Dr Alanna (Leni) Green
PhD, BBiomedSc (Hons).
Clinical Medicine, School of Medicine and Population Health
Research Fellow
+44 114 215 9200
Full contact details
Clinical Medicine, School of Medicine and Population Health
Room FU32, F Floor
The Medical School
Beech Hill Road
Sheffield
S10 2RX
- Profile
-
For enquiries, please contact – ClinMed-Operational@sheffield.ac.uk
I joined the University of Sheffield in 2016 as a Postdoctoral Research Associate in the Sheffield Myeloma Research Team, Department of Oncology and Metabolism working with Dr Andrew Chantry and Dr Michelle Lawson. In July 2019, I joined Professor Thomas Helleday’s team, as a Postdoctoral Research Associate and Project Leader using novel inhibitors to target the cancer-specific enzyme MTHFD2. Since July 2020 I have led the Cancer and Bone (CAB) Lab, developing new drugs to treat cancer with a focus on incurable cancers in bone. My team are developing novel strategies to kill dormant cancer cells in myeloma to improve survival, and even cure, these cancers.
I completed my BBiomedSci at Monash University in 2009 focusing on pharmacology and biochemistry, receiving a High Achievement Award. In 2010, I completed my Honours year in the Stem Cell Regulation Unit at St Vincent’s Institute of Medical Research (SVI), The University of Melbourne receiving first-class honours and a place on the Dean’s Honours List (first in class). I continued my research career working as a Research Assistant at SVI, followed by my PhD in the Department of Medicine (SVI), The University of Melbourne, which was completed in December 2016. My PhD identified that retinoic acid receptor signalling regulates mesenchymal stem cell fate and bone biology leading to altered haematopoiesis. This provided insight into a mechanism by which blood and bone cells interact in health and disease. Understanding the roles of microenvironment cells is vital for improving haematopoietic recovery following chemotherapy or bone marrow transplants and crucial for enhanced targeting of dormant tumour cells in the bone marrow exhibiting chemotherapy-resistance. I also created a new method for FACS isolation of primary bone cells, particularly cells involved in regulating haematopoiesis, improving the way diseases involving aberrant microenvironment cells (such as myeloma) are studied and understood.
I have been recognised as ‘one of the most talented young researchers in the bone field’ by the two largest international bone societies globally: the ECTS and ASBMR. Throughout my career I have been awarded >20 awards for my research including 6 Young Investigator awards, 5 Best Oral/Poster Prizes, an award for Teaching, an award for outreach activities and in 2020 I won the Faculty MDH Early Career Researcher Prize. I graduated 1st in class from The University of Melbourne, the #1 Medical School in Australia.
I have been an elected committee member of the Bone Research Society (BRS) since 2019, and on the annual conference committees 2020-2022. I am organising the BRS Basic Course in Bone and Cartilage Biology and Disease 2022 (Sheffield). I was the Founder, Co-President and Co-Chair of The Inaugural EMBL Australia PhD Symposium in 2014, a conference with 100 attendees and both national and international invited speakers.
- Research interests
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My research interests focus on bone-cancer interactions, in particular in the cancer multiple myeloma. I am interested in how cancer induces destructive bone disease and also how bone regulates tumourigenic processes like dormancy, relapse and metastasis to bone. My research has developed advanced preclinical models of myeloma to improve testing of novel therapeutics. Using these mouse models we have shown that bone anabolic therapy can heal myeloma bone disease through a mechanism similar to intramembranous fracture repair. I also have extensive experience in studying how the bone marrow microenvironment regulates haematopoiesis. Findings from my PhD identified a novel bone lining cell type that is a putative niche for early B lymphopoiesis.
Currently, my research focuses on identifying whether novel therapies involved in oxidative damage and the DNA damage response (DDR), can be used to treat cancers, and specifically targeting chemotherapy-resistance, dormant cancer cells in bone.
Our work recently led to inclusion of myeloma patients in a clinical trial (NCT04077307).
I collaborate with researchers in Materials Science and Engineering to understand the mechanical and material properties of bone following anabolic therapy. I am also interested in the mechanisms by which bone regulates tumour dormancy and haematopoiesis.
This shows a mouse tibia with myeloma bone disease, and the same bone after 2 weeks of treatment with a bone anabolic (TGFβ inhibitor; SD-208) and chemotherapy (bortezomib and lenalidomide). For details on this study see our paper in JBMR.
Current Projects
- Sheffield Hospitals Charity Project Grant: ‘Targeting minimal residual disease to find a cure for myeloma’ .
- Publications
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Show: Featured publications All publications
Featured publications
Journal articles
- Targeting MTHFD2 to exploit cancer-specific metabolism and the DNA damage response. Cancer Research.
- Formate overflow drives toxic folate trapping in MTHFD1 inhibited cancer cells. Nature Metabolism, 5(4), 642-659.
- The role of the bone microenvironment in regulating myeloma residual disease and treatment. Frontiers in Oncology.
- Mediators of inflammation in bone physiology and diseases. Mediators of Inflammation, 2022. View this article in WRRO
- Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress. Nature Cancer, 3(2), 156-172. View this article in WRRO
- The characterization of distinct populations of murine skeletal cells that have different roles in B lymphopoiesis. Blood, 138(4), 304-317.
- TGFβ Inhibition Stimulates Collagen Maturation to Enhance Bone Repair and Fracture Resistance in a Murine Myeloma Model. Journal of Bone and Mineral Research, 34(12), 2311-2326. View this article in WRRO
- Mesenchymal lineage cells and their importance in B lymphocyte niches. Bone, 119, 42-56. View this article in WRRO
- Retinoic Acid Receptor γ Activity in Mesenchymal Stem Cells Regulates Endochondral Bone, Angiogenesis, and B Lymphopoiesis. Journal of Bone and Mineral Research, 33(12), 2202-2213. View this article in WRRO
- Extrinsic Regulation of Hematopoietic Stem Cells and Lymphocytes by Vitamin A. Current Stem Cell Reports, 4(4), 282-290.
- Preventing and repairing myeloma bone disease by combining conventional antiresorptive treatment with a bone anabolic agent in murine models. Journal of Bone and Mineral Research. View this article in WRRO
- Retinoic acid receptor signalling directly regulates osteoblast and adipocyte differentiation from mesenchymal progenitor cells. Experimental Cell Research, 350(1), 284-297. View this article in WRRO
- Retinoic Acid Receptor γ Regulates B and T Lymphopoiesis via Nestin-Expressing Cells in the Bone Marrow and Thymic Microenvironments. The Journal of Immunology, 196(5), 2132-2144.
- The role of vitamin A and retinoic acid receptor signaling in post-natal maintenance of bone. The Journal of Steroid Biochemistry and Molecular Biology, 155(A), 135-146.
- RARγ is a negative regulator of osteoclastogenesis. The Journal of Steroid Biochemistry and Molecular Biology, 150, 46-53.
Chapters
- Role of The Osteoclast in Cancer, Encyclopedia of Bone Biology (pp. 180-200). Elsevier
Conference proceedings papers
- Machine learning approaches for cancer bone segmentation from micro computed tomography images. Proceedings of 2020 IEEE 23rd International Conference on Information Fusion (FUSION) (pp 1-6). Rustenburg, South Africa, 6 July 2020 - 9 July 2020. View this article in WRRO
All publications
Journal articles
- Abstract B109: MTHFD1/2 inhibitor TH9619 targets the DNA damage response and causes cancer-specific folate trapping with an unprecedented therapeutic window. Molecular Cancer Therapeutics, 22(12_Supplement), B109-B109.
- Targeting MTHFD2 to exploit cancer-specific metabolism and the DNA damage response. Cancer Research.
- Formate overflow drives toxic folate trapping in MTHFD1 inhibited cancer cells. Nature Metabolism, 5(4), 642-659.
- The role of the bone microenvironment in regulating myeloma residual disease and treatment. Frontiers in Oncology.
- Mediators of inflammation in bone physiology and diseases. Mediators of Inflammation, 2022. View this article in WRRO
- Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress. Nature Cancer, 3(2), 156-172. View this article in WRRO
- The characterization of distinct populations of murine skeletal cells that have different roles in B lymphopoiesis. Blood, 138(4), 304-317.
- TGFβ Inhibition Stimulates Collagen Maturation to Enhance Bone Repair and Fracture Resistance in a Murine Myeloma Model. Journal of Bone and Mineral Research, 34(12), 2311-2326. View this article in WRRO
- Mesenchymal lineage cells and their importance in B lymphocyte niches. Bone, 119, 42-56. View this article in WRRO
- A population of nonneuronal GFRα3-expressing cells in the bone marrow resembles nonmyelinating Schwann cells. Cell and Tissue Research, 378(3), 441-456.
- Retinoic Acid Receptor γ Activity in Mesenchymal Stem Cells Regulates Endochondral Bone, Angiogenesis, and B Lymphopoiesis. Journal of Bone and Mineral Research, 33(12), 2202-2213. View this article in WRRO
- Extrinsic Regulation of Hematopoietic Stem Cells and Lymphocytes by Vitamin A. Current Stem Cell Reports, 4(4), 282-290.
- Preventing and repairing myeloma bone disease by combining conventional antiresorptive treatment with a bone anabolic agent in murine models. Journal of Bone and Mineral Research. View this article in WRRO
- Retinoic acid receptor signalling directly regulates osteoblast and adipocyte differentiation from mesenchymal progenitor cells. Experimental Cell Research, 350(1), 284-297. View this article in WRRO
- Retinoic Acid Receptor γ Regulates B and T Lymphopoiesis via Nestin-Expressing Cells in the Bone Marrow and Thymic Microenvironments. The Journal of Immunology, 196(5), 2132-2144.
- The role of vitamin A and retinoic acid receptor signaling in post-natal maintenance of bone. The Journal of Steroid Biochemistry and Molecular Biology, 155(A), 135-146.
- RARγ is a negative regulator of osteoclastogenesis. The Journal of Steroid Biochemistry and Molecular Biology, 150, 46-53.
- Wnt inhibitory factor 1 (WIF1) is a marker of osteoblastic differentiation stage and is not silenced by DNA methylation in osteosarcoma. Bone, 73, 223-232.
Chapters
- Role of The Osteoclast in Cancer, Encyclopedia of Bone Biology (pp. 180-200). Elsevier
Conference proceedings papers
- Machine learning approaches for cancer bone segmentation from micro computed tomography images. Proceedings of 2020 IEEE 23rd International Conference on Information Fusion (FUSION) (pp 1-6). Rustenburg, South Africa, 6 July 2020 - 9 July 2020. View this article in WRRO
- Machine Learning Approaches for Cancer Bone Segmentation from Micro Computed Tomography Images. PROCEEDINGS OF 2020 23RD INTERNATIONAL CONFERENCE ON INFORMATION FUSION (FUSION 2020) (pp 1263-1268)
Other
- Figure S1. from Targeting MTHFD2 to Exploit Cancer-Specific Metabolism and the DNA Damage Response.
- Data from Targeting MTHFD2 to Exploit Cancer-Specific Metabolism and the DNA Damage Response.
- Figure S1. from Targeting MTHFD2 to Exploit Cancer-Specific Metabolism and the DNA Damage Response.
- Data from Targeting MTHFD2 to Exploit Cancer-Specific Metabolism and the DNA Damage Response.
- Targeting MTHFD2 to exploit cancer-specific metabolism and the DNA damage response. Cancer Research.
- Grants
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Blood Cancer UK Project Grant (2023-2026) Karonudib: a novel treatment for myeloma. Dr A.C. Green & Dr H.E. Bryant (£280,000)
Sheffield Hospitals Charity Project Grant (2022-2023) ‘Targeting minimal residual disease to find a cure for myeloma’. Dr A.C. Green, Dr A.D. Chantry & Dr M.A. Lawson (£43,000).
WARP Funding (2022-2023) Dr A.C. Green. (£10,000).
NC3Rs studentship award (2021-2023). Development and validation of 3D in vitro dormant myeloma cell models to reduce and replace animal studies. Dr M.A. Lawson & Dr A.C. Green (£90,00).
Sheffield Hospitals Charity Project Grant (2018-2019). The plateau phase model: an improved murine model for testing novel anti-cancer and bone-repair therapies to cure myeloma. Dr A.C. Green, Dr A.D. Chantry & Dr M.A. Lawson (£30,000).
WARP Funding (2018-2019) Dr A.C. Green. (£10,000).
Pump-Prime Grant (2019) ‘Machine Learning Methods for 3D Bone Lesion Detection in Cancer-affected Bones’ Prof Lyudmila Mihaylova, Dr A.C. Green & Lingzhong Guo (£5,000).
- Teaching activities
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I lecture, tutor and provide research supervision on the MSc(Res) Translational Oncology course (OCP605, OCP606, OCP607) and lecture on MSc Molecular Medicine (MED6040).
- Professional activities and memberships
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I am a member of the ECTS Academy and was a committee member for the Bone Research Society (BRS) 2019-2023. I am a founding editorial board member for the International Federation for Musculoskeletal Research Societies (IFMRS)’s online learning environment HubLE.org, I am an editor of HubLE Publications and I was the Moderator for the first HubLE Debate; a panel discussion on Equality for Mothers in Research. I am a Review Editor for Frontiers in Cell and Developmental Biology and on the Reviewer Board for Cancers and I regularly peer-review for the Journal of Bone and Mineral Research (JBMR), Bone, FASEB Journal, Stem Cells International, Biomolecules, Nutrients and Cancers. I am currently a Guest Editor for a Special Issue in Frontiers in Cell and Developmental Biology: Skeletal abd Hematopoietic System Crosstalk: Roles of Metabolic and Endocrine Pathways.
Roles at TUOS
- Home Office Project Licence Holder.
- Faculty of Health Co-Lead for Supportive and Collaborative Culture (One University).
- ECR Representative, University ECR Committee.
- ECR representative on the Clinical Medicine Research Strategy Committee.
- Committee Member of the FoH Research Staff Association (RSA).
Memberships
- ECTS Academy Member
- Member of the Bone Research Society (BRS).
- Editorial Board Member of IFMRS HubLE.
- Member of NCRI ECR Forum.
- Member of UKRI ECR Forum.
- Member of the American Society for Bone and Mineral Research (ASBMR).
- Member of the Australia and New Zealand Bone and Mineral Society (ANZBMS).
- Member of the Cancer and Bone Society (CABS).
- Member of the European Calcified Tissue Society (ECTS).
- Member of the European Molecular Biology Laboratories (EMBL) Australia.
- Member of the British Association for Cancer Research (BACR).
Past committee roles
- Committee member of the BRS (2019-2023)
- Co-Founder, Co-President and Co-Chair for the EMBL Australia Inaugural PhD Symposium 2014.
- Co-President of the St Vincent’s Student Society 2013-2014.
- Committee Member of the BiomedLink Student Conference 2013, 2014.
- Awards
Throughout my research career I have received >20 highly competitive awards and scholarships for research innovation, academic achievement and outreach from organisations in Australia, the UK and internationally. In 2022, I was awarded a place in the European Calcified Tissue Society (ECTS) Academy.
Some of these include the Australian Postgraduate Award (Australian Federal Government), St Vincent’s Institute Foundation Award and the Postgraduate Research Experience Scholarship (The University of Melbourne).
I have been selected to give presentations of my work at >20 conferences for which I have received 2 Best Oral, 1 Best Snap Oral and 1 Best Poster award. I have also received 5 Young Investigator Awards, including the prestigious AIMM-ASBMR John Haddad Young Investigator Award.
In 2017, I was the winner of the Kroto Research Inspiration Poster Competition (The University of Sheffield).