Biography
I am a hematology physician scientist fascinated by how nutrition and metabolism can cause DNA damage in our body, how this can affect ageing and cancer, and motivated to translate this knowledge to novel therapy.
I am a MD PhD graduate from University of Cambridge, UK. My PhD was with Professor Michael Neuberger at the MRC Laboratory of Molecular Biology focusing on B cell immunology. I completed my residency clinical training at King’s College Hospital in London, followed by hematology specialist fellowship in Cambridge. During this time, I was awarded the Cancer Research UK Clinician Scientist Fellowship to conduct my postdoc with Professor KJ Patel and Professor George Vassiliou. I studied aldehydes as a metabolic source of DNA damage in blood stem cells that can cause leukemia and ageing of the bone marrow.
Since March 2023, I started my lab as Assistant Professor in the Division of Nutritional Science at Cornell University. My lab combines genetic models of DNA damage with ultra-sensitive mass spectrometry to identify novel metabolic sources of DNA damage, and to therapeutically target these pathways to improve health.
Research interests
The overarching research goals in my lab are to discover the chemicals produced within our body that cause DNA damage and understand how our genome is protected from these genotoxins. This knowledge could explain how health is maintained throughout human life and how/when it can go wrong thus leading to ageing and cancer.
Student opportunities
Indication of whether or not this person is accepting new undergraduate and graduate students is shown by academic year below.
Graduate students
| 2023 - 2024 | Available |
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Undergraduate students
| 2022 - 2023 | Available |
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| 2023 - 2024 | Available |
1. What are the identities and origins of the reactive metabolites that damage our DNA?
Everyday our genome suffers from a diverse range of chemical damage. Failure to repair such DNA damage can be catastrophic. To this end, we have evolved a diverse range of DNA repair pathways to protect our genome. Whilst some sources of DNA damage are known such as reactive products of water and oxygen, the genotoxic origin of many types of DNA damage remains elusive. What are these genotoxic metabolites? Are there diets or physiological states that regulate their production? To address these questions, we will utilise genetic, metabolomic and mass spectrometry methods to detect specific DNA damage, and trace their metabolic origins in cell line and murine models.
2. What are the consequences when the pathways that protect against these metabolic genotoxins fail?
We will use unbiased genetic screens in sensitised cellular models to identify the pathways that protect our genome against these metabolic genotoxins. Some of these pathways will be known DNA repair enzymes, but may also be metabolic detoxification proteins, or entirely novel pathways. We will then study the effects from inactivation of these pathways in cell lines and murine models to understand whether these genotoxins matter in physiology.
3. Can we therapeutically target these reactive genotoxins to improve health?
The majority of cancer treatment consistent of chemotherapy and radiotherapy that rely on inducing DNA damage to cancer cells. However these treatments lack specificity and inevitably lead to toxic side effects. If we are able to identify the metabolic pathways that generate endogenous genotoxins in cancer cells, perhaps we can harness these reactive metabolites for anti-cancer therapy. To explore these therapeutic potentials, we will interrogate the level of metabolic genotoxins in healthy and cancer tissues, combined with targeted methods and unbiased screens to identify cancer-specific vulnerabilities to these genotoxins.
First author:
Wang M, Brandt L, Wang X, Garaycoechea JI, Wilson N, Kingston SJ, Gottgens B, Patel KJ (2022) Aldehyde genotoxic stress prematurely ages hematopoietic stem cells in a p53 driven manner. Under revision
Wang M, Bolli N, Vassiliou G. The molecular basis of haematological malignancies. Postgraduate Haematology, Under revision
Wang M, Dingler FA, Patel KJ. Genotoxic aldehydes in the hematopoietic system. Blood, 2022 Apr 7;139(14):2119-2129. doi: 10.1182/blood.2019004316.
Dingler FA*, Wang M*, Mu A*,...Takata M, Patel KJ. (2020) Two aldehyde clearance systems are essential to prevent lethal formaldehyde accumulation in mice and humans. Molecular Cell, 80(6):996- 1012 *Joint authors.
Wang M, Wang W, Abeywardane A, et al. (2015). Autoimmune hemolytic anemia after allogeneic hematopoietic stem cell transplantation: analysis of 533 adult patients transplanted at King’s College Hospital, Biology of Blood and Marrow Transplantation, 21(1):60-6.
Wang M, Medeiros BC, Erba HP, Deangelo, DJ, Giles FJ, Swords RT (2011). Targeting protein neddylation: a novel therapeutic strategy for the treatment of cancer. Expert Opin Ther Targets 15, 253- 64.
Wang M, Rada C and Neuberger MS (2011). A high throughput assay for DNA deaminases. Methods in Molecular Biology 718, 171-84.
Wang M, Rada C and Neuberger MS (2010). Altering the spectrum of immunoglobulin V gene somatic hypermutation by modifying the active site of AID. The Journal of Experimental Medicine 207, 141-153.
Wang M, Yang Z, Rada C and Neuberger MS (2009). AID upmutants isolated using a high-throughput screen highlight the immunity/cancer balance limiting DNA deaminase activity. Nature Structural & Molecular Biology 16, 769-776.
Contributing author:
Wu RA, Semlow DR, Kamimae-Lanning AN, Kochenova OV, Chistol G, Hodskinson MR, Amunugama R, Sparks JL, Wang M, Deng L, Mimoso CA, Low E, Patel KJ, Walter JC. TRAIP is a master regulator of DNA interstrand crosslink repair. Nature. 2019 Mar;567(7747):267-272.
Kollmann K, Warsch W, Gonzalez-Arias C, Avezov E, Milburn J, Li J, Nice F, Dimitropoulou D, Biddie S, Wang M, Poynton E, Anand S, McDermott U, Huntly B, Green A (2017). A novel signalling screen demonstrates that CALR mutations activate essential MAPK signalling and facilitate megakaryocyte differentiation. Leukemia Apr;31(4):934-944.
Eskiocak U, Ramesh V, Gill JG, Zhao Z, Yuan SW, Wang M, Vandergriff T, Shackleton M, Quintana E, Johnson TM, DeBerardinis RJ, Morrison SJ (2016). Synergistic effects of ion transporter and MAP kinase pathway inhibitors in melanoma. Nature Communications 7:12336. doi: 10.1038/ncomms12336
Rajendra E, Oestergaard VH, Langevin F, Wang M, Dornan GL, Patel KJ and Passmore LA (2014). The Genetic and Biochemical Basis of FANCD2 Monoubiquitination. Molecular Cell 54, 858-69.
General Medical Registration (2011-present) to practice clinical medicine and hematology in the UK
Fellow of The Royal College of Pathologists
Membership of Royal College of Physicians (London)
Membership of British Society for Haematology
Clinical Research Associate - Department of Haematology, University of Cambridge
Associate Lecturer - Anglia Ruskin University Medical School
Bye-Fellow - Selwyn College, University of Cambridge
2023, Hematology Certificate of Completion of Training (US Board equivalent), Clinical Hematology, National Health Service
2022, Cancer Research UK Clinician Scientist Fellowship, Department of Haematology, University of Cambridge
2017, FRCPath, Hematology, Royal College of Pathology
2015, M.Phil, Clinical Sciences, University of Cambridge
2011, M.D., University of Cambridge Medical School
2010, Ph.D., Biological Sciences , MRC Laboratory of Molecular Biology, University of Cambridge
2005, B.A. (Cantab), Medical and Veterinary Science Tripos, University of Cambridge