Associate Professor, Pharmacology
Associate Professor, Chemistry & Biochemistry
My research focuses on understanding how transforming growth factor beta (TGF-beta) signaling controls a wide spectrum of molecular and cellular effects ranging from proliferation to differentiation and cell motility. While gene regulation is the primary mode of signal transduction, often occurring in a highly context-specific manner, our long-term goals include characterizing novel mechanisms by which the canonical effectors, namely the nuclear shuttling SMAD transcription factors and TGF-beta-activated kinase 1 (TAK1), directly modulate cellular activities.
Along with traditional biochemical, biophysical and cellular approaches, we have employed mass spectrometry/proteomics as a key strategy to identify new binding partners and their transcription-independent roles across cell types. We previously discovered that transcriptionally “inactive” SMAD proteins residing in the cytoplasm can influence mitochondrial dynamics through interaction with mitofusin 2 (MFN2), a GTPase critical for mitochondrial fusion in mammalian systems. We found that SMADs do not act alone, but rather as a protein scaffold complex with RIN1 (guanine nucleotide exchange factor) to enhance the MFN2 GTP-binding properties and promote mitofusion.
Likewise through similar methods, we recently characterized new protein interactions between TAK1 and a subset of microtubule modifying enzymes. We are interested in learning how these interactions control microtubule functions including their mechanical stability as well as cellular transport of protein cargo. Collectively, these findings represent major new facets of TGF-beta biology and directions for the lab as we explore how disease-causing mutations impact their functional interactions in cancer, metabolic and neurologic conditions.