Kodi Ravichandran Lab

Research focus

​Engulfment of apoptotic cells - the art of eating a good meal. Every day, we turn over billions of cells as part of normal development and homeostasis. The recognition and phagocytic removal of such cells destined to die (mostly via 'apoptosis') is fundamentally important for our health. Failure to promptly and efficiently clear apoptotic cells can lead to chronic inflammation, autoimmunity and developmental defects. The apoptotic cell clearance is usually done by neighboring cells or by professional phagocytes such as macrophages and dendritic cells. In studying this process, we consider four broad issues related to 'eating an apoptotic meal'. The first issue is getting to the meal itself. This involves the release of so called 'find-me signals' from apoptotic cells that serve as attraction cues to recruit monocytes and macrophages near an apoptotic cell. We have identified a critical for the nucleotides ATP and UTP as find-me signals that are released in a regulated way very early on during apoptosis (Elliott et al. Nature, 2009; Checkeni et al., Nature, 2010; Poon et al., Nature 2014).

The second issue is determining what is on the menu, and distinguishing the apoptotic cell from the neighboring healthy cells. This is achieved through expression of 'eat-me' signals on apoptotic cells and their recognition by receptors on phagocytes. Here, we focus on the ligands on the dying cell and receptors on phagocytes that are involved in the specific recognition of apoptotic cells. Our further work has identified a novel type of engulfment receptor (BAI1) that recognizes phosphatidylserine, a key eat-me signal exposed on apoptotic cells (Park et al. Nature 2007, Park et al. Current Biology, 2009; Hochreiter-Hufford et al., Nature 2013).

The third issue is the act of eating the meal itself. Here, we focus on the specific intracellular signals that are initiated within the phagocyte when it comes in contact with apoptotic cells, and how this leads to cytoskeletal rearrangements of the phagocyte and internalization of the target. We have defined the signaling pathway downstream of BAI1 involving the proteins ELMO1, Dock180 and the small GTPase Rac. We have also defined a second signaling module that involves the membrane protein LRP1 and a small intracellular adapter protein GULP. (Gumienny et al. Cell , 2001, Brugnera et al. Nature Cell Biology, 2002; Lu et al. Nature Str Mol. Biol. , 2004; deBakker et al. Currently Biology, 2004; Lu et al. Current Biology , 2005; Ravichandran, Cell, 2003).

Steps in apoptotic cell clearance: Recruitment, recognition, engulfment and processing. Our laboratory investigates all of these steps as well as the anti-inflammatory signaling associated with apoptotic corpse uptake, and how this differs from other forms of cell death.


We have also generated mice with knockout of specific engulfment genes and are currently characterizing them (Elliott et al., Nature, 2010). The fourth relates to 'after-the-meal' issues. Contrary to other types of phagocytosis (such as bacterial uptake), engulfment of apoptotic cells is 'immunologically silent' and is actively anti-inflammatory. We are interested in determining how apoptotic cells induce an anti-inflammatory state of the phagocyte, and how this relates to immune tolerance or suppression of inflammation (Juncadella et al., Nature, 2013, Mauldin et al., Current Biology, 2013). Another fun problem in considering one cell eating another is that the phagocyte essentially doubles its cellular contents (including protein, cholesterol, nucleotides etc.). We are addressing how the ingested cargo is processed within the phagocyte, and how the phagocyte manages homeostasis (Kinchen et al. Nature Cell Biology, 2008; Kiss et al. Current Biology, 2007; Ravichandran et al. Nature Rev Immunol. 2007; Kinchen et al, Nature 2010; Fond et al., J of Clinical Investigation, 2015), and what controls an appetite of the phagocyte in ingesting multiple apoptotic cells (Park et al., Nature, 2011). Recently, we have also become very interested in how phagocytes communicate with each other in a tissue (Han et al., Nature, 2016), and how one can boost cell clearance in vivo (Lee et al., Immunity, 2016). The overall goal of these studies is to understand the signaling pathways and the consequences of engulfment at the molecular, cellular, and whole organism levels. We use a combination of molecular biology, cell biology, biochemistry, coupled with C. elegans and mouse knockout studies, to gain insights on how specific proteins orchestrate the intracellular signaling during engulfment and lead to the immunologically silent clearance of apoptotic cells. These could have implications for future therapies aimed at limiting inflammation (Elliott et al., Journal of Cell Biol, 2010, Developmental Cell, 2016).

Movie of a phagocyte engulfing an apoptotic cell.  Here the phagocyte is unlabeled but the apoptotic cell is labeled with a dye Cypher5E that has low basal fluorescence but in the acidic pH of the lysosomes (within the phagocyte), fluoresces brighter. This provides a convenient way to track engulfed apoptotic cells.


A noncanonical role for the engulfment gene ELMO1 in neutrophils that promotes inflammatory arthritis.Arandjelovic Sanja@ Perry Justin S Lucas Christopher Penberthy Kristen Kim Tae-Hyoun Zhou Ming Rosen Dorian Chuang Tzu-Ying Bettina Alexandra Shankman Laura Cohen Amanda Gaultier Alban Conrads Thomas Kim Minsoo Elliott Michael Ravichandran Kodi@NATURE IMMUNOLOGY, 20, 141-151, 2019@: corresponding authors
Living on the Edge: Efferocytosis at the Interface of Homeostasis and PathologyMorioka S Maueröder Christian Ravichandran Kodi@IMMUNITY, 50, 1149-1162, 2019@: corresponding authors
Interpreting an apoptotic corpse as anti-inflammatory involves a chloride sensing pathway.Perry Justin S Morioka Sho Medina Christopher Iker Etchegaray J Barron Brady Raymond Michael Lucas Christopher Onengut-Gumuscu Suna Delpire Eric Ravichandran KodiNATURE CELL BIOLOGY, 21, 1532-1543, 2019
Phosphatidylserine on viable sperm and phagocytic machinery in oocytes regulate mammalian fertilization.Rival Claudia Xu Wenhao Shankman Laura Morioka Sho Arandjelovic Sanja Lee Chang Sup Wheeler Karen Smith Ryan Haney Lisa Isakson Brant Purcell Scott Lysiak Jeffrey@ Ravichandran Kodi@Nature Communications, 10, 4456, 2019@: corresponding authors
Efferocytosis induces a novel SLC program to promote glucose uptake and lactate release.Morioka Sho Perry Justin S Raymond Michael Medina Christopher Zhu Yunlu Zhao Liyang Serbulea Vlad Onengut-Gumuscu Suna Leitinger Norbert Kucenas Sarah Rathmell Jeffrey Makowski Liza Ravichandran Kodi@NATURE, 563, 714-718, 2018@: corresponding authors

Job openings


5 VIB researchers receive an exceptional ERC Advanced grant

27/03/2019 - The European Research Council is unique in its kind in Europe supporting individual top researchers from anywhere in the world for 5 years. Five VIB researchers have been awarded this competitive & widely acknowledged benchmarks of scientific excellence

Kodimangalam Ravichandran

Kodimangalam Ravichandran

Research area(s)

Model organism(s)


PhD: Univ. of Massachusetts, Amherst, USA, 1992
Postdoc: Harvard Medical School, Boston, USA, 1992-96
Professor: Univ. of Virginia, Charlottesville, Virginia, USA, 1996-present
Director: Center for Cell Clearance, Univ. of Virginia, USA, 2008-present
Chair: Dept. of Microbiol., Immunol. & Cancer Biol., Univ. of Virginia, USA, 2010-present
Group leader at VIB since January 2017

Contact Info

VIB-UGent Center for Inflammation ResearchUGent-VIB Research Building FSVMTechnologiepark 71 9052 GENTRoute description