James A. Walker, PhD

  • Lab Phone: 617-569-4671


Research Investigator Profile

James A. Walker, PhD

Collaborators

Center for Human Genetic Research

  • Scott Plotkin, Vamsi Mootha, Vishal Gohil

MGH Cancer Center

  • Luisa Di Stefano, Nick Dyson

Alexander Fleming Institute, Greece

  • Makis Skoulakis, Jean Gouzi

James A. Walker, PhD

  • Instructor in Neurology,
    Harvard Medical School

 

 


Research Description

We use Drosophila as a model system to study orthologs of genes involved in several human neurological diseases. Genetic screens, combined with biochemical, molecular and cellular biological techniques provide a powerful to approach to uncovering the signaling pathways involved in disease processes.

a) Neurofibromatosis type-1 (NF1) is a common genetic disease for which there is currently no effective therapy. Patients with mutations in the tumor suppressor gene NF1 are predisposed to benign and malignant tumors, many of which affect the peripheral and central nervous system (CNS). By studying the function of NF1 in growth control and learning/memory in Drosophila we are uncovering novel signaling pathways regulated by NF1 that may provide possible therapeutic targets.

b) Schwannomatosis is characterized by multiple spinal, peripheral, and cranial nerve schwannomas. Recently we have been using Drosophila to shed light on the role of the tumor suppressor genes NF2 and SMARCB1 in this disease.

c) We are also using Drosophila to study the normal function of Huntingtin (Htt), the gene responsible for Huntington’s Disease.  Considerable work has been conducted on the mutant form of Htt, which contains polyglutamine repeats. However, it is likely that loss of normal Htt function also contributes to disease progression and it is hoped that Drosophila will be useful as a model system for determining the normal roles of Htt.

UAS-GFP reporter staining for actin Insulin produced in neuroendocrine cells NF1 regulates growth eye tissue overgrowth

Select any image to view captions.

Biography Dr. Jim Walker is an Instructor in Neurology at Harvard Medical School and an Assistant in Genetics at Massachusetts General Hospital. Working at the Center for Human Genetic Research (CHGR) he uses the fruit fly, Drosophila melanogaster, as a model system to study several human neurological diseases. Many basic biological, physiological, and neurological properties are conserved between mammals and Drosophila and nearly 75% of human disease-causing genes are believed to have a functional ortholog in the fly. The Walker laboratory uses genetic, biochemical, molecular and cell biology techniques to gain insights into disease processes and identify potential therapeutic targets. Novel findings from Drosophila are subsequently used to guide experiments in mammalian systems. Dr. Walker is interested in Neurofibromatosis type-1 (NF1), a common genetic disease, affecting 1 in ~3000 people worldwide, that predisposes patients to benign and malignant tumors, many of which affect the peripheral and central nervous system. In addition, he is interested in Huntington's Disease (HD), a rare, progressive and fatal neurodegenerative disorder. There are currently no effective disease-modifying treatments for either NF1 or HD. Dr. Walker is a member of the Center for Neurofibromatosis and Allied Disorders (CNfAD) at Harvard Medical School. The Walker laboratory gratefully acknowledges funding from the Children’s Tumor Foundation (CTF), The Department of Defense (DoD) and the CHDI.
Research interests Control of cell and organismal growth; tumor suppressors; signal transduction; chromatin remodeling; neuropeptides
Research techniques Drosophila genetics, molecular and cellular biology, biochemistry
Diseases studied Neurofibromatosis, schwannomatosis, Huntington’s Disease
Selected publications
  1. Walker, JA, Tchoudakcova, AV, McKenney, PT, Brill, S, Wu, D, Cowley, GS, Hariharan, IK, Bernards, A. Reduced growth of Drosophila neurofibromatosis 1 mutants reflects a  non-cell-autonomous requirement for GTPase Activating Protein activity in larval neurons. Genes and Development 2006; 20(23): 3311-3323.
  2. Walker, JA, Bernards, A. Drosophila melanogaster neurofibromatosis-1: ROS, not Ras? Nature Genetics 2007; 39, 4: 443-445.
NIH biosketch James A. Walker, PhD
E-mail address jwalker@helix.mgh.harvard.edu
Lab mailing address MGH Center for Cancer Research
Room 7119, Building 149
149 13th Street
Charlestown, MA 02129
Lab website

Bernards Lab, Center for Cancer Research

Gusella Lab, CHGR