, alpha-synuclein protein is the main component of Lewy bodies, the pathological signature for PD. We are elucidating both the physiological functions and pathological properties of alpha-synuclein, in an effort to understand its central role in PD. Our lab uses mouse genetics in combination with biochemical, biophysical, and cell biological approaches to tackle these important questions.

Extensive Research Description

  • Identification of the physiological function of synucleins
  • Role of CSP alpha in synapse maintenance
  • Identification of novel synapse maintenance genes
  • Interplay between PARK genes
  • Protein palmitoylation and neuronal ceroid lipofuscinosis

Selected Publications

Edit this profile

Contact Info

Sreeganga S Chandra, PhD
Mailing Address
295 Congress Avenue
BCMM 154D

New Haven, CT 06536

Chandra Lab

Research Image 2

Synuclein null synapses showing a deficit in HRP-cholera toxin positive vesicles (black vesicles). This experiment in synuclein null neurons supports a physiological role for alpha-synuclein in synaptic vesicle endocytosis.