BBS Faculty Member - Lee Gehrke

Lee Gehrke

Department of Health Sciences and Technology
Department of Microbiology and Immunobiology

Massachusetts Institute of Technology
Building E25-406
45 Carleton Street
Cambridge, MA 02142
Tel: 617-253-7608
Fax: 509-357-7835
Lab Members: 1 postdoctoral fellow, 4 graduate students, 1 visiting scientist
Visit my lab page here.

We work on positive strand RNA viruses, with a current focus on understanding how cells sense viral invaders to initiate an immune response. We also have interests in global health, and we collaborate with engineers to develop a rapid point of care diagnostic device to detect pathogens for real-time epidemiology.

Distinguishing self from non-self is a key to detecting intracellular foreign invaders. Viral RNAs have features referred to as Pathogen Associated Molecular Patterns (PAMPs) that are recognized as non-self by host Pattern Recognition Receptors (PRR). Following recognition of PAMPs by PRRs, a signal transduction cascade is activated, leading to the establishment of an anti-viral state. This innate immune response is very rapid and precedes the adaptive immune response that produces antibodies. We work on defining the sequence and structural features present in viral RNA molecules that are responsible for innate immune activation. Evidence suggests that individual viral RNAs have distinct signals that stimulate specific receptors. For example, influenza activates the RIG-I receptor, while poliovirus activates the MDA5 receptor. Surprisingly, dengue virus RNA activates both, for reasons unknown.

Why don’t our own (self) RNAs activate an innate immune response? The answer to this question seems to be 1) self RNAs lack some of the structural features that are known to activate PRR (like a 5’ triphosphate group), and 2) self RNAs contain modified nucleotides that somehow block activation of innate immune signaling. These modifications include, for example, methylations. We work on understanding how RNAs containing modified nucleotides evade innate immune surveillance and activation.

Rapid diagnostics are badly needed to 1) identify the infectious agent responsible for patients’ fevers, 2) identify food pathogens, and 3) identify pathogens used in a bioterror attack. We are leading an NIH-funded multidisciplinary group that is developing a multiplexed rapid point of care diagnostic device that is machine-readable for GIS and real time epidemiology. The device is being designed for the “citizen-sensor” to be used without specialized reagents or equipment.

Last Update: 7/27/2015


For a complete listing of publications click here.



Yen CW, de Puig H, Tam JO, Gomez-Marquez J, Bosch I, Hamad-Schifferli K, Gehrke L. Multicolored silver nanoparticles for multiplexed disease diagnostics: distinguishing dengue, yellow fever, and Ebola viruses. Lab Chip. 2015;15(7):1638-41. doi: 10.1039/c5lc00055f. PubMed PMID: 25672590; PMCID: 4375736.

Odendall C, Dixit E, Stavru F, Bierne H, Franz KM, Durbin AF, Boulant S, Gehrke L, Cossart P, Kagan JC. Diverse intracellular pathogens activate type III interferon expression from peroxisomes. Nature immunology. 2014. doi: 10.1038/ni.2915. PubMed PMID: 24952503.

de Puig H, Tam JO, Yen CW, Gehrke L, Hamad-Schifferli K. The extinction coefficient of gold nanostars. The Journal of Physical Chemistry. 2015; in press.

© 2015 by the President and Fellows of Harvard College