T he Miller-Jensen laboratory uses a systems immunology approach: we combine quantitative experiments with integrated computational analyses to account for the multiple molecular and cellular processes, non-linear outputs, and complex intercellular interactions that ultimately enable robust immune regulation. We are specifically focused on the sources and consequences of cellular response diversity. Considering the precision of immune cell responses to diverse pathogenic threats, it is counterintuitive that genetically identical immune cells respond to perturbations with a high degree of cell-to- cell variability, or “noise”; but recent research makes clear that this variability is an indispensable feature of immune system function.
Heterogeneity of macrophage communication behavior. Macrophages are cells of the innate immune system that perform a range of functions important in host defense against pathogens. To carry out diverse functions, macrophages maintain a functional plasticity, or flexibility, in their responses to microenvironmental stimuli, and we hypothesize this is partially enabled by cell-to-cell heterogeneity. We are studying how heterogeneous macrophage subsets coordinate activation of neighboring macrophages and other cells via paracrine signaling in response to pathogens and in the tumor microenvironment.
Regulatory logic of signal–response relationships. We are also interested in the mechanisms that regulate cell-to-cell variability. Single-cell analyses provide a direct way to evaluate signal–response relationships. As a centrally important example, we focus on the NF-κB pathway, which regulates both endogenous inflammatory genes in macrophages and HIV gene expression in T cells. We are studying how targeting cell-to-cell response variability can modulate phenotypic outcomes in these contexts.
Kathryn worked previously at the National Academies, Merck Pharmaceuticals, the Chinese Academy of Sciences, and Monitor Group. She received her Ph.D. in Chemical Engineering at MIT with Doug Lauffenburger. and her B.E. & B.A. degrees at Dartmouth College.
She can be reached via either of the following methods:
Congrats, Dr. Muñoz-Rojas. Andrés successfully defended his thesis, "Analysis of macrophage polarization: single-cell responses in controlled and tumor microenvironments". Congrats!. Posted 2018-03-23
Congrats, Dr. Fong. Linda successfully defended her thesis, "Data-Driven Analysis of Phospho-Signaling Network Responses Enables Latent HIV-Infected T Cell Targeting". Congrats!. Posted 2017-11-20
Elise is awarded a PEB Training grant slot. Elise Bullock was awarded a slot on Yale's NIH T32 Training grant supporting the Integrated Graduate Program in Physical and Engineering Biology. Posted 2017-06-08
Amanda is awarded an NSF Grad Student Fellowship. Amanda Alexander was awarded a Graduate Student Research Fellowship from the National Science Foundation. Posted 2016-04-05
Ramesh's device is in the news. . Posted 2015-07-15