Ghosh is research professor and chief scientist in the Center for Secure Information Systems (CSIS) at George Mason University. He is also the founder of Secure Command, LLC, a start-up developing next generation Internet security products. Ghosh's research focuses on combating malicious software. He has developed novel approaches for securing desktops using virtualization. He is also developing techniques for detecting malicious code within enterprise networks by classifying network traffic flows. 

Prior to joining Mason, Ghosh was senior scientist and program manager in the Advanced Technology Office of the Defense Advanced Research Projects Agency (DARPA) where he managed an extensive portfolio of information assurance and information operations programs. He has served as principal investigator on contracts from DARPA, NSA, and NIST's Advanced Technology Program and has written more than 40 peer-reviewed conference and journal articles. Ghosh is also author of three books on computer network defense