Anura Rambukkana

Tel: 0131 651 9500
Email: a.rambuka@ed.ac.uk

Street: Centre for Regenerative Medicine,
Institute for Regeneration and Repair,
The University of Edinburgh,
Edinburgh BioQuarter,
5 Little France Drive,
City: Edinburgh
Post code: EH16 4UU

Biography

Background

Prof Rambukkana relocated to the Centre for Regenerative Medicine in 2010 from The Rockefeller University New York where he was a faculty member since 2000; his laboratory was funded mainly by the grants from the US National Institutes of Health (NIH; NINDS and NIAID) and Medical Research Council (MRC) UK. He obtained his PhD from the University of Amsterdam, The Netherlands, and continued his first postdoctoral training in the Academic Medical Center, University of Amsterdam. He then moved to Rockefeller University for his second postdoctoral training before obtaining his faculty position at Rockefellar University. Prof Rambukkana is also a member of Edinburgh Infectious Diseases and Centre for Discovery Brain Scineces.

For further info please check ORCID

Edinburgh Infectious Diseases

Centre for Discovery Brain Scineces

Rambukkana Laboratory Group Page

Full list of publications on PubMed

Teaching & PhD supervision

Open to PhD supervision enquiries?

Yes

Research

Research summary

Adult tissue cell plasticity, reprogramming and regeneration

Our laboratory uses a pioneering and disruptive approach to exploit the thematic intersection of the biology of bacterial-induced partial host cell reprogramming with regeneration and aging.

By harnessing naturally-occurring and evolutionarily refined bacterial strategies and using machine-learning/artificial intelligence tools our ultimate future goals are to develop new therapeutics for treating chronic human diseases affecting those tissues/organs with high regenerative capacity – the peripheral nerves, liver, skin and intestine. Our bacterial agents naturally target these tissues in their animal and human hosts promoting tissue growth and regeneration either by reprogramming cells or propagating existing tissue stem cells rendering them to a more “rejuvenated” or ‘youthful’ state.

Learning from this, our research focuses to translate bacterial mechanisms that engage these regenerative pathways into strategies to develop therapeutics that promote tissue repair in diseased or aging tissues/organs.

These bacterial strategies could inform the development of new therapeutic approaches to reprogram cancers into a less aggressive phenotype to promote patient survival.

Our discovery that strictly host-dependent bacterial pathogens like Mycobacterium leprae hijacks the notable plasticity of adult regenerative host tissues also holds promise for developing strategies for targeting key host-encoded functions of cell reprogramming as an alternative approach for combating bacterial infections, particularly the emerging global threat by drug/antibiotic-resistant bacteria.

“Look deep into Nature and you will understand everything Better” – Albert Einstein

"In every walk with Nature one receives far more than he seeks." - John Muir (Scottish-American naturalist)

Aims and areas of interest

Our laboratory studies a pioneering approach from a natural bacterial infection process with partial host cell reprogramming capacity to address the basic biology of adult tissue stem cells and their properties in regulating homeostasis, regeneration and rejuvenation of tissues, We seek to translate our discoveries to develop interventions for tissue repair and reversing the cellular aging process. Many years of our studies on the cell biology of Mycobacterium leprae infection of peripheral glial cells Schwann cells (highlighted in: Cell, 1997; 2000; Science, 1998; 2002; PNAS, 1999, 2005; Nature Medicine, 2006), led to the discovery that this bacterium has a striking capacity to naturally partially reprogram adult Schwann cells to stem cell-like cells (Cell, 2013). Building on this concept our current studies are focused on how this bacterial ingenuity of partially reprogram adult tissue cells to progenitor state can be exploited to regenerate diseased tissues and rejuvenate aging tissues. We are also studying how these reprogrammed progenitor/stem cells can be combined with endogenous innate immune cells with natural regenerative and tissue protective properties to promote repair processes without adverse effects in tissues with high regenerative capacities, peripheral nerves, liver, skin and intestine in varying model systems, in vitro, ex vivo and in vivo models. These concepts have now translated to in vivo studies using exotic larger mammals, nine-banded armadillo and pigs. Studies in nine-banded armadillos showed that bacteria employ their ingenuities of partial host cell reprogramming to promote the growth of adult liver at an organ level in living animals (Cell Rep Medicine, 2022). If we could detail the mechanism of how bacteria grow the adult liver as a functional organ without causing adverse effects in living animals, we may be able to translate that knowledge to develop safer therapeutic interventions to rejuvenate aging livers and to regenerate damaged tissues in humans in future. Learning from evolutionary refined bacterial strategies of tissue growth and regeneration our long-term goals are to develop common and safer interventions for therapeutic regeneration and rejuvenation for tissues/organs with high regenerative capacities, namely the peripheral nerves, liver, skin and intestine, where our bacterial models naturally target in their animal and human host.

The original scientific discoveries in the following publications are the flagship of our laboratory

Rambukkana A*, Salzer JL, Yurchenco PD, Tuomanen EI: Neural targeting Mycobacterium leprae Mediated by the G domain of the laminin alpha2 chain. Cell 88: 811-821, 1997 (*corresponding author). DOI:10.1016/s0092-8674(00)81927-3

Rambukkana A*, Yamada, H, Sanazzi, G, Salzer JL, Yurchenco PD, Campbell, KP: Role of alpha-dystroglycan as a Schwann cell receptor for Mycobacterium leprae. Science 282: 2076-2079, 1998 (*corresponding author).

Shimoji Y, Ng V, Matsumura K, Fischetti VA, Rambukkana A: A novel surface protein of M. leprae binds peripheral nerve laminin-2 and mediates Schwann cell invasion. Proc Natl Acd Sci.USA 96: 9857-9862, 1999.

Ng V, Zanazzi, G, Salzer, JL, Timpl R, Talts JF, Brennan P, Rambukkana A: Role of the cell wall Phenolic Glycolipid-1 in the peripheral nerve predilection of Mycobacterium leprae. Cell 103: 511-524, 2000.

Rambukkana A *, Zanazzi G, Tapinos N, Salzer JL: Contact-dependent demyelination by Mycobacterium leprae in the absence of immune responses. Science 296: 927-931, 2002 (*corresponding author).

Rambukkana A *, Kuntz, S, Min, J, Kampbell, KP. Oldstone, MB: Targeting Schwann cells by nonlytic arenaviral infection selectively inhibits myelination. Proc Natl Acad Sci USA.100: 16071-10676, 2003 (*corresponding author).

Tapinos N, Rambukkana A: Insights into regulation of human Schwann cell proliferation by ERK-1/2 via a MEK-independent and p56Lck-dependent pathway from leprosy bacilli. Proc Natl Acad Sci USA 102: 9188-9193, 2005.

Tapinos N, Ohnishi M, Rambukkana A: ErbB2 receptor tyrosine kinase mediates early demyelination induced by leprosy bacilli. Nature Medicine 12, 961-966, 2006.

Masaki T, Qu J, Cholewa-Waclaw J, Burr, K, Raaum R, Rambukkana A: Reprogramming adult Schwann cells to stem cell-like cells by leprosy bacteria promote dissemination of infection. Cell 152, 51-67, 2013.

Masaki T, Qu J, Cholewa-Waclaw J, Burr K, Raaum R, Rambukkana A. 2013. Reprogramming Adult Schwann Cells to Stem Cell-like Cells by Leprosy Bacilli Promotes Dissemination of Infection. Best of Cell 2013, online issue, 2014.

Hess S, Kendall TJ, Pena M, Yamane K, Soong D, Adams L, Truman R, Rambukkana A. In vivo partial reprogramming by bacteria promotes adult liver organ growth without fibrosis and tumorigenesis. Cell Rep Medicine. 2022 Nov 15;3(11):100820. doi: 10.1016/j.xcrm.2022.100820.

Rambukkana Laboratory Group Page

Publications

In vivo Partial Reprogramming by Bacteria Promotes Adult Liver Organ Growth without Fibrosis and Tumorigenesis (45 pages) 15 Nov 2022 In: Cell Reports Medicine, vol. 3
DOI: https://doi.org/10.1016/j.xcrm.2022.100820
Research output: Contribution to Journal › Article (Published)
Cell Biology of Intracellular Adaptation of Mycobacterium leprae in the Peripheral Nervous System 19 Jul 2019 In: Microbiology Spectrum, vol. 7
DOI: https://doi.org/10.1128/microbiolspec.BAI-0020-2019
Research output: Contribution to Journal › Article (Published)
Draft Genome Sequences of Lawsonia intracellularis Swine Strains Causing Proliferative Enteropathy in Japan 6 Sep 2018 In: Microbiology Resource Announcements, vol. 7
DOI: https://doi.org/10.1128/MRA.01021-18
Research output: Contribution to Journal › Article (Published)
Bacterial-induced cell reprogramming to stem cell-like cells: new premise in host-pathogen interactions (10 pages) Feb 2015 In: Current Opinion in Microbiology, vol. 23, pp. 179-88
DOI: https://doi.org/10.1016/j.mib.2014.11.021
Research output: Contribution to Journal › Literature review (Published)
The Armadillo as a Model for Peripheral Neuropathy in Leprosy (11 pages) 1 Dec 2014 In: ILAR Journal, vol. 54, pp. 304-314
DOI: https://doi.org/10.1093/ilar/ilt050
Research output: Contribution to Journal › Article (Published)
Innate Immune Response Precedes Mycobacterium leprae–Induced Reprogramming of Adult Schwann Cells Feb 2014 In: Cellular Reprogramming, vol. 16, pp. 9-17
DOI: https://doi.org/10.1089/cell.2013.0064
Research output: Contribution to Journal › Article (Published)
Reprogramming Adult Schwann Cells to Stem Cell-like Cells by Leprosy Bacilli Promotes Dissemination of Infection (17 pages) 17 Jan 2013 In: Cell, vol. 152, pp. 51-67
DOI: https://doi.org/10.1016/j.cell.2012.12.014
Research output: Contribution to Journal › Article (Published)
Reprogramming diminishes retention of Mycobacterium leprae in Schwann cells and elevates bacterial transfer to fibroblasts 2013 In: F1000Research, vol. 2
DOI: https://doi.org/10.12688/f1000research.2-198.v2
Research output: Contribution to Journal › Article (Published)
A Histone-Like Protein of Mycobacteria Possesses Ferritin Superfamily Protein-Like Activity and Protects against DNA Damage by Fenton Reaction (11 pages) 16 Jun 2011 In: PLoS ONE, vol. 6, pp. -
DOI: https://doi.org/10.1371/journal.pone.0020985
Research output: Contribution to Journal › Article (Published)
Usage of signaling in neurodegeneration and regeneration of peripheral nerves by leprosy bacteria (6 pages) Jun 2010 In: Progress in neurobiology, vol. 91, pp. 102-107
DOI: https://doi.org/10.1016/j.pneurobio.2009.12.002
Research output: Contribution to Journal › Literature review (Published)
ErbB2 receptor tyrosine kinase mediates early demyelination induced by leprosy bacilli 2006 In: Nature Medicine, pp. 961-966
DOI: https://doi.org/10.1038/nm1433
Research output: Contribution to Journal › Letter (Published)
Insights into regulation of human Schwann cell proliferation by Erk1/2 via a MEK-independent and p56Lck-dependent pathway from leprosy bacilli 28 Jul 2005 In: Proceedings of the National Academy of Sciences (PNAS), vol. 102, pp. 9188-93
DOI: https://doi.org/10.1073/pnas.0501196102
Research output: Contribution to Journal › Article (Published)
Mycobacterium leprae-induced demyelination: A model for early nerve degeneration (8 pages) 1 Aug 2004 In: Current Opinion in Immunology, vol. 16, pp. 511-518
DOI: https://doi.org/10.1016/j.coi.2004.05.021
Research output: Contribution to Journal › Review article (Published)
Expression of Toll-like receptor 2 on human Schwann cells: a mechanism of nerve damage in leprosy (7 pages) Mar 2003 In: Infection and Immunity, vol. 71, pp. 1427-33
DOI: https://doi.org/10.1128/IAI.71.3.1427-1433.2003
Research output: Contribution to Journal › Article (Published)
Targeting Schwann cells by nonlytic arenaviral infection selectively inhibits myelination 2003 In: Proceedings of the National Academy of Sciences (PNAS), vol. 100 , pp. 16071-16076
Research output: Contribution to Journal › Article (Published)
Contact-dependent demyelination by Mycobacterium leprae in the absence of immune responses 2002 In: Science, vol. 296, pp. 927-931
Research output: Contribution to Journal › Article (Published)
Role of the cell wall phenolic glycolipid-1 in the peripheral nerve predilection of Mycobacterium leprae (14 pages) 27 Oct 2000 In: Cell, vol. 103, pp. 511-24
DOI: https://doi.org/10.1016/s0092-8674(00)00142-2
Research output: Contribution to Journal › Article (Published)
How does Mycobacterium leprae target the peripheral nervous system? (6 pages) 1 Jan 2000 In: Trends in Microbiology, vol. 8, pp. 23-8
DOI: https://doi.org/10.1016/s0966-842x(99)01647-9
Research output: Contribution to Journal › Review article (Published)
A 21-kDa surface protein of Mycobacterium leprae binds peripheral nerve laminin-2 and mediates Schwann cell invasion (6 pages) 17 Aug 1999 In: Proceedings of the National Academy of Sciences (PNAS), vol. 96, pp. 9857-62
DOI: https://doi.org/10.1073/pnas.96.17.9857
Research output: Contribution to Journal › Article (Published)
Role of alpha-dystroglycan as a Schwann cell receptor for Mycobacterium leprae (4 pages) 11 Dec 1998 In: Science, vol. 282, pp. 2076-9
DOI: https://doi.org/10.1126/science.282.5396.2076
Research output: Contribution to Journal › Article (Published)

View all 20 publications on Research Explorer

Media

In the press

Lab in the News

Building on the previous discovery that a bacterial pathogen naturally reprograms adult tissue cells to progenitor cells/stem cells (Masaki et al Cell 2013), we have translated this concept to a naturally infected animal model, nine-banded armadillos. We have shown that the same leprosy bacteria not only reprogram infected animal livers but also grow the liver as a functional organ without causing adverse effects (Cell Rep Medicine 2022). This work made headlines around the world and in was featured in major Science magazines. Below: the commentary from Cell Press and selected articles from over 570 news media websites across the globe:

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