Prabhodh Abbineni, PhD
Assistant Professor
Microbiology & Immunology
Research Interests:
- Molecular regulation of the secretory pathway to understand how this pathway modulates intercellular communication innate immunity, and inflammation.
Education
PhD, Western Sydney University, Sydney Australia
Research Interests
Major Research Interests:
We investigate the molecular regulation of secretory pathways that modulate innate immunity and inflammation.
Upon detection of pathogens, innate immune cells secrete molecules such as cytokines and chemokines, which are vital for triggering inflammation and activating adaptive immunity. However, uncontrolled inflammation due to excessive cytokine release can lead to severe health issues, contributing to the pathology of infectious and autoimmune diseases. While targeted anti-cytokine therapies exist, their effectiveness is limited in complex conditions involving multiple cytokines, such as viral infections and bacterial sepsis.
Our research focuses on the secretory pathways that release these pro-inflammatory cytokines. Most secreted proteins contain endoplasmic reticulum (ER) targeting signal-peptides and are release via the ER-Golgi secretory pathway. However, several cytoplasmic proteins critical for innate immunity are released via less understood ER-Golgi independent routes, known as “unconventional” cytoplasmic protein secretion (UCPS). By understanding these pathways, we aim to uncover new strategies to broadly suppress inflammation, offering potential therapeutic targets for various inflammatory disorders.
Approach:
We employ a multidisciplinary approach that combines live-cell imaging, high-throughput proteomics, and CRISPR-Cas9-based forward genetics to investigate secretory pathways. Total Internal Reflection Fluorescence (TIRF) microscopy provides high signal-to-noise imaging of cell surface events, allowing us to directly observe secretory vesicle fusion with the plasma membrane and monitor protein release. We have developed image analysis techniques to quantify the kinetics and extent of release. Our goal is to apply these techniques to understand how secretory pathways in innate immune cells respond to pathogen and damage-associated molecular patterns.
We also examine the secretome, which comprises all proteins secreted by cells under specific conditions, by using mass-spectrometry-based secretomics. We’ve developed novel analyses to specifically identify unconventionally secreted cargoes by utilizing this approach. This allows us to identify secretome changes in response to external stressors, including pathogenic components. By integrating this with CRISPR-Cas9-mediated gene knockouts, we aim to define the specific secretory routes activated upon cellular detection of these stimuli. Additionally, by leveraging genome-wide CRISPR screens combined with next-generation sequencing, we are identifying novel genes that regulate the cellular response to inflammatory stimuli, pushing forward our understanding of immune regulation at the molecular level.
Publications/Research Listings
Publications (past 5 years; 2019-2024):
Abbineni P, Baid S, Weiss MJ. A Moonlighting Job for alpha-Globin in Blood Vessels. 2024. Blood. PMID: 38848504
Tang VT, Xiang J, Chen Z, McCormick J, Abbineni PS, Chen XW, Hoenerhoff M, Emmer BT, Khoriaty R, Lin JD, Ginsburg D. Functional overlap between the mammalian Sar1a and Sar1b paralogs in vivo. 2024. Proceedings of the National Academy of Sciences. PMID: 38687799
Tang VT, Abbineni PS, Veiga Leprevost FD, Basrur V, Khoriaty R, Emmer BT, Nesvizhskii AI, Ginsburg D. Identification of LMAN1-and SURF4-Dependent Secretory Cargoes. 2023. Journal of Proteome Research. PMID: 37844105
Abbineni PS, Tang VT, da Veiga Leprevost F, Basrur V, Xiang J, Nesvizhskii AI, Ginsburg D. Identification of secreted proteins by comparison of protein abundance in conditioned media and cell lysates. 2022. Analytical biochemistry. PMID: 35973625
Abbineni PS, Briguglio JS, Chapman ER, Holz RW, Axelrod D. VAMP2 and synaptotagmin mobility in chromaffin granule membranes: implications for regulated exocytosis. 2022. Molecular Biology of the Cell. PMID: PMID: 34851717
Rituper B, Guček A, Lisjak M, Gorska U, Šakanović A, Bobnar ST, Lasič E, Božić M, Abbineni PS, Jorgačevski J, Kreft M. 2022. Vesicle cholesterol controls exocytotic fusion pore. 2022. Cell Calcium. PMID: 34844123
Abbineni PS, Bohannon KP, Bittner MA, Axelrod D, Holz RW. Identification of β-synuclein on secretory granules in chromaffin cells and the effects of α-and β-synuclein on post-fusion BDNF discharge and fusion pore expansion. 2019. Neuroscience letters. PMID: 30711526
Abbineni PS, Bittner MA, Axelrod D, Holz RW. Chromogranin A, the major lumenal protein in chromaffin granules, controls fusion pore expansion. 2019. Journal of General Physiology. PMID: 30504267
Full list of publications: https://pubmed.ncbi.nlm.nih.gov/?term=abbineni+prabhodh&sort=pubdate