Insulin Resistance

Kin Yui Alice Lo is a joint graduate student also in Ernest Fraenkel's lab in the Biological Engineering Department at MIT. She is adopting a systems approach to understand multiple forms of insulin resistance in adipocytes at the transcriptional level due to various physiological and pathological insults. Using the 3T3-L1 adipogenesis model we have used extensively, she adopted the mRNA-seq technique to study how the transcriptional outcomes of diverse insulin resistance models differ from each other and how they compare to in vivo models of insulin resistance. She confirmed a previous observation made by a former post-doc, Hong Ruan, that TNFalpha induced insulin resistance by suppressing many adipocyte important genes (eg Pparɣ, Adipoq) and inducing many preadipocyte genes. She is investigating if this phenomenon is also present in other insulin resistance models. Among all the in vitro models that she set up, she has found a certain model that most able to mimic the changes that we observe in vivo. In order to understand gene regulation, she is also using the DNA-hypersensitivity cum sequencing technique to investigate chromatin changes and transcriptional factor binding that lead to the diverse transcriptional outcomes.

Heide Christine Patterson, a new post-doc in the laboratory and a pathologist at Brigham and Women’s Hospital, is investigating whether a kinase important for signal transduction in immune cells also mediates activation of pathways critical for cellular insulin resistance in adipocytes in response to the same stimuli used by Alice Lo and whether this kinase controls glucose homeostasis in vivo.