Ilia Droujinine, PhD
Scripps Research Joint Appointments
Research Focus
Secreted proteins coordinate functions of organs and organisms, and compose a yet uncharacterized communication network. For example, in homeostasis, fat-derived adipokines leptin and adiponectin serve as inter-organ secreted metabolic regulators, and in behavior, major urinary proteins serve as inter-organism excreted pheromones regulating aggression. Secreted factors are also relevant for disease: resulting from poorly-characterized dysfunctional inter-organ signaling, obesity affects 40% of the US population (https://www.cdc.gov/obesity/data/adult.html). Despite their relevance for understanding novel biological processes and diseases, identifying the secreted proteins involved has been challenging. Existing analysis methods have serious limitations that preclude comprehensive identification of low-abundance factors and their origins and destinations. Thus, many additional physiologically- and disease-relevant factors remain to be identified. To address this, our new lab will broadly aim to apply novel high-throughput quantitative approaches we developed to inter-organ and inter-organism communication, in order to understand the nature of the signals involved, which tissue(s) they originate from and target, their functions, and how they are regulated in stress or disease.
We using mice as our primary model system
We established an in vivo global proteomic platform using BirA*G3 to investigate secreted protein trafficking between organs in Drosophila, and identified a fat body (similar to mammalian liver and adipose tissues) conserved secreted protein that regulates muscle activity. This protein acts on muscles through the interaction with a specific receptor. Due to the success of the BirA*G3 method, we have developed and characterized inducible BirA*G3 mice that we are now using to characterize interorgan communication proteins and peptides.
Secreted proteins also coordinate functions of organisms. Animals use chemical cues from their environment and conspecifics to inform decisions necessary for survival. Much is known about how small volatile molecules and pheromones guide behavior; however, whether and how other molecules secreted by conspecifics can influence behavior is unclear. Our research aims to uncover the roles of secreted proteins and peptides in this process.
Projects for new lab members:
- Identification of novel interorgan communication factors in homeostasis and stress in mammals
- Identification of novel interorganism communication factors in homeostasis and stress in mammals
- Mechanistic characterization of novel conserved interorgan and interorganism secreted peptides
Awards & Professional Activities
2021 Ellen Browning Scripps Foundation Award
2021 ASBMB Annual Meeting Presentation Award
2019 EMBO Poster/Presentation Prize, EMBO Workshop on Organ Crosstalk
2017 Herbert Tabor Young Investigator Award, J Biol Chem/ASBMB (best research at a FASEB meeting)
2014-2017 HMS Innovation Grant Program (IGP) Research Award, Harvard Medical School (HMS)
2014-2017 Osher Center for Integrative Medicine Pre-Doctoral Fellowship, HMS
2012-2015 NSERC PGS-D, HMS
2011 Alumni Gold Medal (Highest ranked graduating student in the Univ. of Waterloo Faculty of Science)
2011-2012 NSERC PGS-M, Harvard University
2010 Ontario International Opportunity Education Scholarship, Cambridge, MA
2009 Gretchen Mueller Memorial Biochemistry Scholarship (top biochemistry student), University of Waterloo
2009 Max Planck Society International Research School Scholarship, Freiburg, Germany
2009 President’s International Experience Award, Freiburg, Germany
2009 J.R. Coutts International Experience Award, Freiburg, Germany
2008 NSERC USRA (Undergraduate Student Research Award), University of Waterloo
2008 President’s Research Award, University of Waterloo
2006-2007 CHEM 13 News Research Assistantships (top 0.3% finish in Canada in chemistry exam)
2006-2011 Queen Elizabeth II Aiming for the Top Scholarship, Government of Ontario
2006 President’s Scholarship of Distinction, University of Waterloo
Selected References
*co-first author; #Corresponding author
Yang R*, Meyer AS*, Droujinine IA*, Udeshi ND, Hu Y, Guo J, McMahon JA, Carey DK, Xu C, Fang Q, Sha J, Qin S, Rocco D, Wohlschlegel J, Ting AY, Carr SA, Perrimon N, McMahon AP. A genetic model for in vivo proximity labeling of the mammalian secretome. Open Biol 12, 220149 (2022). DOI:10.1098/rsob.220149. PMCID: PMC9364151. Preprint available on April 15, 2022 (BioRxiv 2022.04.13.488228).
Droujinine IA#, Meyer AS, Wang D, Udeshi ND, Hu Y, Rocco D, McMahon JA, Yang R, Guo JJ, Mu L, Carey DK, Svinkina T, Zeng R, Branon T, Tabatabai A, Bosch JA, Asara JM, Ting AY, Carr SA, McMahon AP, Perrimon N#. Proteomics of protein trafficking by in vivo tissue-specific labeling. Nat Commun 12, 2382 (2021). DOI:10.1038/s41467-021-22599-x. PMCID: PMC8062696. Preprint available on April 15, 2020 (BioRxiv 2020.04.15.039933).
Droujinine I#. Elucidating protein communication between organs and organisms in homeostasis and stress. Harvard University PhD Thesis (2020).
Droujinine IA#, Perrimon N#. The Multidimensional Organization of Interorgan Communication Networks. Dev Cell 50(4), 395-396 (2019).
Mu L*#, Droujinine IA*#, Lee J, Wipf M, Davis P, Adams C, Hannant J, Reed MA#. A nanoelectronic platform for ultrasensitive detection of protein biomarkers in serum using DNA amplification. Anal Chem 89, 11325-11331 (2017).
Droujinine IA#, Perrimon N#. Interorgan communication pathways in physiology: Focus on Drosophila. Annu Rev Genet 50, 539-570 (2016).
Kwon Y, Song W, Droujinine IA, Hu Y, Asara JM, Perrimon N. Sysemic organ wasting induced by localized expression of the secreted insulin/IGF antagonist ImpL2. Dev Cell 33(1), 36-46 (2015).
Droujinine IA, Yan D, Perrimon N. A sharp end to sugary Wingless travels. J Cell Biol 206(7), 819-821 (2014).
Mu L, Droujinine IA, Rajan NK, Sawtelle SD, Reed MA. Direct, rapid, and label-free detection of enzyme-substrate interactions in physiological buffers using CMOS-compatible nanoribbon sensors. Nano Lett 14(9), 5315-5322 (2014).
Droujinine, IA#, Perrimon N#. Defining the interorgan communication network: systemic coordination of organismal cellular processes under homeostasis and localized stress. Front Cell Infect Microbiol 3, 82 (2013).
Droujinine, IA, Eckert M, Zhao W. To grab the stroma by the horns: From biology to cancer therapy with mesenchymal stem cells. Oncotarget 4(5), 651-664 (2013).
Babona-Pilipos R, Droujinine IA, Popovic MR, Morshead CM. Adult subependymal neural precursors, but not differentiated cells, undergo rapid cathodal migration in the presence of direct current electric fields. PLoS ONE 6(8), e23808 (2011).
Zhao W, Loh W, Droujinine IA, Teo W, Kumar N, Schafer S, Cui CH, Zhang L, Sarkar D, Karnik R, Karp JM. Mimicking the inflammatory cell adhesion cascade by nucleic acid aptamer programmed cell-cell interactions. FASEB J 25, 3045-3056 (2011).
Zhao W, Schafer S, Choi J, Yamanaka Y, Lombardi ML, Bose S, Carlson A, Phillips JA, Teo W, Droujinine IA, Cui C, Sarkar D, Jain RK, Lammerding J, Love JC, Lin CP, Karp JM. Cell surface sensors for real-time probing of cellular environments. Nat Nanotechnol 6, 524-531 (2011).